warfarin and Blood-Coagulation-Disorders

Point-of-care (POC) testing is generally less precise and has higher reagent costs per test than laboratory-based assays. However, POC hemostasis testing can offer significant advantages in particular situations: patient-managed warfarin therapy as well as rapid turnaround time heparin management for intraoperative patients. Of note, POC hemostasis testing is generally approved for the purposes of anticoagulation monitoring and is inferior to laboratory coagulation testing for the diagnosis of congenital or acquired coagulopathy.. The frequently used POC coagulation instruments for POC international normalized ratio and activated clotting time are reviewed, as well as their typical performance relative to central laboratory testing (where available).. Several cases are discussed that highlight the benefits, as well as pitfalls, of POC coagulation testing.. POC coagulation testing for anticoagulation monitoring offers advantages in particular situations. Clear policies and protocols must be developed to guide proper use of POC versus central laboratory hemostasis testing.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Heparin; Humans; International Normalized Ratio; Point-of-Care Systems; Point-of-Care Testing; Warfarin

This article aims to review the latest literature on prophylactic and therapeutic anticoagulation and the safety profile of anticoagulants in patients with cirrhosis.. The understanding of hematological hemostasis is cirrhotic patients has changed drastically in recent years. Although in the past, cirrhotic patients were often considered to be 'auto-anticoagulated' and at higher risk of bleeding, recent studies have demonstrated that there may be a rebalance in procoagulation and anticoagulation factors in patients with cirrhosis. This, and clinical experience, suggest that cirrhotic patients are at risk of development of venous thrombosis, pulmonary embolism and ischemic strokes and as such, the best management approaches in these patients remains controversial. The bulk of the data suggest that patients with cirrhosis who are at risk for thrombotic or embolic complications should be anticoagulated. However, it is imperative that they be closely monitored.. The medical literature on anticoagulation in patients with liver cirrhosis is conflicting and limited to small sample observational studies. However, most studies suggest that in patients with early stages of liver cirrhosis and no history of varices, anticoagulation appears to be well tolerated.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Blood Coagulation Factors; Comorbidity; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Liver Cirrhosis; Partial Thromboplastin Time; Portal Vein; Prothrombin Time; Pulmonary Embolism; Stroke; Thrombosis; Venous Thrombosis; Warfarin

Cryptogenic stroke is one-fourth among cerebral infarction, but most of them could be ascribed to embolic stroke. ESUS was proposed for unifying embolic stroke of undetermined sources by Hart et al. in 2014. The etiologies underlying ESUS included minor-risk potential cardioembolic sources, covert paroxysmal atrial fibrillation, cancer-associated coagulopathy and embolism, arteriogenic emboli, and paroxysmal embolism. Extensive evaluation including transesophageal echocardiography and cardiac monitoring for long time could identify the etiology of these patients. Although anti-platelet drug is recommended in ESUS in the current guideline, clinical trials are ongoing to determine the efficacy of non-vitamin K antagonist oral anticoagulant in ESUS patients.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Blood Coagulation Disorders; Clinical Trials as Topic; Embolism; Foramen Ovale, Patent; Humans; Intracranial Embolism; Neoplastic Cells, Circulating; Platelet Aggregation Inhibitors; Stroke; Thrombolytic Therapy; Warfarin

Which antibiotics should you consider when a patient is taking warfarin? Which ones are associated with drug-induced, prolonged QT intervals? Read on.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anticoagulants; Bacterial Infections; Blood Coagulation Disorders; Drug Interactions; Female; Hemorrhage; Humans; Male; Middle Aged; Warfarin

Recent studies have greatly expanded our understanding of the coagulopathy of cirrhosis. It is clear that cirrhosis patients are at a risk of both bleeding and thrombosis. While prediction of these events remains challenging, cirrhosis patients are not protected from the development of venous and arterial thrombosis. In fact, studies show that hypercoagulability may promote hepatic decompensation and development of fibrosis. Anticoagulation for thrombosis is now becoming a common prospect in many clinical situations. Our understanding of the efficacy and safety of commonly used therapeutics is only beginning to emerge and the risks and benefits remain unclear in this unique population. In this review, we discuss the role of anticoagulation in the treatment and prevention peripheral and splanchnic thrombosis in patients with cirrhosis, as well as examine the potential role of anticoagulants in altering the progression of chronic liver disease.

Topics: Anticoagulants; Blood Coagulation Disorders; Heparin; Humans; Liver Cirrhosis; Venous Thrombosis; Warfarin

For patients undergoing colonoscopy with polypectomy, current guidelines recommend temporary cessation of blood-thinning medications. The data regarding periprocedural management of these medications are sparse.. To perform a systematic review and meta-analysis to determine the risk of post-polypectomy bleeding (PPB) in patients taking anti-platelet, anti-coagulant and/or thienopyridine medications.. We searched Pubmed, Scopus, Web of Science, Biosis and Proceedings First from 1970 to 2015. PPB was defined as overt haemorrhage or drop in haemoglobin of at least 2 g/dL.. Of 1490 articles identified, we included 3 papers and 1 abstract with patients on aspirin and/or NSAIDs, 1 paper on warfarin, 2 abstracts on clopidogrel, and 2 papers on clopidogrel plus aspirin and/or NSAIDs. While the rate of immediate PPB on aspirin and/or NSAIDs was not increased (OR = 1.1, 95% CI 0.7-1.9, P = 0.7), the risk of delayed PPB was increased (OR = 1.7, 95% CI 1.0-2.4, P = 0.0009, I(2)  = 60%) but rendered non-significant with elimination of a small study. There was an elevated risk of delayed PPB on clopidogrel (OR = 9.7, 95% CI 3.1-30.8, P = 0.0, I(2)  = 0). There was an increased risk of delayed PPB in patients on clopidogrel + aspirin and/or NSAIDs (OR = 3.4, 95% CI 1.3-8.8, P = 0.01, I(2)  = 0). Based on a single study on warfarin, the PPB rate was elevated. There were no data regarding PPB and usage of the newer anti-coagulant agents.. Usage of aspirin or NSAIDs does not increase risk of post-polypectomy bleeding. Clopidogrel and warfarin should be discontinued in the periprocedural period to prevent the occurrence of post-polypectomy bleeding.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Blood Coagulation Disorders; Colonic Polyps; Colonoscopy; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Pyridines; Risk Factors; Warfarin

The aim of the study was to summarize available literature regarding the interaction between vitamin K antagonists (VKAs) and trimethoprim-sulfamethoxazole (co-trimoxazole, TMP-SMX), and to provide recommendations for managing patient risk from this interaction. Data sources were English-language publications in the medical literature and Internet databases. Relevant publications that directly or indirectly addressed the VKA-TMP-SMX interaction were selected and reviewed. The mechanism of the VKA-TMP-SMX interaction, frequency of concurrent use, effect on international normalized ratio (INR), increased risk of bleeding, and strategies for risk reduction are summarized. The concurrent use of VKA and TMP/SMX rapidly and consistently raises INR and is associated with a two- to five-fold increase in bleeding. Concurrent use of VKA and TMP-SMX should be avoided when possible. When VKA and TMP-SMX are co-prescribed, VKA dose reduction is usually required. Patient education as well as early and frequent INR monitoring is recommended to reduce risk from this interaction.

Topics: Aged, 80 and over; Anti-Infective Agents; Anticoagulants; Blood Coagulation Disorders; Drug Interactions; Female; Humans; International Normalized Ratio; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin K; Warfarin

The heterogeneous Brazilian population, with European, African and Amerindian ancestral roots is a model case for exploring the impact of population admixture on the frequency distribution of polymorphisms in pharmacogenes, and the design and interpretation of pharmacogenomics trials. Examples drawn from studies carried out by researchers of the Brazilian pharmacogenomics network, support the following conclusions: the distribution of polymorphisms varies across geographical regions and self-reported 'race/color' categories, and is best modeled as continuous functions of individual proportions of European and African ancestry; the differential frequency of polymorphisms impacts the calculations of sample sizes required for adequate statistical power in clinical trials performed in different segments of the Brazilian population; and extrapolation of pharmacogenomics data from well-defined ethnic groups to Brazilians is plagued with uncertainty. Data for warfarin and tacrolimus are reviewed to highlight the advantages and challenges of performing pharmacogenomic trials in Brazilians.

Topics: Blood Coagulation Disorders; Brazil; Ethnicity; Genetics, Population; Haplotypes; Humans; Immunosuppression Therapy; Pharmacogenetics; Polymorphism, Single Nucleotide; Tacrolimus; Warfarin

To perform a meta-analysis of Russian prospective studies comparing the pharmacogenetic versus conventional warfarin dosing procedures.. Publications were sought in the PubMed and eLibrary through September 30, 2013. Seven prospective studies comparing the pharmacogenetic method of warfarin dosing with consideration for CYP2C9, VKORC1, and CYP4F2 gene polymorphisms with the conventional one were selected. The number of minor and major bleedings and hypocoagulation episodes was taken into account. The meta-analysis was performed using MIX Pro 2.0.. Six studies compared the number of bleedings in experimental and control groups. Analysis of statistical heterogeneity showed that extraneous factors did not influence the results of meta-analysis. The pharmacogenetic approach decreases the risk of bleeding. The pooled odds ratio (OR) was significant for minor (OR = 0.49; 95% confidence interval (CI), 0.31 to 0.78; p = 0.002), major (OR = 0.07; 95% CI, 0.008 to 0.54; p = 0.01) and both minor and major bleedings (OR = 0.49; 95% CI, 0.31 to 0.78; p = 0.002). Six studies estimated the number of hypocoagulation cases. There was no evidence for statistical heterogeneity (Q-test p = 0.13; I2 = 40%). Four studies showed a group difference in the number of hypocoagulation cases (p < 0.05). The pooled OR was 0.21 (95% CI, 0.15 to 0.3; p < 0.01). The pharmacogenetic dosing groups had fewer hypocoagulation episodes than the control ones.. The pharmacogenetic approach decreases the risk of bleeding and the episodes of hypocoagulation. The performed meta-analysis covered only two randomized trials. Improving the metalogic quality and statistical power of Russian studies will be able to get more reliable data on the impact of pharmacogenetic testing on clinical outcomes during warfarin therapy.

Topics: Anticoagulants; Blood Coagulation Disorders; Clinical Trials as Topic; Female; Hemorrhage; Humans; Male; Pharmacogenetics; Prospective Studies; Russia; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Factor VIIa; Female; Humans; Male; Monitoring, Physiologic; Plasma; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vitamin K; Warfarin

Topics: Ambulatory Care; Anticoagulants; Asymptomatic Diseases; Blood Coagulation Disorders; Humans; International Normalized Ratio; Risk Assessment; Warfarin

Two novel oral anticoagulants, dabigatran and rivaroxaban, have recently been approved. They differ in many ways from warfarin, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of need for monitoring, and no need for titration or dose adjustments. These novel agents represent a landmark shift in anticoagulant care; however, many aspects of their use will be unfamiliar to practicing clinicians, despite the imminent widespread use of these agents in the community. The management of these anticoagulants when transitioning from or back to warfarin, around surgery or in case of major hemorrhage, requires knowledge of their pharmacokinetics and mechanism of action. Unfortunately, there is a limited evidence base to inform decisions around management of these agents. We present our practice in these settings supported, where available, with literature evidence.

Topics: Anticoagulants; Blood Coagulation Disorders; Drug Interactions; Drug Substitution; Drug Therapy, Combination; Drugs, Investigational; Humans; Patient Selection; Platelet Aggregation Inhibitors; Time Factors; Warfarin

As chronic kidney disease (CKD) is a contraindication to the use of the new anticoagulants, the vitamin K antagonists (VKA) are still valid in patients with CKD, though their use may be harmful. During overanticoagulation, some patients can develop acute kidney injury (AKI), especially those with CKD, by obstruction of the renal tubules and Bowman's spaces by erythrocytes. In addition, VKA increase atherogenesis through vitamin K deficiency, which is essential for the carboxylation of proteins that inhibit calcification of vessels. Eventually, hemodialysed patients under VKA have an increased risk of stroke, especially those over 75 years of age. Therefore anticoagulation with VKA in patients with CKD should be carefully implemented and its monitoring more frequent than in non-CKD patients.

Topics: 4-Hydroxycoumarins; Acute Kidney Injury; Anticoagulants; Atherosclerosis; Blood Coagulation Disorders; Cerebrovascular Disorders; Coumarins; Humans; Indenes; Renal Insufficiency, Chronic; Vitamin K; Warfarin

Anticoagulant drugs are taken by millions of patients throughout the world. Warfarin has been the most widely prescribed anticoagulant for decades. In recent years, new oral anticoagulants have been approved for use, are being positioned as alternatives to warfarin, and represent an enormous market opportunity for pharmaceutical companies. Requests for urgent reversal of anticoagulants are not uncommon especially in the setting of critical bleeding. This review summarizes information on reversal of warfarin by vitamin K, plasma, prothrombin complex concentrates, and recombinant VIIa. In addition, we emphasize the lack of current evidence supporting reversibility of the new oral direct thrombin inhibitors and Factor Xa inhibitors. This review is presented to assist transfusion medicine specialists, hematologists, and other clinicians who prescribe blood components for reversal of drug-induced anticoagulation.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Hematology; Hemorrhage; Humans; Models, Biological; Plasma; Vitamin K; Warfarin

Patients with bleeding disorders pose a challenge for dentists. Most of these conditions can be safely treated in the general dental practice. Patients who are on anticoagulants represent a large group of bleeding disorders. This article reviews the latest evidence in regard to managing those patients. Most of the articles reviewed seem to agree on the negligible risk of modification or interruption of oral anticoagulants when performing most dental treatments because a decreased risk of excessive bleeding might be associated with an increased risk of thrombo-embolic complications. However, extensive pre-operative assessment is essential to reduce the risk of serious complications.. Patients with bleeding disorders pose a challenge for dentists. Adequate understanding of the underlying medical condition is essential to reduce the risk of dangerous complications.

Topics: Anticoagulants; Blood Coagulation Disorders; Dental Care for Chronically Ill; Heparin; Humans; Patient Care Planning; Perioperative Care; Risk Assessment; Warfarin

Thrombosis or thromboembolism are significant concerns in companion animals and can be associated with cardiac, metabolic, neoplastic disease processes or can be one manifestation of inflammatory, infectious, and neoplastic disease conditions. Options for thromboprophylaxis available for clinical use in small animal patients are very limited, with heparin (primarily unfractionated, but more recently low-molecular-weight forms) and aspirin predominating. Controlled studies evaluating the use of these drugs are few, but there is some limited evidence for efficacy in prevention of formation of thrombi. Use of the vitamin K antagonist warfarin has been described, but the narrow therapeutic window has resulted in a high rate of serious adverse events. In human patients, the efficacy of aspirin, heparins, and vitamin K antagonists is well documented in a variety of thrombotic conditions, but there are significant limitations to each of these options. These limitations have prompted the search for new alternatives, some of which are now in wide clinical use in humans. Although the use of some of the drugs discussed here has not yet been described in veterinary patients at risk for thrombosis, many of these agents have been evaluated experimentally in dogs, cats, or both. These new thromboprophylactic agents may soon be beneficial in management of small animal patients at risk for thrombosis.

Topics: Animals; Anticoagulants; Aspirin; Blood Coagulation Disorders; Cat Diseases; Cats; Clopidogrel; Dog Diseases; Dogs; Heparin; Platelet Aggregation Inhibitors; Thromboembolism; Ticlopidine; Warfarin

Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Drug Monitoring; Factor Xa Inhibitors; Hematology; Hemostasis; Humans; Thrombin; Vitamin K; Warfarin

Intracerebral hemorrhage in patients with warfarin-associated coagulopathy is an increasingly common life-threatening condition that requires emergent management. The evolution of therapeutic options in this setting, as well as recently published guidelines, has resulted in some heterogeneity in recommendations by professional societies. This heterogeneity can be attributed to lack of evidence-based support for plasma therapy; the variability in availability of prothrombin complex concentrates; the variability in the coagulation factor levels and contents of prothrombin complex concentrates; ambiguity about the optimal dose and route of administration of vitamin K; and the lack of standardized clinical care pathways, particularly in community hospitals, for the management of these critical care patients. In this review, we summarize the relevant literature about these controversies and present recommendations for management of patients with warfarin-associated coagulopathy and intracerebral hemorrhage.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Cerebral Hemorrhage; Female; Humans; Male; Vitamin K; Warfarin

Warfarin is the most common form of oral anticoagulant therapy. Although it has indisputable benefit in the management of thromboembolic disease, warfarin-associated coagulopathy (WAC) is a well-documented complication of its use. As warfarin exerts its effect by impairing formation of the vitamin K-dependent clotting factors, a cornerstone of WAC management is vitamin K replacement. Daily vitamin K supplementation is an emerging approach to regulate international normalized ratios in difficult-to-control patients. Mild WAC without bleeding can often be managed with warfarin withdrawal alone. For excessive international normalized ratio elevation in the absence of bleeding, low-dose oral vitamin K (1?2.5 mg) is sufficient and achieves the same degree of international normalized ratio correction by 24 h as intravenous therapy. The stable patient with WAC and minor bleeding can also be given oral vitamin K, with correction of the underlying defect. Major bleeding should first be managed with factor replacement for immediate correction of the coagulopathy, using either a prothrombin complex concentrate or fresh-frozen plasma. High-dose vitamin K (10 mg) should be given concurrently via intravenous infusion to confer lasting correction. Warfarin resistance and vitamin K-associated anaphylaxis are rare. Despite development of new oral anticoagulant therapy compounds, warfarin will probably retain a prominent role in thromboembolism management for several years to come.

Topics: Blood Coagulation Disorders; Humans; International Normalized Ratio; Vitamin K; Warfarin

Blood dose not normally coagulate in the blood vessels covered with endothelial cells, because these cells contain some substances responsible for antithrombotic action such as thrombomodulin, heparin-like substance, prostacyclin, nitric oxide and tissue plasminogen activator. Most important role of blood coagulation is hemostasis. Blood can coagulate in two ways: intrinsic coagulation pathway and extrinsic coagulation pathway that is activated by negatively charged substances and FVIIa-tissue-factor (TF) complex, respectively. Prothrombin time(PT) can represent extrinsic pathway, while activated partial thromboplastin time (APTT) can represent intrinsic pathway. PT is prolonged in such diseases as vitamin K deficiency, hepatic failure and warfarin intake, while APTT is prolonged such diseases as hemophilia A & B, von Willebrand disease and lupus anticoagulant. Cross mixing test is very useful to assess prolonged clotting time. FDP means fibrin/fibrinogen degradation products and D-dimer is the smallest products of fibrin degradation. These markers are often used to diagnose disseminated intravascular coagulation (DIC) and deep vein thrombosis (DVT). Thrombin-antithrombin complex (TAT) and plasmin-alpha2 plasmin inhibitor (PIC) can be used to evaluate the extent of coagulation and fibrinolysis activation, respectively. These two markers is essential for classify the pathophysiology of DIC: DIC with suppressed fibrinolysis, enhanced fibrinolysis or balanced fibrinolysis. In conclusion, exact interpretation of hemostatic and fibrinolytic markers is one of the most important abilities in clinical situation.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Dabigatran; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Hemostasis; Humans; Partial Thromboplastin Time; Plasminogen Activators; Prothrombin Time; Thrombomodulin; Warfarin

Numerous risk factors for instability of oral anticoagulation have been identified, including variability in vitamin K intake. However, few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a randomized clinical trial suggest that dietary vitamin K manipulation is a viable option for managing stability of oral anticoagulant therapy. The approach appears to be effective for those patients who are under-anticoagulated and consume a small number of vitamin K-rich food sources. While an encouraging option for management of warfarin therapy, longer-term studies in different patient populations are required.

Topics: Anticoagulants; Blood Coagulation Disorders; Drug Stability; Humans; Randomized Controlled Trials as Topic; Vitamin K; Warfarin

Pharmacologic therapies are essential in the management of patients with hemostatic and thrombotic diseases because these therapies are able to modify components of the coagulation pathway and platelet response. Nevertheless, responses to different drugs vary significantly, and the best clinical outcome frequently involves a delicate risk/benefit balance. The recent exponential growth of pharmacogenomics has led to the emergence of individualized medicine that has revolutionized modern medical practice, allowing for a deeper understanding of pathophysiology, increased diagnostic specificity, and better markers for risk stratification and an enhanced potential for gene therapy. Management of drugs prescribed to treat thrombotic and hemostatic abnormalities may benefit from pharmacogenetics, and our focus in this review will be on the pharmacogenetics related to some of the more common drugs that fall into this category.

Topics: Anticoagulants; Aspirin; Blood Coagulation Disorders; Drug Therapy; Environmental Monitoring; Hemostasis; Humans; Pharmacogenetics; Platelet Aggregation; Platelet Aggregation Inhibitors; Warfarin

D-dimer as an activation marker of coagulation and fibrinolysis is a recognized diagnostic criterion of deep vein thrombosis, pulmonary thromboembolism, and disseminated intravascular coagulation. In recent years, this laboratory test has been most frequently used for other purposes: to detect the activation of coagulation, to predict the course of diseases, and to determine the duration of anticoagulant therapy. Our investigation examined 1514 D-dimer measurements in 1370 outpatients without acute abnormalities, including 72 patients receiving warfarin and 32 patients after myocardial revascularization. 36.1% of cases were found to have values of more than 0.5 mkg/ml. Adequate anticoagulant therapy (INR 2-3) caused a reduction in the level of D-dimer that is an important additional laboratory test for the evaluation of antithrombotic defense. Further investigations are needed to determine cutoff values for various clinical situations.

Topics: Ambulatory Care; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Outpatients; Warfarin

Acute bleeding during oral anticoagulant therapy is a major challenge in medicine -with millions of patients receiving oral anticoagulant therapy worldwide, the frequency of severe bleeding episodes ranges from 2% to 13%, according to clinical trial data. The major risk associated with the use of oral anticoagulants is haemorrhage, which might be severe or even life-threatening. Treatment decisions for the reversal of oral anti-coagulation (OAC) depend on factors such as urgency of the situation, as determined by the international normalised ratios (INR), location and seventy of bleeding, and indication for anticoagulation. Currently available therapeutic options for the reversal of OAC include vitamin K for non-emergency situations and fresh frozen plasma (FFP) and coagulation factor concentrates such as prothrombin complex concentrate (PCC) for urgent situations. Complete and rapid reversal of warfarin-induced bleeding can be achieved more successfully with PCC than with FFP. In addition, PCC is associated with a more rapid normalisation of the INR and a better clinical outcome due to the balanced ratio of four vitamin-K-dependent clotting factors plus the coagulation inhibitors protein C and Protein S. PCC products containing four factors are the preferred option for the emergency reversal of OAC, according to some clinical treatment guidelines. Other advantages of PCC over FFP include smaller infusion volumes, no blood group testing and virus-inactivated blood product.

Topics: Anticoagulants; Blood Coagulation Disorders; Hemorrhage; Humans; Warfarin

Bleeding can be a major problem in patients on oral anticoagulation therapy. Beriplex P/N is a prothrombin complex concentrate (PCC) that has been developed for the rapid reversal of anticoagulation in patients requiring immediate haemostatic control. Beriplex P/N contains high concentrations of the coagulation factors II, VII, IX and X, together with the inhibitors protein C and protein S, and it can be rapidly prepared and administered at an infusion rate of up to 8.0 mL/min. The efficacy of Beriplex P/N in patients requiring emergency reversal of oral anticoagulation has been demonstrated in a prospective, open-label, uncontrolled study involving 43 patients; 17 with acute bleeding and 26 requiring emergency surgery. Beriplex P/N was administered at a dose of 25-50 IU/kg, according to baseline international normalised ratio (INR) in conjunction with vitamin K. Mean INR 30 minutes post-infusion was 1.18, and 93% of patients achieved an INR of

Topics: Anticoagulants; Blood Coagulation Disorders; Clinical Trials, Phase III as Topic; Drug Combinations; Factor IX; Factor VII; Factor X; Humans; Prothrombin; Warfarin

Patients taking oral anticoagulants with an international normalized ratio (INR) greater than 4.0 are at increased risk for bleeding. We performed a meta-analysis to determine the effectiveness of phytonadione (vitamin K) in treating excessive anticoagulation.. The MEDLINE, EMBASE, and Cochrane Library databases were searched (without language restrictions) for articles published between January 1985 and September 2004. Randomized controlled trials or prospective, nonrandomized trials that used vitamin K to treat patients without major hemorrhage with an INR greater than 4.0 due to oral anticoagulant use were included. The primary outcome was achievement of the target INR (1.8-4.0) at 24 hours after vitamin K administration. Summary estimates were calculated using a random effects model.. Twenty-one studies (10 randomized and 11 prospective trials) were included. Among oral vitamin K treatment arms (4, n = 75), the proportion with a target INR at 24 hours was 82% (95% confidence interval [CI], 70%-93%), which was similar to intravenous vitamin K treatment arms (6, n = 69; target INR, 77%; 95% CI, 60%-95%). Treatment arms of subcutaneous vitamin K (3, n = 58; 31%; 95% CI, 7%-55%) and placebo/observation (2, n = 27; 20%; 95% CI, 0%-47%) were less likely to achieve target INR at 24 hours. Only 1 of 21 trials appropriately assessed for adverse events, so a summary estimate for bleeding risk could not be generated.. Limited evidence suggests that oral and intravenous vitamin K are equivalent and more effective for excessive anticoagulation than simply withholding warfarin sodium. Subcutaneous vitamin K, however, is inferior to oral and intravenous vitamin K for this indication and is similar to placebo. Whether treatment with vitamin K decreases hemorrhagic events cannot be determined from the published literature.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Clinical Trials as Topic; Humans; International Normalized Ratio; Vitamin K 1; Warfarin

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Blood Coagulation Disorders; Humans; Practice Guidelines as Topic; Reference Standards; Risk Factors; Stroke; Warfarin

Excessive anticoagulation is a frequent complication of anticoagulant therapy. The risk of hemorrhage approximately doubles for each one point increase in the International Normalized Ratio (INR) above 3.0. Reducing a prolonged INR to within the desired therapeutic range requires that oral anticoagulants be withheld. In addition, vitamin K may be administered. Since this latter treatment can produce rapid reductions in the INR, it must be carefully tailored to meet individual needs, balancing the risk of bleeding against the potential risk of causing thromboembolism.. To review available literature on the management of coumarin-associated coagulopathy in asymptomatic patients, a Medline search was carried out and papers published in English from 1966 and 2003 were identified. All available information on the management of asymptomatic patients presenting with coumarin-associated coagulopathy was analyzed.. Following the results of clinical studies that only used an elevated INR as a surrogate end-point for the risk of bleeding, low dose oral vitamin K appears as the preferable strategy for rapidly restoring therapeutic INR levels in asymptomatic patients who present with an excessively prolonged INR due to warfarin therapy. For the treatment of patients with asymptomatic acenocoumarol-induced coagulopathy, vitamin K does not add any benefit to the strategy of simply withholding oral anticoagulant treatment.. Large randomized trials using clinical end-points are now required to provide evidence-based treatment recommendations for patients with coumarin-associated coagulopathy.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Costs and Cost Analysis; Coumarins; Hemorrhage; Humans; International Normalized Ratio; Risk Factors; Vitamin K; Warfarin; Withholding Treatment

Dental patients often give a medical history that suggests the possibility of a coagulopathy from drugs, with a corresponding risk for prolonged bleeding during and following an invasive procedure. Identification of patients who may be prone to oral bleeding requires specific medical history information and the proper use of laboratory tests. Some NSAIDs are reported to cause prolonged oral bleeding, but scientific evidence is lacking. Likewise, the risk of oral bleeding from anticoagulants such as warfarin is often over stated, and unnecessary adjustment of NSAID or warfarin dosage puts patients at risk for significant morbidity and mortality. Some commonly employed laboratory tests such as the prothrombin time provide helpful information when used in the appropriate setting, but others, such as the bleeding time test, provide little or no predictive value in the determination of patients at risk for oral bleeding. Dental management of patients with potential coagulopathies from medications requires an understanding of basic principles of coagulation. The vast majority of these patients can be managed in the community setting without risk and without alteration of anticoagulant drug regimes.

Topics: Alcohol Drinking; Algorithms; Analgesics; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antineoplastic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Dental Care for Chronically Ill; Dietary Supplements; Humans; Oral Hemorrhage; Warfarin

Venous thrombosis is a cause of considerable morbidity and is often responsible for chronic venous disorders that frequently lead to visits to dermatologists and others involved in wound healing. Over the past several years, many new causes of thrombophilia have been identified and have dramatically altered the approach to patients presenting with thrombosis. Newly described abnormalities associated with thrombophilia include the syndrome of activated protein C resistance, the prothrombin 20210A mutation, hyperhomocysteinemia, and elevated levels of coagulation factors VIII and XI. Clinicians can now frequently determine causes of thromboses that have previously been deemed idiopathic.

Topics: Activated Protein C Resistance; Anticoagulants; Blood Coagulation Disorders; Contraceptives, Oral; Factor V; Female; Humans; Hyperhomocysteinemia; Mutation; Pregnancy; Pregnancy Complications, Cardiovascular; Prothrombin; Recurrence; Risk Factors; Warfarin

Warfarin therapy has proved safe and effective in a number of randomized controlled trials of stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF), reducing the risk of stroke in these patients by two thirds. However, participants in the clinical trials were carefully selected and younger than patients in actual clinical practice.. This analysis sought to determine whether the results of clinical trials in patients with NV can be extrapolated to the general population seen in clinical practice.. A MEDLINE search from 1966 to the present was used to identify observational trials of anticoagulation in patients with NVAF that addressed warfarin use, anticoagulation control, efficacy, and complications. The search terms used were atrial fibrillation and anticoagulation.. Although warfarin prophylaxis against stroke in patients with NVAF appeared to be as well tolerated and effective in clinical practice as in clinical trials, it was generally underused, particularly in the elderly. Anticoagulation control was not as good in clinical practice as in clinical trials, although the rates of stroke and major bleeding were comparable.. Judicious use of warfarin, tailored to individual stroke risk, seems to be a reasonable policy. Warfarin therapy increases quality-adjusted survival in patients at high risk for stroke, and it is recommended for medium-risk patients unless their risk of bleeding is high or their quality of life while taking warfarin would be poor. Patients at a low risk for stroke will have equivalent health outcomes and incur lower costs if treated with aspirin. Despite the increased risk of hemorrhage in elderly patients, the net benefit of warfarin therapy is greater in this age group because of the higher risk of stroke. Active involvement of patients and their caregivers in an anticoagulation service setting may improve outcomes of anticoagulation therapy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Clinical Trials as Topic; Cost-Benefit Analysis; Humans; MEDLINE; Stroke; Warfarin

People without hemophilia but with autoantibodies specifically directed against the procoagulant activity of factor VIII are known to have acquired hemophilia. The bleeding diathesis in these patients is often severe and life-threatening. The definite laboratory diagnosis of this disorder includes demonstration of low factor VIII levels in plasma with a high titer of factor VIII inhibitors, but the initial suspicion for its presence should rise in view of a prolonged partial thromboblastin time (PTT) and a normal prothrombin time associated with an acquired bleeding disorder. Oral anticoagulant treatment is known to prolong PTT as well, and the merger of these 2 situations may cause delayed diagnosis of acquired hemophilia with devastating consequences. We describe here the first reported case of acquired hemophilia diagnosed in a patient treated with warfarin. In such patients prolonged PTT may be ascribed to warfarin therapy rather than to acquired hemophilia, thus causing a dangerous delay in diagnosis.

