warfarin and Vascular-Diseases

Monitoring warfarin with Fiix-prothrombin time (Fiix-PT), which is only affected by coagulation factors II and X, stabilizes anticoagulation and reduces thromboembolism compared to PT/INR monitoring. We compared outcome in nonvalvular atrial fibrillation (NVAF) patients treated with Fiix-warfarin, direct oral anticoagulants (DOACs), or PT-warfarin.. A systematic efficacy and safety assessment by retrieving data from the Fiix trial and the four major phase III DOAC trials in NVAF. Prespecified outcomes included stroke and systemic embolism (SSE), SSE and myocardial infarction (MI), major bleeding (MB), composite major vascular events (SSEMI and MB; CMVE), and deaths. We calculated relative risk, 95% CI, and 95% confidence limits (CL) for each outcome and performed meta-analysis using fixed- and random-effects modeling.. There were 613 and 628 observation years with Fiix-warfarin and PT-warfarin in the Fiix trial, and 70 628 and 57 962 with DOACs and PT-warfarin in DOAC trials. Populations were comparable although death rates were lower in the Fiix trial. Compared to pooled PT-warfarin, Fiix-warfarin reduced SSE (RR 0.54;95% CI 0.26-1.10/95% CL <1.00), SSEMI (0.51;0.26-0.99/<0.90), MB (RR 0.63;0.37-1.07/<0.99), and CMVE (RR 0.66;0.43-1.00/<0.94). Vascular death was lower (RR 0.13;0.04-0.47/<0.42). Compared to pooled DOACs, Fiix-warfarin consistently had lower point estimates for the RR for efficacy and safety, but only significant for lower death rates (vascular death RR 0.14;0.04-0.49/<0.43). Meta-analysis comparing Fiix-warfarin and DOACs with PT-warfarin consistently found Fiix-warfarin to have the lowest point estimates for efficacy.. Monitoring warfarin with Fiix-PT reduces risk of vascular events in NVAF patients as much as DOACs. Warfarin monitored with Fiix-PT is an improved anticoagulant.

Topics: Atrial Fibrillation; Drug Monitoring; Humans; Prothrombin Time; Randomized Controlled Trials as Topic; Treatment Outcome; Vascular Diseases; Warfarin

To review the rationale, clinical practice guideline recommendations, and clinical trial data describing bleeding and clinical outcomes associated with the use of the combination of aspirin, a thienopyridine, and warfarin.. An English-language literature search was conducted using MEDLINE (1966-March 2008) and the search terms aspirin, clopidogrel, ticlopidine, thienopyridine, warfarin, antiplatelet, anticoagulant, myocardial infarction, atrial fibrillation, and percutaneous coronary intervention (PCI). Additional references were identified by reviewing reference citations of articles retrieved.. Applicable data were extracted from published reports and studies that included either clinical outcomes or adverse events.. Clinical guidelines recommend the combination of antiplatelets and anticoagulants based largely on writing committee consensus. To date, only one randomized clinical trial has evaluated the safety and efficacy of adding warfarin to dual antiplatelet therapy (ie, triple antithrombotic therapy). Other published data are from case series, observational studies, and case-controlled studies primarily of patients undergoing PCI with intracoronary stent placement. Four of 12 studies reported no increased risk of major bleeding events. In the other 8 studies, a 3- to 6-fold increase in bleeding events was reported with triple antithrombotic therapy. Ischemic events were reported in only 6 of the studies. Only 2 studies observed an additional benefit in the reduction of ischemic events, and 1 study reported worsened ischemic outcomes with the triple antithrombotic regimen compared with dual antithrombotic therapy.. Available guidelines pertaining to the concomitant administration of aspirin, a thienopyridine, and warfarin are based on limited trial data and consensus judgment. Overall, selection of triple antithrombotic therapy for patients with vascular disease is considered a matter of clinical judgment for an individual patient based on the prescriber's perceived balance between the patient's risk for recurrent ischemic events, expected duration of treatment, and patient's risk for bleeding.

Topics: Anticoagulants; Aspirin; Clinical Trials as Topic; Clopidogrel; Drug Interactions; Drug Therapy, Combination; Hemorrhage; Humans; Ischemia; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Ticlopidine; Vascular Diseases; Warfarin

Vitamin K-dependent proteins (VKDPs) require carboxylation to become biologically active. Although the coagulant factors are the most well-known VKDPs, there are many others with important physiologic roles. Matrix Gla Protein (MGP) and Growth Arrest Specific Gene 6 (Gas-6) are two particularly important VKDPs, and their roles in vascular biology are just beginning to be understood. Both function to protect the vasculature; MGP prevents vascular calcification and Gas-6 affects vascular smooth muscle cell apoptosis and movement. Unlike the coagulant factors, which undergo hepatic carboxylation, MGP and Gas-6 are carboxylated within the vasculature. This peripheral carboxylation process is distinct from hepatic carboxylation, yet both are inhibited by warfarin administration. Warfarin prevents the activation of MGP and Gas-6, and in animals, induces vascular calcification. The relationship of warfarin to vascular calcification in humans is not fully known, yet observational data suggest an association. Given the high risk of vascular calcification in those patients with chronic kidney disease, the importance of understanding warfarin's effect on VKDPs is paramount. Furthermore, recognizing the importance of VKDPs in vascular biology will stimulate new areas of research and offer potential therapeutic interventions.

Topics: Animals; Anticoagulants; Blood Vessels; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Matrix Gla Protein; Protein Processing, Post-Translational; Risk Assessment; Risk Factors; Vascular Diseases; Vitamin K; Warfarin

Topics: Animals; Anticoagulants; Calcinosis; Chronic Disease; Humans; Renal Dialysis; Renal Insufficiency; Vascular Diseases; Vitamin K; Vitamin K Deficiency; Warfarin

Atrial fibrillation (AF) is a common arrhythmia that is associated with an increased risk for vascular events, particularly stroke. Two different therapies have been extensively evaluated for prevention of vascular events in AF: oral anticoagulation (such as warfarin), and aspirin. Placebo-controlled trials of warfarin have been performed and summarized in a meta-analysis. There is clear evidence of a benefit, with a relative risk reduction in stroke of 67% and in total vascular events of 42%. Aspirin also has been studied and is effective, but with a more modest benefit (relative risk reduction of 22%). Several studies have compared warfarin and aspirin, and showed a clear benefit in favor of warfarin for reduction of vascular events and stroke. Compared to aspirin, the risk of major hemorrhage with oral anticoagulation is increased by 70% to 100%. Current practice guidelines recommend oral anticoagulation therapy for high-risk patients with AF, unless there is an increased risk for bleeding. Nonetheless, oral anticoagulation therapy with drugs such as warfarin is difficult for both patients and physicians because of the increased risk for bleeding and the need for ongoing monitoring of coagulation status. Many patients do not receive anticoagulation therapy despite its proven benefits.

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Contraindications; Controlled Clinical Trials as Topic; Evidence-Based Medicine; Hemorrhage; Humans; Placebo Effect; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Practice Patterns, Physicians'; Risk Factors; Stroke; Treatment Outcome; Vascular Diseases; Warfarin

The long-term use of oral anticoagulants like warfarin in artery disease has long been controversial. Possible aims of treatment include the primary or secondary prevention of systemic embolism, preventing recurrence after myocardial infarction or the progression of transient cerebral ischemia to a complete stroke, and the prevention of artery graft occlusion. The value of long-term anticoagulation is generally accepted in the few situations where, as in patients with mechanical heart valve prostheses, mitral valve disease and atrial fibrillation, or idiopathic dilated cardiomyopathy, the risk of arterial thromboembolism without anticoagulation is known to be high and there is good evidence that anticoagulants are effective, so the benefit:risk balance strongly favours their use. In many settings, however, it is hard to justify long-term warfarin treatment as the benefit:risk balance remains unknown; either because the risk of thromboembolism without anticoagulation remains to be clearly defined (as in the case of patients with 'lone' atrial fibrillation), or because possible benefits have not been well documented (as after transient cerebral ischemia or peripheral vascular surgery). Finally, there is the difficult problem of estimating the benefit from long-term anticoagulation after myocardial infarction. It seems that warfarin can reduce the likelihood of non-fatal reinfarction with relative safety in highly selected patients, but whether it reduces mortality, and how its effect compares with that of other, more recent, therapies aimed at preventing reinfarction, remains unknown.

