warfarin and Hemophilia-A

The phase III non-vitamin K dependent oral anticoagulants (NOAC) studies and recently published real world data on the use of dabigatran and rivaroxaban have shown that the bleeding profile in particular of intracranial and other life-threatening bleeding of NOAC is more favourable than that of warfarin. In case of a bleeding complication in a patient treated with a NOAC the recently updated EHRA practical guide offers management strategies. Idarucizumab, the specific antidot for dabigatran is approved to reverse the anticoagulant effect of dabigatran-treated patients who have serious bleeding and require an urgent procedure. Andexanet alfa, a specific antidot for direct and indirect factor Xa-inhibitors will be available in the future. The frequency of thrombocytopenia in ICU patients is high whereas the heparin induced thrombocytopenia (HIT) only counts for a small minority of patients with thrombocytopenia. To avoid an overdiagnosis of HIT a reliable and complete clinical and laboratory workup has to be performed. New immunoassays have been developed to provide results within a short period of time. These tests appear to have improved diagnostic accuracy compared with ELISAs in patients with suspected HIT and may reduce misdiagnosis and overtreatment. Acquired haemophilia (AH) is a rare and often life threatening bleeding disorder caused by autoantibodies against factor VIII. Susoctocog alfa is a B-domain deleted recombinant factor VIII porcine sequence that has recently been approved to treat severe bleeding in patients with AH. Susoctocog alfa offers the ability to effectively titrate and monitor dosing based on factor VIII activity levels.

Topics: Anticoagulants; Dabigatran; Hemophilia A; Hemorrhage; Heparin; Humans; Intensive Care Units; Rivaroxaban; Thrombocytopenia; Thrombosis; Warfarin

The hemostatic properties of recombinant activated factor VII (rFVIIa) are established in patients with inherited or acquired hemophilia with inhibitors and in patients with congenital factor VII deficiencies. Emerging clinical evidence suggests that there may be a wider role for rFVIIa in the management of hemorrhage associated with traumatic injury/accident and severe bleeding associated with critical surgery. This article considers recent data from studies in which rFVIIa was used in an attempt to control bleeding in clinical situations as diverse as coagulopathy associated with chronic liver disease, massive perioperative bleeding and bleeding during prostatectomy, organ transplantation and orthopedic surgery, uncontrollable obstetric hemorrhage, and intracerebral hemorrhage. In nontrauma settings involving acute and potentially life threatening bleeding, there may be a place for rFVIIa as adjunctive therapy in the control of hemostasis.

Topics: Anticoagulants; Factor VII; Factor VIIa; Hemophilia A; Hemorrhage; Humans; Liver Transplantation; Postoperative Complications; Randomized Controlled Trials as Topic; Recombinant Proteins; Warfarin

Most cases of epistaxis are due to simple causes and are easily treated on an out-patient basis. However, there are some cases where the origin of bleeding is not obvious or arises from an unusual pathological source. The authors describe a case of epistaxis due to a mass in the maxillary antrum that when biopsied showed the histological appearances of a haemophilic pseudotumour. The patient was anticoagulated on warfarin for a cardiac valve replacement and this was thought to be the cause of the ongoing haemorrhage necessary for development of the pseudotumour. Even in haemophiliacs, pseudotumours are rare and we believe this case is unique in that the patient is a non-haemophiliac. The epistaxis was eventually controlled by external beam radiotherapy to the pseudotumour. The management of this case is outlined as well as a review of the literature on haemophilic pseudotumour.

Topics: Aged; Anticoagulants; Cysts; Epistaxis; Hemophilia A; Humans; Male; Paranasal Sinus Diseases; Paranasal Sinuses; Tomography, X-Ray Computed; 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

The present study summarizes the results of 12 cardiac surgical procedures performed in a carrier of Haemophilia B and in six patients with Haemophilia A at a single centre from 1979 to 1998. The median age of the patients at the time of intervention was 56 years ranging from 18 years to 73 years. The six patients with Haemophilia A ranged in severity from moderately to mildly affected. Three patients were hepatitis C antibody positive. No patients were HIV antibody or hepatitis B surface antigen positive. The cardiac procedures included cardiac catheterization (n=4), coronary artery bypass surgery (n=2), percutaneous transluminal coronary angioplasty (n=1), cardiac valve replacement (AVR n=1 and AVR/MVR n=2), and closure of an atrial septal defect and subsequent drainage of a pericardial effusion (n=1). No patients had demonstrable inhibitors at the time of surgery. Haemostasis was achieved with AHF in 10/11 procedures and high purity factor IX (Immunine) in one procedure. The initial procedures involved intermittent bolus factor therapy while more recently, AHF was administered by continuous intravenous infusion. All patients demonstrated excellent intra- and post-operative haemostasis. These results, although from a small and varied group of patients, demonstrate that cardiac surgical procedures can be performed safely in patients with Haemophilia.

