warfarin and Hyperhomocysteinemia

Venous thromboembolism (VTE) is a chronic disease with a 30% ten-year recurrence rate. The highest incidence of recurrence is in the first 6 months. Active cancer significantly increases the hazard of early recurrence, and the proportions of time on standard heparin with an APTT ≥ 0.2 anti-X(a) U/mL, and on warfarin with an INR ≥ 2.0, significantly reduce the hazard. The acute treatment duration does not affect recurrence risk after treatment is stopped. Independent predictors of late recurrence include increasing patient age and body mass index, leg paresis, active cancer and other persistent VTE risk factors, idiopathic VTE, antiphospholipid antibody syndrome, antithrombin, protein C or protein S deficiency, hyperhomocysteinemia and a persistently increased plasma fibrin D-dimer. A recommendation for secondary prophylaxis should be individualized based on the risk for recurrent VTE (especially fatal pulmonary embolism) and bleeding. The appropriateness of secondary prophylaxis should be continuously reevaluated, and the prophylaxis stopped if the benefit no longer exceeds the risk.

Topics: Age Factors; Anticoagulants; Antiphospholipid Syndrome; Body Mass Index; Chronic Disease; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Hyperhomocysteinemia; International Normalized Ratio; Neoplasms; Paresis; Protein C Deficiency; Protein S Deficiency; Recurrence; Risk Factors; Time Factors; Venous Thromboembolism; Warfarin

The association between the progestin-only pill used for treatment of menstrual disorders and central venous sinus thrombosis (CVST) has rarely been reported in the literature. This report describes a case of central venous sinus thrombosis following intake of norethindrone acetate for dysfunctional uterine bleeding secondary to polycystic ovary syndrome in a young woman with undiagnosed underlying hyperhomocysteinemia.. A 23-year-old woman presented with severe headache, followed by hemiparesis, seizures, and altered sensorium. She had been prescribed norethindrone acetate for the management of dysfunctional uterine bleeding secondary to polycystic ovary syndrome. Investigations revealed acquired hyperhomocysteinemia, presumably due to nutritional deficiencies, and evidence of CVST on MRI and magnetic resonance venography. Investigations showed no evidence of inherited thrombophilia. The patient was treated with low molecular weight heparin, followed by warfarin, vitamin B12, vitamin B6, and folic acid, and recovered successfully.. Although venous thrombosis is usually linked to the ingestion of estrogen, rather than progestogen, this case illustrates that patients who are prescribed progestogen-only pills for gynaecological disorders may develop thrombosis, especially if they have predisposing metabolic disorders.

Topics: Contraceptives, Oral, Synthetic; Female; Heparin, Low-Molecular-Weight; Humans; Hyperhomocysteinemia; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Menorrhagia; Norethindrone; Nutrition Disorders; Polycystic Ovary Syndrome; Sinus Thrombosis, Intracranial; Treatment Outcome; Warfarin; Young Adult

In the mid-19th century, Virchow identified hypercoagulability as part of the triad leading to venous thrombosis, but the specific causes of hypercoagulability remained a mystery for another century. The first specific cause to be identified was antithrombin III deficiency. Many other causes of thrombophilia, both genetic and acquired, have been discovered since then. The 2 most common genetic causes of thrombophilia are the Leiden mutation of factor V and the G20210A mutation of prothrombin. The most common acquired cause is antiphospholipid syndrome. These factors increase the relative risk of an initial episode of venous thromboembolism (VTE) by a factor of 2 to 10, but the actual risk remains relatively modest. Therefore, thrombophilia screening to prevent initial episodes of VTE is not indicated, except possibly in women with a family history of idiopathic VTE who are considering oral contraceptive therapy. Some physicians screen for thrombophilia to aid decision making concerning the duration of anticoagulant therapy. However, several studies have demonstrated that, with the exception of antiphospholipid syndrome, thrombophilia does not significantly increase the risk of recurrent VTE. On the other hand, idiopathic VTE significantly increases the risk of recurrence in patients with or without thrombophilia.

Topics: Anticoagulants; Factor V; Humans; Hyperhomocysteinemia; Mass Screening; Recurrence; Risk Assessment; Risk Factors; Thromboembolism; Thrombophilia; Vitamin K; Warfarin

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

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

Cerebral venous thrombosis is relatively rare and characterized by a wide spectrum of clinical features. It is more common in young adults with women affected more than men. The diagnosis of cerebral venous thrombosis is easier nowadays due to easy access to advanced neuroimaging techniques. Abnormalities in thrombophilic profile are associated with enhanced risk of cerebral venous thrombosis. It has varied etiologies such as hypercoagulable states, infection, dehydration, pregnancy, and substance abuse. Hyperhomocysteinemia is found to be closely associated with an enhanced risk of cerebral venous thrombosis.. Here we report a case of cerebral venous thrombosis secondary to hyperhomocysteinemia caused by vitamin B. There are conflicting reports in the literature about the association of hyperhomocysteinemia, B

