vitamin-k-semiquinone-radical and Antithrombin-III-Deficiency

The families of eight unrelated patients were studied with regard to a hereditary deficiency in antithrombin III (ATIII), protein C, or protein S. These deficiencies were recognized in the course of investigations for deep-vein thrombosis (DVT) in the eight patients. A group of 31 individuals (patients and family members), mostly less than 40-year-old was explored. Two cases of AT III deficiency were discovered, as well as 21 of protein C deficiency, and seven of protein S. Ten of the 30 have had recurrent venous thrombosis at the time of bedrest, trauma, surgery, pregnancy, postpartum or during oral contraceptive treatment. Spontaneous DVT occurred in three cases. Seventeen patients had remained asymptomatic till then. Such patients need antithrombotic treatment during surgery or pregnancy. Prophylactic treatment with enoxaparin in one patient (deficiency in protein C) during her second pregnancy is discussed. It seems that low molecular weight heparin may be a safe alternative to unfractionated heparin. Oral anticoagulants are efficient in preventing reoccurring venous thromboembolism in patients with AT III deficiency. The questions of whether oral anticoagulants should be continued in the long-term in patients with protein C or protein S deficiency who have had a DVT, and whether asymptomatic deficient patients should be given any antithrombotic treatment outside circumstances likely to induce a DVT, remain as yet unanswered.

Topics: Adolescent; Adult; Antithrombin III; Antithrombin III Deficiency; Blood Coagulation Disorders; Child; Female; Glycoproteins; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pedigree; Protein C; Protein C Deficiency; Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Antithrombin III Deficiency; Chromogenic Compounds; Factor X; Factor Xa; Heparin; Humans; Indenes; Vitamin K

Topics: Adult; Aged; Anticoagulants; Antithrombin III Deficiency; Blood Coagulation Tests; Critical Care; Drug Interactions; Hematoma; Hemorrhage; Humans; Middle Aged; Vitamin K

Topics: Antithrombin III Deficiency; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Fibrinolysis; Hemostasis; Humans; Neoplasms; Thrombosis; Vitamin K

Topics: Adult; Anticoagulants; Antithrombin III; Antithrombin III Deficiency; Factor IX; Hematoma; Humans; Male; Muscular Diseases; Mutation; Phenprocoumon; Protein Precursors; Venous Thrombosis; Vitamin K

Topics: Anticoagulants; Antithrombin III Deficiency; Disease-Free Survival; Genetic Predisposition to Disease; Hemorrhage; Humans; Incidence; Pedigree; Protein C Deficiency; Protein S Deficiency; Recurrence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K

Hereditary deficiencies of protein S, protein C and antithrombin are known risk factors for first venous thromboembolism. We assessed the absolute risk of recurrence, and the contribution of concomitant thrombophilic defects in a large cohort of families with these deficiencies. Annual incidence of recurrence was estimated in 130 deficient patients, with separate estimates for those with each of protein S, protein C, and antithrombin deficiency, and in eight non-deficient patients with prior venous thromboembolism. All patients were also tested for factor V Leiden, prothrombin G20210A, high levels of factors VIII, IX and XI, and hyperhomocysteinemia. There were 81 recurrent events among 130 deficient patients. Median follow-up was 4.6 years. Annual incidences (95% confidence interval) of recurrent venous thromboembolism were 8.4% (5.8-11.7) for protein S deficiency, 6.0% (3.9-8.7) for protein C deficiency, 10.0% (6.1-15.4) for antithrombin deficiency, and overall 7.7% (6.1-9.5). Relative risk of recurrence in patients with a spontaneous versus provoked first event was 1.5 (0.95-2.3). Cumulative recurrence rates at 1, 5 and 10 years were 15%, 38% and 53%. Relative risk of recurrence with concomitant defects was 1.4 (0.7-2.6) (1 defect) and 1.4 (0.8-2.7) (> or =2 defects). Annual incidence was 1.0% (0.03-5.5) in eight non-deficient patients. Annual incidence of major bleeding in deficient patients on oral anticoagulant treatment was 0.5% (0.2-1.0). We conclude that patients with a hereditary protein S, protein C or antithrombin deficiency appear to have a high absolute risk of recurrence. This risk is increased after a first spontaneous event, and by concomitance of other thrombophilic defects.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III Deficiency; Disease-Free Survival; Female; Genetic Predisposition to Disease; Hemorrhage; Humans; Incidence; Male; Middle Aged; Pedigree; Protein C Deficiency; Protein S Deficiency; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K; Young Adult