Topics: Adolescent; Adult; Aged; Aortic Valve; Aspirin; Cardiac Catheterization; Coronary Angiography; Coronary Artery Bypass; Factor IX; Factor VIII; Heart Valve Prosthesis Implantation; Hemophilia A; Hemophilia B; Hemorrhage; Hemostasis; Hepatitis B Surface Antigens; Hepatitis C Antibodies; HIV Antibodies; Humans; Isoantibodies; Middle Aged; Myocardial Ischemia; Thoracic Surgical Procedures; Warfarin

A 77-year-old man with a mechanical mitral valve on warfarin presented with an acute drop in haemoglobin and large spontaneous haematoma. He was found to have a new coagulopathy with initial labs notable for a prolonged activated partial thromboplastin time (APTT). Further workup revealed factor VIII levels less than 1%, abnormal mixing studies and elevated Bethesda titres, which was consistent with an acquired factor VIII inhibitor. Given his bone marrow biopsy result, which was positive for plasma cell myeloma, this coagulopathy was thought to be an acquired haemophilia A secondary to multiple myeloma. Anticoagulation was a challenge in this patient given his mechanical mitral valve and acquired haemophilia A. Although the patient was at risk of thrombosis due to a mechanical mitral valve, he had a bleeding diathesis and anaemia not responsive to transfusion. The decision was made to hold anticoagulation and the patient was started on myeloma treatment which included CyBorD, rituximab and daratumumab. After initiation of treatment APTT and factor VIII normalised. He eventually restarted anticoagulation under direction of his primary care doctor.

Topics: Aged; Anticoagulants; Antineoplastic Agents; Drug Therapy, Combination; Heart Valve Prosthesis; Hematoma; Hemophilia A; Humans; Male; Multiple Myeloma; Partial Thromboplastin Time; Warfarin

Taking advantage of an interesting clinical scenario, we want to introduce a discussion about fatality in our daily practice and the need to accept that. An 80 year-old man with non-traumatic spontaneous bleeding tendency came to the clinics. Although being on warfarin as a consequence of primary thrombotic prophylaxis due to an atrial fibrillation, full assessment was performed. Not only the rare entity found on him, but also the severe complication that happened afterwards challenged clinicians and led them to risky treatment options.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Fatal Outcome; Hemophilia A; Humans; Male; Stroke; Warfarin

Mice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-of-function approach involving injections of recombinant FVIII to complement the coagulation deficiency should ameliorate the pathogenesis. As expected, a sublethal dose of LT caused mortality in the mice that were non-lethally pretreated with an anticoagulant (warfarin). By contrast, treatments of recombinant FVIII reduced the mortality from a lethal dose of LT in mice. Our results indicated that LT-induced deficiency of FVIII is involved in LT-mediated pathogenesis. Using recombinant FVIII to correct the coagulant defect may enable developing a new strategy to treat anthrax.

Topics: Animals; Anticoagulants; Antigens, Bacterial; Bacillus anthracis; Bacterial Toxins; Blood Coagulation; Blood Coagulation Factors; Cell Death; Cell Line, Tumor; Cells, Cultured; Factor VIII; Hemophilia A; Hep G2 Cells; Humans; Liver; Male; Mice; Recombinant Proteins; Warfarin

Acquired haemophilia is a rare coagulation disorder more commonly seen in elderly patients. Diagnosis and effective treatment can be delayed if patients are on warfarin treatment, as the bleeding symptoms may be erroneously attributed to this agent. We present a case report of a 75-year-old woman whose unexplained, severe and persistent bleeding was treated with surgical decompression and plasma transfusions, an appropriate management based on the assumption that warfarin was the cause of the bleeding. It was only when the patient's international normalised ratio returned to normal that a persistent abnormal activated partial thromboplastin time was noted. This delayed the correct diagnosis and treatment. Awareness of acquired haemophilia as a possible cause of sudden bleeding should be encouraged, and the wider dissemination of any relevant experience of similar cases would also be welcome.