Topics: Adult; Anticoagulants; Anticonvulsants; Brain; Diuretics, Osmotic; Glycerol; Heparin; Humans; Hyperhomocysteinemia; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Mannitol; Seizures; Valproic Acid; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex; Warfarin

We report a case of Hughes-Stovin syndrome (HSS) associated with hyperhomocysteinemia. A 24-year-old man who has no clinical features suggestive of Behcet's disease was admitted for hemoptysis and dyspnea. Radiological and laboratory evaluation revealed multifocal pulmonary artery aneurysms involving bilateral segmental pulmonary artery, thrombi in right atrium and ventricle, and hyperhomocysteinemia. Accordingly, HSS associated with hyperhomocysteinemia was diagnosed, and the clinical and radiological improvement was achieved after treatment with prednisolone, warfarin, and folic acid.

Topics: Anti-Inflammatory Agents; Anticoagulants; Dyspnea; Folic Acid; Hematinics; Hemoptysis; Humans; Hyperhomocysteinemia; Male; Prednisolone; Syndrome; Treatment Outcome; Warfarin; Young Adult

Livedoid vasculopathy is an idiopathic, chronic disorder manifested by painful, purpuric macules on the lower extremities that superficially ulcerate, resulting in atrophic, stellate scars with peripheral telangiectasias and hyperpigmentation.. A 50-year-old man presented with recurrent, painful ulcerations on the medial aspect of his malleoli and calves. The clinical presentation, histologic findings, and results of laboratory evaluation confirmed the diagnosis of livedoid vasculopathy in this case. Despite being refractory to treatment with multiple other medications, the lesions responded dramatically to oral warfarin sodium therapy.. Treatment with warfarin may be a beneficial therapy for patients with livedoid vasculopathy.

Topics: Anticoagulants; Biopsy; Cryoglobulinemia; Cryoglobulins; Diagnosis, Differential; Fibrinogens, Abnormal; Follow-Up Studies; Humans; Hyperhomocysteinemia; Male; Middle Aged; Skin; Skin Diseases, Vascular; Warfarin

Topics: Anticoagulants; Cystathionine beta-Synthase; Factor V; Genetic Predisposition to Disease; Genetic Testing; Homocysteine; Humans; Hyperhomocysteinemia; Ischemic Attack, Transient; Methylenetetrahydrofolate Reductase (NADPH2); Platelet Activation; Platelet Aggregation; Polymorphism, Genetic; Prognosis; Protein S Deficiency; Prothrombin; Secondary Prevention; Stroke; Thrombophilia; Warfarin

We describe a family in which four generations (eight members) had deep vein thrombosis of the lower limb and three of the alive members had documented hyperhomocysteinemia. In addition, one of the family members had evidence of arterial thrombosis in the form of cerebral infarcts. Interestingly, all affected members in the family were males.

Topics: Adult; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Nitroprusside; Pedigree; Venous Thrombosis; Vitamin B 12; Warfarin

Although hyperhomocysteinemia is an established risk factor for venous thromboembolism there is no consensus for routine determination of circulating homocysteine in the UK, either at the beginning or end of oral anticoagulation therapy. The purpose of this study was to evaluate the prevalence of hyperhomocysteinemia and its relationship to folate and vitamin B12 status in subjects with venous thromboembolism 4 weeks after discontinuation of warfarin therapy. In 78 consecutively recruited patients, plasma homocysteine was significantly higher (p < 0.001) and red cell folate significantly lower (p = 0.03) than in controls. Plasma vitamin B12 was similar in both groups. Strikingly, 38.5% of patients had hyperhomocysteinemia (> 15 micromol/l). Retrospective analysis revealed a significant positive association between plasma total homocysteine and duration of warfarin therapy (p < 0.001) but a negative, though non-significant (p = 0.06), trend with warfarin dose. The results do not suggest any direct interaction between warfarin and plasma homocysteine but raise the possibility of reduced intake of a common food source of folate and vitamin K. One possibility is the shortage of green-leafy vegetables since patients are often advised to limit their intake of this major source of vitamin K. On the basis of this study we suggest that homocysteine screening should be carried out at the time that patients begin warfarin therapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Folic Acid; Genotype; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Retrospective Studies; Substance Withdrawal Syndrome; Thromboembolism; Vitamin B 12; Warfarin

We describe a 36-year-old man with familial protein S deficiency and homozygosity to the methylene tetrahydrofolate reductase (MTHFR) thermolabile variant who had a stroke followed by an episode of idiopathic osteonecrosis that was successfully managed by surgical core decompression. The patient's symptomatic thrombophilia, as well as that of several of his first-degree relatives who also had thrombotic events, raises the possibility that the thrombophilia was a contributing factor to the development of his osteonecrosis.

Topics: Adult; Anticoagulants; Femur Head; Folic Acid; Humans; Hyperhomocysteinemia; Magnetic Resonance Imaging; Male; Osteonecrosis; Paresis; Pedigree; Protein S Deficiency; Radiography; Stroke; Thromboembolism; Thrombophilia; Warfarin