Topics: Cerebrovascular Disorders; Embolism; Humans; Myocardial Infarction; Vascular Diseases; Warfarin

Topics: Adult; Angina Pectoris; Anticoagulants; Cerebrovascular Disorders; Coronary Disease; Heart Failure; Heart Valve Prosthesis; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Prothrombin Time; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Vascular Diseases; Warfarin

We investigated the impact of polyvascular disease in patients enrolled in ROCKET AF.. Cox regression models were used to assess clinical outcomes and treatment effects of rivaroxaban compared with warfarin in patients with atrial fibrillation and coronary, peripheral, or carotid artery disease, or any combination of the 3.. A total of 655 (4.6%) patients had polyvascular disease (≥2 disease locations), and 3,391 (23.8%) had single-arterial bed disease. Patients with polyvascular disease had similar rates of stroke/systemic embolism but higher rates of cardiovascular and bleeding events when compared with those without vascular disease. Use of rivaroxaban compared with warfarin was associated with higher rates of stroke in patients with polyvascular disease (hazard ratio [HR] 2.41, 95% CI 1.05-5.54); however, this was not seen in patients with single-bed (HR 0.90, 95% CI 0.64-1.28) or no vascular disease (HR 0.85, 95% CI 0.69-1.04; interaction P = .058). There was a significant interaction for major or nonmajor clinically relevant bleeding in patients with polyvascular (HR 1.23, 95% CI 0.91-1.65) and single-bed vascular disease (HR 1.30, 95% CI 1.13-1.49) treated with rivaroxaban compared with warfarin when compared with those without vascular disease (HR 0.95, 95% CI 0.87-1.04; interaction P = .0006). Additional antiplatelet therapy in this population did not improve stroke or cardiovascular outcomes.. The use of rivaroxaban compared with warfarin was associated with a higher risk of stroke and bleeding in patients with polyvascular disease enrolled in ROCKET AF. Further studies are needed to understand the optimal management of this high-risk population.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Female; Hemorrhage; Humans; Male; Outcome Assessment, Health Care; Risk Assessment; Risk Factors; Rivaroxaban; Severity of Illness Index; Stroke; Vascular Diseases; Warfarin

To determine whether computer-aided dosing of warfarin is superior to physician dosing to maintain a patient in a rehabilitation hospital within a target international normalized ratio goal.. Randomized, double-blinded, clinical trial in an inpatient rehabilitation hospital. A total of 30 consecutive patients admitted receiving warfarin were randomized to either clinician dosing or computer-aided warfarin dosing for the duration of their hospitalization. The main outcome measures included the percentage of days in a therapeutic anticoagulation range and the number of blood draws. Exclusion criteria included short length of stay (n=110, 39%) and a physician declared international normalized ratio target range of <2.0 (n=67, 23%). A total of 73 patients were excluded because of heme-positive stools at admission, recent gastrointestinal bleed, early discharge or consent refusal. Dawn AC software was used to determine warfarin dosage and frequency of blood draws to maintain a target international normalized ratio of 2.0-3.0 for the computer-dosed group (n=14). Several physicians recommended warfarin dosages for the second group (n=16). Two were dropped from the computer model secondary to lost data files for these two patients.. Computer-aided dosing of warfarin resulted in 61.7% of days within the therapeutic range (international normalized ratio, 2-3), whereas clinician dosing resulted in only 44.1%. There were no significant differences in the number of blood draws or demographic variables between the two groups.. Computers were significantly better at maintaining patients within a therapeutic international normalized ratio range than physicians. There were no significant differences in the number of recommended blood draws.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Boston; Double-Blind Method; Drug Monitoring; Drug Therapy, Computer-Assisted; Female; Humans; International Normalized Ratio; Length of Stay; Male; New York; Outcome and Process Assessment, Health Care; Rehabilitation Centers; Stroke; Vascular Diseases; Venous Thrombosis; Warfarin

To evaluate the activation of clotting systems in patients with sickle cell disease (SCD) by measuring the plasma D-dimer level and to determine the effect of low-dose warfarin on D-dimer level during vaso-occlusive crisis.. Plasma D-dimer level was measured in 65 blood samples of 37 adult patients with SCD who were hospitalized for vaso-occlusive painful crisis. D-dimer level of patients who were on low-dose warfarin was compared with those patients who were not on any anticoagulation treatment. Analysis of variance (anova) was carried out to determine factors significantly associated with low D-dimer level in patients with SCD. The following factors were included in the anova model; warfarin, homozygous hemoglobin S, history of blood transfusion in past 3 months, hydroxyurea, hemoglobin S%, hemoglobin F%, white blood cell counts, hemoglobin level, platelet count, and plasma fibrinogen level.. Overall median D-dimer level in 65 samples was 2.7 microg fibrinogen equivalent units (FEU)/mL (0.34-4). Patients who were on low-dose warfarin had a median D-dimer level of 0.81 microg FEU/mL (0.34-1.8) compared with 3.1 microg FEU/mL (0.94-4) in those patients who were not on anticoagulation treatment. Using anova to model D-dimer levels, only warfarin was significantly correlated with low D-dimer levels after controlling for other variables.. Patients with SCD during vaso-occulsive painful crisis have an elevated D-dimer level. Low-dose anticoagulation treatment is associated with a significant reduction in the D-dimer levels.

Topics: Adult; Analysis of Variance; Anemia, Sickle Cell; Anticoagulants; Blood Coagulation; Constriction, Pathologic; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Vascular Diseases; Warfarin

The results of a large prospective randomized trial have shown the efficacy of oral anticoagulation in the secondary prevention of major vascular events in patients with nonrheumatic atrial fibrillation (NRAF); less well established is the role of antiplatelet agents. The present study compared the effects of indobufen, a reversible inhibitor of platelet cyclooxygenase, with those of warfarin in this setting.. A total of 916 patients with NRAF and a recent (< or = 15 days) cerebral ischemic episode were admitted to this multicenter, randomized study, during which they were treated with either indobufen (100 or 200 mg BID) or warfarin (to obtain an international normalized ratio of 2.0 to 3.5) for 12 months. The two groups (462 on indobufen and 454 on warfarin) were well balanced in terms of their main baseline characteristics. The primary outcome of the study was the combined incidence of nonfatal stroke (including intracerebral bleeding), pulmonary or systemic embolism, nonfatal myocardial infarction, and vascular death.. At the end of follow-up, the incidence of primary outcome events was 10.6% in the indobufen group (95% confidence interval, 7.7% to 13.5%) and 9.0% in the warfarin group (95% confidence interval, 6.3% to 11.8%), with no statistically significant difference between treatments. The frequency of noncerebral major bleeding complications was low: only four cases (0.9%) of gastrointestinal bleeding were observed, all of them in the warfarin group.. We conclude that, within the limitations of its design, this study may help the medical community in devising appropriate antithrombotic strategies for NRAF patients for whom oral anticoagulants are contraindicated or do not represent a feasible approach to treatment.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Cyclooxygenase Inhibitors; Female; Follow-Up Studies; Humans; Isoindoles; Male; Middle Aged; Phenylbutyrates; Prospective Studies; Treatment Outcome; Vascular Diseases; Warfarin

We conducted a retrospective, multicenter study to compare the efficacy of warfarin with aspirin for the prevention of major vascular events (ischemic stroke, myocardial infarction, or sudden death) in patients with symptomatic stenosis of a major intracranial artery. Patients with 50 to 99% stenosis of an intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral; or basilar) were identified by reviewing the results of consecutive angiograms performed at participating centers between 1985 and 1991. Only patients with TIA or stroke in the territory of the stenotic artery qualified for inclusion in the study. Patients were prescribed warfarin or aspirin according to local physician preference and were followed by chart review and personal or telephone interview. Seven centers enrolled 151 patients; 88 were treated with warfarin and 63 were treated with aspirin. Median follow-up was 14.7 months (warfarin group) and 19.3 months (aspirin group). Vascular risk factors and mean percent stenosis of the symptomatic artery were similar in the two groups, yet the rates of major vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group (stroke rate, 10.4/100 patient-years; myocardial infarction or sudden death rate, 7.7/100 patient-years) compared with 8.4 per 100 patient-years of follow-up in the warfarin group (stroke rate, 3.6/100 patient-years; myocardial infarction or sudden death rate, 4.8/100 patient-years). Kaplan-Meier analysis showed a significantly higher percentage of patients free of major vascular events among patients treated with warfarin (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aspirin; Cerebral Angiography; Cerebral Hemorrhage; Cerebrovascular Disorders; Cohort Studies; Constriction, Pathologic; Female; Guinea Pigs; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Vascular Diseases; Warfarin

Topics: Adult; Age Factors; Aged; Blindness; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Retinal Vein; Streptokinase; Vascular Diseases; Visual Acuity; Warfarin

Arterial media calcification is an active cell process. This encompasses osteochondrogenic transdifferentiation of vascular smooth muscle cells followed by the deposition of calcium-phosphate crystals. Increasing evidence suggests a significant role for endothelial cells (ECs) in the development of arterial media calcification. This manuscript explores a role for endothelial dysfunction in the disease progression of arterial media calcification. Male rats were randomly assigned to four different groups. The first group received standard chow. The second group was given L-NAME (≈50 mg kg