Topics: Aged; Anticoagulants; Autoantibodies; Blood Coagulation Disorders; Diagnosis, Differential; Factor VIII; Female; Hemophilia A; Humans; Partial Thromboplastin Time; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Dental Care for Chronically Ill; Genetic Therapy; Hemophilia A; Humans; International Normalized Ratio; Male; Self Administration; von Willebrand Diseases; Warfarin

Treatment with coumarin oral anticoagulants, such as warfarin, is effective antithrombotic therapy, but patients treated with these drugs are at significant risk of bleeding. The risk of haemorrhage increases with increasing intensity of anticoagulation and overanticoagulation is common. Reversal can be achieved by stopping the coumarin drug or administration of vitamin K, fresh frozen plasma or coagulation factor concentrates. However, there are surprisingly few studies defining the optimum dose of these products and there are no randomized studies comparing the relative benefit and risk of coagulation factor concentrates versus fresh frozen plasma. Guidelines for the management of overdose are based on level III and IV evidence and are, therefore, only grade B recommendations at best. Further studies are required to determine the most effective use of products and the dose required for safe reversal of overanticoagulation.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Drug Overdose; Hemorrhage; Humans; Plasma; Vitamin K; Warfarin

Nonvalvular atrial fibrillation is associated with an overall risk of stroke of 4.5% per year. Advancing age, prior stroke or transcient cerebral ischemia, diabetes and hypertension are known risk factors. Ischemic stroke in patients with atrial fibrillation are generally more severe than ischemic stroke in patients with sinus rhythm. Warfarin is effective for primary and secondary prevention of ischemic stroke, reducing the risk by 68%. The effect of aspirin is still controversial, reducing the risk by 18-44%. Recent clinical trials have investigated the effect of warfarin given at a very low intensity either alone or combined with aspirin. The results from the SPAF III study demonstrated that a combination of mini-intensity warfarin plus aspirin was insufficient for stroke prevention in atrial fibrillation. Other trials now indicate, that oral anticoagulation at INR-values below 2.0 is not effective for stroke prevention in these patients. It is recommended that patients at high risk of stroke are treated with warfarin at an intensity of INR 2.0-3.0. Patients younger than 65 without other risk factors can be given aspirin 325 mg/day. The present clinical challenge is to ensure effective and safe oral anticoagulation to patients with atrial fibrillation at high risk of stroke.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Cerebrovascular Disorders; Hemorrhage; Humans; Risk Factors; Thromboembolism; Warfarin

Warfarin, like all the 4-hydroxycoumarin compounds, has an asymmetric carbon atom. The clinically available warfarin preparations consist of a racemic mixture of equal amounts of 2 distinct S and R isomers, the former being 4-times more potent as anticoagulant and more susceptible to drug interaction. Warfarin is highly water soluble and rapidly absorbed from the stomach and the upper gastrointestinal tract; its plasma concentrations peak 60 to 90 minutes after oral administration. Warfarin binds to the enzyme vitamin K 2,3-epoxide reductase in liver microsomes, stopping the cycle of vitamin K and reducing gamma-carboxylation of the precursors of vitamin D-dependent pro- and anticoagulant factors. A variable fraction of the binding with the target enzyme, albeit small, can be reversed by competitive displacers, such as dithiol-reducing agent activity. Differences in dithiol-reducing activity have been suggested as a contributing factor to the wide interindividual differences in sensitivity to oral anticoagulants. The anticoagulant effect is caused by a small fraction of the drug, since most (97 to 99%) is protein bound (mainly to albumin) and ineffective. Drugs that can displace the albumin binding will increase the action of warfarin, even though this effect is counteracted by a more rapid elimination of the drug. The elimination half-life of warfarin varies greatly among individuals, ranging from 35 to 45 hours; the S isomer has, however, an average half-life shorter than the R isomer. The plasma levels of vitamin K-dependent proteins are determined by a dynamic equilibrium between their synthesis and half-life times. The delay before warfarin takes effect reflects the half-life of the clotting proteins; the levels of factor VII and protein C (with shorter half-lives) are reduced earlier, reaching steady inhibited levels in about 1 day, whereas factor II takes more than 10 days. Oral anticoagulant therapy (OAT) with warfarin or other coumarin derivatives is increasingly administered to patients for primary or secondary prevention of various arterial or venous thromboembolic diseases. If in some clinical conditions OAT is given indefinitely, in others--such as venous thromboembolism or after tissue heart valve replacement--anticoagulants are usually given only for the high risk period of thrombotic complication. A recent large prospective study performed by the Italian Federation of Anticoagulation Clinics showed that about 30% of the patients who began

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Humans; Thromboembolism; Warfarin

We describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.

Topics: Acenocoumarol; Administration, Oral; Age Factors; Blood Coagulation Disorders; Contraindications; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Female; Genetic Predisposition to Disease; Heparin; Homozygote; Humans; Middle Aged; Necrosis; Protein C Deficiency; Skin; Skin Diseases; Thrombophlebitis; Warfarin

Activation of coagulation and of the fibrinolytic system has been identified in small cell and non-small cell cancers respectively. For the clinician this poses the diagnostic problem of a thrombosis, which is most often venous with or without pulmonary emboli, complicating the evolution of an already diagnosed cancer. The inverse is that these features may reveal an underlying neoplasm and amongst the most common of these would be bronchopulmonary cancer. Numerous laboratory studies have shown the existence of a state of hyper-coagulability, with disseminated intra-vascular coagulation, which is more or less compensated and is the more marked, the more advanced the cancer is. One should not fail to recognise that this state of hyper-coagulability may be aggravated by certain cytotoxic drugs. At the level of the tumour itself, there seems to be interactions between the cancer cells and the coagulation and fibrinolytic system: these interactions are very different according to the histological type as to whether they are small cell or non-small cell bronchopulmonary cancers.

Topics: Anticoagulants; Antineoplastic Agents; Blood Coagulation; Blood Coagulation Disorders; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Disseminated Intravascular Coagulation; Female; Fibrinolysis; Humans; Lung Neoplasms; Male; Middle Aged; Randomized Controlled Trials as Topic; Thromboembolism; Thrombosis; Warfarin

Significant advances have been made in defining the regulatory mechanisms that control blood clotting. These are reviewed, with special attention to the functions of the natural inhibitors antithrombin III, protein C, and protein S. Congenital deficiencies of these inhibitors as well as acquired abnormalities, such as defective fibrinolysis, and their role in promoting thrombosis are also discussed, as are thrombotic complications of pregnancy. Pregnancy decreases levels of protein S to 40% to 50% of normal levels. The decrease occurs early in pregnancy and persists into the postpartum period; it appears to be a hormonal rather than a dilutional effect. It is not known whether the thrombotic risk associated with pregnancy is increased in women who are congenitally deficient in protein S. Oral contraceptives decrease levels of protein S by about 20%. Women with a personal or family history of thrombosis should be evaluated for predisposing conditions before they start an oral contraceptive, as should women taking oral contraceptives who develop deep venous thrombosis.. Most people who experience venous thrombosis have normal hemostasis. Some people have inherited deficiencies of protein C, protein S, and antithrombin iii. They tend to have deep venous thrombosis which increases their risk for pulmonary emboli. Some acquired disorders which predisposes people to thrombosis include defective fibrinolysis which often occurs after surgery or infection, Trousseau's syndrome (excessive coagulant activity linked with adenocarcinoma), and lupus anticoagulant which is an immunoglobulin G or M antibody directed against negatively charged phospholipids. Hormones and probably not a dilution effect reduces free and bound protein S levels during pregnancy. Functional protein S activity is still 40-50% below normal levels 1-3 days after delivery. This decrease appears to protect against bleeding but does have venous thrombosis and pulmonary emboli during pregnancy as side effects. Non-oral-contraceptive (OC) users have greatly higher protein S levels than do OC users (28.6 mcg/ml vs. 24.3 mcg/ml; p.005) which gives more credence to the belief that hormones are responsible for the fall in protein S activity during pregnancy. OCs reduce free and total protein S levels almost 20%. Smoking may even further reduce these levels in women during pregnancy and who use Ocs. Women who have had venous thrombosis should not use OCs. Physicians should also consider family history especially age of affected family member, severity of thrombotic episodes, and the clinical setting. They should look for an underlying abnormality in patients who develop thrombosis while using OCs. If thrombosis develops during pregnancy, physicians should call for a venogram, venous duplex scanning, and, if required, invasive tests. The most sensible treatment is intravenous heparin for 5-7 days then therapeutic doses of heparin. Heparin therapy should stop before delivery and be reinstituted shortly thereafter and continued throughout the postpartum period. Physicians should take extra precautions when performing surgery on an OC user.

Topics: Antithrombin III; Antithrombin III Deficiency; Blood Coagulation; Blood Coagulation Disorders; Contraceptives, Oral; Female; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Protein C; Protein C Deficiency; Protein S; Protein S Deficiency; Recurrence; Thrombophlebitis; Warfarin

The sudden development of cyanotic lesions on the feet may be a result of atheroembolic disease or a number of medical conditions. A careful history and physical examination, basic laboratory tests, and noninvasive vascular assessment usually distinguish between medical and surgical causes and direct the choice of further investigations. Specific therapy is often available for medical conditions causing this syndrome. The management of atheroembolic disease is more controversial. In particular, further research is necessary to determine which patients need surgical intervention and which patients can be managed safely by medical therapy.

Topics: Adrenal Cortex Hormones; Blood Coagulation Disorders; Calcinosis; Cyanosis; Embolism; Humans; Ischemia; Postoperative Complications; Skin Diseases; Syndrome; Toes; Vasculitis; Warfarin

Topics: Acute Disease; Adolescent; Adult; Aged; Antithrombin III Deficiency; Blood Coagulation; Blood Coagulation Disorders; Female; Fibrinogen; Fibrinolysis; Glycoproteins; Humans; Male; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Protein C; Thrombophlebitis; Warfarin

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Clofibrate; Ecchymosis; Humans; Male; Middle Aged; Prothrombin Time; Vitamin E; Vitamin K; Warfarin

Topics: Anticoagulants; Biopsy; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Drug Resistance; Drug Synergism; Factor IX; Factor VII; Factor X; Fibrinolysis; Humans; Liver; Liver Diseases; Prothrombin; Vitamin K; Vitamin K Deficiency; Warfarin

Warfarin-associated coagulopathy commonly occurs in patients undergoing treatment with this anticoagulant. This trial aimed to determine the efficacy of using low-dose orally administered vitamin K. This was a double-blind, placebo-controlled, randomized trial. Chinese patients with mechanical heart valves who were undergoing warfarin treatment and who had INR values from 4.0 to 10.0 without bleeding were the subjects of this study. These patients were randomized into two treatment groups and were orally administered either vitamin K. In total, 80 patients were enrolled in the present study, and 40 patients each were assigned to the placebo and vitamin K1 treatment groups. Patients administered vitamin K. Low-dose oral vitamin K

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; China; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Vitamin K 1; Warfarin

The Q analyzer is a recently launched fully automated photo-optical analyzer equipped with primary tube cap-piercing and capable of clotting, chromogenic, and immunoturbidometric tests. The purpose of the present study was to evaluate the performance characteristics of the Q analyzer with reagents from the instrument manufacturer. We assessed precision and throughput when performing coagulation screening tests, prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen assay by Clauss assay. We compared results with established reagent instrument combinations in widespread use. Precision of PT/INR and APTT was acceptable as indicated by total precision of around 3%. The time to first result was 3  min for an INR and 5  min for PT/APTT. The system produced 115 completed samples per hour when processing only INRs and 60 samples (120 results) per hour for PT/APTT combined. The sensitivity of the DG-APTT Synth/Q method to mild deficiency of factor VIII (FVIII), IX, and XI was excellent (as indicated by APTTs being prolonged above the upper limit of the reference range). The Q analyzer was associated with high precision, acceptable throughput, and good reliability. When used in combination with DG-PT reagent and manufacturer's instrument-specific international sensitivity index, the INRs obtained were accurate. The Q analyzer with DG-APTT Synth reagent demonstrated good sensitivity to isolated mild deficiency of FVIII, IX, and XI and had the advantage of relative insensitivity to mild FXII deficiency. Taken together, our data indicate that the Q hemostasis analyzer was suitable for routine use in combination with the reagents evaluated.

Topics: Anticoagulants; Automation; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Chromogenic Compounds; Coagulation Protein Disorders; Colorimetry; Drug Monitoring; Equipment Design; Fibrinogen; Heparin; High-Throughput Screening Assays; Humans; Indicators and Reagents; International Normalized Ratio; Nephelometry and Turbidimetry; Partial Thromboplastin Time; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Warfarin

Increasing numbers of children are being administered warfarin therapy as thromboprophylaxis. Warfarin has a narrow therapeutic window with a target international normalised ratio (INR) of 2-3.5, called the therapeutic range. The length of time a patient's INR remains within the therapeutic range is calculated as 'time in the therapeutic range'. Risk for haemorrhage in children receiving warfarin is 0.5%/patient-year and minor bleeding 2.3%/patient-year, which increases exponentially for INRs >5.0. Practice among non-bleeding adults with INRs ≥5 and ≤9 is to withhold warfarin and allow the INR to return to the therapeutic range. Faster warfarin clearance is correlated with younger age.. The study objective was to determine the safety and effectiveness of a conservative approach for management of INRs >5 in children receiving warfarin. Children receiving warfarin with INRs ≥5 had warfarin withheld followed by a next day INR without vitamin K administration. Eighty-nine children (1-16 years) participated in the study with 2353 INRs performed. Twenty-six children had INRs ≥5, 5% of the total performed, with a mean INR of 5.9. The next day repeat mean INR after withholding one dose of warfarin was 3.3 (range 1.2-6.8) with 89% of INRs falling below 5. There were no overt bleeds or symptomatic thrombotic events in the month following the INR >5. Time in the therapeutic range for children with INRs ≥5 was 68%.. Withholding warfarin alone for management of non-bleeding INRs ≥5 and ≤8 appears to be safe and effective.

Topics: Adolescent; Anticoagulants; Blood Coagulation Disorders; Child; Child, Preschool; Drug Administration Schedule; Drug Monitoring; Humans; Infant; International Normalized Ratio; Prospective Studies; Thrombosis; Treatment Outcome; Warfarin

Patients receiving warfarin who have unstable control of anticoagulation have a significantly lower intake of dietary vitamin K compared with their stable counterparts. We hypothesized that supplementation with oral vitamin K would improve stability in patients with previously unstable control of anticoagulation. Seventy warfarin-treated patients with unstable anticoagulation control were randomly assigned in a double-blinded fashion to receive a daily amount of 150 mug oral vitamin K or placebo orally for 6 months. Measures of stability of anticoagulation control in the 6-month study period were compared with those in the 6 months immediately prior to it. Vitamin K supplementation resulted in a significantly greater decrease in standard deviation of international normalized ratio (INR) compared with placebo (-0.24 +/- 0.14 vs -0.11 +/- 0.18; P < .001) and a significantly greater increase in percentage time within target INR range (28% +/- 20% vs 15% +/- 20%; P < .01). Anticoagulation control improved in 33 of 35 patients receiving vitamin K supplementation; of these, 19 fulfilled our criteria for having stable control of anticoagulation. However, only 24 of 33 patients receiving placebo demonstrated some degree of improvement, with only 7 patients fulfilling the criteria for having stable control. Concomitant supplementation of vitamin K, perhaps through reducing the relative day-to-day variability in dietary vitamin K intake, can significantly improve anticoagulation control in patients with unexplained instability of response to warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Dietary Supplements; Drug Stability; Female; Humans; Male; Middle Aged; Vitamin K; Warfarin

We determine the efficacy of active reversal of warfarin anticoagulation with intravenous vitamin K compared to withholding warfarin in patients requiring urgent orthopedic trauma surgery.. This was a prospective cohort with immediate prehypothesis consecutive retrospective comparative case series conducted at a level 1 university hospital trauma unit.. Forty-eight consecutive patients between 1998 and 2004 in a study composed of a prospective cohort were compared with a retrospective consecutive case series of warfarinized orthopedic trauma patients requiring urgent surgery. The prospective arm directly followed the historic case series from which the hypothesis was generated.. Vitamin K administration.. Primary outcome was time to surgery. Secondary outcomes were problems with active reversal, length of time for warfarin stabilization after surgery, and complications.. The mean time to surgery in warfarinized patients not given vitamin K was 111.9 hours; in the intervention group, it was 67.4 hours, giving a mean difference of 44.5 hours (P = 0.01). Vitamin K reduced the international normalized ratio (INR) to less than 2.0 in 74% of patients within 24 hours. There were no complications of vitamin K administration. A dose of vitamin K costs approximately 1/1000 of a hospital bed day cost. A loading dose of warfarin on the second postoperative day took approximately 1 day longer to reach an INR of greater than 2.0 in the intervention patients than in those who had not been given vitamin K.. Warfarin reversal with vitamin K was successful and facilitated earlier surgery in all patients; the first dose was effective in approximately three quarters of patients. It is cost-effective, with no side effects caused in this study.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Cohort Studies; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Male; Orthopedic Procedures; Preoperative Care; Thrombosis; Treatment Outcome; Vitamin K; Warfarin; Wounds and Injuries

Patients on warfarin for mechanical heart valves are at increased risk for thromboembolic events and intracranial hemmorhage. In current guidelines, a low dose of vitamin K is the recommended treatment for moderate over-anticoagulation based on studies in which only minority patients participating had mechanical heart valves. We performed a randomized controlled trial to compare the efficacy and safety profile of low-dose intravenous vitamin K and fresh frozen plasma (FFP) for patients with mechanical heart valves and mild to moderate over-anticoagulation (international normalized ratio [INR] 4 to 7). In a 24-month period, we randomized 102 patients to (1) vitamin K or (2) FFP. The baseline INR at presentation between the vitamin K group and the FFP group was 4.61 +/- 0.007 vs 4.78 +/- 0.07 (p = 0.11). Six hours after treatment, patients in the FFP group had a significantly lower mean INR compared with the vitamin K group (2.75 +/- 0.06 vs 3.44 +/- 0.10, p = 0.01). No patient in both groups had over-correction (INR < 2). One week later, there was no significant difference in mean INR between both groups (2.7 +/- 0.11 vs 2.56 +/- 0.12, p = 0.41). Fifty-eight percent of patients in the FFP group and 51% in the vitamin K group had an INR within the target range. There were no adverse reactions or outcomes in both groups. In conclusion, intravenous low-dose vitamin K is a safe alternative to FFP infusion for warfarin overdose in patients with mechanical heart valves.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Component Transfusion; Coagulants; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Infusions, Intravenous; International Normalized Ratio; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Vitamin K; Warfarin

Several studies suggest that patient self-management (PSM) may improve the quality of oral anticoagulation therapy as measured by time spent within the international normalised ratio (INR) target range. We performed a prospective randomised control trial to determine whether the improvement in quality of treatment afforded by PSM is greater than that achieved by patient self-testing (PST) alone. A total of 104 of 800 eligible patients aged 22-88 years (median = 59.8), attending our hospital anticoagulant clinic and receiving long-term warfarin for >8 months agreed to participate. Patients were randomised to PSM (n = 55) or PST (n = 49). Both groups measured their INR using the CoaguChek S every 2 weeks or more frequently if required, for a period of 6 months. Seventy-seven of 104 (74%) patients completed the study (PSM = 41 and PST = 36). The 'drop out' rates for both groups were similar. There was no significant difference between the percentage time in target therapeutic range for PSM (69.9%) and PST (71.8%). Both groups combined showed a significant improvement over the previous 6 months (71.0% vs. 62.5%; P = 0.04). Changes in time within the therapeutic range in individual patients (+5.86) also showed a significant difference. The quality of warfarin control in both PST and PSM may be superior to that achieved by conventional management in a specialised hospital anticoagulation clinic.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Female; Humans; International Normalized Ratio; Male; Middle Aged; Patient Compliance; Prospective Studies; Quality Control; Self Administration; Self Care; Treatment Outcome; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Female; Heart Valve Prosthesis; Humans; International Normalized Ratio; Male; Middle Aged; Vitamin K; Warfarin

To evaluate the effect of anticoagulant therapy on the survival of patients with idiopathic pulmonary fibrosis (IPF).. Prospective study.. Five hospitals located in the Miyagi prefecture in Japan, including a university hospital, a Red Cross hospital, two public general hospitals, and a municipal hospital.. Fifty-six patients with IPF (mean age, 69.4 years; range, 47 to 89) admitted to the hospitals from April 2001 to April 2004.. Patients were assigned to receive prednisolone alone or prednisolone plus anticoagulant therapy. The anticoagulants included oral warfarin in an outpatient setting and low-molecular-weight heparin for rehospitalized patients with severely progressive respiratory failure.. There was no difference in baseline characteristics, including age, gender, clinical condition, pulmonary function, and plasma d-dimer level between the non-anticoagulant group and the anticoagulant group. The overall survival and hospitalization-free periods were assessed. There was a significant difference between survival curves of the non-anticoagulant group and the anticoagulant group, with a 2.9 hazard ratio (p = 0.04, Cox regression model). There was no significant difference in the probability of a hospitalization-free period between groups. The major cause of clinical deterioration was acute exacerbation during follow-up in the present study. Therefore, the mortality and plasma d-dimer levels in patients with an acute exacerbation were also assessed. The mortality associated with acute exacerbations of IPF in the anticoagulant group was significantly reduced compared to that in the non-anticoagulant group (18% vs 71%, respectively; p = 0.008, Fisher Exact Test). Furthermore, the plasma d-dimer levels in patients who died were significantly higher than those in survivors during acute exacerbation of IPF (3.3 +/- 2.3 microg/mL vs 0.9 +/- 0.7 microg/mL, p < 0.0001). Histologic analysis performed in three patients who died due to an exacerbation of IPF in the non-anticoagulant group demonstrated the features of usual interstitial pneumonia and acute lung injury.. Our data suggested that plasma d-dimer levels are associated with mortality in patients with an acute exacerbation of IPF, and that anticoagulant therapy has a beneficial effect on survival in patients with IPF.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Anticoagulants; Biomarkers; Blood Coagulation Disorders; Female; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Prednisolone; Prospective Studies; Pulmonary Fibrosis; Survival Analysis; Treatment Outcome; Warfarin

Excessive anticoagulation due to warfarin use is associated with hemorrhage. Subcutaneously administered vitamin K has not been evaluated for the treatment of warfarin-associated coagulopathy, yet it is widely used.. To show that oral vitamin K is more effective than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy.. Randomized, controlled trial.. Two teaching hospitals.. Patients with an international normalized ratio (INR) between 4.5 and 10.0.. Warfarin therapy was withheld, and 1 mg of vitamin K was given orally or subcutaneously.. The primary outcome measure was the INR on the day after administration of vitamin K. Secondary outcome measures were hemorrhage and thrombosis during a 1-month follow-up period.. 15 of 26 patients receiving oral vitamin K and 6 of 25 patients receiving subcutaneous vitamin K had therapeutic INRs on the day after study drug administration (P = 0.015; odds ratio, 4.32 [95% CI, 1.13 to 17.44]).. Oral vitamin K lowers INR more rapidly than subcutaneous vitamin K in asymptomatic patients who have supratherapeutic INR values while receiving warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Humans; Injections, Subcutaneous; International Normalized Ratio; Male; Middle Aged; Risk Factors; Vitamin K; Warfarin

An assay based on free oscillating rheometry to measure the activity of coagulation factors is described. The method can be used in blood and plasma and is particularly suitable for screening and monitoring coagulation disturbances in point-of-care testing (POCT) in environments where quick analysis with minimal preanalytical work is needed. In this study the endpoint as clotting onset time (COT) is determined by a deviation from initial viscoelastic properties of an oscillating sample. The model system entails the clotting of citrated blood or plasma clotting by repletion of Ca2+. COT was shown to give a dose-dependent response to added thrombin and to be resistant to high concentrations of corn trypsin inhibitor, indicating measurement of the tissue-factor-dependent pathway of coagulation activation. COT in recalcified blood and plasma covariated with prothrombin time (PT) according to Owren, and activated partial thromboplastin time (aPTT). The technique and instrument used proved to be quick and easy to handle, and suitable for POCT as well as for examinations in the laboratory.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Critical Care; Hemostatics; Humans; Partial Thromboplastin Time; Plasma; Point-of-Care Systems; Prothrombin Time; Reproducibility of Results; Rheology; Thrombin; Warfarin

Malignancy is a risk factor for thromboembolism and anti-cancer chemotherapy can increase this risk. Prophylaxis of thrombosis with very-low-dose warfarin given concurrently with chemotherapy has a significantly reduced rate of thromboembolism in a randomized trial in women with stage IV breast cancer. In a group of 32 patients randomized in one center (16 subjects on warfarin and 16 on placebo), we have prospectively studied the plasma levels of: 1. Markers of 'in vivo' clotting activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2] and D-dimer), 2. Factor VII (FVII), and 3. Natural anticoagulants (protein C [PC] and antithrombin [AT]). The aims of this study were: 1. to examine whether laboratory tests predicted those patients who developed thrombosis, and 2. to evaluate the effect of very-low-dose warfarin on hemostatic variables. The patients' hemostatic parameters were evaluated before entry into the study and after starting chemotherapy +/- prophylaxis, before each course for nine courses. Before-treatment results were compared to those of a sex and age-matched non-cancer control group. There was a significant elevation of plasma levels of TAT (p <0.001), F1+2 (p <0.001), D-dimer (p <0.0001) and FVIIa (p <0.05), as well as an increase of FVII proteolysis (p <0.05), whereas plasma PC and AT concentrations were not different from controls. After starting chemotherapy, markers of clotting activation were progressively lower in the group receiving warfarin prophylaxis compared to the group on placebo. Differences between the groups became statistically significant (p <0.01) after the 4th course of chemotherapy. Deep vein thrombosis occurred in two patients in the placebo arm. The results of this study indicate that before therapy, an hypercoagulable state is present in stage IV breast cancer, and after starting chemotherapy, abnormalities of hypercoagulation markers persist, however they are reduced by very-low-dose-warfarin. None of the laboratory variables could predict thrombosis in the single patient.

Topics: Adult; Aged; Anticoagulants; Biomarkers, Tumor; Blood Coagulation Disorders; Breast Neoplasms; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Middle Aged; Neoplasm Metastasis; Prospective Studies; Risk Factors; Thromboembolism; Warfarin

In a preliminary pilot study of 30 treatments in 26 patients with osteonecrosis of the jaws and chronic disabling facial pain, our specific aim was to determine whether, to what degree, and how safely therapy of hypofibrinolysis and thrombophilia would ameliorate the chronic pain associated with osteonecrosis of the mandible and maxilla.. Thrombophilia was treated with Coumadin (DuPont) in 10 patients; hypofibrinolysis was treated with Winstrol (Sanofi-Winthrop) in 20 patients, including 4 who had mixed thrombophilia and hypofibrinolysis and had previously been treated with Coumadin. The initial treatment period was targeted to be 4 months. Each patient was asked to keep a daily written pain-relief numeric rating score and side-effects diary and to provide a summary pain-relief numeric rating score and side effects compilation for the total treatment period.. There were 4 men and 22 women in the study group; their mean age was 49 +/- 11 years. The mean onset of their osteonecrosis pain was at age 45 +/- 12 years, and the mean duration of their facial pain prior to therapy was 4.5 +/- 4.2 years. Ten patients had one or more thrombophilic traits (there were two patients with protein C deficiency, five with resistance to activated protein C and/or the mutant Factor V Leiden gene, and four with high anticardiolipin antibodies). The 10 patients who were thrombophilic were treated with Coumadin (the international normalized ratio was targeted to 2.5-3.0) for 22 +/- 9 weeks. By self-reported pain-relief numeric rating scores, 6 of the 10 patients with thrombophilia (60%) had > or = 40% pain relief, 2 (20%) had no change, and 2 (20%) had increased pain (30% and 80% worse). Nine of the 10 patients with thrombophilia (90%) had no Coumadin-related side effects; 1 patient (10%) stopped Coumadin therapy (after 28 weeks) because of nosebleeds. Winstrol (6 mg per day) was used for 16 +/- 9 weeks in 20 patients with hypofibrinolysis, some of whom had one or more hypofibrinolytic traits (10 had high levels of plasminogen activator/inhibitor activity, usually accompanied by low stimulated tissue plasminogen activator activity; 13 had high Lp[a] lipoprotein). Of these 20 patients with hypofibrinolysis, 9 patients (45%) had > or = 40% pain relief, 3 patients (15%) had 20% to 30% relief, 5 patients (25%) had no improvement, and 3 patients (15%) had increased pain (30% worse, 60% worse, and 70% worse). Six of the 20 patients with hypofibrinolysis (30%) had no Winstrol-related side effects, while 14 (70%) had side effects that could be attributed to Winstrol, including weight gain, peripheral edema, increased facial and body hair, and acne--all of which were reversed within 6 weeks of stopping Winstrol therapy.. We postulate that thrombophilia and hypofibrinolysis lead to impaired venous circulation and venous hypertension of the mandible/maxilla with subsequent development of osteonecrosis and chronic facial pain. In many patients, facial pain can be ameliorated by treating the pathogenetic coagulation defects with Coumadin or Winstrol. Large, double-blind, placebo-controlled crossover studies will be required in the future to validate these preliminary results and to determine whether pain relief with Coumadin or Winstrol justifies the risks and side effects associated with these medications, especially for long-term use, in osteonecrosis of the jaws.