Topics: Aged; Anticoagulants; Factor VIII; Female; Glucocorticoids; Hemophilia A; Hemorrhage; Humans; Partial Thromboplastin Time; Prednisolone; Warfarin

Lupus anticoagulant (LA) is an antibody that interferes with one or more in vitro coagulation reactions, which are dependent on interactions with protein-phospholipid complexes. For LA diagnosis, a mixing test is considered useful for differentiating the inhibitor from a factor deficiency. However, the usefulness and the index of circulating anticoagulant (ICA) in a mixing test with activated partial thromboplastin time (APTT) has not been adequately investigated, and there is scant information regarding the effects of warfarin, heparin, and hemophilia plasma on ICA. We evaluated the usefulness of ICA by investigating the correlation of that index with international normalized ratio (INR), heparin concentration, and factor VIII activity in hemophilia patients.. We examined samples from 28 patients positive for LA, 23 receiving warfarin, 19 receiving unfractionated heparin, and 29 with hemophilia A, as well as 61 normal samples. APTT-SLA, Actin FSL, APTT-SP, and PTT-LA were used as reagents in this study.. The correlation coefficient values between ICA and INR, heparin concentration, and factor VIII activity ranged from 0.031-0.342, 0.764-0.843, and 0.564-0.754, respectively, with the 4 reagents. The ICA values for the LA-positive samples were significantly higher than for the normal, warfarin, heparin, and hemophilia samples with all APTT reagents. Samples with a high heparin concentration above approximately 0.5U/ml showed ICA values greater than 15.. ICA was able to distinguish LA-positive samples from the normal, warfarin, and hemophilia samples, but not heparin samples. ICA calculated from APTT clotting time is useful for LA diagnosis.

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor VIII; Hemophilia A; Heparin; Humans; Immunoglobulins; International Normalized Ratio; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Sensitivity and Specificity; Warfarin

Immune responses to therapeutic factor VIII remain a major problem, affecting 30% of patients with severe hemophilia A. The primary factors that drive immune responses in these patients remain elusive. There have been conflicting reports on a role of coagulation (or thrombin) in anti-FVIII immune responses.. To assess the importance of coagulation-associated processes for the onset of the anti-FVIII immune response.. Using FVIII-deficient mice, we compared the immunogenicity of recombinant FVIII or the inactive FVIII(V) (634M) mutant. In parallel, the involvement of tissue factor (TF) activity in the anti-FVIII immune response was investigated upon injection of a neutralizing anti-TF antibody or by the use of chimeric mice that lack TF expression in myeloid cells. The development of the anti-FVIII immune response was also monitored after treatment with warfarin.. The kinetics of the development of antibody responses to FVIII(V) (634M) were indistinguishable from those of wild-type FVIII. Inhibition of TF activity did not modulate immune responses to exogenous FVIII. Additionally, global inhibition of coagulation with warfarin failed to reduce the anti-FVIII immune response.. Thrombin generation or coagulation-associated processes do not modulate the anti-FVIII antibody response in mouse model of severe hemophilia A.

Topics: Animals; Antibodies, Neutralizing; Blood Coagulation; Disease Models, Animal; Factor VIII; Hemophilia A; Immunity, Humoral; Inflammation; Mice; Mutation; Plasmids; Protein Structure, Tertiary; Recombinant Proteins; Thrombin; Thromboplastin; Warfarin

The standard clinical coagulation assays, activated partial thromboplastin time (aPTT) and prothrombin time (PT) cannot predict thrombotic or bleeding risk. Since thrombin generation is central to haemorrhage control and when unregulated, is the likely cause of thrombosis, thrombin generation assays (TGA) have gained acceptance as "global assays" of haemostasis. These assays generate an enormous amount of data including four key thrombin parameters (lag time, maximum rate, peak and total thrombin) that may change to varying degrees over time in longitudinal studies. Currently, each thrombin parameter is averaged and presented individually in a table, bar graph or box plot; no method exists to visualize comprehensive thrombin generation data over time. To address this need, we have created a method that visualizes all four thrombin parameters simultaneously and can be animated to evaluate how thrombin generation changes over time. This method uses all thrombin parameters to intrinsically rank individuals based on their haemostatic status. The thrombin generation parameters can be derived empirically using TGA or simulated using computational models (CM). To establish the utility and diverse applicability of our method we demonstrate how warfarin therapy (CM), factor VIII prophylaxis for haemophilia A (CM), and pregnancy (TGA) affects thrombin generation over time. The method is especially suited to evaluate an individual's thrombotic and bleeding risk during "normal" processes (e.g pregnancy or aging) or during therapeutic challenges to the haemostatic system. Ultimately, our method is designed to visualize individualized patient profiles which are becoming evermore important as personalized medicine strategies become routine clinical practice.