Topics: Animals; Calcinosis; Calcium; Disease Progression; Endothelial Cells; Male; NG-Nitroarginine Methyl Ester; Rats; Tunica Media; Vascular Calcification; Vascular Diseases; Warfarin

Topics: Administration, Oral; Antifibrinolytic Agents; Antithrombins; Atrial Fibrillation; Consensus; Delphi Technique; Diabetes Complications; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Stroke; Vascular Diseases; Warfarin

The authors analysed oral anticoagulant agents prescribed in the postoperative period to patients after endured reconstructive operative intervention on arteries of the femorotibial segment. The study included a total of 104 patients subjected to femoropopliteal or femorotibial bypass grafting using an autologous vein or a prosthesis. Depending on the prescribed anticoagulation agent, the patients were subdivided into two groups. Group One patients (n=43) in the postoperative period received rivaroxaban, and Group Two patients (n=61) took warfarin. Efficacy of therapy was evaluated by the frequency of haemorrhage and thromboses in the early and remote postoperative periods. The findings of the immediate postoperative period demonstrated comparable rates of haemorrhagic complications, early thromboses and redo interventions in both Groups (p=0.7). The duration of long-term postoperative period varied from 3 months to 5 years. No statistically significant differences in patency of the performed reconstructions were revealed between the groups. The 3-year primary assisted patency rate in the rivaroxaban group and warfarin group amounted to 89 and 80%, respectively. The incidence of haemorrhagic complications in the postoperative period was insignificant in the studied groups. Hence, rivaroxaban may be prescribed in the early and remote postoperative period to patients who underwent open reconstructive operative intervention on arteries of the infrainguinal zone.. Проведен анализ оральных антикоагулянтных препаратов, назначенных в послеоперационном периоде больным, которым осуществлено реконструктивное оперативное вмешательство на артериях бедренно-берцового сегмента. В исследование включено 104 пациента, каждому из них проводилось бедренно-подколенное или бедренно-берцовое шунтирование с использованием аутовены или протеза. В зависимости от назначаемого антикоагулянтного препарата больные были разделены на две группы. Пациенты 1 группы (n=43) в послеоперационном периоде получали ривароксабан, пациенты 2 группы (n=61) - варфарин. Эффективность терапии оценивалась по частоте развития кровотечений и тромбозов в раннем и отдаленном послеоперационном периодах. В ближайшем послеоперационном периоде отмечен сопоставимый уровень геморрагических осложнений, ранних тромбозов и повторных вмешательств в двух группах (р=0,7). Срок наблюдения в отдаленном послеоперационном периоде составил от 3 месяцев до 5 лет. Статистически значимой разницы в проходимости выполненных реконструкций между группами не выявлено. Первичная ассистированная проходимость через 3 года в группе ривароксабана достигала 89%, в группе варфарина - 80%. Частота развития геморрагических осложнений в послеоперационном периоде была незначимой в исследуемых группах. Таким образом, ривароксабан может быть назначен в раннем и отдаленном послеоперационном периоде пациентам, которым проведено открытое реконструктивное оперативное вмешательство на артериях инфраингвинальной зоны.

Topics: Anticoagulants; Arteries; Blood Vessel Prosthesis Implantation; Femoral Artery; Humans; Lower Extremity; Popliteal Artery; Retrospective Studies; Rivaroxaban; Tibial Arteries; Treatment Outcome; Vascular Diseases; Vascular Patency; Warfarin

The quality of anticoagulation is closely associated with efficacy and safety in warfarin users. Although genetic polymorphisms have been related to warfarin dosages and vascular events(VE), genetic evaluations have not been recommended for all warfarin users. The aim is to evaluate the significance of the maintenance dose of warfarin (MDW) on VE, considering the time in therapeutic range (TTR).. This retrospective study analyzed the data of patients who received warfarin for any reasons. A total of 11,835 patients with warfarin were divided into quartiles by MDW. We assessed TTR using the Rosendaal method and VE.. VE occurred in 9.1% of the warfarin users. The mean TTR level was 34.0 ± 25.7%, and the MDW was 3.38 ± 1.06 mg per day. Patients with VE were more likely to have a lower MDW and lower TTR levels. In moderate- or well-controlled TTR status, a lower MDW was significantly related to under-controlled anticoagulation and associated with higher risks of VE. Lower MDW had a higher risk of stroke or arterial/venous thromboembolism (Q1: OR, 1.57; 95% CI 1.25 to 1.96; Q2: OR, 1.40; 95% CI 1.12 to 1.75; Q3: OR, 1.35; 95% CI 1.08 to 1.68).. We suggest that patients with very low MDW might be at risk when using warfarin. Therefore, we propose that patients with a very low MDW might be alternatively considered for novel oral anticoagulants rather than warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Vascular Diseases; Warfarin

To investigate the impact on outcomes of changing treatment guideline recommendations by comparing the proportion of patients with atrial fibrillation (AF) recommended oral anticoagulants (OACs) under the 2011 and 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines.. We used the "National Health Insurance Research Database" in Taiwan, which included 354,649 patients with AF from January 1, 1996 through December 31, 2011. Patients with a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score of 2 or more and a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) score of 2 or more were considered to have a definitive indication for receiving OACs according to the 2011 and 2014 ACC/AHA guidelines, respectively.. The percentages of patients with AF recommended OACs increased from 69.3% (n=245,598) under the 2011 guideline to 86.7% (n=307,640) under the new 2014 guidelines, an increment of 17.5% (95% CI, 17.4-17.6). Most women with AF (94.1%) and patients older than 65 years (97.2%) would receive OACs on the basis of the 2014 guidelines. Among patients previously not being recommended OACs in older guidelines, OAC use under the new guidelines was associated with a lower risk of adverse outcomes (ischemic stroke or intracranial hemorrhage or bleeding requiring blood transfusion or mortality) with an adjusted hazard ratio of 0.89 (95% CI, 0.85-0.94).. In this nationwide cohort study, use of the 2014 guidelines led more patients with AF to receive OACs for stroke prevention, and this increased OAC use was associated with better outcomes. Better efforts to implement guidelines would lead to improved outcomes for patients with AF.

Topics: Administration, Oral; Age Distribution; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; Insurance Claim Review; Intracranial Hemorrhages; Male; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Risk Assessment; Sex Distribution; Stroke; Taiwan; Vascular Diseases; Warfarin

Essentials Anticoagulation in the elderly is still a challenge and suspension of warfarin is common. This is an observational study reporting reasons and consequences of warfarin suspension. Vascular disease, age, time in therapeutic range, and bleedings are associated with suspension. After suspension for bleeding or frailty, patients remain at high-risk of death or complications.. Background Anticoagulation in elderly patients with non-valvular atrial fibrillation (NVAF) is still a challenge, and discontinuation of warfarin is common. The aim of this study was to analyze the aspects related to warfarin discontinuation in a real-world population. Methods This was an observational cohort study on very elderly NVAF patients naive to warfarin therapy (VENPAF). The included subjects were aged at least 80 years, and started using warfarin after a diagnosis of NVAF. Warfarin discontinuation was assessed, and the reason reported for discontinuation, the person who decided to stop treatment, subsequent antithrombotic therapy and mortality, ischemic and bleeding events were collected. Results Over a period of 5 years, warfarin was discontinued in 148 of 798 patients. Despite similar CHA

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Male; Multivariate Analysis; Proportional Hazards Models; Risk Factors; Stroke; Thromboembolism; Treatment Outcome; Vascular Diseases; Vitamin K; Warfarin

Spontaneous isolated superior mesenteric artery dissection is a rare disease that may cause bowel ischemia or aneurysm rupture and subsequent death. Thus, the establishment of a correct diagnosis in the early stage is quite important.. To describe the presentation of 3 patients diagnosed with spontaneous isolated supramesenteric artery dissection and briefly summarize the diagnostic procedure, treatment, and clinical course.. We experienced three cases of isolated mesenteric artery dissection in the past 5 years. A definitive diagnosis was obtained by abdominal spiral computed tomography in two cases and angiography in one case. All patients were provided anticoagulation therapy.. One patient died of bowel ischemia, 2 were discharged within 21 days without complications, and one was able to discontinue anticoagulation therapy 12 months after discharge. The remaining patient has continued warfarin, making it difficult to determine the end point of anticoagulation.