Topics: Adult; Aged; Anabolic Agents; Anticoagulants; Blood Coagulation Disorders; Facial Pain; Female; Fibrinolysis; Humans; Jaw Diseases; Male; Middle Aged; Osteonecrosis; Pilot Projects; Stanozolol; Thrombophilia; Warfarin

The hemostatic condition under low-intensity anticoagulation in cardiac disorders is not fully elucidated. The aim of this study was to ascertain whether hemostatic molecular markers are a useful assessment for anticoagulation to detect the hypercoagulable state. A hematologic study was performed in 75 outpatients, without thromboembolic episodes, treated with low-intensity anticoagulation (average international normalized ratio [INR] 1.72) because of potential cardiac sources of arterial emboli, and in 40 age-matched control subjects. The average level of thrombin-antithrombin III complex (TAT) was significantly lower in patients than in control subjects (p = 0.005), and the mean value of D-dimer was not statistically different between patients and control subjects. Although TAT correlated moderately with D-dimer (r = 0.45, p = 0.0001), INR did not correlate with TAT or D-dimer. Elevated TAT > 3.0 ng/ml and/or D-dimer S 150 ng/ml were observed in 15 patients (20.0%), whereas the remaining 60 patients (80.0%) had no obvious increase in the level of TAT or D-dimer at overall INR. Antithrombin III activity did not correlate significantly with INR, but protein C activity and free protein S antigen showed a significant negative relation to INR (r = 0.82, r = 0.62, respectively, p = 0.0001). Low-intensity anticoagulation was sufficient to reduce coagulation and subsequent fibrinolytic activation in cardiac disorders, but may not be sufficient in some patients with elevated TAT or D-dimer concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Tests; Embolism; Female; Fibrin Fibrinogen Degradation Products; Heart Diseases; Humans; Male; Middle Aged; Peptide Hydrolases; Warfarin

Hemostatic profiles and cardiac enzymes were studied in 55 acute myocardial infarct (AMI) patients to assess SK and rt-PA therapy. Hypofibrinogenemia occurred 85% in SK group and 55% in rt-PA group with high FDP and D-Dimer, indicating systemic fibrinogenolysis and local crosslinked fibrin clot lysis. The incidence of bleeding in SK and rt-PA groups combined with anticoagulants were the same but lower in rt-PA with antiplatelet. The mean FDP was significantly higher in the bleeding group (p < 0.01). Cardiac enzymes: CK, CK-MB peak values indicated reperfusion were 26.6%, 60% and 90% in conventional, SK and rt-PA therapy, respectively. Early and late occlusion did not occur either in SK or rt-PA followed by anticoagulants. Late occlusion was found in patients treated with rt-PA and antiplatelet. Mortality rate was 20% in conventional therapy.

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Dipyridamole; Drug Monitoring; Drug Therapy, Combination; Female; Heparin; Humans; Male; Myocardial Infarction; Streptokinase; Tissue Plasminogen Activator; Warfarin

Nine out of 47 (19%) patients on chronic anticoagulation with warfarin, as secondary prophylaxis after myocardial infarction, initially treated with streptokinase, had thromboembolic complications within 4 weeks after sudden (7/25) or gradual (2/22:NS) warfarin withdrawal. The biochemical effects of warfarin withdrawal were repeatedly studied in 20 of the patients during the first 14 days following drug cessation. During the first 4 days, the levels of coagulation factors VII and IX increased more rapidly than proteins C and S. Thus, a gap was created between the factors provoking and inhibiting the coagulation process. Furthermore, plasma concentrations of fibrinopeptide A (FPA) increased, reflecting activation of the coagulation system. These laboratory findings suggest that withdrawal of warfarin creates a transient hypercoagulable state, imposing a risk of thromboembolic events in patients given anticoagulant treatment as secondary prophylaxis following myocardial infarction.

Topics: Adult; Aged; Angina, Unstable; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Streptokinase; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

In 228 ambulatory patients receiving treatment with warfarin, there was a progressive decline in the dose required to produce an equivalent degree of anticoagulant control with increasing age from the third decade onwards. However, the relationship between age and dose was significant only in patients receiving warfarin after episodes of venous thromboembolism or because of coronary artery disease. Patient weight was also related to warfarin requirements, although it was less important a determinant than age.

Topics: Adult; Aged; Aging; Angina Pectoris; Blood Coagulation Disorders; Body Weight; Clinical Trials as Topic; Drug Administration Schedule; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Prospective Studies; Prothrombin Time; Sex Factors; Thromboembolism; Warfarin

After withdrawal of warfarin (Marevan), 48-72 hours are required to raise the Thombotest values from a therapeutic level (range 5-10%) to 12% or higher. By i.v. administration of 1 mg vitamin K1 (Konakion) and without changing the dose of the anticoagulant, this effect could be obtained within 24 hours. Furthermore, the effect of vitamin K vanished within 2-5 days. The use of small amounts of vitamin K may therefore be a simple and reliable way of obtaining a rapid, temporary reduction in anticoagulant effect.

Topics: Blood Coagulation; Blood Coagulation Disorders; Drug Antagonism; Humans; Time Factors; Vitamin K; Warfarin

A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin.. Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction.. Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ =  -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR.. PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

Topics: Anticoagulants; Bilirubin; Blood Coagulation Disorders; Humans; International Normalized Ratio; Prothrombin Time; Retrospective Studies; Warfarin

4-F PCC is administered for reversal of factor Xa inhibitor-associated coagulopathy despite a lack of quality evidence demonstrating hemostatic efficacy. The aim of this study was to evaluate the hemostatic efficacy of 4-F PCC in intracerebral hemorrhage patients who received factor Xa inhibitors versus warfarin.. This was a multi-center, retrospective, observational cohort study at a large healthcare system. Patients taking warfarin received 4-F PCC 25-50 units/kg based on the presenting INR, while patients taking a factor Xa inhibitor received 35 units/kg. The primary outcome was the percentage of patients with good or excellent hemostatic efficacy as assessed by modified Sarode scale, with neurologic outcomes assessed as a secondary endpoint. Patients were included in the primary outcome population if they had a repeat CT scan within 24 h.. One hundred fifty-seven patients were included in the primary outcome population; [warfarin (n = 76), factor Xa inhibitors (n = 81)]. Hemostatic efficacy was 83 % in the warfarin group versus 75 % in the factor Xa inhibitor group (p = 0.24). The hemostatic efficacy risk difference between the groups was 7.6 % (95 % CI 5.1 %, 20.2 %). Good neurologic outcome (mRS 0-2) at discharge was 17 % in warfarin patients versus 12 % in the factor Xa inhibitor patients (p = 0.40).. There was no significant difference in hemostatic efficacy or clinical outcomes between patients taking warfarin or a factor Xa inhibitor following reversal with 4-F PCC. This study provides further support that 4-F PCC can be used for the reversal of factor Xa inhibitor-associated coagulopathy.

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebral Hemorrhage; Factor IX; Factor Xa; Factor Xa Inhibitors; Hemostatics; Humans; Retrospective Studies; Warfarin

Contamination of synthetic cannabinoids with toxic coumarin derivatives known as superwarfarins can induce a persistent coagulopathy. In comparison to warfarin, these derivatives have prolonged half-lives and laboratory assays for detection are not readily available in clinical practice. To our knowledge, factor-guided diagnosis of coagulopathy secondary to coumarin-contaminated synthetic cannabinoids has not been described previously. Our case report details a young adult who presented to the hospital with an acute elevation in INR without any reported past medical history or illicit substance use. Factor levels were obtained and resulted quickly revealing deficiencies in factors II, VII, IX, and X, which led to a possible diagnosis of coagulopathy secondary to coumarin-contaminated synthetic cannabinoids. Upon further questioning, the patient admitted to use of synthetic cannabinoids. A bromadiolone assay was sent for testing, which resulted positive after patient discharge. Toxic coumarin derivative assays are not immediately available for reference. Given the patient's confirmed synthetic cannabinoid consumption and the possibility of coagulopathy from coumarin-contamination, factor levels served as a guide for diagnosis and treatment prior to the confirmatory assay. Obtaining factor levels in patients with an unexplained coagulopathy and suspected cannabis or synthetic cannabinoid use may aid clinicians in a more prompt diagnosis and treatment.

Topics: Blood Coagulation Disorders; Cannabinoids; Cannabis; Coumarins; Humans; Warfarin; Young Adult

Warfarin induces coagulopathy. Guidelines protocolize reversal of supratherapeutic international normalized ratio (INR) in patients dependent on anticoagulation, but practices vary for reversing warfarin-induced coagulopathy after overdose in non-warfarin-dependent patients.. A restrictive approach to coagulopathy reversal in non-warfarin-dependent patients with intentional warfarin overdose may result in worsening coagulopathy, bleeding, and lengthy hospital stay. Given the risk for significant, prolonged coagulopathy, these patients should be treated early with VK1, with subsequent serial INR monitoring and probable additional VK1 dosing. Delayed peak warfarin concentrations support consideration of gastrointestinal decontamination in late presenters.

Topics: Adolescent; Anticoagulants; Blood Coagulation Disorders; Drug Overdose; Female; Hemorrhage; Humans; International Normalized Ratio; Vitamin K; Warfarin

A 70-year-old woman on warfarin was transported to the emergency department after a ground-level fall, injuring her left backside. Criteria for geriatric trauma activation was not met. An episode of haematuria created suspicion for an intra-abdominal injury, prompting a point-of-care ultrasound (POCUS) Focused Assessment with Sonography for Trauma scan, which was positive. Subsequent pan-scanning discovered a multitude of injuries, including low-grade left renal and splenic lacerations, multiple left rib fractures and a haemothorax. Patient also had a supratherapeutic International Normalized Ratio (INR), which was reversed with 4-factor Prothrombin Complex Concentrate (4F-PCC). She was admitted to the intensive care unit, underwent urgent thoracostomy and had a complicated hospital course. Moreover, an incidental large staghorn calculus in the left kidney might have contributed shearing forces. In summary, under triage of this patient emphasised the importance of performing detailed primary and secondary surveys, including POCUS, for all geriatric ground-level fall patients on anticoagulants to allow for rapid diagnosis and treatment of potential serious injuries.

Topics: Abdominal Injuries; Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Humans; International Normalized Ratio; Retrospective Studies; Staghorn Calculi; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Apolipoproteins E; ATP Binding Cassette Transporter, Subfamily B; Blood Coagulation Disorders; China; Cytochrome P-450 CYP2C9; Female; Genotype; Humans; Male; Polymorphism, Single Nucleotide; Vitamin K Epoxide Reductases; Warfarin

The venom of the boomslang (Dispholidus typus) has potent effects on the coagulation system. It is known to produce a venom-induced consumptive coagulopathy (VICC) through the proposed activation of clotting factor II (prothrombin), factor X, and possibly factor IX. Warfarin, an anticoagulant medication, decreases the circulating vitamin K-dependent clotting factors II, VII, IX and X. We report a unique case of a boomslang bite in a patient on warfarin therapy. During the patient's hospital stay he developed abnormal clotting profiles indicating an underlying VICC, but without major bleeding. He received monovalent antivenom and recovered with no complications. We discuss two possible outcomes of a boomslang bite in a patient on warfarin therapy, exploring the underlying pathophysiology that could lead to the presentation of a reduced risk of overall bleeding or, alternatively, that the bleeding could be compounded and exacerbated. It is possible that in our case the anticoagulant effect of warfarin was wholly obscured by the VICC of the boomslang venom. The composition of the snake venom may have been a contributory factor in the reduced clinical bleeding observed.

Topics: Anticoagulants; Antivenins; Blood Coagulation; Blood Coagulation Disorders; Drug Interactions; Humans; Male; Middle Aged; Snake Bites; Snake Venoms; Warfarin

Bleeding assessment tools (BATs) aim to screen and estimate bleeding risk in patients with inherited bleeding disorders. However, the use of BAT as a standardized measure for comparing bleeding in patients on long-term thromboprophylaxis has not yet been validated. We developed a self-administrable BAT to assess bleeding in patients undergoing long-term thromboprophylaxis with aspirin or warfarin. Eligible participants were invited to complete the warfarin-aspirin -BAT (WA-BAT) online. The WA-BAT was readministered a number of weeks later to determine intrarater reliability. The WA-BAT showed substantial intrarater reliability and assesses major and minor bleeding associated with long-term warfarin or aspirin use.

Topics: Adolescent; Anticoagulants; Aspirin; Blood Coagulation Disorders; Blood Coagulation Tests; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Predictive Value of Tests; Warfarin

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Dabigatran; Humans; Pharmacogenetics; Warfarin

Patients with hip fracture who present anticoagulated with warfarin often require reversal of anticoagulation for safe hip fracture surgery. Vitamin K is typically administered for this, but requires 24-48 hours for maximal effect. These patients have an increased delay to surgery and increased mortality. Octaplex is a prothrombin complex concentrate (PCC) that reverses warfarin anticoagulation in less than an hour. This study assesses the effectiveness and safety of Octaplex for reversal of warfarin anticoagulation for hip fracture surgery.. We reviewed the medical records of all patients with hip fracture in Calgary who received Octaplex between 2009 and 2015. Timing of admission, Octaplex administration and hip fracture surgery were recorded. Mortality and cardiac, thrombotic and orthopedic complications were assessed.. Median time from Octaplex administration to an international normalized ratio of 1.4 or lower was 1.1 hours. The median time from admission to surgery was 22 hours. Thirty-day mortality was 15.2%, with 4 cases of cardiac arrest and 1 respiratory arrest. Patients who received both Octaplex and fresh frozen plasma (FFP) had a lower rate of 30-day survival than those who received only Octaplex (95.7% v. 60.0%,. There were significant rates of cardiac events and 30-day mortality among patients who received Octaplex, but this is unsurprising in this population with multiple medical comorbidities. We caution against administrering both FFP and a PCC in patients for warfarin reversal. Octaplex is effective for rapidly reversing warfarin anticoagulation and reducing delays to hip fracture surgery. Further study comparing Octaplex to reversal using only vitamin K is required.. Les patients avec fracture de la hanche qui sont sous anticoagulothérapie par warfarine au moment de consulter ont souvent besoin qu'on inverse leur anticoagulation pour être opérés sans danger. La vitamine K est généralement administrée à cette fin, mais il lui faut de 24 à 48 heures pour exercer son plein effet. Chez ces patients, le délai est plus long avant la chirurgie et la mortalité est plus élevée. Octaplex est un concentré de complexe prothrombique (CCP) qui inverse l'anticoagulation due à la warfarine en moins d'une heure. Cette étude évalue l'efficacité et l'innocuité d'Octaplex pour l'inversion de l'anticoagulation due à la warfarine lors d'une chirurgie pour fracture de la hanche.. Nous avons passé en revue les dossiers médicaux de tous les patients avec fracture de la hanche à Calgary qui ont reçu Octaplex entre 2009 et 2015. Nous avons enregistré le moment de l'admission, de l'administration d'Octaplex et de la chirurgie pour fracture de la hanche. Nous avons évalué la mortalité et les complications cardiaques, thrombotiques et orthopédiques.. L'intervalle médian entre l'administration d'Octaplex et l'obtention d'un ratio international normalisé de 1,4 ou moins a été de 1,1 heure. L'intervalle médian entre l'admission et la chirurgie a été de 22 heures. La mortalité à 30 jours a été de 15,2 %, incluant 4 arrêts cardiaques et 1 arrêt respiratoire. Les patients qui ont reçu Octaplex et du plasma frais congelé (PFC) ont eu un taux de survie à 30 jours moins élevé que ceux qui ont reçu Octaplex seulement (95,7 % c. 60,0 %,. On a observé des taux significatifs d'événements cardiaques et de mortalité à 30 jours chez les patients traités par Octaplex, mais cela est peu surprenant dans cette population présentant plusieurs comorbidités médicales. Nous formulons une mise en garde contre l'utilisation de PFC et d'un CCP chez les patients soumis à une inversion de l'effet de la warfarine. Octaplex est efficace pour inverser rapidement l'anticoagulation due à la warfarine et accélérer l'accès à la chirurgie pour fracture de la hanche. Il faudra approfondir la recherche et comparer l'inversion par Octaplex plutôt que par la vitamine K seulement.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Hip Fractures; Humans; International Normalized Ratio; Male; Retrospective Studies; Time Factors; Time-to-Treatment; Treatment Outcome; Warfarin

For reversal of warfarin-induced coagulopathy, FDA labeling of four-factor prothrombin complex concentrate (4F-PCC) endorses a dosing strategy based on body weight and baseline INR. Recent literature suggests lower, fixed doses of 4F-PCC may be equally efficacious. The present evaluation aims to characterize the relationship between 4F-PCC dose and degree of reduction in INR.. This is a retrospective, single-center review of 4F-PCC administrations for warfarin reversal between May 2014 and August 2017. The primary endpoint evaluates the relationship between doses of 4F-PCC and INR measurement after reversal, represented as a linear regression. Exploratory endpoints characterize the relationships of both body weight and baseline INR, the components determining initial 4F-PCC dose, with INR after reversal. Additionally, for records presenting with an INR of 2-3.9, mean INR after reversal was characterized as a function of two 4F-PCC dose cohorts (< 30 and ≥30 IU fIX/kg).. This evaluation found no clinically relevant relationship with 4F-PCC doses and degree of INR reversal. Further prospective study is required to determine optimal dosing schemes of 4F-PCC for warfarin reversal.

Topics: Aged; Aged, 80 and over; Blood Coagulation Disorders; Blood Coagulation Factors; Body Weight; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Linear Models; Male; Retrospective Studies; Warfarin

Results of a study to determine the proportion of anticoagulation clinic workload that could be performed by clinical pharmacy technicians (CPTs) and the potential impact on operational efficiency of pharmacist-managed anticoagulation clinics (ACCs) are reported.. In a quality improvement project involving 11 Veterans Affairs (VA) medical centers, investigators conducted a 3-day time study in pharmacist-managed ACCs followed by scoring of task appropriateness for CPTs via the RAND/UCLA appropriateness method by the VA Anticoagulation Subject Matter Expert (SME) Workgroup. The primary outcome was the percentage of tasks deemed appropriate for a CPT to perform.. The Anticoagulation SME Workgroup determined that a wide variety of mainly administrative ACC tasks could be completed by a CPT. At the 11 VA ACCs, an average of 53.4% (range, 39.9-76.1%) of tasks being performed by pharmacists were deemed appropriate for CPTs. The average percentage of total clinic time associated with performing tasks appropriate for a CPT equated to an estimated 1,111 hours per year. Shifting that portion of the annual work hours to a CPT could potentially result in cost avoidance of $55,302.. At the ACCs evaluated, a significant proportion of tasks (53.4% on average) may be appropriate to assign to CPTs to improve the operational efficiency of these clinics. This finding supports development of business plans for the addition of CPTs in ACCs along with elements to inform crafting of an effective template for ACC structure, including clearly defined CPT roles.

Topics: Anticoagulants; Blood Coagulation Disorders; Drug Monitoring; Efficiency, Organizational; Hemorrhage; Hospitals, Veterans; Humans; International Normalized Ratio; Outpatient Clinics, Hospital; Pharmacy Service, Hospital; Pharmacy Technicians; Professional Role; Program Evaluation; Warfarin; Workload

PCC (Kcentra®) is an Food and Drug Administration (FDA)-approved 4-factor PCC used for the treatment of warfarin-related coagulopathy (WRC), but it has also been used off-label to treat non-WRC. Three-factor PCC in the form of coagulation factor IX human (Bebulin®) has also been used for WRC and off-label to treat non-WRC. It is unclear whether the use of 3- or 4-factor PCCs is effective for the treatment of non-WRC,.. Our aim is to characterize the use of 3- and 4-factor PCCs for patients identified with a non-WRC.. A retrospective analysis of patients who received PCCs for both WRC and non-WRC between January 2012 and July 2015 was conducted.. A total of 187 patients with elevated international normalized ratio (INR) who received PCCs were analyzed; 53.9% of patients in the WRC group and 27.7% in the non-WRC group corrected to an INR of 1.3 or less after 3- or 4-factor PCC administration. In those patients with non-WRC and who had underlying liver disease, 3- and 4-factor PCCs reduced mean INR by 0.98 and 1.43, respectively.. Three and 4-factor PCCs can reduce INR in patients with WRC and in those with non-WRC secondary to liver disease.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Warfarin; Young Adult

: In patients with inherited bleeding disorders undergoing surgery, we recommend assessment of individual risk for venous thromboembolism, taking into account the nature of the surgery and anaesthetic, type and severity of bleeding disorder, age, BMI, history of thrombosis, the presence of malignancy and other high-risk comorbidities. Venous thromboembolism risk should be balanced against the increased bleeding risk associated with anticoagulant use in patients with known bleeding disorders (Grade 1C). In these patients undergoing major surgery, we recommend against routine postoperative use of pharmacological thromboprophylaxis, especially for patients with haemophilia A and B (Grade 1B). Glomerular filtration rate should be assessed before initiation of each direct oral anticoagulant, and also at least once a year or more frequently as needed, such as postoperatively before the resumption of therapeutic direct oral anticoagulant administration, when it is suspected that renal function could decline or deteriorate (Grade 1C). Reduced dosages of low molecular weight heparins may be used relatively safely during transient severe (<50 × 10 l) thrombocytopaenia (Grade 2C). Monitoring of anti-Xa levels may be used to adjust the doses of low molecular weight heparin in patients with moderate or severe thrombocytopaenia (Grade 2C). The delay between major gastrointestinal bleeding and resuming warfarin should be at least 7 days (Grade 2C). For patients at a high risk of thromboembolism and with a high bleeding risk after surgery, we consider that administering a reduced dose of direct oral anticoagulant on the evening after surgery and on the following day (first postoperative day) after surgery is a good practice (Grade 2B).

Topics: Administration, Oral; Age Factors; Aged; Anesthesiology; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Clinical Trials, Phase III as Topic; Critical Care; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Gastrointestinal Hemorrhage; Glomerular Filtration Rate; Heparin, Low-Molecular-Weight; Humans; Perioperative Care; Platelet Count; Risk Factors; Societies, Medical; Surgical Procedures, Operative; Time Factors; Venous Thromboembolism; Warfarin

'Pharmacoepigenomics' methods informed by omics datasets and pre-existing knowledge have yielded discoveries in neuropsychiatric pharmacogenomics. Now we evaluate the generality of these methods by discovering an extended warfarin pharmacogenomics pathway.. We developed the pharmacoepigenomics informatics pipeline, a scalable multi-omics variant screening pipeline for pharmacogenomics, and conducted an experiment in the genomics of warfarin.. We discovered known and novel pharmacogenomics variants and genes, both coding and regulatory, for warfarin response, including adverse events. Such genes and variants cluster in a warfarin response pathway consolidating known and novel warfarin response variants and genes.. These results can inform a new warfarin test. The pharmacoepigenomics informatics pipeline may be able to discover new pharmacogenomics markers in other drug-disease systems.

Topics: Anticoagulants; Blood Coagulation Disorders; Computational Biology; Genetic Variation; Genome-Wide Association Study; Humans; Lithium Compounds; Pharmacogenetics; Polymorphism, Single Nucleotide; Warfarin

Screening for primary hypercoagulable states (PHSs) in venous thromboembolism (VTE) patients was not mandated in the EINSTEIN trials; and therefore, few patients with a known PHS were available for analysis. We sought to assess the effectiveness and safety of rivaroxaban versus warfarin for treatment of VTE in patients with a known PHS.. Using MarketScan claims data from 1/2012-9/2015, we identified adults with a primary diagnosis of VTE during a hospitalization/emergency department visit (the index event), with ≥180-days of continuous insurance coverage prior to the index event, a documented diagnosis for a PHS and newly-initiated as an outpatient on rivaroxaban or warfarin within 30-days of the index VTE. Rivaroxaban and warfarin users were 1:1 propensity-score matched. Balance between cohorts was evaluated by inspecting standardized differences for baseline covariates (<0.1 considered well-balanced). Patients were followed up to 12-months from the index event or until occurrence of an endpoint, switch/discontinuation of index oral anticoagulation or insurance disenrollment. Rates of recurrent VTE and major bleeding were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).. We matched 403 rivaroxaban and 403 warfarin patients with VTE and a known PHS. All baseline covariates had a standardized difference < 0.1. Rivaroxaban use was associated with a non-significant reduction in recurrent VTE (HR = 0.70, 95%CI = 0.33-1.49) and major bleeding (HR = 0.55, 95%CI = 0.16-1.86) versus warfarin.. In routine practice, the effectiveness and safety of rivaroxaban versus warfarin in VTE patients with a known PHS appears to be similar to that observed in the EINSTEIN trial program.

Topics: Anticoagulants; Blood Coagulation Disorders; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Outpatients; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Warfarin- and superwarfarin-type anticoagulants are commonly used as rodenticides. Exposure to these agents, especially superwarfarins with long-acting anticoagulant effect, can cause life-threatening coagulopathy in humans. Most superwarfarin poisoning cases had an obvious history of exposure, though occult cases without exposure history have also been reported. The current study aims to examine anticoagulant-type rodenticide poisoning in Hong Kong and to identify the similarities and differences between patients with known exposure history and those whose exposure is recognized only through laboratory testing.. The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. This was a retrospective cohort study of all patients with biochemically confirmed anticoagulant-type rodenticide exposure, from 2010 to 2014.. Superwarfarin was the most common group of anticoagulant-type rodenticides identified (87.8%), in which bromadiolone and brodifacoum were the most frequently encountered. Among the 41 cases identified, 31 had an obvious exposure history, and 10 were occult poisoning in which the context of exposure remained unidentified. All occult poisoning patients without exposure history presented with bleeding events. These occult poisoning cases often went unrecognized by frontline clinicians, leading to delayed investigation and initiation of treatment. This group of patients was associated with a longer time to diagnose coagulopathy (p < 0.001) and confirm rodenticide poisoning (p < 0.05), a higher rate of international normalized ratio (INR) rebound after initiation of antidote (p < 0.001), and a longer time needed for normalizing INR (p < 0.05).. Occult superwarfarin poisoning is an important yet under-recognized differential cause of unexplained coagulopathy. A high index of clinical suspicion and availability of specialized toxicological test for superwarfarins play a vital role in diagnosis and early initiation of appropriate management. The underlying cause of such poisoning remains obscure and warrants further study.

Topics: 4-Hydroxycoumarins; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Cohort Studies; Female; Hemorrhage; Hong Kong; Humans; Infant; International Normalized Ratio; Male; Middle Aged; Poisoning; Retrospective Studies; Rodenticides; Vitamin K; Warfarin; Young Adult

Suprachoroidal haemorrhage is a rare complication of either medical anticoagulation treatment or intraocular surgical procedures. Suprachoroidal haemorrhages often have devastating visual outcome despite conservative and/or surgical intervention.. A patient with known Open Angle Glaucoma and Atrial Fibrillation on warfarin presents symptoms and signs suggestive acute angle closure. Examination reveals the underlying cause is a large, macula involving, spontaneous suprachoroidal haemorrhage secondary to loss of anti-coagulation control. Following aggressive medical treatment and surgical intervention, including drainage combined cataract extraction with intraocular lens implant, pars-plana vitrectomy, and external drainage of suprachoroidal haematoma, we managed to preserve the patient's eye and some of its function.. Spontaneous suprachoroidal haemorrhages are rare complications of loss of anticoagulation control. Our case shows that aggressive treatment in selected cases can offer a relatively good outcome.

Topics: Acute Disease; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Choroid Hemorrhage; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Male; Visual Acuity; Warfarin

In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant.. We reviewed physician-reported data from patients admitted to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April 21, 2018, and included in a case series adult patients who met the criteria used to diagnose synthetic cannabinoid-associated coagulopathy. A confirmatory anticoagulant poisoning panel was ordered at the discretion of the treating physician.. A total of 34 patients were identified as having synthetic cannabinoid-associated coagulopathy during 45 hospitalizations. Confirmatory anticoagulant testing was performed in 15 of the 34 patients, and superwarfarin poisoning was confirmed in the 15 patients tested. Anticoagulant tests were positive for brodifacoum in 15 patients (100%), difenacoum in 5 (33%), bromadiolone in 2 (13%), and warfarin in 1 (7%). Common symptoms at presentation included gross hematuria in 19 patients (56%) and abdominal pain in 16 (47%). Computed tomography was performed to evaluate abdominal pain and revealed renal abnormalities in 12 patients. Vitamin K. Our data indicate that superwarfarin adulterants of synthetic cannabinoids can lead to clinically significant coagulopathy. In our series, in most of the cases in which the patient presented with bleeding diathesis, symptoms were controlled with the use of vitamin K

Topics: 4-Hydroxycoumarins; Abdominal Pain; Adult; Anticoagulants; Blood Coagulation Disorders; Blood Transfusion; Cannabinoids; Female; Hematuria; Hemorrhage; Humans; Illinois; International Normalized Ratio; Male; Middle Aged; Patient Readmission; Vitamin K; Warfarin

: To evaluate the efficacy of international normalized ratio (INR) reversal using four-factor prothrombin complex concentrate (4F-PCC) in nonmedication-induced coagulopathy. We performed a single-site, retrospective cohort study of patients receiving off-label use of 4F-PCC. Cohorts included liver dysfunction if they had acute liver decompensation or cirrhosis without other causative factors of liver failure such as sepsis, coagulopathy of acute sepsis (CAS) if they had documentation of sepsis and no underlying liver disorder, known factor deficiencies, or medication-induced coagulopathy, or warfarin if they were taking warfarin. Patients with unknown medication or direct oral anticoagulant usage were excluded. 4F-PCC was administered 32 times in 26 patients for nonvitamin-K antagonist related coagulopathy (11 CAS and 21 liver dysfunction) and 47 administrations were in warfarin patients. Liver dysfunction patients had a mean model for end-stage liver disease score of 28 ± 10. CAS and warfarin patients had significant INR reductions (ΔINR 1.9, P < 0.01; ΔINR 3.9, P < 0.01, respectively). Liver dysfunction patients mean change in INR trended toward significance (ΔINR 0.7, P = 0.09). Patients who received 4F-PCC based upon previously established dosing guidelines for moderate elevations in INR (20-30 IU/kg) doing demonstrated similar reductions in INR between CAS and warfarin patients (ΔINR 1.3, P = 0.03, ΔINR 1.0 P < 0.01, respectively). 4F-PCC significantly reduces the INR in CAS patients and trended toward significant reductions in liver dysfunction patients. Adequately powered, prospective trials are needed to demonstrate 4F-PCC efficacy in reversal of these coagulopathies.

Topics: Blood Coagulation Disorders; Humans; Middle Aged; Prothrombin; Retrospective Studies; Warfarin

Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR) for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle) and maximum clot stiffness (MA) were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG). To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57-0.77, p<0.04) and all LSR parameters demonstrated good correlation with TEG (r = 0.61-0.87, p<0.04). To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01). LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01). Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing.

Topics: Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Dose-Response Relationship, Drug; Female; Humans; Male; Partial Thromboplastin Time; Point-of-Care Systems; Prothrombin Time; Rheology; Swine; Warfarin

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebral Hemorrhage; Humans; Male; Warfarin

Several studies have reported that daptomycin induced artificial prolongation of prothrombin time (PT) in some test reagents, particularly in warfarin users. However, it remains unknown whether the artificial prolongation can be affected by coagulation abnormalities other than the use of warfarin. Thus, we investigated the effect of daptomycin on PT with two types of coagulation abnormalities.. Plasma samples were pooled by four groups: healthy volunteers (Plasma A), warfarin users with a PT-international normalized ratio (INR) of approximately 2.0 (Plasma B) or 3.0 (Plasma C), and patients with liver cirrhosis with a PT-INR of approximately 2.0 (Plasma D). Plasma A was composed of plasma from two healthy individuals (9 mL from each individual). Plasma B, C, and D were composed of plasma from 36 patients (0.5 mL from each patient). Daptomycin was added to each sample to create solutions with several concentrations (0-150 μg/mL). The PT-INR for each solution was measured with three PT reagents. Linear regression analyses were used to determine the association between daptomycin concentration and PT-INR. The relative change in PT-INR due to daptomycin concentrations was calculated.. Daptomycin induced the artificial prolongation of PT-INR in a concentration-dependent manner, particularly in plasma samples with an elevated baseline PT-INR. PT should be evaluated at the trough levels of daptomycin.