Topics: Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Computer Simulation; Factor VIII; Female; Hemophilia A; Humans; Kinetics; Male; Middle Aged; Models, Biological; Pregnancy; Premedication; Protein C; Thrombin; Warfarin; Young Adult

Topics: Abdominal Pain; Adult; Anticoagulants; Aortic Valve; Heart Valve Prosthesis; Hematoma; Hemophilia A; Humans; Male; Muscular Diseases; Psoas Muscles; Tomography, X-Ray Computed; Warfarin

Spontaneous intramural hematoma of the small intestine is a rare clinical condition that may result in potentially serious complications. The purpose of this study was to present our experience with the diagnosis and management of spontaneous intramural hematoma of the small intestine.. The medical records of the patients with spontaneous intramural hematoma of the small intestine were retrospectively reviewed. Six patients were included in this study.. Anticoagulation therapy and factor VIII deficiency were found to be responsible for the intramural hemorrhage in five patients (83%) and one patient, respectively. Acute abdominal pain followed by nausea and vomiting were the most common presenting symptoms. Abdominal computed tomography scan was diagnostic in five of the six patients. Four patients were followed up with conservative therapy. Surgical intervention was required in two patients due to acute abdomen. All patients were discharged from the hospital uneventfully.. The patient's medical history, physical examination and radiological evaluation proved adequate for the diagnosis. Conservative therapy provides regression of the hematoma in most patients. Surgery should be reserved only for the complicated cases.

Topics: Adult; Aged; Anticoagulants; Aspirin; Hematoma; Hemophilia A; Humans; Intestinal Diseases; Intestine, Small; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Coagulation is an important process in hemostasis and comprises a complicated interaction of multiple enzymes and proteins. We have developed a mechanistic quantitative model of the coagulation network. The model accurately describes the time courses of coagulation factors following in vivo activation as well as in vitro blood coagulation tests of prothrombin time (PT, often reported as international normalized ratio (INR)) and activated partial thromboplastin time (aPTT). The model predicts the concentration-time and time-effect profiles of warfarin, heparins, and vitamin K in humans. The model can be applied to predict the time courses of coagulation kinetics in clinical situations (e.g., hemophilia) and for biomarker identification during drug development. The model developed in this study is the first quantitative description of the comprehensive coagulation network.

Topics: Algorithms; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Computer Simulation; Hemophilia A; Hemostatics; Heparin; Humans; International Normalized Ratio; Kinetics; Models, Biological; Models, Statistical; Partial Thromboplastin Time; Predictive Value of Tests; Prothrombin Time; Snake Bites; Vitamin K; Warfarin

Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for successful treatment. Early laboratory detection could minimize its potentially devastating consequences and reduce mortality but when a masking element such as anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged activated partial thromboplastin time (APTT) may be falsely attributed to warfarin alone, particularly when it is associated with oral anticoagulant overdose. We describe two patients on treatment with warfarin who presented with a bleeding diathesis and disproportionately prolonged APTT, which led to the diagnosis of antibodies directed against factor VIII.

Topics: Aged; Anticoagulants; Autoantibodies; Autoimmune Diseases; Factor VIII; Female; Hemophilia A; Hemorrhage; Humans; Partial Thromboplastin Time; Radiography; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Embolism; Genetic Therapy; Hemophilia A; Humans; Pulmonary Embolism; Thrombophilia; Thrombosis; Vena Cava Filters; Warfarin

Topics: Anticoagulants; Fibrin Fibrinogen Degradation Products; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemophilia A; Humans; Mitral Valve; Thrombosis; 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

We present two patients who acquired factor VIII antibodies in the immediate postoperative period. One patient was receiving warfarin that was temporarily discontinued but reintroduced after the procedure. Preoperatively, none gave a history of bleeding, even with past surgeries, and both had normal coagulation tests. Within days of surgery, hemorrhage with prolonged activated partial thromboplastin time, low factor VIII levels, and demonstrable factor VIII antibodies were observed. For the patient who was receiving warfarin the severe bleeding was attributed, at the beginning, only to the high international normalized ratio (INR), which resulted in a fatal delay in diagnosis and appropriate treatment. We would like to raise awareness of surgery as a precipitating cause of acquired hemophilia, which is something to be considered with unusual postoperative bleeding. This syndrome is remarkable for its abrupt onset within days of surgery, severe bleeding but potential successful outcome with combined hemostatic control with recombinant activated FVII (rFVIIa) and elimination of the antibody by immunosuppression.