Topics: Abdominal Pain; Adult; Anticoagulants; Heparin; Humans; Male; Mesenteric Artery, Superior; Mesenteric Ischemia; Middle Aged; Rupture, Spontaneous; Tomography, Spiral Computed; Vascular Diseases; Warfarin

Warfarin, a widely used anticoagulant, is a vitamin K antagonist impairing the activity of vitamin K-dependent Bone Gla Protein (BGP or Osteocalcin) and Matrix Gla Protein (MGP). Because dabigatran, a new anticoagulant, has no effect on vitamin K metabolism, the aim of this study was to compare the impact of warfarin and dabigatran administration on bone structure and vascular calcification.. Rats with normal renal function received for 6 weeks warfarin, dabigatran or placebo. Bone was evaluated immuno-histochemically and hystomorphometrically after double labelling with declomycin and calcein. Aorta and iliac arteries were examined histologically.. Histomorphometric analysis of femur and vertebrae showed significantly decreased bone volume and increased trabecular separation in rats treated with warfarin. Vertebra analysis showed that the trabecular number was higher in dabigatran treated rats. Osteoblast activity and resorption parameters were similar among groups, except for maximum erosion depth, which was higher in warfarin treated rats, suggesting a higher osteoclastic activity. Therefore, warfarin treatment was also associated with higher bone formation rate/bone surface and activation frequency. Warfarin treatment may cause an increased bone turnover characterized by increased remodelling cycles, with stronger osteoclast activity compared to the other groups. There were no differences among experimental groups in calcium deposition either in aortic or iliac arteries.. These findings suggest for the first time that dabigatran has a better bone safety profile than warfarin, as warfarin treatment affects bone by reducing trabecular size and structure, increasing turnover and reducing mineralization. These differences could potentially result in a lower incidence of fractures in dabigatran treated patients.

Topics: Animals; Anticoagulants; Antithrombins; Aorta; Bone and Bones; Bone Diseases, Metabolic; Bone Remodeling; Calcinosis; Dabigatran; Female; Fractures, Spontaneous; Iliac Artery; Kidney; Minerals; Osteoblasts; Osteoclasts; Random Allocation; Rats; Rats, Sprague-Dawley; Vascular Diseases; Vitamin K; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Calcinosis; Female; Hip; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Radiography; Renal Dialysis; Vascular Diseases; Warfarin

Mesenteric venous thrombosis (MVT) is a rare but life threatening form of bowel ischemia. It is implicated in 6%-9% of all cases of acute mesenteric ischemia. The proportion of patients with primary (or idiopathic) MVT varies from 0% to 49%, with a decrease in frequency secondary to more recent availability of newer investigations for hypercoagulability. The presence of factor V Leiden (FVL) and prothrombin G20210A mutations (PGM) have been well documented in these cases. However, there have been scarce case reports describing MVT in heterozygotes of both these mutations occurring simultaneously and its implications on long term management. Our case describes acute MVT in a previously asymptomatic young patient with no prior history of venous thromboembolism. The patient was found to be heterozygous for FVL and PGM and treated with lifelong anticoagulation with warfarin (goal international normalized ratio: 2-3) and avoidance of hormonal contraceptives.

Topics: Activated Protein C Resistance; Anticoagulants; Blood Coagulation; DNA Mutational Analysis; Factor V; Female; Genetic Predisposition to Disease; Heterozygote; Humans; International Normalized Ratio; Ischemia; Mesenteric Ischemia; Mesenteric Vascular Occlusion; Mesenteric Veins; Mutation; Phenotype; Phlebography; Prothrombin; Tomography, X-Ray Computed; Vascular Diseases; Venous Thrombosis; Warfarin; Young Adult

This unfortunate patient case highlights the problems with "overdiagnosis" of HIT. Despite "positive" tests for HIT antibodies, the low pretest probability for HIT and the known propensity of patients with APS to yield false-positive HIT antibody results suggests that the patient did not have a true diagnosis of HIT. Moreover, the early administration of warfarin and the choice of argatroban for parenteral anticoagulation when monitoring was hindered by a prolonged baseline aPTT likely play a key factor in the progression of UE DVT to VLG. Ironically, the problems of anticoagulant monitoring posed by the prolonged baseline aPTT likely contributed to the subsequent overanticoagulation and fatal pulmonary hemorrhage. With benefit of hindsight, avoiding the temptation to test for HIT in a low pretest probability situation, and treatment with either heparin using anti-factor Xa monitoring or with non-aPTT-monitored therapy such as LMWH or fondaparinux would likely have resulted in a more favorable clinical course.

Topics: Anticoagulants; Antiphospholipid Syndrome; Arginine; Diagnostic Errors; Drug Monitoring; Fatal Outcome; Female; Gangrene; Hemorrhage; Humans; Lung Diseases; Middle Aged; Pipecolic Acids; Sulfonamides; Thrombocytopenia; Upper Extremity; Vascular Diseases; Warfarin

Vascular access site complications are among the most frequently observed complications after catheter ablation of atrial fibrillation (AF). We sought to determine whether implementation of a three-point strategy would reduce major vascular complications resulting from catheter ablation of atrial fibrillation.. Three hundred twenty-four consecutive patients undergoing catheter ablation of AF were studied: 162 in each group (with and without the test strategy). The three-point test strategy included the following: (1) performing the procedure on Warfarin with an INR from 2.0 to 3.5 (mean INR of 2.44), rather than stopping Warfarin prior to the procedure and bridging the patient back to Warfarin with low molecular heparin, (2) using a small 21 G needle to obtain femoral vein access rather than a larger 18 G needle, and (3) eliminating the use of femoral arterial access. Major vascular complications were defined as complications requiring either blood transfusion or surgical/percutaneous repair.. Major vascular complications were identified in 6/162 (3.7%) of the control patients without the strategy listed above compared to 0/162 (0%) in the test patients with implementations of this strategy (p = 0.03). The frequency of other complications was comparable between the two groups (tamponade requiring drainage: 1/162 control, 1/162 test; pericardial effusion not requiring drainage: 0/162 control, 1/162 test; transient ischemic attack: 1/162 control and 1/162 test; stroke: 1/162 control, 0/162 test): (p = NS for each).. A three-point strategy including performing procedures with therapeutic Warfarin, using a small gauge needle to obtain vascular access and eliminating femoral arterial access significantly reduced major vascular access complications and did not affect other major complications, during catheter ablation of AF. Implementation of this strategy may be useful to reduce groin complications resulting from AF ablation.

Topics: Anticoagulants; Atrial Fibrillation; Blood Transfusion; Catheter Ablation; Female; Femoral Vein; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Needles; Postoperative Complications; Punctures; Treatment Outcome; Vascular Diseases; Warfarin

To determine the warfarin maintenance dose in Iranian patients.. This multicenter study was conducted between January 2007 and January 2008 in 5 different large cities of Iran. Patients older than 12 years receiving warfarin were included. During the first days of warfarin use, international normalized ration (INR) was measured daily and after that every 1-2 weeks, with a duration of at least one month. The warfarin dose was considered to be stabilized if the INR remained unchanged on 3 consecutive measurements at a level between 2-3. Then mean dose of the last 3 warfarin doses was calculated.. One hundred and fifty patients receiving warfarin took part in this study. No significant differences were noted in the mean warfarin dosage among the 5 cities, and between men and women (p=0.228). The warfarin daily dose and INR did not shown any statistical difference between men and women. The warfarin dose statistically decreased in patients older than 60 years old (p=0.004 versus 45-60 years, and p=0.002 versus 30-45 years). This study showed that the required mean warfarin dose in Iranian patients was approximately 4 mg to achieve an INR between 2-3.. Considering geographic and ethnic differences of Iranian patients, attention to the dose determination of warfarin is of importance.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Body Mass Index; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Iran; Male; Middle Aged; Reference Values; Retrospective Studies; Vascular Diseases; Warfarin; Young Adult

Portal vein complications after liver transplantation (LT) are serious complications that can lead to graft liver failure. Although the treatment of interventional radiology (IVR) by means of balloon dilatation for portal vein stenosis (PVS) after LT is an effective method, the high rate of recurrent PVS is an agonizing problem. Anticoagulant therapy for PVS is an important factor for preventing short-term recurrence following IVR, but no established regimen has been reported for the prevention of recurrent PVS following IVR. In our population of 197 pediatric patients who underwent living donor liver transplantation (LDLT), 22 patients (22/197, 11.2%) suffered PVS. In the 9 earliest patients, unfractionated heparin was the only anticoagulant therapy given following IVR. In the 13 more recent patients, 3-agent anticoagulant therapy using low-molecular-weight heparin, warfarin, and aspirin was employed. In the initial group of 9 patients, 5 patients (55.6%) suffered recurrent PVS and required repeat balloon dilatation. Among the 13 more recent patients, none experienced recurrent PVS (P = 0.002). In conclusion, our 3-agent anticoagulant therapy following IVR for PVS in pediatric LDLT can be an effective therapeutic strategy for preventing recurrent PVS.