Topics: Anti-Bacterial Agents; Anticoagulants; Blood Coagulation Disorders; Daptomycin; Dose-Response Relationship, Drug; Humans; International Normalized Ratio; Liver Cirrhosis; Prothrombin Time; Warfarin

Long-acting anticoagulant rodenticides, also called superwarfarins, are known for their greater potency, longer half-life and delayed onset of symptoms. Cases of superwarfarin poisoning can pose a diagnostic and clinical challenge due to a wide array of presentations and prolonged severe coagulopathy requiring months of high-dose oral vitamin K therapy. The most common presentation of long-acting anticoagulant rodenticide poisoning is mucocutaneous bleeding, with other common presentations including haematuria, gingival bleeding, epistaxis and gastrointestinal bleeding. We discuss a case of deliberate self-poisoning with long-acting anticoagulant rodenticides presenting with haematuria and coagulation values above measurable limits. This case is important as it required immediate and maintenance therapy in order to prevent profound bleeding, as well as the evaluation of the patient's psychosocial factors to ensure medical compliance and to prevent refractory complications or repeated self-harm.

Topics: Abdominal Pain; Anticoagulants; Antifibrinolytic Agents; Anxiety Disorders; Blood Coagulation; Blood Coagulation Disorders; Chronic Pain; Comorbidity; Delayed-Action Preparations; Gastrointestinal Hemorrhage; Hematuria; Humans; Male; Middle Aged; Referral and Consultation; Suicide, Attempted; Treatment Outcome; Vitamin K; Warfarin

The aim of this study was to review and describe the use of Prothrombinex by a physician-led retrieval service based remote from a hospital blood bank.. This is a retrospective observational study. Patients to whom Prothrombinex was administered by the retrieval team were identified from the retrieval service patient database. The paper case cards of the identified patients were then manually reviewed and the data matched to patients in the state-wide electronic laboratory record.. Between 1 January 2010 and 30 November 2013 38 cases were identified. For 28 the indication was warfarinisation associated with life-threatening bleeding (most commonly intracranial or gastrointestinal tract). In the remaining 10 cases, Prothrombinex was used to treat coagulopathy associated with liver disease or massive haemorrhage. The median time saved by the retrieval team administering PTX-VF, rather than waiting to the receiving centre, was 120 min (interquartile range: 85-195 min). The median dose of PTX-VF administered was 23.25 IU/kg (interquartile range: 20-33 IU/kg). Paired international normalised ratios (INRs) were available for 33 of the 38 patients. In the warfarin group, all patients had an improvement in their INR and 21 of 25 had correction of their INR. In the non-warfarin group, the effect on INR was more variable.. Prothrombinex is a clinically useful product that can be relatively easily stored and used by retrieval services, even if they are based in isolation from a hospital blood bank. More research is required to look at the utility of Prothrombinex for non-warfarin-related bleeding in the pre-hospital and retrieval environment.

Topics: Adult; Aged; Anticoagulants; Blood Banks; Blood Coagulation Disorders; Blood Coagulation Factors; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Liver Diseases; Male; Middle Aged; Retrospective Studies; Statistics, Nonparametric; Time-to-Treatment; Warfarin

Thromboelastography (TEG) has been recommended to characterize post-traumatic coagulopathy, yet no study has evaluated the impact of pre-injury anticoagulation (AC) on TEG variables. We hypothesized patients on pre-injury AC have a greater incidence of coagulopathy on TEG compared to those without AC.. This retrospective chart review evaluated all trauma patients admitted to an urban, level one trauma center from February 2011 to September 2014 who received a TEG within the first 24h. Patients were classified as receiving pre-injury AC or no AC if their documented medications prior to admission included warfarin, dabigatran, or anti-Xa (aXa) inhibitors (apixaban or rivaroxaban). The presence of coagulopathy on TEG or conventional assays was defined by exceeding local laboratory reference standards.. A total of 54 patients were included (AC, n=27 [warfarin n=13, dabigatran n=6, aXa inhibitor n=8] vs. no AC, n=27). Baseline characteristics were similar between groups, including age (72±13years vs. 72±15; p=0.85), male gender (70% vs. 74%; p=0.76) and blunt mechanism of injury (100% vs. 100%; p=1). There was no difference in the number of patients determined to have coagulopathy on TEG (no AC 11% vs. AC 15%; p=0.99). Conventional tests, including the international normalized ratio (INR) and activated partial thromboplastin time (aPTT), identified coagulopathy in a high proportion of anti-coagulated patients (no AC 22% vs. AC 85%; p<0.01).. TEG has limited clinical utility to evaluate the presence of pre-injury AC. Traditional markers of drug induced coagulopathy should guide reversal decisions.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Case-Control Studies; Cohort Studies; Dabigatran; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Male; Middle Aged; Partial Thromboplastin Time; Retrospective Studies; Thrombelastography; Warfarin; Wounds, Nonpenetrating

To determine whether the timing of notification of critical international normalized ratio (INR) results (during or after clinic hours) altered the clinician's ability to affect same-day patient care.. Retrospective chart review.. The Anticoagulation Management Service at the University of Alberta Hospital in Edmonton.. A total of 276 patients with critical INR results (> 5.0) separated by at least 30 days were identified to have 200 critical INR results reported during clinic hours and 200 reported after hours.. Differences in the proportion of patients with critical INR results having same-day care altered (by changing warfarin dose, administering vitamin K, or referring for assessment) between those with results reported during clinic hours compared with those with results reported after clinic hours. Differences by highly critical INR results (> 9.0 vs ≤ 9.0) and whether patients experienced thromboembolism or bleeding within 30 days were also assessed.. Same-day patient care was affected for 174 out of 200 (87.0%) critical INR results reported during clinic hours compared with 101 out of 200 (50.5%) reported after clinic hours (. Same-day care was less likely to be affected by critical INR results communicated after hours, most commonly because the patient had already taken their daily warfarin dose. However, after-hours care was still affected for 1 out of 2 patients, which is meaningful and supports current practice.

Topics: After-Hours Care; Aged; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Referral and Consultation; Retrospective Studies; Thromboembolism; Time Factors; Vitamin K; Warfarin

The aim of this study was to compare the efficacy, safety, and cost-effectiveness of 3-factor prothrombin complex concentrate (3F-PCC) vs 4-factor prothrombin complex concentrate PCC (4F-PCC) in trauma patients requiring reversal of oral anticoagulants.. All consecutive trauma patients with coagulopathy (international normalized ratio [INR] ≥1.5) secondary to oral anticoagulants who received either 3F-PCC or 4F-PCC from 2010 to 2014 at 2 trauma centers were reviewed. Efficacy was determined by assessing the first INR post-PCC administration, and successful reversal was defined as INR less than 1.5. Safety was assessed by reviewing thromboembolic events, and cost-effectiveness was calculated using total treatment costs (drug acquisition plus transfusion costs) per successful reversal.. Forty-six patients received 3F-PCC, and 18 received 4F-PCC. Baseline INR was similar for 3F-PCC and 4F-PCC patients (3.1 ± 2.3 vs 3.4 ± 3.7, P = .520). The initial PCC dose was 29 ± 9 U/kg for 3F-PCC and 26 ± 6 U/kg for 4F-PCC (P = .102). The follow-up INR was 1.6 ± 0.6 for 3F-PCC and 1.3 ± 0.2 for 4F-PCC (P = .001). Successful reversal rates in patients were 83% for 4F-PCC and 50% for 3F-PCC (P = .022). Thromboembolic events were observed in 15% of patients with 3F-PCC vs 0% with 4F-PCC (P = .177). Cost-effectiveness favored 4F-PCC ($5382 vs $3797).. Three-factor PCC and 4F-PCC were both safe in correcting INR, but 4F-PCC was more effective, leading to better cost-effectiveness. Replacing 3F-PCC with 4F-PCC for urgent coagulopathy reversal may benefit patients and institutions.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Calcium; Cost-Benefit Analysis; Critical Care; Female; Hemostatics; Humans; International Normalized Ratio; Male; Retrospective Studies; Safety; Thromboplastin; Trauma Centers; Warfarin; Wounds and Injuries

Topics: Blood Coagulation Disorders; Echocardiography, Transesophageal; Electrocardiography; Female; Follow-Up Studies; Heart Diseases; Humans; Magnetic Resonance Imaging, Cine; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Severity of Illness Index; Thrombosis; Treatment Outcome; Warfarin

The American Heart Association/American College of Cardiology Foundation recommends vitamin K1 for warfarin-related coagulopathy. In Japan, vitamin K2 is used more commonly for such purpose. The difference between vitamins K1 and K2 in reversing warfarin-related coagulopathy has not been discussed. Herein, we report a case that was reversed with vitamin K2; alterations in vitamins K1 and K2 levels and coagulation markers are also presented.

Topics: Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Arm; Blood Coagulation Disorders; Female; Hematoma; Humans; Radiography; Thoracic Wall; Vitamin K 2; Warfarin

Topics: Ambulances; Anticoagulants; Blood Coagulation Disorders; Cerebral Hemorrhage; Emergency Medical Services; Humans; Pilot Projects; Point-of-Care Systems; Stroke; Warfarin

Optimal dosing of prothrombin complex concentrate (PCC) has yet to be defined and varies widely due to concerns of efficacy and thrombosis. We hypothesized a dose of 15 IU/kg actual body weight of a three-factor PCC would effectively correct coagulopathy in acute care surgery patients. Retrospective review of 41 acute care surgery patients who received 15 IU/kg (± 10%) actual body weight PCC for correction of coagulopathy. Demographics, laboratory results, PCC dose, blood and plasma transfusions, and thrombotic complications were analyzed. We performed subset analyses of trauma patients and those taking warfarin. Mean age was 69 years (18-94 years). Thirty (73%) trauma patients, 8 (20%) emergency surgery patients, 2 (5%) burns, and 1 (2%) nontrauma neurosurgical patient were included. Mean PCC dose was 1305.4 IU (14.2 IU/kg actual body weight). Mean change in INR was 2.52 to 1.42 (p 0.00004). Successful correction (INR <1.5) was seen in 78 per cent. Treatment failures had a higher initial INR (4.3 vs 2.03, p 0.01). Mean plasma transfusion was 1.46 units. Mean blood transfusion was 1.61 units. Patients taking prehospital warfarin (n = 29, 71%) had higher initial INR (2.78 vs 1.92, p 0.05) and received more units of plasma (1.93 vs 0.33, p 0.01) than those not taking warfarin. No statistical differences were seen between trauma and nontrauma patients. One thrombotic event occurred. Administration of low-dose PCC, 15 IU/kg actual body weight, effectively corrects coagulopathy in acute care surgery patients regardless of warfarin use, diagnosis or plasma transfusion.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Body Weight; Burns; Drug Dosage Calculations; Emergencies; Humans; International Normalized Ratio; Middle Aged; Plasma; Retrospective Studies; Surgical Procedures, Operative; Thrombosis; Vitamin K; Warfarin; Wounds and Injuries; Young Adult

VKORC1 and CYP2C9 genetic polymorphisms may not accurately predict warfarin dose requirements. We evaluated an existing warfarin dosing algorithm developed for Malaysian patients that was based only on VKORC1 and CYP2C9 genes.. Five Malay patients receiving warfarin maintenance therapy were investigated for their CYP2C9*2, CYP2C9*3, and VKORC1-1639G>A genotypes and their vitamin K-dependent (VKD) clotting factor activities. The records of their daily warfarin doses and international normalized ratio (INR) 2 years prior to and after the measurement of VKD clotting factors activities were acquired. The mean warfarin doses were compared with predicted warfarin doses calculated from a genotypic-based dosing model developed for Asians.. A patient with the VKORC1-1639 GA genotype, who was supposed to have higher dose requirements, had a lower mean warfarin dose similar to those having the VKORC1-1639 AA genotype. This discrepancy may be due to the coadministration of celecoxib, which has the potential to decrease warfarins metabolism. Not all patients' predicted mean warfarin doses based on a previously developed dosing algorithm for Asians were similar to the actual mean warfarin dose, with the worst predicted dose being 54.34% higher than the required warfarin dose.. Multiple clinical factors can significantly change the actual required dose from the predicted dose from time to time. The additions of other dynamic variables, especially INR, VKD clotting factors, and concomitant drug use, into the dosing model are important in order to improve its accuracy.

Topics: Anticoagulants; Asian People; Blood Coagulation; Blood Coagulation Disorders; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Female; Humans; International Normalized Ratio; Malaysia; Male; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Thrombosis; Vitamin K Epoxide Reductases; Warfarin

As the population ages, more trauma patients are admitted with coagulopathy. Fresh frozen plasma is effective in reversing coagulopathy caused by warfarin; however, it is not appropriate for all patients. Prothrombin complex concentrates (PCCs) are an alternative for patients who require emergent reversal, minimal-volume administration and who have a supratherapeutic international normalized ratio (INR). A four-factor PCC initially approved in Europe is now available in the United States. We sought to review our experience with Kcentra (4F-PCC) in the first year following Food and Drug Administration approval.. All trauma patients admitted to an academic Level 1 trauma center between July 15, 2013, and July 15, 2014, who received 4F-PCC for reversal of warfarin-induced coagulopathy were reviewed. 4F-PCC was given as per protocol. Univariate analysis was performed to examine patient demographics, injury characteristics, coagulation studies, 4F-PCC dose, vitamin K use, transfusions, response to reversal, duration of reversal, complications, and mortality.. Twenty-six patients met study criteria. Of these patients, 34.6% were reversed because of intracranial hemorrhage. The mean INR decreased from 5.7 ± 6.1 (range, 1.6-30) to 1.5 ± 0.4 (range, 1.2-2.6) after 4F-PCC administration. One patient (3.8%) received concurrent fresh frozen plasma. For patients with an initial INR greater than 5.0, the mean INR decreased from 12.0 ± 8.2 to 1.6 ± 0.5. Forty-eight hours following 4F-PCC administration, mean INR for all patients remained 1.4 ± 0.4 (range, 1.0-2.6). Of the patients, 80.8% received vitamin K over this period. Fourteen patients had a pre-4F-PCC thromboelastogram; four were hypocoagulable. Two patients had repeat thromboelastograms after 4F-PCC was given, which demonstrated normal coagulation. Of the patients with intracranial hemorrhage, 66.7% showed radiographic progression of the initial insult on post-4F-PCC head computed tomography, while only 11.1% progressed clinically. In-hospital mortality was 0%. There were no thromboembolic complications.. 4F-PCC effectively reverses elevated INRs in trauma patients with warfarin-induced coagulopathy, with results lasting more than 48 hours after administration.. Therapeutic study, level V.

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Drug Approval; Female; Humans; International Normalized Ratio; Male; Retrospective Studies; Thrombelastography; Time Factors; Trauma Centers; Trauma Severity Indices; Warfarin

There are no studies demonstrating that prothrombin complex concentrates (PCC) improves outcome compared FFP in patients with warfarin-associated intracranial hemorrhage.. A prospective, observational study was conducted of patients who received PCC (Bebulin VH), FFP, or PCC + FFP. All groups received vitamin K 10 mg IV. INR reversal (<1.4), adverse events (venous thromboembolism, myocardial infraction, pulmonary edema), major hemorrhage (new or worsened intracranial hemorrhage, anemia requiring transfusion or GI bleed), and 3-month functional outcome were compared between the groups using Chi squared and logistic regression analysis.. Of 64 patients, PCC alone was used in 16 (mean dose 48 IU/kg), FFP alone in 25 (mean dose 12.5 ml/kg), and PCC + FFP in 23 (median doses 47.4 IU/kg and 11.4 ml/kg, respectively). INR correction occurred in 88, 84, and 70 %, respectively. There were no differences in time to INR correction or adverse events between the groups, but FFP alone was associated with more major hemorrhage after administration (52 %, OR 5.0, 95 % CI 1.6-15.4, P = 0.006) and PCC with less (6 %, OR 0.1, 95 % CI 0.01-0.8, P = 0.033). After adjusting for age, admission GCS, initial INR, and bleed type, the use of PCC was associated with a lower risk of death or severe disability at 3-months (adjusted OR 0.02, 95 % CI 0.001-0.8, P = 0.039), while FFP alone was associated with a higher risk (adjusted OR 51.6, 95 % CI 1.2-2163.1, P = 0.039).. PCC adequately corrected INR without any increase in adverse events compared to FFP and was associated with less major hemorrhage and improved 3-month outcomes in patients with warfarin-associated intracranial hemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Vitamin K; Warfarin; Young Adult

Patient self-management (PSM) of oral anticoagulation is under discussion, because evidence from real-life settings is missing. Using data from a nationwide, prospective cohort study in Switzerland, we assessed overall long-term efficacy and safety of PSM and examined subgroups. Data of 1140 patients (5818.9 patient-years) were analysed and no patient were lost to follow-up. Median follow-up was 4.3 years (range 0.2-12.8 years). Median age at the time of training was 54.2 years (range 18.2-85.2) and 34.6% were women. All-cause mortality was 1.4 per 100 patient-years (95% CI 1.1-1.7) with a higher rate in patients with atrial fibrillation (2.5; 1.6-3.7; p<0.001), patients>50 years of age (2.0; 1.6-2.6; p<0.001), and men (1.6; 1.2-2.1; p = 0.036). The rate of thromboembolic events was 0.4 (0.2-0.6) and independent from indications, sex and age. Major bleeding were observed in 1.1 (0.9-1.5) per 100 patient-years. Efficacy was comparable to standard care and new oral anticoagulants in a network meta-analysis. PSM of properly trained patients is effective and safe in a long-term real-life setting and robust across clinical subgroups. Adoption in various clinical settings, including those with limited access to medical care or rural areas is warranted.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Self Care; Treatment Outcome; Warfarin; Young Adult

Warfarin therapy increases the incidence intracranial hemorrhage (ICH), especially in the geriatric population. Timely reversal of international normalized ratio (INR) is integral in the management of these patients for whom fresh frozen plasma (FFP) with vitamin K is the standard of treatment. We hypothesized that implementing a protocol that used prothrombin complex concentrate (PCC) would reverse INR values more swiftly and decrease the amount of FFP administered. In November 2011, a protocol was implemented for administering PCC to the geriatric population on warfarin admitted for life-threatening bleeds. These patients received 25 IU/kg ideal body weight of a three-factor PCC (Profilnine SD) if their INR was over 1.5 or greater. FFP was given if follow-up INR revealed an INR of 1.5 or greater. Retrospectively the data from 29 patients who received PCC were compared with a historical control group of 34 patients. Protocol use resulted in a significantly faster INR reversal (PCC: 151.6 ± 84.3 minutes vs control: 485.0 ± 321 minutes; P < 0.001), time to achieve an INR less than 1.5 (PCC: 484 ± 242 minutes vs control: 971 ± 1208 minutes; P = 0.036), and less FFP administered (PCC: 1.3 ± 1.0 vs control:3.3 ± 1.5; P < 0.001). PCC patients had a decreased incidence of progression of their ICH (PCC: 17.2% vs control: 44.2%; P = 0.031). Rapid reversal of coagulopathy in geriatric patients on warfarin is vital to limit the extent of ICH. PCC allows a much more rapid reversal than standard treatment with only FFP and vitamin K. Adopting such a protocol is associated not only with a more rapid reversal and less FFP use, but also less patients went on to extend their head bleeds.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Craniocerebral Trauma; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Pennsylvania; Retrospective Studies; Trauma Centers; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Female; Humans; Intracranial Hemorrhages; Male; Plasma; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Female; Humans; Intracranial Hemorrhages; Male; Plasma; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Drug Interactions; Humans; Warfarin

To compare the safety and effectiveness of three methods of reversing coagulopathic effects of warfarin in patients with potentially life-threatening intracranial hemorrhage.. A retrospective electronic medical record review of 63 patients with warfarin-related intracranial hemorrhage between 2007 and 2010 in an integrated health care delivery system was conducted. The three methods of rapid warfarin reversal were fresh-frozen plasma (FFP), activated factor VII (FVIIa; NovoSevenRT [Novo Nordisk, Bagsværd, Denmark]), and prothrombin complex concentrate (PCC; BebulinVH [Baxter, Westlake Village, California, USA], ProfilnineSD [Grifols, North Carolina, USA]), each used adjunctively with vitamin K (Vit K, phytonadione). We determined times from reversal agent order to laboratory evidence of warfarin reversal (international normalized ratio [INR]) in the first 48 hours and compared INR rebound rates and complications in the first 48 hours.. Reversal with FFP took more than twice as long compared with FVIIa or PCC. To reach an INR of 1.3, mean (±SD) reversal times were 1933 ± 905 minutes for FFP, 784 ± 926 minutes for FVIIa, and 980 ± 1021 minutes for PCC (P < 0.001; P < 0.01 between FFP and FVIIa, P < 0.05 between FFP and PCC). INR rebound occurred in 0 of 31 patients for FFP, 4 of 8 for FVIIa, and 0 of 7 for PCC (P = 0.001). Complications were uncommon. FVIIa was 15 and 3.5 times as expensive as FFP and PCC, respectively.. As an adjunct to Vit K for rapid warfarin reversal, FVIIa and PCC appear more effective than FFP. Either FVIIa or PCC are reasonable options for reversal, but FVIIa is considerably more expensive and may have greater risk of INR rebound.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Electronic Health Records; Emergency Medical Services; Factor VII; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Recombinant Proteins; Retrospective Studies; Vitamin K; Warfarin

Topics: Acute Disease; Anticoagulants; Attitude of Health Personnel; Blood Coagulation Disorders; Blood Component Transfusion; Double-Blind Method; Health Care Surveys; Humans; International Normalized Ratio; Plasma; Time Factors; Warfarin

To provide a practical formula for fresh frozen plasma (FFP) dosing for warfarin reversal.. We reviewed data on all adult patients who received a total of 7778 units of FFP for warfarin reversal at Sentara Norfolk General Hospital (Norfolk, VA) between April 1, 2009, and March 31, 2010. Patients with advanced liver disease, consumptive or dilutional coagulopathy, and administration of activated factor VII or prothrombin complex concentrate were excluded. First, we used regression analysis on the FFP1 subset (patients whose international normalized ratio [INR] was checked before and after 1 FFP administration) and derived a simple formula: DeltaINR (PreINR - PostINR) after 1 FFP =a × PreINR +b, where PreINR and PostINR are the INR values before and after FFP administration, respectively, and a and b are constants. In the validation step, the formula obtained for the FFP1 subset was repeatedly applied to the FFP2 (patients who received 2 units of FFP back-to-back without an intervening INR check), FFP3, and FFP4 subsets.. A total of 956 patients were included. The formula DeltaINR after 1 FFP = 0.57 × PreINR - 0.72 explained 82.6% of the total variance in INR change in the FFP1 subset (n=308; P<.01). Including age, sex, weight, FFP-to-PostINR interval, or administration of vitamin K marginally improved the model. Repeated application of the FFP1 formula to the FFP2 to 4 subsets combined confirmed the accuracy of the FFP1 formula across the entire data set (n=643; R(2)=95% between predicted and actual DeltaINR; P<.01).. This formula provides a practical and accurate method for FFP dosing for warfarin reversal.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Blood Component Transfusion; Decision Support Techniques; Female; Humans; International Normalized Ratio; Male; Middle Aged; Plasma; Regression Analysis; Reproducibility of Results; Retrospective Studies; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Component Transfusion; Hemorrhage; Humans; Plasma; Practice Guidelines as Topic; Treatment Outcome; Warfarin; Wounds and Injuries

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Component Transfusion; Decision Support Techniques; Female; Humans; Male; Plasma; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Component Transfusion; Decision Support Techniques; Female; Humans; Male; Plasma; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Drug Approval; Humans; Thromboembolism; United States; United States Food and Drug Administration; Warfarin

An 85-year-old man on warfarin for atrial fibrillation presented with skin bleeding. International normalised ratio (INR) and activated partial thromboplastin time (APTT) were elevated and did not correct even after warfarin reversal with vitamin K, prothrombin complex concentrate (PCC) and fresh frozen plasma. Mixing coagulation studies with normal plasma suggested the presence of an inhibitor rather than the multiple coagulation factor deficiencies expected with warfarin. Assays of the common-pathway coagulation factors revealed factor V concentration <2% with inhibitor level elevated to 11 Bethesda units. The bleeding resolved following a course of corticosteroids. Coagulation studies and factor V level returned to normal along with resolution of the inhibitor. We report the case of the diagnostic dilemma posed and successful therapy implemented despite the limited evidence-based data being available for the treatment of this rare condition.

Topics: Aged, 80 and over; Atrial Fibrillation; Blood Coagulation Disorders; Factor V; Glucocorticoids; Hemorrhage; Humans; Male; Prednisolone; Skin Diseases; Warfarin

Thoracentesis is commonly performed to evaluate pleural effusions. Many medications (warfarin, heparin, clopidogrel) or physiological factors (elevated International Normalized Ratio [INR], thrombocytopenia, uremia) increase the risk for bleeding. Frequently these medications are withheld or transfusions are performed to normalize physiological parameters before a procedure. The safety of performing thoracentesis without correction of these bleeding risks has not been prospectively evaluated.. This prospective observational cohort study enrolled 312 patients who underwent thoracentesis. All patients were evaluated for the presence of risk factors for bleeding. Hematocrit levels were obtained pre- and postprocedure, and the occurrence of postprocedural hemothorax was evaluated.. Thoracenteses were performed in 312 patients, 42% of whom had a risk for bleeding. Elevated INR, secondary to liver disease or warfarin, and renal disease were the two most common etiologies for bleeding risk, although many patients had multiple potential bleeding risks. There was no significant difference in pre- and postprocedural hematocrit levels in patients with a bleeding risk when compared with patients with no bleeding risk. No patient developed a hemothorax as a result of the thoracentesis.. This single-center, observational study suggests that thoracentesis may be safely performed without prior correction of coagulopathy, thrombocytopenia, or medication-induced bleeding risk. This may reduce the morbidity associated with transfusions or withholding of medications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Clopidogrel; Cohort Studies; Drainage; Female; Hepatic Insufficiency; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Aggregation Inhibitors; Pleural Effusion; Postoperative Hemorrhage; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Thrombocytopenia; Ticlopidine; Warfarin

The first of this series of three articles discussed the dental management of patients with inherited bleeding disorders. This paper will discuss and outline the dental management of patients with acquired bleeding disorders that can result from drug therapy. These may be associated with vascular defects, platelet defects or coagulation defects. In an age when people are living longer, and medical interventions are continually becoming more advanced, clinicians will need to be aware of systemic disorders and treatments that may cause complications in the dental setting. According to National Statistics, the UK population is projected to increase by 0.7% by 2016. This trend is shared with other European countries which also have ageing populations. The proportion of people aged over 65 is predicted to increase from 16% in 2006 to 22% in 2031.. Being able to recognize which drugs may cause bleeding problems at an early stage will lead to good patient management, particularly in planning and delivering treatment following invasive procedures such as dental extractions. Whilst most patients can be successfully treated in general dental practice, the clinician may need to make a decision on whether or not to refer a patient to specialist services for all dental treatment, or to share care between primary care and specialist services for selected procedures.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antineoplastic Agents; Blood Coagulation Disorders; Clopidogrel; Dental Care for Chronically Ill; Drug Therapy; Hemorrhagic Disorders; Hemostasis; Heparin; Humans; Phytotherapy; Platelet Aggregation Inhibitors; Prothrombin Time; Ticlopidine; Warfarin

Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH). This was a retrospective case-series review of patients treated with an institution-approved warfarin reversal protocol. Patients with intracranial hemorrhage and known warfarin use with an international normalized ratio (INR)>1.4 received fresh frozen plasma (FFP), vitamin K (phytonadione), and weight-based, 3-factor PCC (Profilnine(®) SD) dose based on the initial INR. Demographic and clinical information, the degree of and time to INR normalization, and adverse events were recorded. The thirty study patients included 19 with primary ICH, 7 with SDH, and 4 with SAH. The mean age was 72.8 (±11) years, including 11 (37%) patients ≥80years old. The median presenting INR was 2.3 (IQR 2-3.3) and post-treatment INR was 1.4 (IQR 1.3-1.5, Z score 6.4, p<0.001). Median time from PCC administration to the first follow up INR was 95 (IQR 50-140) min. No patient's INR increased by more than 0.3 over 72h. Nine patients (30%) underwent neurosurgical procedures after PCC administration and no procedure-related bleeding complication was noted. Adverse events included 3 instances of early hematoma expansion, one ischemic stroke in a patient with endocarditis on post-PCC day 1, one pulmonary embolism 5weeks after PCC treatment, and one coronary in-stent thrombosis 60days after PCC treatment. 6 patients died prior to hospital discharge of anticipated complications of their initial event, and none from identifiable thrombotic complications of PCC. A 3-factor PCC preparation (Profilnine(®) SD), administered with FFP and vitamin K to patients with acute warfarin-associated intracranial bleeding is a reasonable approach to urgent warfarin reversal. However, randomized, prospective trials are needed to verify the safety and clinical effectiveness of PCC administration in this population.

Topics: Aged; Aged, 80 and over; Algorithms; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Hemostatics; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Treatment Outcome; Vitamin K; Warfarin

The rapid reversal of warfarin in the setting of traumatic brain injury (TBI) has been associated with improved outcomes. Until now, remote reversal of hypocoagulable states has not been possible in the prehospital environment. This manuscript describes the development and analysis of a prehospital plasma transfusion protocol to reverse warfarin at the earliest possible moment after TBI.. A retrospective review of all TBI patients receiving plasma transfusion(s) in the prehospital environment for warfarin reversal between February 2009 and September 2010 was conducted. Thawed plasma was carried on every air ambulance flight centered at the main campus.. A total of 2836 flights carried over 2500 units of thawed plasma throughout the study period. During this time, 16 patients received prehospital plasma resuscitation, five of who were on warfarin with a concurrent TBI. The median Injury Severity Score was 17 (8.5-27.5) with a median Glasgow Coma Score of 13 (8-15) and a mortality rate of 40%. A median of 2 (1.5-2.0) units of thawed plasma and 0 (0-0) units of RBCs were transfused en route. The pretransfusion point-of-care international normalized ratio improved from 3.1 (2.3-4.0) to 1.9 (1.3-3.6) upon trauma center admission (serum sample). One hundred percent of the transported, but unused, thawed plasma underwent subsequent transfusion prior to expiration.. Remote prehospital plasma transfusions effectively reverse anticoagulation secondary to warfarin administration in TBI patients. It is feasible to transfuse thawed plasma in the prehospital setting via remote damage control techniques without increasing waste. Prospective studies are needed to determine if this practice can improve outcomes in this population.