This article discusses the management of venous thromboembolism (VTE) and thrombophilia, as well as the use of antithrombotic agents, during pregnancy and is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that benefits do, or do not, outweigh risks, burden, and costs. Grade 2 recommendations are weaker and imply that the magnitude of the benefits and risks, burden, and costs are less certain. Support for recommendations may come from high-quality, moderate-quality or low-quality studies; labeled, respectively, A, B, and C. Among the key recommendations in this chapter are the following: for pregnant women, in general, we recommend that vitamin K antagonists should be substituted with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) [Grade 1A], except perhaps in women with mechanical heart valves. For pregnant patients, we suggest LMWH over UFH for the prevention and treatment of VTE (Grade 2C). For pregnant women with acute VTE, we recommend that subcutaneous LMWH or UFH should be continued throughout pregnancy (Grade 1B) and suggest that anticoagulants should be continued for at least 6 weeks postpartum (for a total minimum duration of therapy of 6 months) [Grade 2C]. For pregnant patients with a single prior episode of VTE associated with a transient risk factor that is no longer present and no thrombophilia, we recommend clinical surveillance antepartum and anticoagulant prophylaxis postpartum (Grade 1C). For other pregnant women with a history of a single prior episode of VTE who are not receiving long-term anticoagulant therapy, we recommend one of the following, rather than routine care or full-dose anticoagulation: antepartum prophylactic LMWH/UFH or intermediate-dose LMWH/UFH or clinical surveillance throughout pregnancy plus postpartum anticoagulants (Grade 1C). For such patients with a higher risk thrombophilia, in addition to postpartum prophylaxis, we suggest antepartum prophylactic or intermediate-dose LMWH or prophylactic or intermediate-dose UFH, rather than clinical surveillance (Grade 2C). We suggest that pregnant women with multiple episodes of VTE who are not receiving long-term anticoagulants receive antepartum prophylactic, intermediate-dose, or adjusted-dose LMWH or intermediate or adjusted-dose UFH, followed by postpartum anticoagulants (Grade 2C). For those pregnant women with prior VTE who are receiving l

Topics: Antibodies, Antiphospholipid; Antithrombin III Deficiency; Aspirin; Evidence-Based Medicine; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Assessment; Risk Factors; Thrombophilia; Venous Thromboembolism; Vitamin K

The anticoagulant activities of Tissue Factor Pathway Inhibitor (TFPI), heparin and hirudin were compared in intrinsic (APTT) and extrinsic (PT) activated clotting assays. In contrast to the thrombin inhibitor hirudin, heparin was 10 fold more potent in the APTT assay than in the PT assay, indicating that inhibition of intrinsic activation is important for the anticoagulant activity of heparin as measured in an APTT assay. TFPI was most potent in the PT assay and the effect of TFPI was most pronounced in the presence of other anticoagulants (heparin and hirudin). The activities of the two natural anticoagulants antithrombin III (ATIII) and TFPI were compared in a PT assay with very dilute tissue factor. In this assay system TFPI in normal plasma affected the clotting time more than ATIII in the plasma. However, when heparin was added ATIII was the major anticoagulant, but profound prolongation of the clotting time was only seen when TFPI was also added. In an ATIII deficient plasma heparin did not augment the effect of TFPI, showing that the increased effect of TFPI in the presence of heparin is dependent on the anticoagulant activity of ATIII/heparin. The effect of TFPI at prolonged clotting times was also illustrated by the significant effect of blocking TFPI in the plasma from warfarin-treated patients. Thus TFPI is a major anticoagulant in normal plasma and the effect of TFPI is especially seen at prolonged clotting times.

Topics: Anticoagulants; Antithrombin III Deficiency; Blood Coagulation Tests; Drug Synergism; Heparin; Hirudins; Humans; Lipoproteins; Vitamin K

Topics: Aged; Antithrombin III Deficiency; Cerebral Hemorrhage; Heparin; Humans; Male; Thromboembolism; Vitamin K

Antithrombin III is a well-known coagulation inhibitor. Its heterozygous deficit is demonstrated through concentrations reduced about by 50 p. 100. On a clinical level, about 40 p. 100 to 70 p. 100 patients present with deep venous thrombosis (visceral on the whole) and pulmonary embolisms from puberty. There are both qualitative and quantitative deficits, these appearing to be mostly frequent. Only calculation of activity in the presence of heparin (co-factor of heparin) enables to diagnose these two types of deficits. Treatment performed includes both AT III concentrated agents and heparin in severe cases. Recurrences prevention is performed thanks to antivitamins K. If surgical treatment or delivery, a prevention of any incidents thanks to a vicarious therapy (AT III concentrated agent) is to be used.

Topics: Adult; Anticoagulants; Antithrombin III Deficiency; Blood Coagulation Disorders; Female; Humans; Male; Pedigree; Pregnancy; Thrombophlebitis; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Aged; Anticoagulants; Antithrombin III Deficiency; Female; Genes, Dominant; Humans; Indenes; Male; Middle Aged; Pedigree; Thromboembolism; Vitamin K

Topics: Aged; Antithrombin III; Antithrombin III Deficiency; Female; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Middle Aged; Pedigree; Thrombosis; Vitamin K

In a 7 year-old girl presenting with nephrotic syndrome and repeated episodes of thrombosis, a decrease in antithrombin III and in vitro inactivity of heparin were observed. Treatment by vitamin K antagonists prevented further thromboembolic episodes.

Topics: Antithrombin III Deficiency; Child; Female; Humans; Nephrotic Syndrome; Recurrence; Thrombosis; Vitamin K

Topics: Antithrombin III Deficiency; France; Heparin; Humans; Infant; Male; Pedigree; Thromboembolism; Vitamin K