Topics: Adolescent; Adult; Anticoagulants; Aspirin; Catheterization; Child; Child, Preschool; Constriction, Pathologic; Drug Therapy, Combination; Female; Heparin, Low-Molecular-Weight; Humans; Infant; Liver Transplantation; Living Donors; Male; Portal Vein; Postoperative Complications; Radiology, Interventional; Regional Blood Flow; Retrospective Studies; Secondary Prevention; Treatment Outcome; Ultrasonography; Vascular Diseases; Warfarin; Young Adult

Atrial fibrillation prophylaxis with warfarin and strong antiplatelet agent use in cardiovascular diseases has increased the incidence of anticoagulation in the elderly. We studied traumatic intracranial hemorrhage (TICH) in patients ≥55 years of age on anticoagulation and antiplatelet agents in a stable population.. We used a Level 1 Trauma Center registry study comparing TICH in patients on anticoagulation drugs during the index periods 1999 to 2000 (T1) and 2007 to 2008 (T2).. A total of 526 TICH patients were seen in T1 and T2 (age, 77.6 vs 77.5 years; not significant [NS]), with the rate doubling from 6.2% to 12.3% of all trauma activations (P < .01). There was no increase in atrial fibrillation, warfarin use, or CHADS(2) scores in atrial fibrillation patients on anticoagulation therapy. TICH in patients taking antiplatelet agents increased 5-fold (2.2 % vs 10.3%; P < .01). Overall TICH mortality rate was the same (12.4% vs 12.2%, NS). TICH mortality among patients on therapeutic warfarin was greater in T1 (26%; P < .05), but mortality was similar to TICH in patients not on anticoagulants in T2 (19% vs 12.2%, NS), suggesting treatment improved. Prevalence and mortality of TICH in patients on antiplatelet agents were similar to TICH in patients on warfarin.. TICH in patients on anticoagulants is epidemic in patients ≥55 years of age. Despite national trends, our well-served population has not seen an increase in warfarin use for atrial fibrillation. Instead, use of antiplatelet agents has increased and is associated with an increased incidence of TICH.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Disease Outbreaks; Female; Humans; Incidence; Intracranial Hemorrhage, Traumatic; Male; Middle Aged; Platelet Aggregation Inhibitors; Prevalence; Registries; Vascular Diseases; Warfarin

We describe a case of rapid onset of vascular calcification coincident with the initiation of warfarin therapy in a kidney transplant recipient. Calcification developed within the media of the blood vessel wall, with relative intimal sparing. Medium and small arteries were affected; however, the aorta was mostly free of calcifications, suggesting a differential response to warfarin between the intima and media and between different vascular beds. In addition, unlike the highly calcified native kidney's vessels, the kidney allograft was not calcified, suggesting local genetically determined mechanisms in preventing vascular calcification. Distal subcutaneous necrosis ultimately led to the patient's death.

Topics: Anticoagulants; Atrial Fibrillation; Calcinosis; Fatal Outcome; Humans; Kidney Transplantation; Male; Middle Aged; Tomography, X-Ray Computed; Tunica Intima; Tunica Media; Vascular Diseases; Warfarin

Many hemodialysis patients receive antiplatelet therapy or warfarin; however, little is known about the effect of this on iron requirements. Given the association of antiplatelet therapy with bleeding we hypothesized that there should be a greater need for iron in such patients, which we tested in this study.. Retrospective 1-year cohort study of 205 chronic hemodialysis patients. The primary outcome variable was total iron dose, which was analyzed according to antiplatelet/warfarin use. Data were also collected on potential confounders, allowing for both unadjusted and adjusted (multiple regression) analysis.. 97/205 patients received antiplatelet/warfarin therapy. This group was older, with a higher incidence of macrovascular disease and diabetes and a higher median C-reactive protein (6.0 vs. 3.75 mg/l). Overall, median iron requirement was 1,300 mg/year. In a multiple regression analysis, antiplatelet/warfarin use was associated with an additional iron requirement of 703 mg (95% confidence interval 188-1,220 mg), with the strongest effect observed in patients with normal inflammatory markers.. We found a high requirement for iron in patients receiving antiplatelet agents/warfarin. We argue that the most likely mechanism for this association is chronic, low-grade blood loss, although further study is required before causality can be established.

Topics: Age Factors; Aged; Anemia, Iron-Deficiency; C-Reactive Protein; Comorbidity; Diabetic Nephropathies; Female; Ferric Compounds; Ferritins; Hemorrhage; Humans; Inflammation; Iron; Iron Deficiencies; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Requirements; Platelet Aggregation Inhibitors; Renal Dialysis; Retrospective Studies; Thrombophilia; Transferrin; Vascular Diseases; Warfarin

Isolated systolic hypertension is associated with increased elastase activity, vascular calcification, and vascular stiffness. We sought to determine the importance of elastase activity and matrix degradation in the development of elastocalcinosis.. Elastocalcinosis was induced in vivo and ex vivo using warfarin. Hemodynamic parameters, calcium deposition, elastin degradation, transforming growth factor (TGF)-beta signaling, and elastase activity were evaluated at different time points in the in vivo model. Metalloproteinases, serine proteases, and cysteine proteases were blocked to measure their relative implication in elastin degradation. Gradual elastocalcinosis was obtained, and paralleled the elastin degradation pattern. Matrix metalloproteinase (MMP)-9 activity was increased at 5 days of warfarin treatment, whereas TGF-beta signaling was increased at 7 days. Calcification was significantly elevated after 21 days. Blocking metalloproteinases activation with doxycycline and TGF-beta signaling with SB-431542 were able to prevent calcification.. Early MMP-9 activation precedes the increase of TGF-beta signaling, and overt vascular elastocalcinosis and stiffness. Modulation of matrix degradation could represent a novel therapeutic avenue to prevent the gradual age-related stiffening of large arteries, leading to isolated systolic hypertension.

Topics: Animals; Aorta, Abdominal; Calcinosis; Collagen; Disease Models, Animal; Durapatite; Elastin; Femoral Artery; Male; Matrix Metalloproteinase 9; Osteopontin; Rats; Rats, Wistar; Signal Transduction; Transforming Growth Factor beta; Vascular Diseases; Warfarin

Isolated systolic hypertension results from a gradual stiffening of large arteries, to which medial elastocalcinosis (calcification of elastic lamellae) contributes. There is compelling evidence that reactive oxygen species (ROS) are associated with several disease processes affecting the cardiovascular system, including hypertension. The present study was designed to investigate whether the inhibition of ROS production by alpha-lipoic acid can prevent vascular calcification. Sprague-Dawley rats were treated with warfarin (20 mg/kg/day) and vitamin K (15 mg/kg/day) (WVK) for 4 weeks to induce large artery calcification. Subgroups received either a normal diet or a diet supplemented with lipoic acid (1000 mg/kg/day). The WVK treatment produced a small elevation of aortic superoxide levels that did not reach statistical significance. Alpha-lipoic acid reduced the elevation below baseline levels. In rats treated with alpha-lipoic acid, the WVK-induced elevation of pulse wave velocity (an index of arterial stiffness), left ventricular hypertrophy, and aortic, femoral and carotid elastocalcinosis were not prevented. Although a contribution of oxidative stress has been suggested in the aging cardiovascular system, this alteration does not appear to contribute to the calcification process and the subsequent stiffening of large arteries in the animal model tested.

Topics: Animals; Arteries; Calcinosis; Dietary Fats; Hypertrophy, Left Ventricular; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxides; Thioctic Acid; Vascular Diseases; Vitamin K; Warfarin

Topics: 1-Carboxyglutamic Acid; Anticoagulants; Atherosclerosis; Calcinosis; Humans; Immunohistochemistry; Vascular Diseases; Warfarin

Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin.. To determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular disease.. Recent and usual food intakes were assessed in 115 patients receiving warfarin; and corresponding plasma phylloquinone (vitamin K(1)), serum triglyceride concentrations, prothrombin time (PT), and International Normalized Ratio (INR) were determined. A factor analysis was used to examine the association of specific foods and biochemical variables with anticoagulant data.. Mean age was 59 +/- 15 years. Inadequate anticoagulation, defined as values of INR 2 or 3, was found in 48% of the patients. Soybean oil and kidney beans were the primary food sources of phylloquinone intake. Factor analysis yielded four separate factors, explaining 56.4% of the total variance in the data set. The factor analysis revealed that intakes of kidney beans and soybean oil, 24-h recall of phylloquinone intake, PT and INR loaded significantly on factor 1. Triglycerides, PT, INR, plasma phylloquinone, and duration of anticoagulation therapy loaded on factor 3.. Fluctuations in phylloquinone intake, particularly from kidney beans, and plasma phylloquinone concentrations were associated with variation in measures of anticoagulation (PT and INR) in a Brazilian group of patients with vascular disease.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Diet; Factor Analysis, Statistical; Female; Humans; International Normalized Ratio; Male; Middle Aged; Prothrombin Time; Surveys and Questionnaires; Triglycerides; Vascular Diseases; Vitamin K 1; Warfarin