Topics: Adult; Air Ambulances; Anticoagulants; Blood Coagulation Disorders; Brain Injuries; Emergency Medical Services; Feasibility Studies; Humans; Plasma; Resuscitation; Retrospective Studies; Warfarin

The quality of anticoagulation management is not readily or frequently assessed, particularly between different centres. This study sought to evaluate agreement in oral anticoagulant management decisions between participating centres in UK NEQAS programmes.. Participants were asked to indicate whether they used computerized dosing support software (CDSS) and to complete a series of questions with respect to anticoagulant management provision. Four clinical scenarios were provided, together with past and current International Normalised Ratio (INR) results. Participants were asked to provide recommendations on the target INR they would assign to the patient, the dose of warfarin and a recall interval.. Seven hundred and fifty-nine centres returned results, of which 28% were enrolled in the hospital-based EQA programme, and 72% were participants in the point-of-care testing programme. Six hundred (79%) reported use of CDSS. In one straightforward scenario, there was 99% agreement in dose recommendation. However, for three more complex scenarios, differences were apparent in target INRs employed and both dose and recall recommendations. In some cases, differences related to the software system employed.. The study emphasizes large variation in the approach to managing these scenarios and warrants further investigation, together with education including promoting national guidelines for the assignment of target ranges.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Humans; International Normalized Ratio; Male; Medication Systems; Middle Aged; Software; Surveys and Questionnaires; Warfarin

We read with interest Gartrell's recent report of a woman who developed a factor V inhibitor. Gartrell noted in his report that the inhibitor appeared to exhibit time dependence, as the mixing study showed slightly more prolongation of both the PT and the aPTT after 1 hr than immediately following mixing. We believe Gartrell's article may shed light on a recent intriguing case of a patient with factor V inhibitor at our institution.

Topics: Anticoagulants; Blood Coagulation Disorders; Factor V; Female; Humans; Warfarin

Prothrombin complex concentrates (PCC) are recommended for urgent warfarin reversal. However, disagreement exists regarding the proper dosing strategy (i.e. fixed vs. weight-based). We measured the in vitro effect of PCC dosing on international normalised ratio (INR) and factor activity. Plasma from warfarin-anticoagulated patients with stable INRs was collected. PCC doses of 1,000, 2,000 and 3,000 IU were added to the samples, and INR and factor activity were analysed before and after PCC. Twenty-three of thirty subjects enrolled had complete data for analysis. INRs were below 1.5 in all samples post-1,000 IU, and decreased further with subsequent doses (p<0.001). Factors II, VII, and X increased with consecutive doses (p<0.01). Linear correlation was seen between INR and factors II, VII and X. Factor IX did not increase consistently nor show correlation with INR reversal. Weight-based dosing was then estimated; INRs were all <1.2 (0.9-1.2) and activity >0.50 IU for factors II, VII and X (0.96-1.52, 0.51-1.45 and 0.81-1.38, respectively). Factor IX did not uniformly correct above 0.50 IU (0.31-1.31). We confirm in vitro that 1,000 IU of Octaplex(®) is able to correct INR to <1.5 but factors were not uniformly >0.50 IU until 2,000 IU, and not >1.00 IU until 3,000 IU. This suggests that INR correction alone may not accurately reflect factor activity, and lends support for weight-based dosing.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Body Weight; Drug Dosage Calculations; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Warfarin

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Disorders; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Warfarin

Damage control resuscitation advocates correction of coagulopathy; however, options are limited and expensive. The use of prothrombin complex concentrate (PCC), also known as factor IX complex, can quickly accelerate reversal of coagulopathy at relatively low cost. The purpose of this study is to describe our experience in the use of factor IX complex in coagulopathic trauma patients.. All patients receiving PCC at our Level I trauma center over a two-year period (2008-2010) were reviewed. PCC was used at the discretion of the trauma attending for treatment of coagulopathy, reversal of coumadin, and when recombinant factor VIIa was indicated.. Forty-five trauma patients received 51 doses of PCC. Sixty-two per cent were male and mean Injury Severity Score was 23 (± 14.87). Standard dose was 25 units per kg and mean cost per patient was $1,022 ($504-3,484). Fifty-eight per cent of patients were on warfarin before admission. Mean international normalized ratio (INR) was decreased after PCC administration (p = 0.001). Packed red blood cell transfusion was also reduced after factor IX complex (p = 0.018). Mean INR was reduced in both the nonwarfarin (p = 0.001) and warfarin (p = 0.001) groups. Packed red blood cell transfusion was less in the nonwarfarin group (p = 0.002) however was not significant in the warfarin group. Subsequent thromboembolic events were observed in 3 of the 45 patients (7%). Mortality was 16 of 45 (36%).. PCC rapidly and effectively treats coagulopathy after traumatic injury. PCC therapy leads to a significant correction in INR in all trauma patients, regardless of coumadin use, and concomitant reduction in blood product transfusion. PCC should be considered as an effective tool to treat acute coagulopathy of trauma. Further prospective studies examining the safety, efficacy, cost, and outcomes comparing PCC and recombinant factor VIIa are needed.

Topics: Aged; Blood Coagulation Disorders; Erythrocyte Transfusion; Factor IX; Factor VIIa; Female; Humans; Injury Severity Score; International Normalized Ratio; Male; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Warfarin; Wounds and Injuries

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Contusions; Epistaxis; Female; Hematemesis; Humans; Male; Middle Aged; Vitamin K; Vitamins; Warfarin

A 53 year old female who was maintained on long-term warfarin therapy due to history of pulmonary embolism, repeatedly presents with an abnormally prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). After many asymptomatic episodes were corrected with Vitamin K therapy to temporarily reverse the effects of the warfarin, the cause of the apparent coagulopathy was further investigated. Factor Activity Assays of the common pathway factors II, IX, and X all revealed critically low values; below the threshold even a loading dose of warfarin is typically capable of eliciting. The patient tested strongly positive for Tissue Transglutaminase IgA, which is highly suggestive of a gluten-sensitive enteropathy. One effect of this condition is malabsorption due to flattened intestinal villi. The patient was determined to have an acquired vitamin K deficiency secondary to gluten-sensitive enteropathy. Her condition was exacerbated by the long-term warfarin therapy, resulting in the prolonged PT and PTT. The patient was treated with vitamin K therapy, which reversed the deficiency and corrected her abnormal coagulation results.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Celiac Disease; Drug Hypersensitivity; Female; Humans; International Normalized Ratio; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Warfarin

Both established oral anticoagulants such as warfarin and newer agents such as dabigatran etexilate (DE) effectively prevent thromboembolic disease, but may provoke bleeding. Limited clinical data exist linking oral anticoagulant reversal and bleeding tendency, as opposed to surrogate laboratory markers..  To quantify bleeding in warfarin-anticoagulated and DE-anticoagulated mice by tail transection with or without pretreatment with potential reversal agents: prothrombin complex concentrate (PCC); activated PCC (APCC); recombinant factor VIIa (rFVIIa); or murine fresh-frozen plasma (FFP).. CD1 mice were given warfarin or DE by gavage, and the effects on in vitro coagulation assays, volume of blood loss and the bleeding time following tail transection injury were evaluated with different reversal agents.. PCC (14.3 IU kg(-1) ), but not rFVIIa (3 mg kg(-1) ) or FFP (12 mL kg(-1) ), normalized blood loss and bleeding time in mice with warfarin-induced elevations of mean prothrombin time at two intensities (prothrombin time ratios of either 4.3 or 24). Neither separate nor combined PCC and/or rFVIIa treatment nor APCC (100 U kg(-1) ) treatment significantly reduced blood loss in mice anticoagulated with 60 mg kg(-1) DE 75 min prior to tail transection. Both combined PCC plus rFVIIa treatment and APCC treatment significantly reduced bleeding time in the DE-treated mice.. Our data suggest that PCC treatment prevents excess bleeding much more effectively in warfarin-induced coagulopathy than in DE-induced coagulopathy.

Topics: Animals; Anticoagulants; Antithrombin Proteins; Benzimidazoles; Blood Coagulation Disorders; Dabigatran; Mice; Prothrombin; Pyridines; Warfarin

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Anticoagulants; Blood Coagulation Disorders; Cardiomyopathy, Dilated; Drug Interactions; Hematuria; Humans; International Normalized Ratio; Levofloxacin; Male; Ofloxacin; Shock; Urinary Tract Infections; Warfarin

A case of a baby born preterm with an antenatal diagnosis of aortic coarctation for which prostin was electively started at birth. The baby was found to be profoundly anaemic with no clear obstetric cause. Features consistent with antenatal intracerebral haemorrhage were noted on cranial ultrasonography in the context of severe coagulopathy, prompting investigations which confirmed fetal-maternal haemorrhage. It transpired that, following aortic and mitral valve replacements, the mother was anticoagulated with warfarin at conception, having misunderstood her cardiologist's advice that: 'you cannot get pregnant whilst on warfarin'. Following conversion to low molecular weight heparin, she suffered a stroke, thus warfarin was restarted, with an international normalised ratio of 3-4.7 during pregnancy. Following transfer to the paediatric intensive care unit, fetal warfarin syndrome was diagnosed. The coagulopathy and anaemia were corrected and aortic coarctation was excluded. The baby returned to the neonatal intensive care unit for ongoing care and was discharged home in good condition around his due date. At the present time, there is no clinically overt neurological deficit.

Topics: Abnormalities, Drug-Induced; Anemia; Anticoagulants; Aortic Coarctation; Blood Coagulation; Blood Coagulation Disorders; Female; Fetal Diseases; Heart Valves; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Infant, Premature; Maternal-Fetal Exchange; Nasal Bone; Postoperative Complications; Pregnancy; Premature Birth; Stroke; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Brassica; Humans; Male; Warfarin

The key question when managing patients on warfarin therapy who present with life-threatening bleeding is how to use the international normalized ratio (INR) to best direct corrective therapy. The corollary question for the clinical laboratory is at what level will the INR reflect a critical value that requires notifying the clinician.. To determine the levels of vitamin K-dependent factors over a range of INR values.. Evaluation of the vitamin K-dependent coagulation factor levels on plasma remnants from patients in whom a prothrombin time and INR was ordered to monitor warfarin therapy. There were a total of 83 specimens evaluated with an INR range from 1.0 to 8.26.. The mean activity levels of all 4 factors remained near or above 50% when the INR was less than 1.5. The average factor X level was 23% when the INR range was 1.6 to 2.5, but levels of factors II, VII, and IX did not drop below the hemostatic range until the INR was greater than 2.5. At an INR of 3.6 or more, the activity levels of all 4 factors were less than 30% in more than 90% of the specimens.. Levels of factors II, VII, IX, and X declined with increasing INR but not at the same rate and not to the same level at a given INR. However, most of the values were below the hemostatic value once the INR was 3.6 or more, the level that was also considered critical for physician notification.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Middle Aged; Warfarin

Drug interactions in the neurosciences intensive care unit (NICU) may involve antiepileptic drugs and warfarin. Most commonly used antiepileptic drugs are either potent hepatic enzyme inducers or inhibitors and they affect the metabolism of warfarin. Valproic acid also displaces warfarin from the protein binding sites resulting in significant INR changes but this type of drug interaction is less well known.. Case report.. A 71 year-old female patient with a glioblastoma multiforme presented to the NICU with refractory partial complex seizures. Patient was on warfarin for a prior deep venous thrombosis. After treatment with levetiracetam, seizures recurred and intravenous loading with valproic acid was administered, but resulted in a rapid increase in international normalized ratio (INR) to 7.6. A MRI of the brain showed hemorrhagic tumor, but no new major bleeding.. With both acidic drugs present, a loading dose of valproic acid may displace warfarin from the protein binding sites resulting in redistribution of warfarin in free active form and lead to a rapid increase in INR.

Topics: Aged; Anticoagulants; Anticonvulsants; Blood Coagulation Disorders; Drug Interactions; Female; Humans; International Normalized Ratio; Seizures; Valproic Acid; Warfarin

The authors point to the risk of hypocoagulation by patients with colorectal carcinoma, who use warfarin.. 185 patients with colorectal cancer were examined for plattellets, prothrombin time and D-dimer.. Only 64 patients (35%) had haemocoagulation in the standard, 114 patients (61%) were hypercoagulable and only 7 patients (3.7%) were hypocoagulable. The authors present an interesting case report of a patient who used warfarin. This patient has ileos state by sigmoideal cancer, and in parallel a progressive intramural haematoma in the hepatic flexure of the colon.. Hypocoagulation state with an intramural haematoma of colon may be very dangerous complication for patients with colorectal cancer and ileos state. Very careful choice of surgical strategy is necessary.

Topics: Aged; Blood Coagulation Disorders; Colonic Diseases; Hematoma; Humans; Male; Sigmoid Neoplasms; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Diagnosis, Differential; Dyspnea; Factor V; Female; Humans; Warfarin

Use of a coagulation panel [prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT) and fibrinogen], intended for evaluation of bleeding, tripled over 6 years, out of proportion to admissions, surgery, or transfusions. To determine whether the panels were ordered appropriately, we classified 28,737 sets of panel results into groups followed by chart reviews to determine typical patient histories. In 39% of panels, PT/PTT was normal. Prolonged PT occurred in 33% of results, due to liver failure (8%), warfarin (23%), and presumed vitamin K deficiency (69%). Prolonged PTT occurred in 34% of results and was primarily associated with long PT or lupus inhibitors. Prolonged PTT and TT (15% of panels) indicated heparin therapy. Fibrinogen was normal in 98% and low in 1.4%. Critical fibrinogen (below 100 mg/dl, 0.6% of panels) was associated with bleeding in 90% of patients. Only 8% of panel orders were clinically indicated based on patient history. Clinician interviews indicated many were unaware the panel included fibrinogen and TT. Interventions included an education program and an order form change. The education program had no effect on overall order volume or test selection. A later order form change made TT and fibrinogen a separate order. This reduced TT and fibrinogen testing by 90% without complaints or changes in blood transfusion statistics. We conclude that many coagulation test panel orders were not clinically indicated, that PT more often diagnosed vitamin K deficiency than bleeding risk, and that order-based restriction of testing was more effective than educational programs at introducing change in clinical test utilization.

Topics: Anticoagulants; Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Fibrinogen; Hemorrhage; Humans; Partial Thromboplastin Time; Prothrombin Time; Risk Factors; Thrombin Time; Vitamin K Deficiency; Warfarin

Interpatient variability in the safety and efficacy of oral anticoagulation with warfarin presents several challenges to clinicians, thus underscoring the emergent need for new orally available anticoagulants with predictable pharmacokinetic and pharmacodynamic profiles and ability to target circulating clotting factors. Seven compounds including rivaroxaban, apixaban, betrixaban, and eribaxaban are orally available direct inhibitors of activated factor X currently in development for the prevention and treatment of venous thromboembolism and for thromboprophylaxis in patients with atrial fibrillation or following an acute coronary syndrome. At doses used in phase 2 and 3 clinical trials, rivaroxaban and apixaban demonstrated a predictable onset of effect, maximal plasma concentration, and half-life that was unaffected by age, renal, or hepatic disease. In clinical trials for the treatment and prevention of venous thromboembolism, rivaroxaban and apixaban produced equivalent or superior reductions in the development or progression of venous thromboembolism compared with either low molecular weight heparin or warfarin. Trials comparing the efficacy of rivaroxaban or apixaban to standard therapy for stroke prophylaxis in patients with atrial fibrillation are in process. Rivaroxaban, the sentinel compound in this class, is already approved in the European Union and Canada. It is likely to be approved for use in the United States in 2010.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzamides; Blood Coagulation Disorders; Clinical Trials as Topic; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Warfarin

Carotid dissection has rarely been described in pregnancy. We report a 24-year-old woman who developed an acute stroke 14 days postpartum after a complicated pregnancy. Her left internal carotid artery was found to be occluded, presumably secondary to a carotid dissection. Her neurologic symptoms resolved and she was treated with short-term warfarin therapy and blood pressure control.

Topics: Anticoagulants; Antihypertensive Agents; Blood Coagulation Disorders; Brain; Carotid Artery, Internal; Carotid Artery, Internal, Dissection; Female; Humans; Hypertension; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Pre-Eclampsia; Pregnancy; Stroke; Warfarin; Young Adult

Although S-1 is frequently used in cancer chemotherapy, the drug interaction with warfarin, an anticoagulant agent, is not fully paid attention. In the present study, we investigated retrospectively the timing of expression of blood coagulation abnormality in nine patients treated with warfarin and S-1 concomitantly. In five patients, the dose of warfarin was reduced or interrupted after concomitant use of S-1. The International Normalized Ratio (INR) was significantly increased after combination with S-1 compared with the former value. In all patients, the INR was increased in three weeks after combination with S-1. On the other hand, serum creatinine, aspartate aminotransferase, alanine aminotransferase or serum albumin was not different before and after combination with S-1. These results suggest that the careful monitoring of the blood coagulation ability is necessary in all patients receiving warfarin and S-1 concomitantly.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Drug Combinations; Drug Interactions; Drug Therapy, Combination; Female; Humans; International Normalized Ratio; Male; Middle Aged; Monitoring, Physiologic; Oxonic Acid; Retrospective Studies; Tegafur; Time Factors; Warfarin

Warfarin, a commonly prescribed anticoagulant, has many potential drug interactions. We describe a case of intravaginal miconazole potentiating the effects of warfarin in a patient previously stable on a consistent dose of 8.5 mg warfarin daily. Following a course of intravaginal miconazole and a dosage increase to 9 mg daily, her international normalized ratio (INR) increased from 2.0 to 5. After the course of miconazole was complete, the patient was stable with a therapeutic INR (mean INR 2.9) on 9 mg warfarin daily. Clinicians should consider the possibility of systemic absorption of intravaginal miconazole, and a resultant increase in warfarin's anticoagulant effect.

Topics: Administration, Intravaginal; Anticoagulants; Antifungal Agents; Blood Coagulation; Blood Coagulation Disorders; Drug Interactions; Female; Humans; International Normalized Ratio; Miconazole; Middle Aged; Prothrombin Time; Warfarin

To evaluate whether student participation in ambulatory clinics influenced the percentage of therapeutic international normalized ratio (INR) results among patients on chronic warfarin therapy.. Medical records in outpatient anticoagulation clinics managed by pharmacists under physician protocol were reviewed retrospectively in 2 university-affiliated clinics in Amarillo and Lubbock, TX. Pharmacy student activities included patient interviews, vital sign measurements, fingersticks, counseling, and documentation. Patient visits were conducted by a precepted pharmacy student or a pharmacist without a student, and the INR was measured at the subsequent patient visit.. Records of 1,958 anticoagulation patient visits were reviewed; 865 patients were treated by pharmacists, and 1093 were treated by precepted students. The follow-up INR was therapeutic for 48.5% of third-year (P3) students' patients, 45.6% of fourth-year (P4) students' patients, 51.2% of residents' patients, and 44.7% of pharmacists's patients (p = 0.23). Eight variables were associated with the follow-up INR (baseline INR, warfarin noncompliance, held warfarin doses, a warfarin dosage adjustment, diet change, alcohol use, tobacco use, and any medication changes).. Student participation in the patient-care process did not compromise patient care and no significant difference in patient outcomes was found between patients in an anticoagulation clinic cared for by precepted students and those cared for by pharmacists.

Topics: Ambulatory Care Facilities; Anticoagulants; Blood Coagulation Disorders; Clinical Clerkship; Cohort Studies; Counseling; Drug Monitoring; Follow-Up Studies; Humans; International Normalized Ratio; Logistic Models; Odds Ratio; Patient Compliance; Pharmaceutical Services; Pharmacists; Quality of Health Care; Retrospective Studies; Risk Factors; Students, Pharmacy; Treatment Outcome; Warfarin

Internationally, Factor IX complex (FIX complex) has been used to correct warfarin-induced coagulopathy. We present our experience with 28 patients using FIX complex.. A retrospective chart review was conducted between November 2002 and July 2006 on patients with warfarin-induced coagulopathy. We recorded the dose and timing of FIX complex, serial international normalized ratios (INRs), early adverse events, and patient outcome.. Twenty-eight patients met criteria. The mean INR on admission was 5.1, and after FIX complex infusion was reduced significantly to 1.9 (P = .008). Eleven patients had a repeat INR drawn within 30 minutes after FIX complex infusion. The mean time to correction was 13.5 minutes. There were no early thrombotic events or allergic reactions.. FIX complex results in an immediate reversal of coagulopathy within 15 minutes after administration. Its use should be considered as an alternative treatment to fresh-frozen plasma and recombinant Factor VIIa. Prospective randomized trials are needed to confirm these findings.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Cerebral Hemorrhage, Traumatic; Factor IX; Female; Humans; Male; Middle Aged; Retrospective Studies; Time Factors; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Endocarditis; Gangrene; Humans; Male; Middle Aged; Neoplasms; Palliative Care; Risk Factors; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Drug Monitoring; Heart Valve Prosthesis; Humans; International Normalized Ratio; Self Care; Warfarin

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Cohort Studies; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Male; Orthopedic Procedures; Preoperative Care; Thrombosis; Treatment Outcome; Vitamin K; Warfarin; Wounds and Injuries

Topics: Anticoagulants; Blood Coagulation Disorders; Hemorrhage; Humans; Pharmacogenetics; Warfarin

The scientific rationale for administering fresh frozen plasma (FFP) rests on the assumptions that patients are at risk of adverse effects from inadequate coagulation factors, and that FFP transfusions can decrease those risks. There is a general but unfounded enthusiasm for FFP use across a range of clinical specialties in hospital practice. Plasma for transfusion is most often used when a patient has abnormal results on coagulation screening tests, either as therapy in the face of bleeding, or in patients who are not bleeding as prophylaxis before invasive procedures or surgery. Laboratory abnormalities of coagulation are considered by many clinicians to help predict bleeding before invasive procedures where bleeding risk exists; FFP is presumed to improve the laboratory results and reduce this risk. However, most guideline indications for the prophylactic use of FFP are not supported by evidence from good-quality randomised trials. In fact, the strongest randomised controlled trial evidence indicates that prophylactic plasma for transfusion is not effective across a range of clinical settings. This is supported by data from non-randomised studies in patients with mild-moderate abnormalities in coagulation tests. It is also crucial to clearly understand the risks associated with use of FFP, as no studies have taken adequate account of the extent to which adverse effects might negate the clinical benefits of treatment with FFP. New trials are needed to evaluate the efficacy and adverse effects of plasma, both in bleeding and non-bleeding patients, and to determine whether presumed benefits outweigh the real risks. In addition, new haemostatic tests that better define the risk of bleeding and monitor the effectiveness of FFP use should be validated.

Topics: Algorithms; Anticoagulants; Blood Coagulation Disorders; Blood Transfusion; Coagulation Protein Disorders; Critical Illness; Hemorrhage; Humans; Plasma; Transfusion Reaction; Warfarin

Topics: Blood Coagulation Disorders; Humans; International Normalized Ratio; Liver Failure, Acute; Prognosis; Prothrombin Time; Warfarin

The objective of this study is to show the effectiveness of Factor IX complex concentrate (FIXCC) for rapid reversal of an elevated International Normalized Ratio (INR) in patients with anticoagulation-associated intracerebral hemorrhage (AAICH).. We, retrospectively, analyzed the clinical data of 19 patients with the diagnosis of AAICH from January 2005 to May 2006. A comparison was made among patients treated with FFP and Vit.K [FFP-group (n = 9)] and patients treated with FIXCC in addition to FFP and Vit.K [FIXCC-group (n = 10)]. INR of 1.4 or less was taken as target.. Mean INR on admission for FFP and FIXCC group was 1.84 +/- 0.31 and 2.44 +/- 1.48, respectively (P = 0.315). After administration of therapy, the INR was reduced from 1.84 +/- 0.31 to 1.34 +/- 0.08 (P < 0.05) in FFP group and 2.44 +/- 1.48 to 1.34 +/- 0.07 (P < 0.005) in FIXCC group. Three patients in FFP group (33%) and 8 patients in FIXCC group (80%) reached their target INR in 3-4 h after initiation of therapy (P = 0.012). Mean time taken by both FFP and FIXCC groups to reach the target INR was 8.52 +/- 5.60 h and 4.25 +/- 2.12 h, respectively (P < 0.05). The mean rate of INR correction was 0.06 +/- 0.03 and 0.27 +/- 0.25 per hour for the FFP and FIXCC group, respectively (P < 0.005). There was one death in FIX group and two in FFP group and no thrombotic complications.. Our data suggests that FIXCC in combination with FFP and Vit.K may result in decreased time required when compared to FFP and Vit.K alone for correction of warfarin associated coagulopathy in neurosurgical emergencies.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Cerebral Hemorrhage; Drug Interactions; Drug Therapy, Combination; Factor IX; Female; Humans; International Normalized Ratio; Male; Middle Aged; Plasma; Retrospective Studies; Treatment Outcome; Vitamin K; Vitamins; Warfarin

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Disorders; Humans; Risk Assessment; Safety; Warfarin

CoaguChek S (Roche Diagnostics, Canada) is a portable device designed to monitor international normalized ratio (INR) by capillary puncture. Although the device is used in pediatrics, no study has evaluated its validity in patients of this population.. To evaluate the validity of CoaguChek S as an in-home INR monitor in patients younger than 18 years of age.. Data were based on 129 INR pairs collected from nine patients younger than 18 years of age followed up at an anticoagulation clinic between March 1, 2000, and January 19, 2004. The INRs from both the laboratory and CoaguChek S were used to evaluate concordance between the two methods using the intraclass correlation coefficient.. The overall intraclass correlation coefficient between the CoaguChek S and the laboratory was 0.75 (95% CI 0.66 to 0.82). On average, CoaguChek S underestimated INRs by 0.11+/-0.54 units compared with those of the laboratory. INRs of 3.5 units and higher obtained with CoaguChek S were, on average, 0.49+/-1.09 units higher than those obtained in the laboratory.. CoaguChek S appears to be a valid instrument for in-home INR monitoring for most patients younger than 18 years of age, with INR targets of 2.0 to 3.0 followed up by an anticoagulant therapy clinic's program. However, caution must be used when interpreting INRs higher than 3.5. Parents should perform a second test to confirm all CoaguChek S INR results higher than 4.0.

Topics: Adolescent; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Child, Preschool; Drug Monitoring; Female; Humans; Infant; Infant, Newborn; International Normalized Ratio; Male; Monitoring, Ambulatory; Pediatrics; Point-of-Care Systems; Prothrombin Time; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Dietary Supplements; Drug Stability; Female; Humans; Male; Middle Aged; Vitamin K; Warfarin

Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Blood Coagulation Disorders; Capsaicin; Contraindications; Humans; Osteoarthritis, Knee; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Cytochrome P-450 Enzyme System; Humans; Mixed Function Oxygenases; Vitamin K Epoxide Reductases; Warfarin

Warfarin is commonly used to treat or prevent thromboembolic events. Cranberry juice has been suggested to have an interaction with warfarin. However, there have been few reported cases of warfarin-cranberry juice interaction.. A 78-year-old, 86-kg man receiving warfarin at a total weekly dose of 45 mg for atrial fibrillation presented at the Bakersfield Healthcare Center of the VA Greater Los Angeles Healthcare System with an international normalized ratio (INR) of 6.45, having reported drinking a half gallon of cranberry/apple juice in the week prior to the elevated INR. After discontinuation of the cranberry juice, maintaining the warfarin dose for 5 days, and resuming the warfarin at a total weekly dose of 40 mg, the INR returned to the therapeutic range of 2 to 3.. Possible warfarin-cranberry juice interactions have been reported in the literature. Case reports illustrate INR elevation associated with cranberry juice ingestion concomitantly with warfarin administration and may be associated with bleeding (eg, pericardial, gastrointestinal). In the present case report, cranberry juice was the most likely cause of the patient's elevated INR. The Naranjo probability scale score was 3, suggesting that there was a possible interaction between warfarin and cranberry juice, while the modified Naranjo scale score adapted for anticoagulants was 5, rating the interaction as probable.. The combination of warfarin administration and cranberry juice ingestion appeared to be associated with an elevated INR without bleeding in this elderly patient.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Beverages; Blood Coagulation Disorders; Food-Drug Interactions; Humans; International Normalized Ratio; Male; Vaccinium macrocarpon; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Ascorbic Acid; Blood Coagulation; Blood Coagulation Disorders; Chromatography, High Pressure Liquid; Dietary Supplements; Female; Humans; Male; Middle Aged; Stereoisomerism; Warfarin

Patients with a supratherapeutic international normalised ratio (ST-INR) are at risk for bleeding. ST-INR is corrected by withholding warfarin therapy and often by supplementing vitamin K or providing vitamin K-dependent factors; the exact therapeutic decision is based on the extent of the prolonged INR. Currently, ST-INRs are frequently observed in clinical practice due to the use of sensitive recombinant tissue thromboplastin reagents and automation. However, there are scant data correlating an ST-INR with various vitamin K-dependent factors. This prospective cohort study, set in a large tertiary care teaching hospital for the University of Texas Southwestern Medical Center at Dallas, defined the relationship between ST-INR (>5.0) and measured vitamin K-dependent procoagulant factors. Prothrombin time, INR and vitamin K-dependent factors II, VII, IX and X were measured in 78 patients with an INR > 5.0 (ST-INR) who were on warfarin therapy for more than 2 months. There was no significant relationship between the ST-INR and levels of important vitamin K-dependent factors II and X. These data support the recent guidelines that the management of an INR > 5.0 should be driven by the clinical determinants rather than specific INR values per se.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation Disorders; Blood Coagulation Factors; Factor X; Female; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Prospective Studies; Prothrombin; Regression Analysis; Stroke; Venous Thrombosis; Vitamin K; Warfarin

The extent and complications of the interaction between capecitabine and warfarin are not fully known.. A retrospective study of 77 patients who received capecitabine was performed to analyze coagulation abnormalities with or without warfarin.. Twenty-one patients received warfarin with capecitabine. Twelve were on an average warfarin dosage of 19.4 mg per week (range, 7-35 mg) before capecitabine treatment, with a stable international normalized ratio (INR; range, 0.9-3.3). The dose of capecitabine ranged from 1.6 g/m2 to 2 g/m2 per day. Thirteen patients (11 on warfarin) had an INR > 3 (range, 3.23-11.5), resulting in a probability of an INR > 3 of 32% in the warfarin group versus 4% for those not on warfarin (P = 5.1 x 10(-14)) at 130 days. Six patients required a warfarin dose reduction (1-2.5 mg decrease). There were 7 episodes of bleeding (all gastrointestinal; 5 with warfarin). Seven patients who experienced bleeding had INRs ranging from 1.06 to 8 (average, 3.31) at the time bleeding occurred. Of the 7 bleeding episodes, 5 patients required transfusions, averaging 3.25 units of red blood cells and 2.4 units of fresh frozen plasma. The incidence of bleeding at 130 days of treatment with capecitabine was 18% with warfarin versus 2% without (P = 4 x 10(-13)). Bleeding episodes were not significantly different between patients with or without liver involvement (4 of 40 episodes vs. 3 of 37 episodes, respectively; P = 0.12). Patients with an INR > 3 were evenly distributed between those with or without liver involvement (6 of 40 patients vs. 7 of 37 patients, respectively). No INR increases persisted after discontinuation of capecitabine.. This study confirms a clinically significant interaction between warfarin and capecitabine-based chemotherapy akin to that already known for 5-fluorouracil. In addition to altered coagulation parameters, bleeding can be a complication. These events occurred in patients with and without liver metastases. We recommend weekly monitoring of coagulation parameters for all patients receiving concomitant warfarin and capecitabine, with an appropriate adjustment of warfarin dose. The nature and extent of this interaction requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antimetabolites, Antineoplastic; Blood Coagulation Disorders; Capecitabine; Deoxycytidine; Drug Interactions; Female; Fluorouracil; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Polypharmacy; Retrospective Studies; Warfarin

Studies examining the relationship between patient knowledge regarding warfarin therapy and its safe and effective use are limited by the lack of validated knowledge assessment tools.. To develop and validate an instrument to assess patient knowledge regarding oral anticoagulation therapy.. Four nationally recognized anticoagulation experts participated in the instrument development process to ensure content validity. The Oral Anticoagulation Knowledge (OAK) test was administered to subjects on warfarin and a group of age-matched subjects not on warfarin to assess construct validity. A subgroup of warfarin subjects were retested approximately 2-3 months after initial testing to assess test-retest reliability. Internal consistency reliability was assessed by calculating a Kuder-Richardson 20 value. Item analysis was used to assess performance of individual questions.. An initial 23 item instrument was pilot tested for readability and comprehension. The OAK test was administered to 74 subjects taking warfarin and 27 age-matched subjects not on warfarin. Thirty-two subjects on warfarin repeated the OAK test an average of 75 days following initial administration. Subjects taking warfarin scored significantly higher than those not on warfarin (72% vs 52%, respectively; p < 0.001), supporting the construct validity of the instrument. Test-retest reliability was acceptable, with a Pearson's correlation coefficient of 0.81. Internal consistency reliability was confirmed by a calculated Kuder-Richardson 20 value of 0.76.. The OAK test is a brief, valid, and reliable knowledge assessment instrument that may be a useful tool for research and clinical practice to augment patient education programs.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Pilot Projects; Surveys and Questionnaires; Warfarin

Alterations in vitamin K availability can significantly influence anticoagulation response to warfarin. Apolipoprotein E (APOE) plays a part in the hepatic uptake of lipid-soluble vitamin K. This study aimed to determine the influence of common polymorphisms in the APOE gene on warfarin dose requirements. patients with stable anticoagulation control and with a target International Normalized Ratio (INR) 2.0-3.0 were genotyped for the APOE epsilon2, epsilon3 and epsilon4 variants. Mean +/- SD daily warfarin doses were significantly lower in patients carrying at least one epsilon4 allele compared to the epsilon3epsilon3 reference genotype (3.3 +/- 1.9 versus 4.0 +/- 1.8; P = 0.03; 95% CI: 0.1-1.2). Multivariate regression analysis showed that patient age, height and CYP2C9, VKORC1 and APOE genotypes significantly contributed to warfarin dose requirement (R = 57%). only the epsilon4 allele of APOE was found to make a significant (P = 0.002) but small contribution to warfarin dose requirement. There was no significant difference in fasted plasma vitamin K concentration between patients with the different APOE genotypes. This study suggests that APOE genotype is unlikely to have a clinically significant effect on warfarin dose requirements.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Apolipoproteins E; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Polymorphism, Genetic; Vitamin K Deficiency; Warfarin

Topics: Anticoagulants; Bleeding Time; Blood Coagulation Disorders; Blood Loss, Surgical; Dental Care for Chronically Ill; Gelatin Sponge, Absorbable; Hemostatic Techniques; Hemostatics; Humans; International Normalized Ratio; Oral Hemorrhage; Prothrombin Time; Tooth Extraction; Tranexamic Acid; Warfarin

A complication of long-term anticoagulation is that the optimal dose level varies not only between patients but over time within patients, in response to short-term changes in lifestyle. Consequently, doseage needs to be adaptive but there are as yet no accepted decision rules. Since anticoagulant use is increasing worldwide there is a need for more objective and routine procedures. In this paper, we describe an analysis of observational longitudinal anticoagulant data, aimed at determining an optimal reactive dose-changing strategy. We use the regret parameterization approach advocated by Murphy (J. R. Stat. Soc. Ser. B 2003; 65:331-366). Practical problems encountered in the implementation of the approach are discussed and illustrated.