Topics: Adult; Aged; Autoantibodies; Factor VIII; Female; Hemophilia A; Humans; Male; Middle Aged; Postoperative Hemorrhage; 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 role of Protein C in combined factor V/VIII deficiency was examined by reducing the Protein C concentration using warfarin therapy in a patient with the combined deficiency. The factor VIII deficiency was like Hemophilia-A, with deficiency of VIII:C and VIII:C(Ag), but normal VIIIR:Ag and VIIIR:cof. The factor V deficiency was due to loss of the V antigen. During warfarin therapy the Protein C level was reduced, but concentrations of factors V and VIII did not change. Protein C Inhibitor was normal throughout. Thus combined factor V/VIII deficiency is not related to Protein C levels.

Topics: Adult; Blood Proteins; Factor V Deficiency; Female; Glycoproteins; Hemophilia A; Humans; Protein C; Protein C Inhibitor; Warfarin

Topics: Autoantibodies; Factor IX; Hemophilia A; Hemophilia B; Humans; Immunoassay; Isoantibodies; Reference Values; Warfarin

Topics: Anti-Inflammatory Agents; Drug Interactions; Drug Therapy, Combination; Hemophilia A; Humans; Warfarin

The coagulant of normal human saliva has been identified as tissue factor (thromboplastin, TF) by virtue of its ability to cause rapid coagulation in plasmas deficient in first-stage coagulation factors and to activate factor x in the presence of factor VII and by virtue of the fact that its activity is expressed only in the presence of factor VII and is inhibited by an antibody to TF. The TF is related to cells and cell fragments in saliva. Salivary TF activity has been found to be significantly reduced in patients taking warfarin. The decline in TF activity during induction of warfarin anticoagulation occurs during the warfarin-induced decline in vitamin-K-dependent clotting factor activity, as judged by the prothrombin time. The decrease in TF activity is not related to a reduction in salivary cell count or total protein content or to a direct effect of warfarin on the assay. It is hypothesized that the mechanism by which warfarin inhibits TF activity may be related to the mechanism by which it inhibits expression of the activity of the vitamin-K-dependent clotting factors. Inhibition of the TF activity may be involved in the antithrombotic effect of warfarin.

Topics: Factor VII; Factor VII Deficiency; Factor X; Factor XI Deficiency; Factor XII Deficiency; Freezing; Hemophilia A; Hemophilia B; Humans; Hyaluronoglucosaminidase; Prothrombin; Thromboplastin; Warfarin

Topics: Animals; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Dog Diseases; Dogs; Female; Fibrin Fibrinogen Degradation Products; Hemophilia A; Hemorrhagic Disorders; Male; Purpura, Thrombocytopenic; von Willebrand Diseases; Warfarin

Topics: Alpha-Globulins; Antithrombin III; Antithrombins; Blood Coagulation; Blood Proteins; Factor X; Hemophilia A; Humans; Warfarin

Activated partial thromboplastin times (APTT's) performed with a semi-automated electrical-conductivity type of clot timer on plasmas from patients with hepatic disease and intravascular coagulation, and on warfarin or heparin therapy, were significantly lower than when done on the same plasmas with either a manual optical method or an automated optical-endpoint instrument. Results of APTT's done on normal plasmas by the three methods were not significantly different. Substitution of different activator-phospholipid reagents resulted in some variability in results, but these differences were less than those between the different done with both the electrical clot timer and the automated optical instrument on prepared plasmas containing 5.0 or 1.0% of factor II, V, VIII, IX, OR X revealed shorter times with the electrical clot timer only in the case of factor II- and factor V-deficient plasmas. APTT's done on normal plasmas to which 0.1 or 0.3 units per ml. of heparin had been added vitro also were shorter with the electrical clot itmer than the automatic optical instrument. Prothrombin times done on normal and abnormal control plasmas and on a series of plasmas from patients on warfarin therapy showed no significant difference between the two methods.

Topics: Autoanalysis; Blood Chemical Analysis; Blood Coagulation Tests; Erythrocyte Aggregation; Factor V Deficiency; Factor X Deficiency; Hemophilia A; Hemophilia B; Heparin; Hydrogen-Ion Concentration; Hypoprothrombinemias; Liver Diseases; Optics and Photonics; Phospholipids; Prothrombin Time; Thromboplastin; Time Factors; Warfarin

Topics: Animals; Blood Coagulation; Blood Coagulation Factors; Blood Transfusion; Factor IX; Factor VII; Factor VIII; Freeze Drying; Hemophilia A; Humans; Rabbits; Temperature; Time Factors; 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

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: Animals; Blood Coagulation; Blood Platelets; Dogs; Electrodes; Factor VIII; Factor XII; Hemophilia A; Heparin; Mechlorethamine; Thrombocytopenia; Thrombosis; 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