Inappropriate prescribing encompasses acts of commission i.e. giving drugs that are contraindicated or unsuitable, and acts of omission i.e. failure to prescribe drugs when indicated due to ignorance of evidence base or other irrational basis e.g. ageism. There are considerable published data on the prevalence of inappropriate prescribing; however, there are no recent published data on the prevalence of acts of omission. The aim of this study was to calculate the prevalence of acts of prescribing omission in a population of consecutively hospitalised elderly people.. A screening tool (screening tool to alert doctors to the right treatment acronym, START), devised from evidence-based prescribing indicators and arranged according to physiological systems was prepared and validated for identifying prescribing omissions in older adults. Data on active medical problems and prescribed medicines were collected in 600 consecutive elderly patients admitted from the community with acute illness to a teaching hospital. On identification of an omitted medication, the patient's medical records were studied to look for a valid reason for the prescribing omission.. Using the START list, we found one or more prescribing omissions in 57.9% of patients. In order of prevalence, the most common prescribing omissions were: statins in atherosclerotic disease (26%), warfarin in chronic atrial fibrillation (9.5%), anti-platelet therapy in arterial disease (7.3%) and calcium/vitamin D supplementation in symptomatic osteoporosis (6%).. Failure to prescribe appropriate medicines is a highly prevalent problem among older people presenting to hospital with acute illness. A validated screening tool (START) is one method of systematically identifying appropriate omitted medicines in clinical practice.

Topics: Age Factors; Aged; Aged, 80 and over; Atherosclerosis; Atrial Fibrillation; Calcium; Dietary Supplements; Evidence-Based Medicine; Guideline Adherence; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mass Screening; Osteoporosis; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prevalence; Vascular Diseases; Warfarin

The metabolic syndrome (MetS) is a cluster of risk factors linked to insulin resistance that increase an individual's risk of atherosclerotic vascular disease. The authors evaluated the prevalence and prognosis of the MetS among individuals with symptomatic intracranial arterial stenosis.. Patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease trial were evaluated in this post-hoc analysis. Baseline characteristics and outcome were compared in patients with the MetS vs patients without the MetS.. Among 476 patients, the prevalence of the MetS was 43%. MetS patients were more likely to be younger, female, and white. During a mean follow-up period of 1.8 years, time to the first of ischemic stroke, myocardial infarction, or vascular death was shorter among patients with the MetS with a hazard ratio (syndrome/no syndrome) of 1.6 (95% CI = 1.1 to 2.4, p = 0.0097). Time to ischemic stroke alone was also shorter among patients with the MetS with a hazard ratio (syndrome/no syndrome) of 1.7 (95% CI = 1.1 to 2.6, p = 0.012). When controlling for individual factors of the definition, MetS was not significant (combined outcome: p = 0.14; ischemic stroke: p = 0.074).. The metabolic syndrome is present in about half of individuals with symptomatic intracranial atherosclerotic disease and is associated with a substantially higher risk of major vascular events. The metabolic syndrome may not provide additional ability to predict outcomes beyond the individual factors for patients with intracranial stenosis.

Topics: Aged; Aspirin; Brain Ischemia; Cohort Studies; Comorbidity; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Humans; Incidence; Intracranial Arteriosclerosis; Male; Metabolic Syndrome; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Racial Groups; Randomized Controlled Trials as Topic; Risk; Risk Factors; Survival Analysis; Vascular Diseases; Warfarin

Topics: Adult; Anticoagulants; Heparin; Humans; Risk Factors; Thromboembolism; Travel; Vascular Diseases; Warfarin

Rituximab, a chimeric monoclonal CD20 antibody, is useful in the treatment of B-cell lymphomas and certain autoimmune diseases. We report a successful outcome of rituximab for life threatening hypercoagulable state associated with lupus anticoagulant (LA). A 30-year-old woman initially presented 10 years ago with DVT and positive serology for SLE and LA. While on Coumadin, she suffered from recurrent DVT in the legs and arms, pulmonary emboli, Budd-Chiari syndrome, mesenteric vein thrombosis, bone infarcts, recurrent strokes, and chronic ITP. All measures including plasmapheresis and monthly IV cyclophosphamide were of no benefit. She was recently admitted with spontaneous subdural hematoma with INR of 3.8. Upon discontinuation of anticoagulation for surgical drainage, she developed acute abdomen from thrombosis and recurrent DVT. Because she had failed prior standard measures, 4 weekly infusions of rituximab (375 mg/m2) were given following 2 rounds of plasmapheresis. Subsequently, she made a remarkable recovery over the next month and has been free of thrombosis on Coumadin for over 15 months. LA, IgM antibodies to cardiolipin, and B2GP1 were consistently positive. After rituximab therapy, LA became negative and IgM antibodies to cardiolipin decreased and ITP went into remission. Rituximab induced a lasting remission in a woman suffering from life-threatening hypercoagulable state associated with LA. Her clinical remission was associated with disappearance of LA.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Autoantibodies; Critical Illness; Disease-Free Survival; Female; Humans; Lupus Coagulation Inhibitor; Recurrence; Remission Induction; Rituximab; Thrombophilia; Treatment Failure; Vascular Diseases; Warfarin

Causes of gross hematuria in a patient with end-stage renal disease are limited compared with those in patients with normal renal function. Given the increased likelihood of patients with end-stage renal disease developing renal cell carcinoma, the workup focuses on a careful evaluation of the collecting system. The workup for gross hematuria in a renal transplant recipient is similar; however, the focus shifts toward a more thorough evaluation of the transplanted kidney and bladder because immunosuppression increases the overall risk for malignancy. An immunosuppressed patient also is at risk for infectious processes in the transplanted kidney manifesting as gross hematuria. Concerns for chronic rejection also should be investigated, although microscopic hematuria is more common in this scenario. If this is unrevealing, then close scrutiny of the native kidneys for possible sources of bleeding is warranted. We present an interesting and unusual cause of painless gross hematuria in a patient with end-stage renal disease and transplant nephrectomy 3 months before the onset of bleeding.

Topics: BK Virus; Diagnosis, Differential; Embolization, Therapeutic; Fistula; Graft Rejection; Hematuria; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nephrectomy; Nephritis; Polyomavirus Infections; Postoperative Complications; Renal Artery; Renal Dialysis; Suture Techniques; Thrombosis; Tumor Virus Infections; Urinary Fistula; Urologic Neoplasms; Valsalva Maneuver; Vascular Diseases; Warfarin; Weight Lifting

To identify factors that may influence the function, outcome, and complications associated with tunneled hemodialysis catheters.. Radiology reports and hemodialysis, medical, and Clinical Information System (computerized patient medical record system) records were retrospectively reviewed in 221 consecutive patients who underwent tunneled hemodialysis catheter placement by interventional radiologists between January 11, 1996 and January 13, 2000 at Dartmouth-Hitchcock Medical Center. Various patient characteristics (diabetes, smoking, hypertension, age, sex, atherosclerotic cardiovascular disease, history of cardiac catheterization, coumadin use, functional status, and obesity) were assessed for their relationship to the outcome of hemodialysis catheters. Catheter outcome was examined by calculating infection rate, thrombosis rate, fibrin formation rate, mechanical malfunction rate, and total complication rate. With these patient characteristics and outcome variables, multiple regression analysis was performed with STATA (College Station, TX) statistical analysis software.. Of the 221 patients reviewed, 39 patients were lost to follow-up. Among the remaining 182 patients, 427 catheters were placed for a total number of 36994 catheter-days. For overall complication rate, multiple regression analysis revealed a statistically significant positive correlation only for hypertension (P =.032). Total complication rate was 0.76 events per 100 catheter-days (95% CI: 0.53-1.00) for patients with a documented history of hypertension and 0.27 events per 100 catheter-days (95% CI: 0.08-0.45) for patients without (P =.024, paired student t test). For patients with diabetes versus patients without, the infection rates were 0.34 episodes per 100 catheter-days (95% CI: 0.15-0.53) and 0.12 episodes per 100 catheter-days (95% CI: 0.06-0.18), respectively, (P =.011, paired student t test). Thrombosis rate for patients on coumadin was 0.13 events per 100 catheter-days (95% CI: -0.14-0.40), while thrombosis rate for patients not taking coumadin was 0.03 events per 100 catheter-days (95% CI: 0-0.05) (P =.036, paired student t test).. Hypertension is a risk factor for poor outcome of tunneled hemodialysis catheters as measured by total complication rate requiring catheter removal or exchange. In this retrospective study, no other specific risk factors predicted an increased need for removal or exchange of tunneled hemodialysis catheters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiac Catheterization; Catheterization; Catheters, Indwelling; Diabetes Complications; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Obesity; Predictive Value of Tests; Regression Analysis; Renal Dialysis; Retrospective Studies; Risk Factors; Sex Factors; Smoking; Treatment Outcome; Vascular Diseases; Warfarin