Topics: Algorithms; Anticoagulants; Blood Coagulation Disorders; Data Interpretation, Statistical; Female; Humans; International Normalized Ratio; Logistic Models; Longitudinal Studies; Male; Models, Statistical; Prothrombin Time; Warfarin

Topics: Blood Coagulation Disorders; Combined Modality Therapy; Drug Overdose; Humans; Male; Middle Aged; Suicide, Attempted; Warfarin

Topics: Acute Disease; Aged; Blood Coagulation; Blood Coagulation Disorders; Brain; Brain Ischemia; Drug Interactions; Factor VIIa; Female; Humans; Plasminogen Activators; Prothrombin Time; Stroke; Treatment Outcome; Warfarin

A battery of simple tests for profiling abnormalities of vitamin K-dependent coagulation factors encountered in drug-toxicity studies was verified in rats treated with warfarin (3 and 10 mg/kg, p.o). The thrombotest, or hepaplastin-test, is useful as a follow-up test after routine screening tests for coagulation abnormalities based on PT and APTT, to rule out other coagulation-factor abnormalities. Measurement of coagulation factor activities (factors II, VII, IX and X) using factor-deficient human plasmas provides direct evidence of decreased activities of vitamin K-dependent factors. Furthermore, Echis carinatus venom coagulation time, together with factor II activity, allows us to confirm the generation of PIVKA-II.

Topics: Animals; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Male; Protein Precursors; Prothrombin; Rats; Rats, Inbred Strains; Toxicity Tests; Vitamin K; Warfarin

Topics: Aged; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Heparin; Humans; International Normalized Ratio; Male; Partial Thromboplastin Time; Point-of-Care Systems; Prothrombin Time; Thrombin; Warfarin; Whole Blood Coagulation Time

Bridging anticoagulation with low-molecular-weight heparin (LMWH) is common in patients who require temporary interruption of warfarin before surgery or a procedure, but whether such patients have a residual anticoagulant effect just before a procedure is not known. Consecutive patients who received bridging anticoagulation with LMWH had anti-Xa levels measured just before a procedure. The proportion of patients with a residual anticoagulant effect, defined as an anti-Xa level > or = 0.10 IU/ml, was determined. Multivariable regression analysis identified predictors of a residual anticoagulant effect, expressed as an odds ratio (OR) and corresponding 95% confidence interval (CI). A pre-procedure residual anticoagulant effect was detected in 12 of 73 (16%) patients overall, in 11 of 37 (30%) patients who received therapeutic-dose LMWH, and in 1 of 36 patients (3%) who received low-dose LMWH. Receiving therapeutic-dose LMWH (OR = 118.8; 95% CI: 5.8, 999.9), and increasing age (OR = 4.0; 95% CI: 1.3, 12.5) were predictors of a residual pre-procedure anticoagulant effect. In patients who require bridging anticoagulation with LMWH, a residual anticoagulant effect from LMWH is detected in 1 of 6 patients, and receiving therapeutic-dose LMWH is the strongest predictor of such an effect.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Body Weight; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Preoperative Care; Risk Factors; Surgical Procedures, Operative; Time Factors; Treatment Outcome; Warfarin

Topics: Adolescent; Adult; Anticoagulants; Blood Coagulation Disorders; Family; Female; Fibrinogens, Abnormal; Humans; Male; Point Mutation; Prothrombin; Venous Thrombosis; Warfarin

To examine anticoagulation management at the Bella Coola Medical Clinic in British Columbia.. Charts of all patients in the Bella Coola Valley receiving warfarin were assessed. Data were analyzed using Microsoft Excel.. Bella Coola Medical Clinic on the remote central coast of British Columbia.. Twenty-one patients at the Bella Coola Medical Clinic who were receiving warfarin.. All international normalized ratio (INR) tests over the preceding 12 months were examined for results, time elapsed since previous test, and interval until next scheduled test.. An in-range INR rate of 60% is considered acceptable for anticoagulation services. The clinic had performed 406 INR tests on these 21 patients over the last 12 months. We found that 53% of all INR results fell strictly within the recommended therapeutic range. The relative success of anticoagulation management in Bella Coola probably results from several factors. For instance, physicians usually responded to out-of-range INR results with close monitoring: in 71% of cases, follow-up tests were scheduled within 1 week. On average, patients attended 77% of these visits on schedule; 58% of all out-of-range INR results were followed up with retesting within 1 week.. Our results suggest that primary care physicians can manage anticoagulation adequately, even in remote settings.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; British Columbia; Female; Humans; International Normalized Ratio; Male; Middle Aged; Practice Patterns, Physicians'; Primary Health Care; Rural Health Services; Warfarin

The relationship between dietary intake of vitamin K, fat, plasma vitamin K concentrations and anticoagulation response to warfarin within individuals, as well as the contribution of dietary vitamin K to differences in warfarin dose requirements between individuals were investigated in 53 patients on warfarin therapy who had stably controlled anticoagulation. Each patient completed a dietary record of all foods consumed on a daily basis for 4 weeks. Each week a blood sample was taken for measurement of the international normalized ratio (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations. The patients' genotype for CYP2C9 was also determined. Regression analysis of the data showed that, for each increase of 100 microg in the daily dietary intake of vitamin K averaged over 4 d, the INR was reduced by 0.2. There was no correlation between warfarin daily dose and average daily dietary vitamin K intake when calculated over 28 d. The regression model for warfarin dose showed that, while dietary vitamin K had no effect, CYP2C9 genotype (P = 2%) and age (P < 1%) significantly contributed to inter-patient variability in warfarin dose requirements. A consistent intake of vitamin K could reduce intrapatient variability in anticoagulation response and thus improve the safety of warfarin therapy.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Body Composition; Dietary Supplements; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Regression Analysis; Treatment Outcome; Vitamin K; Warfarin

The accuracy and reproducibility of the CoaguChek S, and its clinical agreement with conventional laboratory international normalized ratio (INR) determination, were evaluated in an outpatient anticoagulation clinic setting. Forty-three patients provided 248 paired INR measurements for analysis. The paired results were highly correlated (r = 0.90). The mean coefficient of variation for the CoaguChek S for a random sample of 21 patients with three repeated tests each, was 4%. Clinical applicability was also measured by discrepant INR values, as defined in the literature by expanded and narrow agreement, and by INR values resulting in a different clinical decision by a blinded haematology registrar. Expanded agreement and narrow agreement between the two INR values occurred 90 and 88% of the time, respectively. The stricter criteria set down by the clinician resulted in 73% of paired results producing the same dosage decision. The CoaguChek S displayed good correlation with laboratory determination of INR and compared relatively well with expanded and narrow clinical agreement criteria.

Topics: Ambulatory Care Facilities; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Monitoring, Ambulatory; Monitoring, Physiologic; Reference Values; Reproducibility of Results; Warfarin

A large proportion of patients use herbal remedies with a potential to interact with prescribed drugs. Such interactions can be dangerous, particularly if the therapeutic window of the prescribed drug is small, as with warfarin.. Our aim was to estimate the prevalence of the use of herbal medicines by patients taking warfarin (co-ingestion).. Postal questionnaire.. General practices in the South West of England.. Thirty-five general practices in Devon and Somerset identified 2600 patients taking warfarin and sent postal questionnaires to them.. One thousand, three hundred and sixty usable responses were received (response rate = 54.2%). One or more of the specified herbal remedies thought to interact with warfarin were taken by 8.8% of all patients. Complementary or homeopathic treatments not specified in the survey questionnaire were taken by 14.3% of responders. Overall, 19.2% of responders were taking one or more such medicines. The use of herbal medicines had not been discussed with a conventional healthcare professional by 92.2% of patients. Twenty-eight point three per cent of responders thought that herbal medicines might or definitely could interfere with other drugs prescribed by their doctor, however, patients taking any non-prescribed medication were less likely to believe this (chi2 = 20, degrees of freedom = 1, P<0.001).. A substantial proportion of patients taking warfarin in southwest England self-medicate with both herbal medicines that are thought to interact with warfarin and with others of unknown effect, usually without informing their healthcare team. Patients have a responsibility to mention such non-prescribed medication to their general practitioners, and general practitioners also have a responsibility to ask whether such co-ingestion is occurring.

Topics: Anticoagulants; Attitude to Health; Blood Coagulation Disorders; Drug Interactions; Female; Humans; Male; Phytotherapy; Plant Preparations; Warfarin

Topics: Blood Coagulation Disorders; Drug-Related Side Effects and Adverse Reactions; Hematuria; Humans; Intracranial Hemorrhages; Male; Middle Aged; Rodenticides; Warfarin

To report a comparison of international normalization ratio (INR) measurements on four near-patient (point-of-care or bedside) whole blood INR monitors in children.. The INR results from 19 ambulatory pediatric subjects (30 hospital visits) receiving warfarin sodium were analyzed on four near-patient monitors and compared with plasma INR measurements on the laboratory CA-1000 Analyze. The instruments evaluated were CoaguChek, Hemochron Jr. Signature, ProTime Microcoagulation System, and RapidpointCoag.. The INR measurements ranged from 1.05 to 5.25. Over the entire INR range, the near-patient instrument with the least bias relative to the CA-1000 was the RapidpointCoag (r(2) = 0.923). The correlations (r(2)) of the CoaguCheck, Hemochron Jr., and ProTime were 0.877, 0.834, and 0.885, respectively. Precision studies involved repeated analysis of one nonmedicated adult (mean CA-1000 INR = 0.908) and one adult receiving oral anticoagulation therapy (mean CA-1000 INR = 2.42). The coefficient of variation on the near-patient monitors for both adult volunteers ranged from 4.9% to 22.3%. Bilirubin levels up to 20 mg/dL did not interfere in any of the methods.. Near-patient testing whole blood INR monitors offer acceptably accurate and precise measurements. Values obtained on near-patient monitors may vary considerably from the reference method, and data obtained should serve as a supplement to, but not a replacement for, routine clinical laboratory measurements.

Topics: Administration, Oral; Adolescent; Anticoagulants; Bilirubin; Blood Coagulation Disorders; Child; Child, Preschool; Female; Hemorrhage; Humans; Infant; International Normalized Ratio; Male; Point-of-Care Systems; Prothrombin Time; Reference Standards; Thrombosis; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Humans; Solutions; Tablets; Vitamin K; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Humans; Solutions; Tablets; Vitamin K; Warfarin

To date there is no routinely used reliable diagnostic test that can be performed in the post-mortem period to investigate whether a deceased had a coagulation disorder. This paper describes a series of experiments to assess the use of an antigen-based method to investigate the vitamin K-dependent factor II function in the deceased. It illustrates that by using this approach the functional status of factor II can be investigated in the post-mortem period. The abnormal proteins that are investigated by this method appear to remain stable for at least 72 h and potentially up to at least 7 days. The method that is illustrated could thus be reliably used in the post-mortem period to identify a natural or drug-induced factor II abnormality. The potential for other protein components of the coagulation cascade to be investigated by similar antigen-based methodology is suggested.

Topics: Aged; Aged, 80 and over; Anticoagulants; Autopsy; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Tests; Child, Preschool; Female; Humans; Male; Middle Aged; Postmortem Changes; Protein Precursors; Prothrombin; Sensitivity and Specificity; Vitamin K; Warfarin

Spontaneous appearance of acquired anticoagulants is a rare phenomenon. We present two cases, where such antibodies against factor VIII were masked by warfarin therapy. The two patients were anticoagulated with warfarin due to mechanical heart valve and recurrent thromboembolic events, respectively. Different therapies against the inhibitor of factor VIII were used in the two cases. One patient received corticosteroids and high-dose gammaglobulin with temporary effect and was then effectively treated with cyclophosphamide. The other patient was successfully treated with cyclosporine. The special problems of keeping the balance between thrombosis and bleeding in this group of patients with need of anticoagulation due to mechanical heart valves or other thrombogenic factors are discussed.

Topics: Autoantibodies; Blood Coagulation Disorders; Factor VIII; Female; Heart Valve Prosthesis; Hemophilia A; Hemorrhage; Humans; Lupus Erythematosus, Systemic; Middle Aged; Thromboembolism; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Humans; Injections, Subcutaneous; International Normalized Ratio; Male; Middle Aged; Risk Factors; Vitamin K; Warfarin

To investigate the clinical suspicion that postpartum women are more difficult to anticoagulate with warfarin than non-pregnant women due to the physiological changes in coagulation proteins that persist into the postpartum period.. A retrospective case-control study.. University Hospital, Nottingham, UK.. Twenty-three postpartum women discharged from the obstetric wards on warfarin and 23 age-matched control women discharged from the medical wards on warfarin were identified using hospital databases.. Warfarin doses and international normalised ratio values were recorded from day one to 35. The number of days and total warfarin dose to achieve therapeutic international normalised ratio were recorded. Doses were compared with those recommended by a dosing nomogram.. The postpartum group took significantly longer and significantly larger doses of warfarin to reach therapeutic international normalised ratio (P < 0.05). The postpartum group required a persistently higher maintenance dose of warfarin. Comparing the warfarin dose given on day three with a standardised nomogram, 79% of women in the postpartum group compared with 57% in the control group were under-dosed.. Postpartum women require larger doses of warfarin to reach therapeutic international normalised ratio than non-pregnant women. We would recommend the use of a dosing nomogram.

Topics: Adult; Anticoagulants; Blood Coagulation Disorders; Case-Control Studies; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Pregnancy; Puerperal Disorders; Retrospective Studies; Time Factors; Warfarin

Topics: Aged; Aged, 80 and over; Anacardiaceae; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Food-Drug Interactions; Fruit; Humans; International Normalized Ratio; Male; Middle Aged; Warfarin

Topics: Abdominal Pain; Angina, Unstable; Anticoagulants; Blood Coagulation Disorders; Fever of Unknown Origin; Humans; Male; Medical Errors; Middle Aged; Nausea; Partial Thromboplastin Time; Prothrombin Time; Renal Dialysis; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Humans; International Normalized Ratio; Risk Factors; Thromboembolism; Vitamin K; Warfarin

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Cucurbitaceae; Drug Combinations; Drug Interactions; Humans; International Normalized Ratio; Male; Middle Aged; Plant Extracts; Sweden; Vitamin E; Vitamin K; Warfarin

To improve patient selection for specialized coagulation testing in the setting of ischemic stroke, the authors sought to identify factors associated with the presence of hypercoagulable states. Of 208 patients with ischemic stroke tested, undetermined stroke subtype was significantly associated with the presence of coagulopathy, but only 60% were treated with warfarin. The frequency of coagulopathy in selected patients with ischemic stroke (5%) is low, and establishing the diagnosis did not uniformly influence treatment.

Topics: Acute Disease; Adult; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Brain Ischemia; Female; Humans; Male; Middle Aged; Patient Selection; Prevalence; Stroke; Warfarin

The cause of cancer-associated venous limb gangrene is unknown but could paradoxically be due to warfarin.. To determine the pathogenesis of venous gangrene in a patient with cancer.. Case report.. University hospital in Ontario, Canada.. 66-year-old woman with metastatic lung cancer and deep venous thrombosis.. Levels of vitamin K-dependent factors, additional coagulation factors, and thrombin-antithrombin complexes (marker of thrombin generation).. During warfarin use, venous limb gangrene developed when the international normalized ratio (INR) reached 6.0 (therapeutic range, 2.0 to 3.0); at this time, the level of protein C (a vitamin K-dependent natural anticoagulant) was severely reduced, but thrombin-antithrombin complexes remained markedly elevated. The supratherapeutic INR was explained by the greatly reduced levels of factor VII, which correlated closely with protein C levels; therefore, the high INR was a surrogate marker for severely reduced protein C activity.. Warfarin may contribute to the pathogenesis of cancer-associated venous limb gangrene by leading to severe depletion of protein C while at the same time failing to reduce thrombin generation.

Topics: Aged; Anticoagulants; Antigen-Antibody Complex; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Gangrene; Humans; Lung Neoplasms; Protein C Deficiency; Thrombin; Thrombocytopenia; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Specimen Collection; Cost-Benefit Analysis; Costs and Cost Analysis; Humans; International Normalized Ratio; Patient Education as Topic; Point-of-Care Systems; Quality Control; Self Administration; United Kingdom; Warfarin

Topics: Aged; Anticoagulants; Antigen-Antibody Complex; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Gangrene; Humans; Lung Neoplasms; Protein C Deficiency; Thrombin; Thrombocytopenia; Venous Thrombosis; Warfarin

The role of oral Vitamin K administration in the reversal of anticoagulation is not yet clear because of a paucity of data on the early effects of treatment, apparent differences in efficacy between preparations and a lack of data comparing oral with intravenous administration. We have compared the effects on the International Normalized Ratio (INR) and activities of the Vitamin K-dependent clotting factors II, VII, IX and X at 4 h and 24 h after administration of three oral Vitamin K preparations and of intravenous Vitamin K in 64 anticoagulated patients who required non-urgent partial correction of anticoagulation. Our data confirm that correction of anticoagulation is more rapid after intravenous administration of Vitamin K than after oral administration of similar or larger doses. At 24 h, satisfactory correction of INR can be achieved using low-dose Vitamin K given by either the intravenous or oral route. Our data, and that from previous studies, suggest that there may be differences in efficacy between orally administered products. Administration of Vitamin K by either route was accompanied by changes in the activities of the Vitamin K-dependent clotting factors that reflected their respective biological half-lives. In the 24 h after treatment, the relationship between the INR and the individual Vitamin K-dependent clotting factors was similar to that described previously in stable anticoagulated patients. We conclude that the reversal of anticoagulation with warfarin is achieved more rapidly by intravenous administration of Vitamin K. Satisfactory, but slower, reversal of anticoagulation can be effected using oral Vitamin K, but there may be differences in efficacy between the products tested in our study.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Disorders; Coagulants; Factor IX; Factor VII; Factor X; Humans; Injections, Intravenous; International Normalized Ratio; Prothrombin; Time Factors; Vitamin K; Warfarin

To determine the pattern of anticoagulation control for post heart-valve surgery for patients on follow up at Kenyatta National Hospital (KNH).. A combined prospective and restrospective hospital-based study. Retrospective period from January 1991 to 31st August 1997, while the prospective period was from 1st September 1997 to 31st November 1999.. Cardiothoracic surgery clinic, Kenyatta National Hospital, Nairobi.. Post heart valve surgery patients on warfarin and attending the cardiothoracic surgery clinic at Kenyatta National Hospital.. Clinic attendance intervals, average warfarin dosages, interval of dosage change, INR values and variations from accepted normal.. A total of 103 patients fulfilled the criteria for inclusion into the study consisting of 77 mitral valve replacements, 18 aortic valve replacements, seven double valve replacements and one mitral valve repair. The total follow up time for the study period is 316.9 patients years. On average, patients attended their anticoagulation clinic once every 59 days. The average dose of warfarin prescribed was 6.81 mg daily (+/-2.67 mg), with double valve replacement patients receiving a statistically significant lower dosage of 6.04 mg (+/-1.36 mg), (95% confidence limits). On average, a warfarin dose change was made 1.48 times a year per patient. For all the patients, the mean INR was 2.50 (+/-1.18). The respective values for mitral, aortic, double valve replacement and the mitral repairs were 2.53 (+/-1.21), 2.32 (+/-1.04), 2.5 (+/-1.05) and 2.02 (+/-0.53), respectively. Mitral valve repair patients maintained a significantly lower level of INR (95% confidence limits). Only during 18% of the follow up time was adequate anticoagulation maintained. During the study period only 6.9% of patients were able to maintain adequate anticoagulation for 50% or more of their follow up time.. Anticoagulation control at the KNH still needs some improvements in clinic attendance and better dosage adjustments to achieve more appropriate INR values.

Topics: Anticoagulants; Blood Coagulation Disorders; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hospitals, Public; Humans; Kenya; Postoperative Complications; Practice Patterns, Physicians'; Prospective Studies; Retrospective Studies; Warfarin

Ciprofloxacin, when given to patients previously anticoagulated with warfarin, can occasionally cause an exaggerated hypoprothombinemic response and bleeding diatheses. Two such cases encountered at our institution are presented and data is combined with 64 cases reported to the Food and Drug Administration's (FDA) Spontaneous Reporting System (SRS) database, which included all cases reported from 1987 through 1997. Of 66 total cases the median age was 72 (range 36-94). The mean time to detection of the coagulopathy following the ciprofloxacin challenge was 5.5 days (n = 50). Hospitalization was reported in 15 cases, bleeding in 25 cases, and death in one case. The median prothrombin time (PT) and International Normalized Ratio (INR) was 38.0 (n = 13) and 10.0 (n = 23), respectively. The mean number of medications taken was 6.5 (n = 45). The mean time to correction was significantly shorter between the treated (2.5 days) and the untreated (4.0 days) groups (P < 0. 008). The ciprofloxacin-warfarin coagulopathy occurred most commonly in patients in their seventh decade and in those who require polypharmacy. Active treatment of the coagulopathy results in more rapid resolution than observation alone. Clinicians should be aware of the potential bleeding complications that can occur with the ciprofloxacin-warfarin drug-drug interaction.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Anticoagulants; Blood Coagulation Disorders; Ciprofloxacin; Drug Interactions; Female; Humans; Hypoprothrombinemias; Male; Middle Aged; Plasma; Prothrombin Time; Vitamin K; Warfarin

Topics: Attitude of Health Personnel; Blood Coagulation Disorders; Blood Specimen Collection; Colorado; Drug Monitoring; Health Care Surveys; Humans; Outpatient Clinics, Hospital; Patient Satisfaction; Pharmacists; Point-of-Care Systems; Surveys and Questionnaires; Warfarin

Topics: Anticoagulants; Antioxidants; Blood Coagulation Disorders; Cardiomyopathies; Coenzymes; Drug Interactions; Humans; Male; Middle Aged; Ubiquinone; Warfarin

Automated human plasma, continuous monitoring of the formation and inactivation of thrombin during the coagulation process provides an adequate way to detect hypo- and hypercoagulant conditions. Here, we describe an analogous procedure to determine the endogenous thrombin potential (ETP), i. e. the free thrombin concentration-time integral, of coagulating rat plasma. When activated with tissue factor, the ETP of plasma from Wistar rats was comparable to the ETP of human plasma, in spite of a relatively short half-life time of free thrombin in rat plasma. The ETP was highly sensitive to heparin as well as to administration of vitamin K antagonist or feeding of the animals with a vitamin K-deficient diet. In plasma that was activated under sub-optimal conditions (reduced levels of tissue factor or vitamin K-dependent coagulation factors), the ETP increased with the rate of thrombin formation in the first minutes of the coagulation process. Since both parameters are dependent of the prothrombin concentration, it appears that this level plays an important role in determining both the initial and total activity of the coagulation system. Thus, automated measurement of free thrombin during the coagulation process of rat plasma allows a detailed analysis of hypocoagulability in this animal model.

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Disease Models, Animal; Electronic Data Processing; Humans; Kinetics; Male; Rats; Rats, Wistar; Sensitivity and Specificity; Thrombin; Thromboplastin; Warfarin

To compare the reliability and relative costs of three international normalised ratio (INR) near patient tests.. Protime (ITC Technidyne), Coaguchek (Boehringer Mannheim), and TAS (Diagnostic Testing).. All patients attending one inner city general practice anticoagulation clinic were asked to participate, with two samples provided by patients not taking warfarin. A 5 ml sample of venous whole blood was taken from each patient and a drop immediately added to the prepared Coaguchek test strip followed by the Protime cuvette. The remainder was added to a citrated bottle. A drop of citrated blood was then placed on the TAS test card and the remainder sent to the reference laboratory for analysis. Parallel INR estimation was performed on the different near patient tests at each weekly anticoagulation clinic from July to December 1997.. 19 patients receiving long term warfarin treatment provided 62 INR results. INR results ranged from 0.8-8.2 overall and 1.0-5.7 based on the laboratory method. Taking the laboratory method as the gold standard, 12/62 results were < 2.0 and 2/62 were > 4.5. There were no statistical or clinically significant differences between results from the three systems, although all near patient tests showed slightly higher mean readings than the laboratory, and 19-24% of tests would have resulted in different management decisions based on the machine used in comparison with the laboratory INR value. The cost of the near patient test systems varied substantially.. All three near patient test systems are safe and efficient for producing acceptable and reproducible INR results within the therapeutic range in a primary care setting. All the systems were, however, subject to operator dependent variables at the time of blood letting. Adequate training in capillary blood sampling, specific use of the machines, and quality assurance procedures is therefore essential.

Topics: Anticoagulants; Blood Coagulation Disorders; Costs and Cost Analysis; Evaluation Studies as Topic; Humans; International Normalized Ratio; Point-of-Care Systems; Quality Assurance, Health Care; Sensitivity and Specificity; Warfarin

Topics: Anti-Bacterial Agents; Azithromycin; Blood Coagulation Disorders; Drug Synergism; Fatal Outcome; Humans; Male; Middle Aged; Multiple Organ Failure; Warfarin

The association between deep vein thrombosis (DVT) and the hypercoagulable state is a well-established entity. However, the association between saphenous vein thrombophlebitis and coagulation abnormalities has not been investigated. Although thrombosis of varicose veins typically runs a benign course, phlebitis of the saphenous system may propagate to the deep system or saphenofemoral junction that requires more aggressive therapy. Given the potential similarity in clinical outcome between saphenous vein thrombophlebitis (SVT) and DVT, we have investigated the coagulation profile of patients presenting with isolated SVT.. Seventeen consecutive patients who presented to our vascular laboratory with isolated SVT had a coagulation profile performed that included antithrombin III (AT III), protein C (PC), protein S (PS) antigen and activity levels, activated protein C (APC) resistance, factor V DNA mutation, and coagulation factors II and X. All patients had duplex scans performed on both the superficial and deep venous systems. Patients with SVT only were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and warm soaks as outpatients, whereas those patients found to have DVT or a clot at the saphenofemoral junction were fully anticoagulated with heparin and coumadin therapy. All 17 patients had at least one repeat coagulation profile performed up to 5 months after their SVT occurrence to ensure that the results of hypercoagulability were not transient.. Ten (59%) of the 17 patients with SVT had abnormal coagulation profiles on initial presentation. All 10 patients who were hypercoagulable had repeat tests and 6 (35%) remained abnormal. Four patients who had abnormal results converted to normal values. Seven patients with normal coagulation profiles on initial presentation had repeat tests and all remained normal.. The incidence of the hypercoagulable state in patients with SVT is high. Thirty-five percent of patients with isolated SVT had consistently abnormal coagulation profiles. Patients with SVT may be prone to the development of DVT or saphenofemoral junction thrombophlebitis and should be closely followed after the initial diagnosis of hypercoagulability.