Isolated systolic hypertension is the predominant form of hypertension in the elderly population. Reduction of arterial compliance appears to contribute to the elevation of pulse pressure (PP) and among potential mechanisms, gradual vascular calcification, fragmentation of elastic lamellae, and augmentation of rigid component like collagen could contribute to increase aortic stiffening. Few experimental models of the disease are currently available.. To induce large artery calcification, rats were treated with warfarin and vitamin K(1) (WK) for 4 and 8 weeks, to inhibit the maturation of matrix Gla protein. The impact of chronic PP elevation was determined on large artery and cardiac remodeling and on aortic endothelial function.. The WK treatment led to aortic medial calcification and a proportional elevation of PP, attributable mainly to a selective elevation of systolic blood pressure. The chronic treatment also increased collagen, whereas elastin decreased in the aorta. Pulse wave velocity, an index of aortic stiffening, increased in rats treated with WK. However, indices of left ventricular and aortic hypertrophy and remodeling remained normal. In addition, the WK treatment did not modify the vasoconstriction to norepinephrine and endothelin-1, and the vasodilatory response to acetylcholine and sodium nitroprusside.. Chronic treatment with WK represents a new model of isolated systolic hypertension with several characteristics of the human disease. The relative ease to induce calcification in this model may help to foster more fundamental research, which is lacking in this type of hypertension.

Topics: Animals; Anticoagulants; Antifibrinolytic Agents; Aorta; Calcinosis; Calcium; Collagen; Disease Models, Animal; Drug Administration Schedule; Elastin; Hemodynamics; Hypertension; Male; Rats; Rats, Wistar; Renin; Systole; Vascular Diseases; Vasomotor System; Vitamin K 1; Warfarin

Aside from anecdotal reports, there are few data on the risk of thrombotic complications in patients in whom use of warfarin and aspirin is discontinued perioperatively for cutaneous operation.. Our aim was to present a large case series of thrombotic complications resulting from this practice and to estimate the incidence of these events.. A total of 504 members of the American College of Mohs Micrographic Surgery and Cutaneous Oncology were surveyed regarding thrombotic complications when blood thinners were withheld perioperatively to ascertain the frequency of these complications and to describe associated morbidity and mortality.. A total of 168 responding physicians reported 46 patients who experienced thrombotic events. Of these patients, 54% (25 of 46) experienced the event when warfarin was withheld and 39% (18 of 46) when aspirin use was discontinued. Thrombotic events included 24 strokes, 3 cerebral emboli, 5 myocardial infarctions, 8 transient ischemic attacks, 3 deep venous thromboses, 2 pulmonary emboli, and 1 retinal artery occlusion leading to blindness. Three deaths were reported. Calculation of incidence yielded an estimated thrombotic risk of 1 event per 12,816 operations, 1 in 6219 operations when use of warfarin was discontinued and 1 in 21,448 when aspirin was withheld.. With no documented increase in severe hemorrhagic complications during continued use perioperatively of blood thinners, these data provide a compelling argument to maintain patients on medically necessary blood thinners during cutaneous operation. All relevant clinical facts must be weighed when making this decision.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Mohs Surgery; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Complications; Stroke; Vascular Diseases; Warfarin

Vascular complications are frequent in long-term dialysis patients. The differential diagnosis is complex and includes immunological derangement (underlying disease, uremia), vasculopathic-atheroembolic diseases, calciphylaxis, infections, neoplasm, coagulation disorders, and adverse drug effects.. We report on a 50-year-old male patient with a long follow-up on renal replacement therapy (20 years), currently on daily hemodialysis. The patient's history of kidney transplantation was complicated by seven acute rejection episodes and by Kaposi sarcoma; comorbidity included HLA-B27 positive ankylosing spondylitis, diffuse vascular disease, recurrent atrial fibrillation, chronic hypotension, HCV positivity. Ten days after the start of warfarin for an atrial fibrillation episode, the patient developed digital necrotising ulcerations, rapidly evolving into partial symmetric digital gangrene at distal phalanxes. The timing and evolution of the lesions and the finding of protein S deficiency were the clues for diagnosing warfarin-induced skin necrosis (WISN); the drug was discontinued and therapy with low-molecular weight heparin, plasma and prostacyclin achieved slow resolution of lesions.. According to a combined MEDLINE and EMBASE search, this is the first report of WISN in a hemodialysis patient: underlining the clinical relevance of this uncommon problem, this case exemplifies the difficult differential diagnosis of acute vascular skin lesions in dialysis

Topics: Anticoagulants; Databases as Topic; Diagnosis, Differential; Dialysis; Fingers; Gangrene; HLA-B27 Antigen; Humans; Male; Middle Aged; Necrosis; Renal Replacement Therapy; Skin; Spondylitis, Ankylosing; Vascular Diseases; Warfarin

The present experiments were carried out to test the hypothesis that arterial calcification is linked to bone resorption by determining whether the selective inhibition of bone resorption with osteoprotegerin will inhibit arterial calcification. In the first test, arterial calcification was induced by treating 22-day-old male rats with warfarin, a procedure that inhibits the gamma-carboxylation of matrix Gla protein and causes extensive calcification of the arterial media. Compared with rats treated for 1 week with warfarin alone, rats treated with warfarin plus osteoprotegerin at a dose of 1 mg/kg per day had dramatically reduced alizarin red staining for calcification in the aorta and in the carotid, hepatic, mesenteric, renal, and femoral arteries, and they had 90% lower levels of calcium and phosphate in the abdominal aorta (P<0.001) and in tracheal ring cartilage (P<0.01). More rapid arterial calcification was induced by treating 49-day-old male rats with toxic doses of vitamin D. Treatment for 96 hours with vitamin D caused widespread alizarin red staining for calcification in the aorta and the femoral, mesenteric, hepatic, renal, and carotid arteries, and osteoprotegerin completely prevented calcification in each of these arteries and reduced the levels of calcium and phosphate in the abdominal aorta to control levels (P<0.001). Treatment with vitamin D also caused extensive calcification in the lungs, trachea, kidneys, stomach, and small intestine, and treatment with osteoprotegerin reduced or prevented calcification in each of these sites. Measurement of serum levels of cross-linked N-teleopeptides showed that osteoprotegerin dramatically reduced bone resorption activity in each of these experiments (P<0.001). Therefore, we conclude that doses of osteoprotegerin that inhibit bone resorption are able to potently inhibit the calcification of arteries that is induced by warfarin treatment and by vitamin D treatment. These results support the hypothesis that arterial calcification is linked to bone resorption.

Topics: Animals; Arteries; Bone Resorption; Calcinosis; Collagen; Collagen Type I; Drug Antagonism; Glycoproteins; Lung; Male; Osteoprotegerin; Peptides; Rats; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Trachea; Vascular Diseases; Vitamin D; Warfarin

The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel

Topics: Aging; Animals; Anticoagulants; Aorta; Aortic Diseases; Arteries; Calcinosis; Drug Combinations; Drug Synergism; Male; Rats; Rats, Sprague-Dawley; Time Factors; Vascular Diseases; Vitamin D; Warfarin

To determine the effect of daily consultation by a team of hospital pharmacists on the accuracy and rapidity of optimizing warfarin therapy.. Comparison of a historical control cohort with a prospective cohort matched for treatment indication.. A 400-bed university teaching hospital.. Sixty consecutive patients hospitalized in 1992 and starting warfarin for the first time, with anticoagulation therapy managed by physicians, were compared with 60 patients matched for warfarin indication hospitalized in 1995, but with anticoagulation therapy managed with pharmacy consultation.. Pharmacist management of initial warfarin therapy resulted in a significant reduction in the length of hospitalization compared with physician dosing, from 9.5 +/- 5.6 days to 6.8 +/- 4.4 days (p = 0.009). The number of patients and patient-days with international normalized ratio (INR) values >3.5 were reduced by pharmacist dosing from 37 patients and 142 days to 16 patients and 29 days, respectively (p < 0.001). Similarly, the number of patients and patient-days with INR >6.0 were reduced from 20 patients and 50 days to two patients and six days, respectively (p < 0.001). There were six documented bleeding complications in 1992 compared with one in 1995 (p = 0.11). The mean INR at discharge was significantly lower in the pharmacy surveillance group, 2.6 +/- 0.58, compared with the physician cohort, 3.3 +/- 2.1 (p = 0.07). Readmissions after discharge due to bleeding or recurrent thrombosis were reduced from five (at 1 mo) and 10 (at 3 mo) to two and five readmissions, respectively, by pharmacist intervention (p = 0.43). The number of patients with concurrently prescribed drugs known to significantly interact with warfarin was significantly lower (6 vs. 13; p = 0.02) in the pharmacy surveillance group.. Among patients starting warfarin for the first time, daily consultation by a pharmacist significantly decreased the length of hospital stay and the number of patients who received excessive anticoagulation therapy. These findings translate into improved quality of care and potentially significant cost savings.