Topics: Adult; Aged; Ambulatory Care; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antigens; Antithrombin III; Blood Coagulation Disorders; DNA; Factor V; Factor X; Female; Femoral Vein; Fibrinolytic Agents; Follow-Up Studies; Heparin; Humans; Incidence; Male; Middle Aged; Mutation; Phlebitis; Postphlebitic Syndrome; Protein C; Protein S; Prothrombin; Saphenous Vein; Serine Proteinase Inhibitors; Thrombophlebitis; Thrombosis; Treatment Outcome; Ultrasonography, Doppler, Duplex; Varicose Veins; Warfarin

To evaluate a modification of a commercially available reagent kit (COATEST APC Resistance Kit) for functional activated protein C (APC) resistance testing, and to determine the ability of the modified assay to demonstrate APC resistance in patients receiving warfarin.. Functional APC resistance testing was performed using both the first-generation COATEST APC Resistance Kit and a modified, or second-generation, version of the COATEST assay that uses predilution of the patient sample with factor V-deficient plasma. Factor V genotyping for APC resistance (FV R506Q) was performed using a well-characterized polymerase chain reaction-restriction fragment length polymorphism method.. University medical center.. Seventy-three individuals referred for hypercoagulability testing who were not receiving warfarin therapy and 29 patients with a history of venous thrombosis who were receiving warfarin therapy.. Sensitivity and specificity as determined by comparing functional APC resistance to the FV R506Q genotype.. In 73 patients referred for hypercoagulability testing, but not receiving warfarin therapy, a sensitivity of 0.86 and a specificity of 0.75 were obtained with the first-generation COATEST assay. In contrast, a sensitivity and specificity of 1.0 were obtained when the second-generation COATEST assay was employed. In 29 patients receiving warfarin, the first-generation assay exhibited a sensitivity and specificity of 0.88 and 0.95, respectively, whereas the sensitivity and specificity for the second-generation assay was 1.0.. Predilution of patient plasma with factor V-deficient plasma results in improved sensitivity and specificity of the COATEST APC Resistance Kit, thus offering a simple modification to enhance APC resistance determination in the routine clinical laboratory setting.

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Evaluation Studies as Topic; Factor V Deficiency; Humans; Partial Thromboplastin Time; Protein C; Reagent Kits, Diagnostic; Sensitivity and Specificity; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Facial Pain; Fibrinolysis; Humans; International Normalized Ratio; Jaw Diseases; Neuralgia; Osteonecrosis; Thrombophilia; Warfarin

The purpose of the present work was to observe local hemostatic function during dental surgery in patients under oral anticoagulant therapy with an INR between 1.7 and 2.5. Thirty seven dental treatments were performed in 15 patients. Group A: nineteen dental treatments (13 scalings, 1 root canal therapy and 5 dental extractions), treated with oral rinse with tranexamic acid (250 mg dissolved in 10 ml of water). Group B: eighteen dental procedures (13 scaling, 1 root canal therapy and 14 dental extractions), in which oral rinse was utilized. Antibiotics were indicated for those patients with root canal therapy or with signs of infection. A cool soft diet was recommended to all patients during the three days following the surgical procedure. Only in five (13.5%) dental extractions (1 from group A and 4 from B) bleeding prolonged was observed, however periodontal disease was also present in those patients hone of them required blood products or withdrawal of the anticoagulant. The results suggest that mouth washing with tranexamic acid prevents excessive oral bleeding in patients treated with oral anticoagulants with an INR between 1.7 and 2.5.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Loss, Surgical; Dental Scaling; Drug Evaluation; Gingival Hemorrhage; Gingivitis; Hemostasis, Surgical; Humans; Mouthwashes; Periapical Abscess; Periodontitis; Postoperative Hemorrhage; Root Canal Therapy; Tooth Extraction; Tranexamic Acid; Warfarin

Membranous obstruction of the inferior vena cava is a rare cause of hepatic venous outflow obstruction in Caucasians. There has been much debate in the literature about its aetiology.. We describe a Caucasian with hepatic venous outflow obstruction due to an inferior vena cava web, who was found to have hypercoagulability due to factor V Leiden. Following balloon rupture of the membrane and anticoagulation, his symptoms resolved and he has remained well for a year.. The age at presentation in this patient, the presence of hypercoagulability and the excellent response to membrane rupture and anticoagulation suggest that in this case the membrane may have been derived from organised thrombus. Balloon rupture of the membrane and anticoagulation appears to be an effective treatment in such cases.

Topics: Anticoagulants; Blood Coagulation Disorders; Budd-Chiari Syndrome; Catheterization; Factor V; Follow-Up Studies; Hepatic Veno-Occlusive Disease; Humans; Male; Middle Aged; Protein C; Vena Cava, Inferior; Warfarin

A 27 year old woman presented with recurrent cerebrovascular strokes in the setting of an ill defined auto-immune disease responsive to corticosteroid therapy. Investigation for a hypercoagulable state revealed activated protein C resistance in the absence of protein C, protein S, or antithrombin III deficiency or anticardiolipin antibodies. Her parents and sibling did not demonstrate APC resistance. This case suggests that activated protein C resistance may be associated with arterial as well as venous thrombotic events and implies that resistance to activated protein C should also be considered in the evaluation of young adults with strokes.

Topics: Adult; Antithrombin III; Autoimmune Diseases; Blood Coagulation Disorders; Brain Ischemia; Drug Resistance; Female; Humans; Intracranial Embolism and Thrombosis; Partial Thromboplastin Time; Prednisone; Protein C; Protein S; Warfarin

Thrombosis can occur on the venous or the arterial side of the circulation. Each has different causes, requires a different diagnostic workup, and responds to different therapies. Venous thrombosis may be situational, but may also reflect inherited or acquired anticoagulation defects. Arterial thrombosis usually results from abnormalities in the blood vessel wall--most often atherosclerosis.

Topics: Adult; Algorithms; Anticoagulants; Arteriosclerosis; Blood Coagulation Disorders; Diagnosis, Differential; Factor V; Heparin; Humans; Male; Partial Thromboplastin Time; Recurrence; Thrombophlebitis; Warfarin

Topics: Aged; Anticoagulants; Bezafibrate; Blood Coagulation Disorders; Drug Synergism; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; International Normalized Ratio; Male; Warfarin

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Blood Coagulation Disorders; Drug Interactions; Hematuria; Humans; Male; Prothrombin Time; Warfarin

Chinese patients are reportedly more sensitive than Caucasians to the anticoagulant effect of warfarin. We examined warfarin dose requirements and their determinants in 151 Chinese out-patients on stable maintenance dose of warfarin with international normalized ratio of 2 to 2.5. Mean daily warfarin requirement was 3.3 +/- 1.4 mg, much lower than reported doses in Caucasian patients. The most important determinant was age (r = -0.43, p < 0.001), with progressively lower warfarin requirement with increasing age (p = 0.0001). There was a weaker association with body weight (r = 0.20, p = 0.01). Patients with chronic rheumatic heart disease tended to require a smaller dose than those with heart valve replacements (2.94 +/- 1.24 vs. 3.69 +/- 1.42 mg, p < 0.01). We confirm that Chinese patients require a smaller dose of warfarin for the same degree of anticoagulation. Age is the most important factor affecting dose requirement, although body weight and underlying disease also play a role.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Asian People; Blood Coagulation Disorders; Body Weight; Cardiovascular Diseases; Drug Administration Schedule; Female; Heart Valve Prosthesis; Hong Kong; Humans; Male; Middle Aged; Rheumatic Heart Disease; Sex Factors; Thrombophlebitis; Warfarin

Topics: Blood Coagulation Disorders; Child; Hematuria; Humans; Male; Rodenticides; Warfarin

Patients often undergo a number of dental procedures that may cause bleeding. Usually these procedures can be performed with little risk to the patient. However, patients on medications such as warfarin (Coumadin) have an altered ability to control, bleeding and may develop bleeding problems subsequent to treatment. Once this potential problem has been recognized, measures can be taken to minimize the risks. Patients on warfarin are on specific medication protocols and often exhibit episodes of hyperanticoagulation. The purpose of this study was to assess patients on warfarin protocols for episodes of hyperanticoagulation. Sixty-two patients undergoing anticoagulation therapy with warfarin were assessed for episodes of hyperanticoagulation with the prothrombin test. Based on these results, it can be concluded that patients taking warfarin had an approximately 42% chance of at least one episode of hyperanticoagulation. No specific warfarin protocol demonstrated any statistical significance for an increased chance of hyperanticoagulation.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Dental Care; Female; Hemorrhage; Humans; Male; Middle Aged; Prothrombin Time; Risk Factors; Warfarin

Topics: Blood Coagulation Disorders; Drug Synergism; Female; Hepatitis C; Humans; Interferons; Middle Aged; Warfarin

A Kinetic Fibrinogen Assay (KFA), a method based on the kinetic reaction of the developing fibrin clot, was used to determine fibrinogen concentration in plasma. Two other methods employing different quantification principles were used for comparison: the von Clauss method and the procedure measuring protein concentration in an isolated and washed plasma clot (World Health Organization [WHO] method). All three methods quantified functional thrombin-coagulable fibrinogen. Plasma specimens were obtained from three groups of patients: those with liver disease and those taking either coumarin derivative or heparin. In all of these conditions, there are deviations from the normal process of fibrin clot formation. The KFA method yielded results that were consistent and provided excellent precision and accuracy allowing quantification of plasma fibrinogen in the range of 70-800 mg/dL (2-23.5 microM). The determination of fibrinogen by the KFA method was not adversely affected using plasma from patients treated with heparin and those undergoing coumarin therapy. Statistical analysis of the results indicated that the KFA method compared very favorably with the von Clauss and WHO methods. In assessing the clinical utility of each method, the WHO method was found to be labor intensive and time consuming; therefore, not suitable for routine use in a clinical laboratory. The von Clauss method required a trained laboratory technician and some laboratory manipulations. The KFA method was not only reliable and accurate, but also fully automated, making it the easiest and the fastest to perform routinely.

Topics: Anticoagulants; Blood Coagulation Disorders; Evaluation Studies as Topic; Fibrinogen; Hematology; Heparin; Humans; Kinetics; Liver Diseases; Osmolar Concentration; Warfarin

Global haemostasis was assessed on blood from patients with established blood clotting abnormalities using a hollow fibre flow device. The instrument monitors pressure changes across a polyethylene fibre through which non-anticoagulated whole blood is perfused. This method of analysis is significant because it (1) minimizes or eliminates common problems associated with routine clinical evaluations, such as sample dilution, completion time, and anticoagulant artifacts, (2) rapidly (under 90 min) and accurately calculates in vitro bleeding time (IVBT) and whole blood clotting time (WBCT), (3) presents a reliable means of distinguishing coagulation defects from platelet dysfunction, and (4) reduces the need for a series of screening tests to a single test that requires a small amount of non-anticoagulated whole blood. Using this technology, global haemostasis of normal volunteers was studied using blood samples spiked with PPACK and prostacyclin. Blood from patients with acquired factor VIII deficiency and Glanzmann's thrombasthenia and from those receiving Coumadin therapy were also studied. The hollow fibre device detailed haemostatic abnormalities of both congenital and therapeutic conditions.

Topics: Bleeding Time; Blood Coagulation Disorders; Hemophilia A; Hemorheology; Hemostasis; Humans; Thrombasthenia; Warfarin

The aetiology of non-arteritic ischaemic optic neuropathy (ION) is multifactorial with local anatomical and systemic haemodynamic abnormalities both playing a role. A careful search for treatable vascular disease risk factors is required to allow rational therapy, to optimise the visual prognosis and to allow new insights into pathogenesis. We describe 7 cases in which there was an associated thrombophilic (prothrombotic) state; 4 had deficiencies of the physiological anticoagulants proteins C and S and antithrombin III and 2 had anti-phospholipid antibody (lupus anticoagulant) syndromes. A further patient had reduced levels of the physiological fibrinolytic agent tissue plasminogen activator (t-PA). In 5 patients other risk factors for small vessel occlusive disease were also present, and 4 had recurrent episodes of ION in the same eye. The visual prognosis in these patients may be improved by anticoagulation with warfarin.

Topics: Adult; Aged; Antithrombin III Deficiency; Blood Coagulation Disorders; Female; Humans; Ischemia; Lupus Coagulation Inhibitor; Male; Middle Aged; Optic Nerve; Optic Nerve Diseases; Prognosis; Protein C Deficiency; Protein S Deficiency; Tissue Plasminogen Activator; Warfarin

Topics: Adolescent; Antibodies, Anticardiolipin; Aspirin; Blood Coagulation Disorders; Humans; Male; Prednisone; Renal Circulation; Thrombocytopenia; Warfarin

Previous studies, mainly autopsy-based, suggest that the spectrum of stroke in cancer patients differs from that of the general population. These studies also suggest that cerebrovascular events frequently are a manifestation of hypercoagulability. However, no studies that address this question in the adult oncological population from a clinical perspective are available. We therefore assessed the clinical impact of cerebral ischemic events in cancer patients and attempted to determine whether their occurrence represents a manifestation of Trousseau's syndrome.. A computerized database that records all neurological admissions and consultations at a tertiary medical center was used to retrospectively identify all patients with cerebral ischemic events and cancer.. Thirty-three patients representing 3.5% of all stroke consultations and admissions seen at the University of Massachusetts Medical Center were identified during the period 1988 through 1992. Large-vessel atherosclerosis was the most frequent cause of stroke. Furthermore, although 30% were determined to have hypercoagulability as a cause using clinical criteria, in only one of nine patients in whom tests were done was sufficient evidence present to make a presumptive diagnosis of disseminated intravascular coagulation. Irrespective of therapy, recurrent cerebral ischemic events were noted in only 6% of patients during a follow-up period averaging greater than 9 months, a figure that is similar to that for the risk of repeated events in the noncancer population.. Recognizing the limitations of this retrospective study, it appears nonetheless that conventional stroke origins account for the majority of cerebral ischemic events in the adult cancer population. Although hypercoagulability is present to a greater extent than in the nononcological population, recurrent strokes seem to occur no more frequently than in the nononcological population, and antiplatelet agents seem sufficient therapy for most patients.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Blood Coagulation Disorders; Brain Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Cohort Studies; Female; Follow-Up Studies; Heparin; Humans; Ischemic Attack, Transient; Male; Middle Aged; Neoplasms; Recurrence; Retrospective Studies; Thrombosis; Warfarin

Three patients are presented with traumatic spinal cord injury (SCI) complicated by acute heterotopic ossification (HO), and concurrent deep vein thrombosis 15 months, 18 months and 22 years after SCI, accompanied by persistent hypercoagulation. The diagnosis of HO preceded deep vein thrombosis in all three patients. All were treated with etidronate disodium and therapeutic heparin followed by oral anticoagulation. As these patients were not acutely injured, the questions arose as to what predisposed them to deep vein thrombosis and when was the appropriate time to discontinue anticoagulation. Over a course of 3 years following deep vein thrombosis, these patients were monitored for evidence of hypercoagulation by D-dimer assay, plasma fibrinogen estimation, and rate of whole blood clotting by Sonoclot coagulation analyzer. The activity of acute HO was assessed by three-phase bone scan. A steady state of hypercoagulation, reflected by an increase in all three parameters, ran parallel to the extent of acute HO for the entire observation period. Moreover, hypercoagulation was persistently greater during increased acute HO activity even when the warfarin-induced prothrombin time ratio was 1.2-1.5. In addition, as acute heterotopic ossification activity decreased, the test values returned to near normal during warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Coagulation Disorders; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heparin; Humans; Male; Middle Aged; Ossification, Heterotopic; Spinal Cord Injuries; Thrombophlebitis; Warfarin

Topics: Adult; Beverages; Blood Coagulation Disorders; Female; Food Contamination; Humans; Hypoprothrombinemias; Magnoliopsida; Prothrombin; Warfarin

Topics: Adult; Blood Coagulation Disorders; Dental Care for Disabled; Female; Humans; Molar, Third; Protein S Deficiency; Thrombophlebitis; Tooth Extraction; Tooth, Impacted; Warfarin

Coagulation factors that interfere with the one-stage prothrombin time (PT) were investigated. PT responded with identical activities (adequately) against coagulation factors VII or X, only half as expected against factor IX, less than expected and nonlinearly against factor II. In multiple coagulation factor deficiencies PT did not differ from factor VII, which was the most reduced coagulation factor in warfarin therapy or liver disease. PT may also be influenced by factor VII at high activities.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Chronic Disease; Humans; Liver Diseases; Prothrombin Time; Warfarin

Topics: Blood Coagulation Disorders; Female; Humans; Middle Aged; Shock, Hemorrhagic; Vitamin K; Warfarin

The cause of a fatal condition characterized by hemorrhagic cardiomyopathy, hemothorax, and coagulation defects in hysterectomy-derived male mice was investigated. Microscopic heart alterations included multifocal hemorrhage and necrosis with variable degrees of acute inflammation and fibroplasia that were most severe in the region of the atrioventricular junction. A spontaneous outbreak was arrested by increasing menadione Na-bisulfite (vitamin K) in the feed to 20 ppm. The complete syndrome including hemorrhagic cardiomyopathy was readily reproduced in germ-free male mice given a vitamin K-free diet, and in conventional male and female mice given Warfarin in the diet. We concluded that the cause of this condition was vitamin K deficiency.

Topics: Animals; Blood Coagulation Disorders; Cardiomyopathies; Female; Hemorrhagic Disorders; Hemothorax; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Myocardium; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Aged; Blood Coagulation Disorders; Drug Synergism; Female; Glyburide; Humans; Middle Aged; Proguanil; Warfarin

We report three patients who had serious disturbance of anticoagulant control while receiving ifosfamide/mesna-containing cytotoxic chemotherapy in association with warfarin. In view of the likely biological potentiation of warfarin by ifosfamide/mesna, close monitoring of anticoagulant control should be performed during the co-administration of these drugs.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation; Blood Coagulation Disorders; Drug Interactions; Drug Synergism; Female; Humans; Ifosfamide; Infusions, Intravenous; Male; Mesna; Middle Aged; Warfarin

Topics: Aged; Autoantibodies; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Female; Glycoproteins; Humans; Infarction; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Necrosis; Phospholipids; Protein C Deficiency; Protein S; Skin; Warfarin

A 68-year-old man, following mitral valve replacement, presented with a low-grade chronic consumptive coagulopathy. Laboratory analysis showed mild fibrinolysis, minimal effect of coumadin therapy, and a prolonged thrombin time (greater than 150 seconds using bovine IIa). When purified human IIa was used the thrombin time normalized to within 17 seconds of controls, suggesting a possible inhibitor of bovine IIa. An anti-IIa antibody was isolated by protein A-Sepharose (Sigma, St Louis, MO) chromatography followed by affinity chromatography using a bovine IIa-Sepharose column. The effects of this purified anti-IIa antibody on both bovine and human IIa procoagulant and anticoagulant functions were studied. The isolated immunoglobulin G (IgG) was observed to inhibit bovine IIa in all assays tested. This IgG was also able to slightly prolong fibrinogen clotting by human IIa. Using an enzyme-linked immunosorbent assay it was observed that the IgG bound to bovine IIa, bovine II, human IIa, but not to human II. Further, binding was detectable at approximately 50-fold lower concentrations to bovine IIa (1 nmol/L IgG concentration) than to human IIa (50 nmol/L IgG concentration). The effect of the antibody on the reaction between IIa and AT III/heparin was investigated. Human IIa was found to be protected from AT III/heparin neutralization in the presence of this antibody. These results suggest that this patient developed an antibody that strongly binds to and inhibits the bovine IIa in all assays tested. However, the antibody only significantly affects human IIa neutralization by AT III/heparin, and has little effect on the human IIa procoagulant activity. These data suggest that the decreased effect of AT III/heparin on this patient's IIa may have been a contributing factor in his coagulopathy. The exact cause of this antibody development is unclear, but the role of bovine topical thrombin used during cardiac valve replacement surgery is suspect.

Topics: Aged; Animals; Antithrombin III; Autoantibodies; Blood Coagulation Disorders; Cattle; Chromatography, Affinity; Enzyme-Linked Immunosorbent Assay; Fibrinogen; Heart Valve Prosthesis; Heparin; Humans; Male; Mitral Valve; Protein C; Thrombin; Thrombin Time; Warfarin

The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.

Topics: 4-Hydroxycoumarins; Administration, Oral; Adult; Blood Coagulation; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Purpura; Rodenticides; Vitamin K; Warfarin

Although the association of coagulopathy and neoplastic disease is well documented, there have been few reports of patients with primary central nervous system tumors who exhibited hypercoagulable states. We report the case of a 58-year-old woman with a recurrent falcine meningioma and repeated episodes of venous thrombosis who developed warfarin-associated breast necrosis on the fifth day of coumadin therapy. Laboratory evaluation at that time demonstrated an elevated prothrombin time and normal activated partial thromboplastin time. Of the 24 cases of warfarin-associated massive necrosis of the breast described in the literature, only one other case was associated with a neoplasm, a resected craniopharyngioma.

Topics: Blood Coagulation Disorders; Breast; Humans; Male; Mastectomy; Meningeal Neoplasms; Meningioma; Middle Aged; Necrosis; Neoplasm Recurrence, Local; Warfarin

The authors assessed the cost effectiveness of monitoring warfarin therapy guided by standard plasma prothrombin times performed on blood samples obtained by venipuncture versus prothrombin times performed on capillary whole blood samples obtained by fingerstick. Twenty patients receiving long-term oral anticoagulation had either standard or capillary prothrombin times determined every other week for eight weeks in a cross-over design. All time intervals were monitored, including receptionist, secretarial, nursing, phlebotomy, etc., and costs for all materials, procedures, and labor were calculated. The total cost per test by the capillary whole blood prothrombin time method was significantly less than by standard prothrombin time methods ($7.55 vs. $15.64) even though the nurse-patient encounter time was greater per test for the capillary method (12.4 minutes vs. 8.3 minutes). The management of oral anticoagulation guided by prothrombin times performed on instrumentation designed to sample capillary whole blood should result in a significant cost savings, and because of the immediate availability of results, provide the potential for improved health care.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Blood Coagulation Disorders; Bloodletting; Cost-Benefit Analysis; Female; Humans; Male; Middle Aged; Prothrombin Time; Warfarin; Whole Blood Coagulation Time

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Heparin; Humans; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Pulmonary Embolism; Warfarin

Voluntary ingestion of concentrated anticoagulant rodenticides leads to prolonged hypocoagulability sometimes accompanied by haemorrhage. The authors report 11 cases referred to the Paris Anti-Poisons Centre. The products implicated were chlorophacinone, bromadiolone, and warfarin. The time interval before medical intervention ranged from 90 minutes to 3 weeks. The absence of early clinical signs probably explains the number of late admissions. Haemorrhage of variable severity was observed in 8 cases. The prothrombin time varied with the administered dose of Vitamin K and/or coagulation factors. Three patients were lost to follow-up at days 9, 24 and 68. The other patients were treated for several weeks (27 to 82 days). Massive overdose with these rodenticides justifies stomach washout when the patients are seen early, daily check-ups of coagulability and treatment with Vitamin K at a dosage adapted to the biochemical abnormalities. Severe haemorrhage requires transfusion and the administration of factors of coagulation. The duration of the abnormalities is unpredictable; the prothrombin time should therefore be checked 48 hours after stopping Vitamin K therapy to detect any recurrence.

Topics: 4-Hydroxycoumarins; Adolescent; Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Female; Humans; Indans; Male; Middle Aged; Rodenticides; Suicide, Attempted; Warfarin

A case is described in which a pregnancy, preceded by two mid-trimester fetal losses, was complicated by deep-vein thrombosis due to the presence of circulating lupus anticoagulant. Warfarin was used as anticoagulant therapy concurrently with high-dose prednisolone. It is suggested that warfarin may have advantages over heparin in managing pregnancies in women with circulating lupus anticoagulant. A technique is described which allowed the monitoring of levels of lupus anticoagulant in the circulation while warfarin is being administered.h3.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Drug Therapy, Combination; Female; Humans; Lupus Coagulation Inhibitor; Monitoring, Physiologic; Prednisolone; Pregnancy; Pregnancy Complications, Hematologic; Thrombophlebitis; Warfarin

An infant with severe homozygous protein C deficiency was brought to medical attention because of purpura fulminans and severe bilateral vitreous hemorrhages in the neonatal period. Infusions of fresh frozen plasma were given for 8 months. On two occasions, attempts to decrease the frequency of fresh frozen plasma infusions to less than twice a day led to episodes of microangiopathic hemolysis, fibrinolysis, and acute renal failure. Infarction of skin and subcutaneous tissues did not recur. Both episodes were controlled after reinstitution of fresh frozen plasma. Complications of therapy with fresh frozen plasma included hyperproteinemia and hypertension. Warfarin therapy was instituted when the baby was 8 months of age, followed by a gradual withdrawal of fresh frozen plasma therapy. The dose of warfarin required to maintain the prothrombin time in a range of 1.8 to 2.2 times normal varied considerably during short periods, a phenomenon that may have been due to several factors: hypercatabolism of the drug with prolonged administration, abnormality of liver function, variation in levels of serum albumin, fluctuations in drug dosage secondary to oral administration, and variations in dietary vitamin K. Protein C determinations by immunologic and functional assays consistently showed detectable but reduced protein C antigen levels with undetectable activity levels, suggesting that a dysproteinemia rather than a deficiency of synthesis is responsible for the child's coagulopathy.

Topics: Blood Coagulation Disorders; Hemolytic-Uremic Syndrome; Homozygote; Humans; Infant, Newborn; Isoantigens; Male; Plasma; Protein C; Protein C Deficiency; Purpura; Vitreous Hemorrhage; Warfarin

In 1980, the Boston City Hospital pharmacy made a bulk purchase of a brand of warfarin sodium that was different from the brand previously stocked. The physician and nurse in charge of the anticoagulation clinic and responsible for regulating patient dosage of warfarin were not aware of the change in warfarin brand. During the period of brand substitution, we observed an increase in the number of patients whose anticoagulation was poorly controlled. There was a concomitant increase in the number of clinic visits and an increased frequency of prothrombin time testing to regulate the dosage in such patients. We performed a retrospective analysis of the medical and economic consequences of the change in brand of warfarin. Our results show that a significant increase in morbidity and overall health care costs resulted from this attempt to economize by changing brands of medication in our municipal hospital setting.

Topics: Blood Coagulation Disorders; Boston; Costs and Cost Analysis; Female; Formularies, Hospital as Topic; Hospital Bed Capacity, 500 and over; Hospitals, Municipal; Humans; Male; Middle Aged; Retrospective Studies; Therapeutic Equivalency; Warfarin

Whether influenza vaccination causes a prolongation in the prothrombin time (PT) and produces bleeding complications in patients receiving chronic warfarin therapy is a clinically important controversy. The degree of anticoagulation during chronic warfarin therapy of 33 patients was assessed before and after vaccination with trivalent types A and B influenza vaccine. Three patients were excluded because of inadequate PT data before vaccination and one patient was unavailable for follow-up after vaccination. Data from five additional patients were excluded from statistical analysis because the warfarin dose was changed within one week of vaccination. PT values obtained at zero to two weeks, three to four weeks, and two, three, and four months after vaccination were compared with each patient's prevaccination baseline value. PT values following vaccination were unchanged except for a decrease that occurred during the first two weeks (p less than 0.05). Complications did not require dosage adjustments and were limited to minor nose bleeds or bruises occurring in two patients before and three patients after vaccination. These data suggest a decrease rather than an increase in PT values following vaccination, and do not support the existence of a serious warfarin-vaccine interaction. The possibility that an occasional patient may experience such an interaction cannot be excluded, but none was seen in these patients.

Topics: Adult; Aged; Blood Coagulation Disorders; Female; Humans; Influenza Vaccines; Male; Middle Aged; Prothrombin Time; Warfarin

Topics: Blood; Blood Coagulation Disorders; Humans; Platelet Aggregation; Platelet Function Tests; Warfarin

Topics: Adolescent; Antithrombin III Deficiency; Blood Coagulation Disorders; Drug Therapy, Combination; Dura Mater; Humans; Male; Oxymetholone; Sinus Thrombosis, Intracranial; Thrombosis; Vena Cava, Inferior; Warfarin

Systemic and local complications associated with the use of warfarin for deep vein thrombosis prophylaxis in total knee arthroplasty (TKA) are significant. Forty-seven patients with primary TKAs considered at high risk for developing thromboembolic disease were treated with a regimen of preoperative and postoperative warfarin. The incidence (n = 2) of systemic complications was 4%. The incidence (n = 6) of wound complications requiring specific treatment or discontinuing physiotherapy was 12%. In this series, wound complications did not jeopardize the end results of TKA. However, such wound complications as may have delayed recovery occurred with a frequency similar to that reported in other series of TKA using different antithromboembolic modalities.

Topics: Aged; Blood Coagulation Disorders; Female; Hemorrhage; Humans; Knee Prosthesis; Male; Middle Aged; Postoperative Complications; Thromboembolism; Warfarin; Wound Healing

To evaluate coagulable state, beta-thromboglobulin (beta-TG) levels have been followed sequentially in 70 postoperative patients with lung cancer. Nineteen out of them were treated with warfarin plus ticlopidine at a dosage enough to prolong the thrombo-test time to approximately 20% of normal value. There was a significant rise in beta-TG compared with control subjects and beta-TG was correlated with stages of disease. Serial beta-TG determinations revealed that beta-TG and CEA levels fairly paralleled with each other which suggested beta-TG might be useful in following tumor progression or response to therapy in postoperative period. As to the relation between beta-TG levels and five-year survivals, patients whose beta-TG were under 50 ng/ml showed more favorable prognoses than those who had higher levels. Long term anticoagulation with warfarin plus ticlopidine reduced the beta-TG levels of 19 stage 3 or 4 patients, especially in stage 4 the rate of reduction was marked. Nineteen patients with anticoagulant-treated group demonstrated a more prolonged time from beginning of treatment to first evidence of disease progression than 18 non-treated patients. Also anticoagulant-treated group had a more prolonged clinical course than non-treated group after disease progression. These results might be associated with disease stabilization which achieved with anticoagulant therapy. Survival at 30 months after initiation of treatment was 74% in the treated group and 64% in the nontreated group. Although there was no statistical difference in two groups, survival of treated group exceeded that of the non-treated group throughout the observation period. In stage 4 patients, however, the difference between two groups was statistically significant.

Topics: Adult; Aged; Anticoagulants; beta-Thromboglobulin; Blood Coagulation Disorders; Female; Humans; Lung Neoplasms; Male; Middle Aged; Postoperative Complications; Thiophenes; Ticlopidine; Warfarin

Topics: Animals; Aspirin; Blood Coagulation Disorders; Cattle; Collagen; Dogs; Hemorrhage; Hemostatic Techniques; Hemostatics; Heparin; Spleen; Thiophenes; Thrombocytopenia; Ticlopidine; Warfarin

Topics: Blood Coagulation Disorders; Drug Labeling; Ethinyl Estradiol; Female; Humans; Middle Aged; Warfarin

Deep venous thrombosis is a complex process involving many factors in the circulatory system, an important one apparently being the intrinsic fibrinolytic system. Specific activators of the process include venous trauma and hypercoagulability states. In spite of efforts at prophylaxis, venous thrombosis will occur, a dangerous condition in itself and also a precursor of pulmonary embolism. Several schemes for prophylaxis, including drug regimens and mechanical means, have been tried, and future research will surely identify others. A patient's best protection against thrombosis at present, however, is a vigilant physician with a high index of suspicion who will expedite diagnosis and treatment if necessary.