Topics: Anticoagulants; Cohort Studies; Drug Monitoring; Female; Hospital Costs; Humans; Inpatients; Length of Stay; Male; Managed Care Programs; Middle Aged; Patient Care Team; Patient Discharge; Pharmacists; Pharmacy Service, Hospital; Referral and Consultation; Vascular Diseases; Warfarin

Warfarin is a 4-hydroxycoumarin anticoagulant drug used for the prevention and management of thromboembolic and vascular diseases. It acts through the inhibition of the vitamin K-dependent transcarboxylation reactions that convert precursors of clotting factors into their active form. Appropriate use of warfarin requires patient monitoring and dosage adjustments, to ensure its safety and efficacy. The aim of this work was to clarify the relationship between traditional (prothrombin time, usually expressed as the international normalized ratio; INR) and alternative (clotting factors II and X) warfarin response markers to establish their usefulness for therapeutic drug monitoring. Seventy adult outpatients, aged between 31 and 86 years old, were involved in the study. All subjects received warfarin in a monotherapy regimen and had been on a stable dosing schedule for at least two weeks to assure a steady-state condition. A total of 81 prothrombin times (expressed as INR), and factor II and factor X activity were simultaneously determined. Eleven patients presented repeated measurements at different time periods under the same dosing regimen. The results obtained from regression and cluster analysis showed a close relationship between factors II and X (r = 0.73), a weak correlation between INR and both factor II (r = -0.35) and factor X (r = -0.36), and a very slight dependency between warfarin and the response markers used. In addition, it seems that independent of the selected response marker, in long-term warfarin therapy, reproducible responses can be obtained over time if a steady-state condition is achieved. The coefficients of variation for factors II and X were greater (35.44 and 37.93%, respectively) than INR (14.50%), indicating that INR is a more precise measure than either factor II or factor X. In conclusion, INR appears to be the most appropriate warfarin response marker for therapeutic drug monitoring due to its universality, objectivity as a direct physiological effect measurement, and the available information regarding appropriate endpoints. However, when INR values are not in accordance with patient response therapy, factor II and factor X should be considered as an alternative to optimize warfarin therapy.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Biomarkers; Dose-Response Relationship, Drug; Drug Monitoring; Factor X; Female; Humans; Male; Middle Aged; Prothrombin; Prothrombin Time; Sensitivity and Specificity; Thromboembolism; Treatment Outcome; Vascular Diseases; Warfarin

High doses of warfarin cause focal calcification of the elastic lamellae in the media of major arteries and in aortic heart valves in the rat. Aortic calcification was first seen after 2 weeks of warfarin treatment and progressively increased in density at 3, 4, and 5 weeks of treatment. By 5 weeks, the highly focal calcification of major arteries could be seen on radiographs and by visual inspection of the artery. The calcification of arteries induced by warfarin is similar to that seen in the matrix Gla protein (MGP)-deficient mouse, which suggests that warfarin induces artery calcification by inhibiting gamma-carboxylation of MGP and thereby inactivating the putative calcification-inhibitory activity of the protein. Warfarin treatment markedly increased the levels of MGP mRNA and protein in calcifying arteries and decreased the level of MGP in serum. Warfarin treatment did not affect bone growth, overall weight gain, or serum calcium and phosphorus levels, and, because of the concurrent administration of vitamin K, prothrombin times and hematocrits were normal. The results indicate that the improved warfarin plus vitamin K treatment protocol developed in this study should provide a useful model to investigate the role of MGP in preventing calcification of arteries and heart valves.

Topics: Animals; Arteries; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Heart Valve Diseases; Male; Matrix Gla Protein; Rats; Rats, Sprague-Dawley; Vascular Diseases; Vitamin K; Warfarin

The effect of sulphinpyrazone administration on the anticoagulant response was investigated in five patients receiving long-term treatment with warfarin. Sulphinpyrazone caused a rapid increase in prothrombin (PT) ratio in all five patients and warfarin dose had to be reduced by a mean of 46% to maintain the PT ratio in the therapeutic range. PT ratio and daily warfarin requirement returned to previous levels when sulphinpyrazone was ceased. Warfarin protein binding was not altered during sulphinpyrazone administration and sulphinpyrazone added to plasma in vitro did not increase warfarin free fraction. The average racemic plasma warfarin concentration over a dosage interval when adjusted for warfarin dose was not altered by sulphinpyrazone administration. The most likely mechanism for this drug interaction is a stereoselective effect of sulphinpyrazone on the metabolism of the warfarin enantiomers.

Topics: Aged; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Protein Binding; Prothrombin Time; Sulfinpyrazone; Vascular Diseases; Warfarin

The incidence of positive ethanol gelation test (EGT) after addition of brinase (a proteolytic enzyme preparation from Aspergillus oryzae) to anticoagulated and non-anticoagulated human plasma was studied. In vitro addition of brinase to plasma causes positive EGT, and the incidence is dose-dependent. In plasma from warfarin-treated patients and/or after addition of heparin to plasma, prior to the addition of brinase, a significantly reduced incidence of positive EGT is observed. The incidence is lowest after heparin. Gels formed in the presence of heparin are easier susceptible to enzymatic degradation than those formed in the absence of heparin.

Topics: Blood Coagulation Tests; Brinolase; Ethanol; Fibrin; Fibrinogen; Gels; Heparin; Humans; Peptide Hydrolases; Time Factors; Vascular Diseases; Warfarin

Topics: Acetaminophen; Anemia, Aplastic; Anticoagulants; Aspirin; Blood Platelets; Bone Marrow; Capillary Fragility; Drug Hypersensitivity; Drug Synergism; Hemorrhagic Disorders; Hemostasis; Heparin; Heparin Antagonists; Humans; Indenes; Platelet Adhesiveness; Purpura; Thrombocytopenia; Vascular Diseases; Warfarin

Topics: Adult; Aged; Anticoagulants; Arteries; Arteriosclerosis; Coronary Disease; Ethyl Biscoumacetate; Female; Follow-Up Studies; Humans; Leg; Long-Term Care; Male; Middle Aged; Phenindione; Prognosis; Thrombosis; Vascular Diseases; Warfarin

Topics: Adult; Age Factors; Aged; Angiography; Blood Vessel Prosthesis; Diabetes Complications; Dicumarol; Female; Femoral Artery; Fluorocarbon Polymers; Follow-Up Studies; Heparin; Humans; Iliac Artery; Intermittent Claudication; Ischemia; Leg; Male; Methods; Middle Aged; Popliteal Artery; Postoperative Complications; Sex Factors; Thrombosis; Transplantation, Autologous; Transplantation, Homologous; Vascular Diseases; Veins; Warfarin

The outcome of 185 consecutive autogenous vein bypass grafts for femoro-popliteal occlusions carried out between January 1962 and June 1968 has been reviewed. One patient died at operation and 21 late deaths have occurred since. The overall five-year patency was 61.5%, but was much lower when the popliteal-tibial runoff arteries were diseased. Distal anastomosis of the graft to the popliteal artery below the level of the knee joint also impaired the results, and if this was performed with a graft of minimal diameter less than 5 mm. sustained patency was obtained in only a quarter of the limbs. Nevertheless, where major amputation was imminent owing to advanced ischaemia three out of four limbs were salvaged.

Topics: Adult; Aged; Arteriosclerosis; Electrocardiography; Female; Femoral Artery; Follow-Up Studies; Humans; Ischemia; Male; Middle Aged; Phenindione; Popliteal Artery; Postoperative Complications; Transplantation, Autologous; Vascular Diseases; Veins; Warfarin

Topics: Adult; Angiography; Ataxia; Carotid Arteries; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Subclavian Steal Syndrome; Vascular Diseases; Vertebral Artery; Vertigo; Warfarin

Topics: Diverticulum; Gastrointestinal Hemorrhage; Gastrostomy; Humans; Jejunum; Male; Middle Aged; Vascular Diseases; Vitamin K; Warfarin

Topics: Adult; Collateral Circulation; Exercise Therapy; Female; Humans; Male; Middle Aged; Vascular Diseases; Warfarin

Topics: Anticoagulants; Coronary Disease; Dicumarol; Heart Defects, Congenital; Heart Valve Diseases; Intracranial Arteriosclerosis; Phlebitis; Pulmonary Emphysema; Thromboembolism; Toxicology; Vascular Diseases; Warfarin

Topics: Blood Coagulation Tests; Cerebrovascular Disorders; Coronary Disease; Crystallization; Dosage Forms; Drug Therapy; Toxicology; Vascular Diseases; Warfarin

Topics: Coumarins; Humans; Peripheral Vascular Diseases; Urticaria; Vascular Diseases; Warfarin