Topics: Antithrombin III Deficiency; Aspirin; Blood Coagulation Disorders; Catheters, Indwelling; Contraceptives, Oral; Dihydroergotamine; Female; Glycoproteins; Heparin; Humans; Parity; Postoperative Complications; Pregnancy; Pregnancy Complications; Protein C; Sulfinpyrazone; Thrombophlebitis; Warfarin

Topics: Animals; Blood Coagulation Disorders; Dog Diseases; Dogs; Male; Warfarin

Topics: Blood Coagulation Disorders; Blood Preservation; Blood Transfusion; Freezing; Humans; Immunologic Deficiency Syndromes; National Institutes of Health (U.S.); Plasma; Research; Risk; Technology Assessment, Biomedical; Transfusion Reaction; United States; Warfarin

A 57-year-old black woman required a daily dosage of 50 mg of warfarin sodium to maintain her prothrombin time in a therapeutic range. The central volume of distribution and clearance of warfarin were normal for this patient. These findings, combined with the patient's requirement for plasma warfarin levels four times greater than those usually required to achieve adequate anticoagulation, indicated that the relative resistance was due to altered pharmacodynamics of warfarin. The only child of the propositus, a daughter, showed a similar relative resistance, confirming that this family is the third to be reported with hereditary resistance to warfarin.

Topics: Adult; Aged; Blood Coagulation Disorders; Drug Resistance; Female; Humans; Kinetics; Middle Aged; Prothrombin Time; Warfarin

Munchausen by proxy has been reported involving children who have been given various drugs or toxins. In addition, there is a body of adult literature regarding covert anticoagulant ingestion. This is a case of an 11-month-old female who appears to combine features of both of these syndromes. This child presented with an acute left hemorrhagic otitis media. The physical examination was unremarkable except for the following: weight, fifth percentile; left external auditory canal filled with blood with the right external canal and tympanic membrane being normal; and several scattered 1 X 2 cm firm, movable, nontender, purple nodules on extremities, chest and forehead. The coagulation studies were consistent with Vitamin K deficiency secondary to anticoagulant ingestion. A serum warfarin study confirmed our suspicions. The mother was noted to have a dependent relationship with her child and characteristics of those involved in Munchausen by proxy: falsifying information and thwarting medical assessment. In addition, she displayed some of the characteristics found commonly in anticoagulant malingerers. She was depressed, with limited medical knowledge, and had access to warfarin. The mother was admitted for inpatient psychiatric care and the patient placed with an extended family member. This case report describes the use of an anticoagulant to induce illness in a child by a psychologically ill mother. This form of child abuse must be considered in the differential diagnoses of hemorrhagic disorders.

Topics: Adult; Blood Coagulation Disorders; Child Abuse; Diagnosis, Differential; Female; Humans; Infant; Munchausen Syndrome; Vitamin K Deficiency; Warfarin

A patient with a circulating lupus anticoagulant in the absence of systemic lupus erythematosus developed recurrent deep venous thromboses and pulmonary emboli. Pulmonary emboli recurred despite prolonged oral anticoagulant therapy and resulted in fatal pulmonary arterial hypertension. Extended anticoagulant therapy alone may not prevent recurrent thromboembolism in patients with a lupus anticoagulant. Pulmonary thromboembolism may be an important factor in the pathogenesis of pulmonary hypertension in patients with a lupus anticoagulant.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Humans; Hypertension, Pulmonary; Lupus Coagulation Inhibitor; Male; Pulmonary Embolism; Thrombophlebitis; Warfarin

In August 1981, pediatric hospitals in Ho-Chi-Minh Ville (Saigon) began to report numerous cases of a haemorrhagic syndrome in infants. A collaborative study with a French epidemilogist began on September 24, 1981, with the aim of finding the cause of this "new" haemorrhagic disease. After having excluded the hypothesis of a viral or bacterial infection, a retrospective study, using questionnaires with 83 items, concerning products of hygiene and nutrition and living conditions, was undertaken. This epidemiological investigation showed this phenomenon was caused by an anticoagulant contained in talcum powder. Analysis of the talcum powders found warfarin; the concentrations ranged between 1.7% and 6.5%. This dramatic episode (741 cases with 177 deaths) ended when the contaminated talc was withdrawn from circulation. The hypothesis of accidental contamination or use of warfarin in lieu of a perfuming agent must be rejected. Accidental addition of a rat-killer seems highly improbable and the possibility of intentional and malevolent adulteration is now under study. An experimental study of hemostasis in two baboons was carried out, using dermal application of the contaminated talc powder. The intoxicated animal died on the 5th day with severe vitamin K deficiency. This accident together with the animal study, shows the transcutaneous uptake of the anticoagulant, which could be of considerable importance in toxicology and in pharmacokinetics.

Topics: Blood Coagulation Disorders; Disease Outbreaks; Drug Contamination; Humans; Infant; Talc; Vietnam; Warfarin

We have measured the fully carboxylated (native) prothrombin antigen and the undercarboxylated (abnormal) prothrombin antigen in patients treated with sodium warfarin using specific immunoassays to evaluate a new approach for monitoring oral anticoagulant therapy. Plasma and serum samples (391) were assayed for the prothrombin time, native prothrombin antigen, and abnormal prothrombin antigen. The results were correlated with the presence of bleeding or thromboembolic complications at the time of phlebotomy. The native prothrombin antigen correlated with the occurrence of complications in 95% of samples. Of 13 samples from patients with bleeding complications, 13/13 (100%) had a native prothrombin of 12 micrograms/mL or lower. Of seven samples from patients with thromboembolic complications, 6/7 (86%) had a native prothrombin of 24 micrograms/mL or greater. By comparison, a prothrombin time index of 1.5 to 2.5, 1.5 to 2.2, 1.5 to 2.0, or 1.3 to 1.8 identified 6/20 (30%), 9/20 (45%), 11/20 (55%), or 12/20 (60%) patients at risk, respectively. Although the prothrombin time index did correlate with the presence of bleeding complications, the native prothrombin antigen correlated closely with the presence of bleeding and thromboembolic complications. According to these results, the native prothrombin antigen, maintained in a range of 12 to 24 micrograms/mL by regular adjustment of the warfarin dosage, may be associated with a reduced risk of complications due to excessive or insufficient warfarin therapy. On the basis of these preliminary data, we recommend that the native prothrombin antigen be considered to monitor warfarin therapy.

Topics: Administration, Oral; Adult; Aged; Antigens; Blood Coagulation Disorders; Female; Hemorrhage; Humans; Male; Middle Aged; Prothrombin; Prothrombin Time; Thromboembolism; Warfarin

There are a number of important drug interactions with amiodarone. This agent appears to have a marked effect on the kinetics of some commonly used cardiovascular drugs, such as warfarin, digoxin, quinidine, and procainamide, and has dynamic interactions with others, such as the beta blockers and some calcium antagonists. Bleeding has been reported, apparently caused by a potentiation of the anticoagulant effect of warfarin by amiodarone. Torsades de pointes has been observed when quinidine, propafenone, or mexiletine is given together with amiodarone. Furthermore, amiodarone may interact with beta-blocking agents and some of the calcium antagonists to produce symptomatic sinus bradycardia and sinus arrest, especially in a latent or overt sick sinus syndrome. During surgery, amiodarone may induce hypotension and an atropine-resistant bradycardia, possibly by interacting with anesthetic agents. A knowledge of the time of onset, extent, duration, and possible mechanisms of the interactions of amiodarone with other cardioactive drugs is still incomplete, but further studies are of great therapeutic importance.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmia, Sinus; Benzofurans; Blood Coagulation Disorders; Calcium; Digoxin; Drug Interactions; Drug Synergism; Heart Arrest; Humans; Kinetics; Quinidine; Tachycardia; Warfarin

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Drug Interactions; Heart Atria; Heart Ventricles; Humans; Tachycardia; Warfarin

Topics: Aged; Blood Coagulation Disorders; Cerebral Infarction; Humans; Male; Warfarin

Forty-seven patients presenting with acute chest pain had in vivo platelet activity assessed by measuring plasma levels of the platelet-specific protein beta thromboglobulin (BTG), and by screening for the presence of circulating platelet aggregates. Nineteen patients with transmural myocardial infarction (MI), 21 patients with acute coronary ischaemia (CI), and 7 patients with non-cardiac chest pain (NCCP) were investigated in a serial study and compared with a normal control group. The means of all BTG determinations in the MI (34, +/- SD = 21-57) and CI (33, +/- SD = 19-57) groups were significantly higher than those in the NCCP group (24, +/- SD equal 17-34; p less than 0.01) and normal subjects (22,5 +/- SD = 14-37; p less than 0.001). There was no difference in BTG between those with MI or CI, nor between the NCCP group and normal subjects. Raised numbers of circulating platelet aggregates could not be detected in either MI or CI. The mean BTG levels in both MI and CI patients were significantly raised, compared to normal subjects, on the first day of admission to hospital and remained so on each of the subsequent nine days. Neither heparin plus warfarin nor sulphinpyrazone had any significant effect in lowering BTG levels. 15/40 patients (37.5%) following MI and CI had repeatedly raised BTG levels throughout the study period, and it is suggested that these patients represent an "at risk" group that may benefit from anti-platelet therapy in secondary prevention studies.

Topics: Acute Disease; Adolescent; Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Blood Coagulation Disorders; Blood Platelets; Coronary Disease; Heparin; Humans; Middle Aged; Myocardial Infarction; Pain; Sulfinpyrazone; Thorax; Warfarin

The validity of a previously described technique for predicting warfarin requirements based on the anticoagulant response to a fixed loading dose was assessed prospectively in 57 patients. There was a close relationship between the predicted and initially observed daily warfarin dose required to maintain the patient within the therapeutic range for anticoagulation. The significant relationship between predicted and observed maintenance dose persisted at 4 and 12 weeks although it decreased with increasing time. The relationship between observed and predicted maintenance requirement of warfarin was not affected by the concomitant use of intermittent intravenous injections of heparin when 9 hr was allowed to elapse between the previous dose of heparin and the thrombotest estimation on which the prediction was based. It is concluded that the method is valuable in predicting an individual's warfarin requirement, although it does not obviate the need for regular monitoring of anticoagulant control.

Topics: Anticoagulants; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Humans; Injections, Intravenous; Prothrombin Time; Warfarin

Antithrombin III is a potent coagulant inhibitor in plasma. Congenital deficiency of antithrombin III may predispose to thrombotic events and may complicate surgical management. We describe a patient with congenital antithrombin III deficiency who developed superior mesenteric vein thrombosis after the cessation of warfarin therapy which resulted in venous gangrene of the small intestine. Initial treatment of this deficiency with fresh frozen plasma and subsequent long-term management with warfarin therapy has been effective in avoiding further thrombotic events.

Topics: Adult; Antithrombin III Deficiency; Blood Coagulation Disorders; Blood Transfusion; Child; Female; Gangrene; Humans; Intestine, Small; Male; Mesenteric Veins; Pedigree; Thrombosis; Warfarin

Activation of blood coagulation, as characterized by the occurrence of disseminated intravascular coagulation, increased levels of plasma FPA, and the local deposition of fibrin, is common in both experimental animals and patients with malignant tumors. Many mechanisms have been proposed for the mediation of this response to tumors, including tumor-associated proteases, platelet adherence to tumors, surface activation of blood coagulation by tumor cells, and activation of coagulation by tissue factor derived from either tumor tissue or reactive leukocytes. We have investigated the hypothesis that MTF generation may contribute to increased fibrin generation in cancer patients. Plasma FPA levels and in vitro unstimulated MTF generation were measured simultaneously in samples obtained from 35 patients with lung cancer. FPA levels were significantly elevated in these patients as compared to a group of 20 normal volunteers (p = 0.03). Although unstimulated MTF generation showed considerable variability in both the patients and the normal volunteers, a high degree of correlation was observed between simultaneous levels of FPA and MTF regardless of whether MTF was expressed per cell (r = 0.83), per monocyte (r = 0.95), or per volume of peripheral blood (r = 0.96). MTF generation was also significantly decreased in a group of patients receiving sodium warfarin (p less than 0.001). These results suggest a potential role for MTF generation in the activation of blood coagulation in neoplasia and also suggest the possibility that inhibition of MTF generation by warfarin may be partially responsible for the decreased FPA values previously reported in anticoagulated cancer patients.

Topics: Aged; Blood Coagulation Disorders; Cells, Cultured; Fibrinopeptide A; Humans; Lung Neoplasms; Middle Aged; Mitogens; Monocytes; Reference Values; Warfarin

Human Factor X was isolated from Cohn fraction III and characterized by polyacrylamide gel electrophoresis, amino acid composition, and isoelectric focusing. Two molecular forms with biological activity were observed at isoelectric points of 4.8 and 5.0. Antisera generated to Factor X was monospecific and used to establish an equilibrium competitive inhibition radioimmunoassay. This assay was specific for human Factor X and did not cross-react with human prothrombin or bovine Factor X within the sensitivity range of 6-300 ng Factor X antigen/ml. The mean concentration of Factor X based on the antigen was 11.9 mug/ml, whereas concentration values based on coagulant activity was 7.8 mug/ml. This 30% difference in measurement appears to result from the presence of a subpopulation of Factor X molecules devoid of coagulant activity. The radioimmunoassay was used to qualitatively and quantitatively compare purified Factor X to plasmic Factor X obtained from normal, warfarintreated, acquired Factor X-deficient, and congenitaldeficient patients. In all but one case, the Factor X present in these plasmas was immunochemically identical to the purified Factor X and permitted precise quantitation of these abnormal Factor X molecules. Factor X procoagulant activity was analyzed relative to Factor X antigen and the specific activities were used to characterize normal and abnormal Factor X molecules. Reduced Factor X activity in plasmas from warfarin-treated and acquired Factor X-deficient patients was attributed to both decreases in Factor X antigen and decreased function of the Factor X molecules. Congenitally deficient patients, in general, showed a reduction in Factor X antigen in parallel with Factor X procoagulant activities resulting from comparable decreases in specific biological activity of the molecules.

Topics: Amino Acids; Blood Coagulation Disorders; Electrophoresis, Polyacrylamide Gel; Epitopes; Factor X; Factor X Deficiency; Humans; Hypoprothrombinemias; Isoelectric Focusing; Radioimmunoassay; Warfarin

Two hundred twenty patients admitted to a Coronary Care Unit were studied by serial plasma fibrinogen chromatography--a method for quantification of HMWFCs, native fibrinogen, and other fibrinogen derivatives in plasma. Enhanced formation of fibrin (intravascular coagulation/thrombosis) is reflected by elevation of plasma HMWFC. One hundred ten patients suffering from documented acute myocardial infarction showed early, sharp elevation of plasma HMWFC (p less than 0.001 when compared to normal and cardiac control groups), a finding which persisted for 10 to 20 days after infarction. Forty-three of the patients did not receive anticoagulant therapy, and the others received either initial heparin, heparin plus warfarin, or werfarin therapy. Plasma fibrinogen chromatographic findings, days 1 to 5, did not differ between the anticoagulated and nonanticoagulated treatment groups, although there were minor differences in the data for days 6 to 10. The results demonstrate that patients with acute myocardial infarction develop a coagulopathy characterized by enhanced fibrin formation, which is influenced to only a minor degree by conventional dosage anticoagulant therapy.

Topics: Anticoagulants; Blood Coagulation Disorders; Fibrinogen; Heart Failure; Heparin; Humans; Myocardial Infarction; Warfarin

Topics: 1-Carboxyglutamic Acid; Amino Acids; Animals; Blood Coagulation Disorders; Cycloheximide; Female; Half-Life; In Vitro Techniques; Male; Microsomes, Liver; Protein Biosynthesis; Prothrombin; Rats; Sex Factors; Vitamin K; Vitamin K Deficiency; Warfarin

This study reports the correlation of the thrombin generation test and the plasma clot impedance test with clinical evidence of hypercoagulability. Thrombin generation is increased and the rate of change of plasma from a liquid to a gel (clot impedance) is increased in situations where the risk of thrombosis is increased. These situations include increasing clinical signs and/or symptoms of thromboembolism, positive lung scans, postoperative total hip replacement, patients over 40 years old, low serum antithrombin III, thrombocytosis, transient cerebral ischemia, and positive isotope venogram for thrombosis. The two tests failed to indicate a significant effect of antiplatelet drugs on the hypercoagulable state. This study shows that the thrombin generation and plasma clot impedance tests are practical, rapid and useful tests for the detection and monitoring of the hypercoagulable state.

Topics: Adult; Aging; Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Tests; Brain Ischemia; Dose-Response Relationship, Drug; Female; Heparin; Hip; Humans; Lung; Male; Phlebography; Radionuclide Imaging; Thrombin; Thrombocytosis; Time Factors; Warfarin

Topics: Blood Coagulation Disorders; Diabetes Mellitus; Humans; Prothrombin Time; Warfarin

Thrombotest clotting times of mixtures of coumarin plasmas and normal plasma yielded a patterm similar to that observed in mixtures of plasma with congenital coagulation disorders and normal plasma. The presence of 10 or 20% of test plasma in the mixture failed to affect the clotting times which resulted in normal limits. The only exception to this rule was the hemophilia BM plasma. In this case even the presence of 10-20% of patient plasma in the mixture caused a prolongation of the clotting time. This indicates that no inhibitor is present in coumarin plasmas and in the plasma of congenital coagulation disorders of the prothrombin complex save for hemophilia BM plasma which does contain an inhibitor.

Topics: Acenocoumarol; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Hemophilia B; Humans; Male; Prothrombin; Thromboplastin; Warfarin

In 66 months, a general hospital's outpatient Anticoagulation Service (ACS) monitored 263 patients who received 280 courses of warfarin sodium totalling 254 patient treatment years. Major hemorrhagic morbidity was 4% of courses and there was no mortality attributable to warfarin therapy. Major hemorrhage occurred in patients with increased anatomic risk of bleeding (diverticulosis, hemorrhoids, cystitis), and was not a function of patient age, sex, anticoagulation control, or medications administered concurrently with warfarin. Control of anticoagulation was not correlated with age or other medications, but was worsened significantly by the presence of congestive heart failure. We attribute a favorable experience with outpatient ACS to careful patient selection, patient education and monitoring, attention to duration of anticoagulation, and continuing communication with primary physicians who retained responsibility for medical care. An ACS offers safety, consistency, efficiency, and a unified approach to outpatient anticoagulation in the general hospital setting.

Topics: Aged; Blood Coagulation Disorders; Female; Gastrointestinal Hemorrhage; Health Education; Heart Failure; Hematuria; Humans; Male; Maryland; Middle Aged; Outpatient Clinics, Hospital; Prothrombin Time; Thromboembolism; Time Factors; Warfarin

Normotest (sample volume: 25 micronl) and Thrombotest were performed in parallel on 150 consecutive capillary blood samples from patients on long term oral anticoagulant therapy. The ratio of Normotest to Thrombotest decreased from 2.50 at a Thrombotest level of 5-5.5% to 1.95 at a Thrombotest level of 13-13.5%, indicating that the effects of PIVKA were more pronounced at lower levels of coagulation activity. The influence of varying sensitivity of the thromboplastin reagents to PIVKA is discussed. The therapeutic range of Thrombotest (5-10%) corresponded to a Normotest level of 12-20%.

Topics: Administration, Oral; Blood Coagulation Disorders; Blood Coagulation Tests; Humans; Warfarin

A secific, sensitive, and reproducible radioimmunoassay for human Hageman factor (HF, factory XII) has been developed with purified human HF and monospecific rabbit antibody. Precise measurements of HF antigen were possible for concentrations as low as 0.1% of that in normal pooled plasma. A good correlation (correlation co-efficient = 0.82) existed between the titers of HF measured by clot-promoting assays and radioimmunoassays among 42 normal adults. Confirming earlier studies, HF antigen was absent in Hageman trait plasma, but other congenital deficient plasmas, including those of individuals with Fletcher trait and Fitzgerald trait, contained normal amounts of HF antigen. HF antigen was reduced in the plasmas of patients with disseminated intravascular coagulation or advanced liver cirrhosis, but it was normal in those of patients with chronic renal failure or patients under treatment with warfarin. HF antigen was detected by this assay in plasmas of primates, but not detectable in plasmas of 11 nonprimate mammalian and one avian species.

Topics: Adult; Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor XII; Female; Fetal Blood; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Radioimmunoassay; Warfarin

With the kaolin-cephalin activated partial thromboplastin time technic, the plasmas of persons who have Fletcher factor deficiency have shown considerable shortening of clotting times when contact activation has been lengthened from 3 (PTT-3) to 10 minutes (PTT-10). The authors demonstrate that in plasma of most normal individuals, and in coagulopathies of other sorts, only slight shortening usually occurs. Abnormal shortening occurs in plasmas of a few otherwise normal people, the "slow activators," and patients receiving coumarin drugs, who have greatly prolonged prothrombin times. Longer activation may produce greatly prolonged PTT's in plasmas containing heparin in relatively high concentrations. The authors discuss the significance of these findings.

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Heparin; Humans; Prekallikrein; Thromboplastin; Time Factors; Warfarin

Patients at high risk of having thromboses can be identified not only on the basis of clinical criteria but also on the basis of laboratory studies. With use of a condensed coagulation profile consisting of six laboratory tests, the clinical impression of hypercoagulability can be confirmed in approximately 90 per cent of cases. Therapy directed to correct specific laboratory abnormalities may be more efficacious than nonspecific therapy.

Topics: Adult; Aged; Aspirin; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Heparin; Humans; Male; Middle Aged; Warfarin

A young woman presented with a 2 year history of a severe bleeding disorder and marked deficiencies in all four vitamin-K-dependent factors. Metabolic studies with tracer doses of tritium-labelled vitamin K1 suggested that the patient might be taking an oral anticoagulant; and subsequently her plasma was found to contain a substance identical to phenindione in its spectrophotometric and chromatographic properties. The half-disappearance times of factors II, IX, X were measured after the administration of a concentrate of these factors and were found to conform with published figures. The concentrate controlled the patient's excessive bruising and prolonged skin and gingival bleeding. It would therefore seem that factor VII may not be essential in reversal of the bleeding disorder induced by anticoagulant overdose.

Topics: Adult; Anemia; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Chromatography, Gas; Chromatography, Thin Layer; Diabetes Complications; Female; Glucosephosphate Dehydrogenase; Hematemesis; Hematuria; Humans; Menorrhagia; Phenindione; Self Medication; Spectrum Analysis; Substance-Related Disorders; Vitamin K; Warfarin

Acetylsalicylic acid and phenylbutazone increased the bleeding significantly from standardized wounds in dogs defibrinogenated with Defibrase. Administration of dipyridamole and Xylocain had no effect. The results were the same in dogs treated with warfarin sodium. The results demonstrate the value of using laboratory animals with an induced coagulopathy when establishing the effect on the haemostasis exerted by drugs known in vitro to interfere with platelet functions. Acetylsalicylic acid and dipyridamole did not alter the activity of the K-vitamin-dependent coagulation factors, factors V, VIII, platelet count or fibrinogen concentration.

Topics: Afibrinogenemia; Animals; Aspirin; Batroxobin; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Dogs; Hemostasis; Peptide Hydrolases; Phenylbutazone; Warfarin

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Cerebral Arteries; Dose-Response Relationship, Drug; Heparin; Humans; Leg; Migraine Disorders; Thrombophlebitis; Vasodilator Agents; Warfarin

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Hemorrhage; Humans; Male; Malingering; Neurotic Disorders; Prothrombin Time; Self Medication; Vitamin K; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Clofibrate; Hemorrhage; Humans; Male; Methods; Middle Aged; Prothrombin Time; Pulmonary Embolism; Sodium; Vitamin E; Vitamin K; Vitamin K Deficiency; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Heparin; Humans; Time Factors; Warfarin

Topics: Animals; Blood Coagulation Disorders; Cattle; Factor VII Deficiency; Factor X; Humans; Hypoprothrombinemias; Prothrombin; Rabbits; Swine; Thromboplastin; Warfarin

Topics: Aged; Antithrombins; Blood Coagulation Disorders; Blood Coagulation Tests; Coronary Disease; Depression, Chemical; Female; Fibrinogen; Humans; Immunodiffusion; Macroglobulins; Male; Middle Aged; Thrombosis; Warfarin

Topics: Blood Coagulation Disorders; Humans; Immunoelectrophoresis; Myocardial Infarction; Phenylbutazone; Prednisone; Prothrombin; Prothrombin Time; Thrombophlebitis; Time Factors; Warfarin

Topics: Blood Coagulation Disorders; Disulfiram; Drug Synergism; Humans; Warfarin

Topics: Agranulocytosis; Anus Diseases; Anus Neoplasms; Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Blood Transfusion; Colitis, Ulcerative; Colonic Diseases; Colonic Neoplasms; Factor V Deficiency; Factor VII Deficiency; Gastrointestinal Hemorrhage; Hemophilia A; Humans; Hypoprothrombinemias; Liver Diseases; Lymphoma; Rectal Diseases; Warfarin

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Cats; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver; Liver Function Tests; Maternal-Fetal Exchange; Phenytoin; Pregnancy; Prothrombin Time; Thromboplastin; Vitamin K; Warfarin

Topics: Blood Coagulation; Blood Coagulation Disorders; Humans; Kidneys, Artificial; Perfusion; Polyurethanes; Silicone Elastomers; Surface Properties; Thrombosis; Uremia; Warfarin; Water

Topics: Animals; Blood Coagulation Disorders; Dogs; Rabbits; Rats; Vitamin K 1; Warfarin

Topics: Blood Coagulation Disorders; Female; Fetus; Hemorrhage; Heparin; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pre-Eclampsia; Pregnancy; Warfarin

Patients with disorders of hemostasis who undergo surgical procedures are in danger of hemorrhage. While the careful medical history remains the most sensitive test of a bleeding tendency, some such patients can give no suggestive history. In three patients with coagulopathy-one with mild classical hemophilia, one with Christmas disease, and one with warfarin toxicity-the abnormality was missed by routine preoperative history but promptly detected by the routine preoperative use of the activated coagulation time (act). Either this test or the activated partial thromboplastin time should be included in the routine preoperative work-up, along with appropriate additional tests of the hemostatic mechanism.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Female; Hemophilia A; Hemophilia B; Humans; Male; Middle Aged; Postoperative Complications; Preoperative Care; Warfarin

Topics: Analysis of Variance; Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Brain; Cattle; Coumarins; Factor VII; Factor VII Deficiency; Factor X; Humans; Hypoprothrombinemias; Indicators and Reagents; Methods; Prothrombin Time; Rabbits; Thromboplastin; Warfarin

Ninety studies on 58 patients undergoing chronic warfarin therapy included Quick prothrombin times, partial thromboplastin times, thromboplastin generation tests and assays for clotting factors II, V, VII, VIII, IX, X, XI and XII. The results indicate no benefit from supplementation of the Quick tests by any of these other procedures. It is suggested that the Quick test uniformly performed, using a standard uniform thromboplastin, would be the procedure of choice.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Humans; Prothrombin Time; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Cholesterol; Drug Synergism; Heparin; Heparinoids; Humans; Myocardial Infarction; Warfarin

Topics: Beta-Globulins; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Chronic Disease; Cryoglobulins; Dipyridamole; Female; Fibrinogen; Heparin; Humans; Immunodiffusion; Immunoelectrophoresis; Middle Aged; Ovarian Neoplasms; Ultracentrifugation; Warfarin

Topics: Aged; Animals; Antidotes; Blood Coagulation Disorders; Child, Preschool; Chromatography; Coumarins; Dicumarol; Female; Humans; Male; Pedigree; Pharmacogenetics; Protein Binding; Prothrombin Time; Rabbits; Rats; Vitamin K; Vitamin K 1; Warfarin

Topics: Animals; Blood Coagulation Disorders; Carotid Arteries; Hypoprothrombinemias; Prothrombin; Prothrombin Time; Rabbits; Thrombosis; Vitamin K 1; Warfarin

Topics: Aminocaproates; Animals; Blood Coagulation Disorders; Blood Transfusion; Drug-Related Side Effects and Adverse Reactions; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Rats; Streptokinase; Thrombosis; Warfarin

Topics: Animals; Benzopyrans; Blood Coagulation Disorders; Injections, Intravenous; Rats; Splenectomy; Warfarin

Topics: Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Cortisone; Endotoxins; Fibrinogen; Iodine Isotopes; Kidney Glomerulus; Leukocytes; Nitrogen Mustard Compounds; Rabbits; Vitamin K; Warfarin

Topics: Acid Phosphatase; Afibrinogenemia; Blood Coagulation Disorders; Blood Proteins; Bone Marrow Examination; Diethylstilbestrol; Factor V; Factor VIII; Fibrinogen; Humans; Male; Middle Aged; Prostatic Neoplasms; Warfarin

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrin; Fluorescent Antibody Technique; Male; Mice; Microscopy, Electron; Nephritis; Serum Albumin; Serum Globulins; Staining and Labeling; Warfarin

Topics: Animals; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Hemorrhage; Rats; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Humans; Prothrombin; Renal Dialysis; Warfarin

Topics: Blood Coagulation Disorders; Hemorrhage; Humans; Middle Aged; Oxyphenbutazone; Warfarin

Topics: Adult; Animals; Blood Coagulation; Blood Coagulation Disorders; Guinea Pigs; Humans; Male; Prothrombin; Rabbits; Skin Absorption; Warfarin

Topics: Angiography; Anticoagulants; Blood Coagulation Disorders; Cerebral Hemorrhage; Deoxyribonuclease I; Drug Therapy; Fibrinogen; Heparin; Intracranial Embolism; Intracranial Embolism and Thrombosis; Streptodornase and Streptokinase; Streptokinase; Stroke; Thrombosis; Toxicology; Warfarin

Topics: Ammonium Compounds; Biomedical Research; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Protein Electrophoresis; Blood Transfusion; Hemostasis; Heparin; Humans; In Vitro Techniques; Prothrombin Time; Quaternary Ammonium Compounds; Tissue Extracts; Warfarin

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Diagnosis, Differential; Ecchymosis; Female; Humans; Menorrhagia; Minnesota; Thromboplastin; Toxicology; Warfarin

Topics: Adolescent; Adult; Animals; Anticoagulants; Blood Coagulation Disorders; Bone Development; Child; Child, Preschool; Female; Fibrin; Fractures, Bone; Fractures, Ununited; Hematoma; Hemophilia A; Heparin; Humans; Infant; Male; Periosteum; Pseudarthrosis; Rabbits; Radiography; Radius Fractures; Warfarin; Wound Healing

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Dicumarol; Factor VII; Factor X; Humans; Myocardial Infarction; Pharmacology; Prothrombin; Research; Warfarin