Immune Bernard Soulier-like syndrome associated with anti-glycoprotein-IX antibody.
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Biomedical subjects
Publications and source records attributed to S N Gitel.
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Dental extraction in patients receiving long-term oral anticoagulant therapy is a controversial issue. Continuation of anticoagulation exposes the patient to serious hemorrhage, whereas cessation of therapy increases the risk of thromboembolism. Forty patients treated by coumarin underwent 63 tooth extractions, without a change in the therapeutic protocol of anticoagulation. The biologic adhesive Beriplast was used successfully to achieve local hemostasis at the site of the surgical wound. Apart from one patient who had mild oozing, there were no incidences of postsurgical hemorrhage.
A multiphase intervention trial based on education, implementation of criteria, and restriction, aimed at modifying the established clinical policy of mandatory preoperative screening for coagulation abnormalities, was carried out on five surgical wards of a general hospital. The education period did not influence the ordering of partial thromboplastin time tests, despite a significant posteducational change in surgeons' attitudes. In contrast, administrative restriction of coagulation test orders led to a 50% decline on four of the five study wards. We conclude that an educational intervention followed by administrative restriction may be considered an acceptable means of overcoming clinician reluctance to change well-established but redundant clinical policy.
Antibodies that recognize unmodified heparin bound to positively charged macromolecules have been obtained by immunizing rabbits with a methylated bovine serum albumin-heparin precipitate. These antibodies have been used to develop an immunoassay that can quantitate heparin at a concentration of 5 ng/ml in buffer solutions, and at a concentration of 25 ng/ml in plasma without pretreatment of the sample. The specificity of the antibodies is such that they do not recognize other glycosaminoglycans and are able to distinguish among different commercial heparin samples that are otherwise indistinguishable by specific anticoagulant activity or molecular weight distribution.
Thromboembolic obstruction to three major components of the circulation--arterial, venous and intravascular foreign surfaces--contributes to premature death and disability in Western society. In many, but not all, of these conditions associated with thromboembolism, heparin and warfarin are the drugs of choice. It is the purpose of this presentation to provide some common ground in the area of anticoagulant prophylaxis that will be of intrinsic value for decision making in cardiac, cerebral and peripheral vascular disease. Only those aspects of the hemostatic mechanism most relevant to the antithrombotic action of heparin and warfarin are discussed. Assays for both drugs as well as some practical guidelines for their use in low, medium and high dose regimens are outlined. Techniques for improving the benefit/risk ratio for each drug are specifically detailed.
Protein-heparin complexes, prepared by a water-soluble carbodiimide coupling technique, were used to produce anti-heparin antibodies in rabbits. Antiserums that recognized carbodiimide-treated heparin, but not untreated heparin, were obtained. Carbodiimide-treated heparan sulfate exhibited 10% to 20% cross-reactivity compared with a similarly treated heparin, whereas there was no cross-reactivity with five other carbodiimide-treated mucopolysaccharides. 3H-1-ethyl-3-(3-trimethylammoniumpropyl) carbodiimide iodide was used to demonstrate that carbodiimide forms a stable adduct with heparin and other mucopolysaccharides. Using an antibody fraction that eluted from 1-ethyl-3-(3-trimethylammoniumpropyl) carbodiimide iodide-treated heparin-Sepharose with 2 mol/L KI, it was demonstrated that, for the antibody population studied, the addition of one carbodiimide per heparin molecule resulted in complete epitope expression without loss of anticoagulant activity. The addition of up to eight additional carbodiimide molecules to heparin did not increase the extent of epitope formation, although anticoagulant activity was lost. Except for heparan sulfate, the addition of radiolabeled carbodiimide to other mucopolysaccharides did not result in epitope formation. These data demonstrate that antibodies to an epitope derived from heparin can be formed, that the epitope is fully expressed while anticoagulant activity is present, and that the antibody is specifically directed against an altered portion of the polysaccharide.
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Heparin and warfarin are antithrombotic agents effective against venous thrombosis as well as pulmonic and systemic emboli. They can exert a favorable effect on mortality and morbidity in a diverse group of illnesses associated with thrombosis. Proper use of these agents will increase their efficacy and diminish the risk of serious hemorrhage.
The antimetabolite 6-azauridine blocks the de novo synthesis of pyrimidines and causes increased serum levels of several amino acids including homocystine. 6-Azauridine was was withdrawn from clinical use for the treatment of psoriasis because of the occurence of arterial and venous thromboembolic episodes in some psoriatic patients. Utilizing a standard animal model for the recognition of venous and arterial thrombosis, 6-azauridine was demonstrated in this study to cause thrombosis without producing homocystinemia when administered orally or intravenously.
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This investigation was undertaken to identify and correlate one factor that makes patients undergoing total hip replacement more susceptible to venous thrombosis and pulmonary embolism than those who have almost any other elective orthopaedic procedure, and to determine why the operation of total hip replacement has proved to be relatively resistant to antithrombotic prophylaxis compared with general surgical procedures. Using the depletion of antithrombin III as a marker of activation of the coagulation system, two groups of patients were compared: twenty-one who were subjected to hip arthroplasty and fourteen who underwent general surgical procedures. Both during and after operation the decrease in the quantity of antithrombin III in hip-arthroplasty patients was significantly greater (p less than 0.05) than the decrease in general surgical patients. Seventy-three per cent of hip-replacement patients had venographic evidence of recent thrombosis, 60 per cent of which were discontinuous femoral-vein thrombi. Femoral-vein thrombosis occurs frequently in hip-arthroplasty patients and is relatively resistant to current antithrombotic prophylaxis. The data presented suggest that during hip surgery there is a strong systemic activation of the clotting cascade that is associated with local vessel injury and local stasis in the femoral vein, an association not found in most general surgical procedures.
An animal model for the production of stasis thrombi was employed to obtain the data reported in this study. Rabbits treated with warfarin (1.5 mg/kg/day) exhibited a maximal increase in prothrombin time and decreases in factor VII, factor X, and prothrombin within 48 hr with no additional changes occurring after 10 days of drug administration. In contrast, Xa inhibitory activity was unchanged after 48 hr of warfarin treatment but was significantly increased by the tenth day. When thrombosis was induced by infusions of 60 micrograms of tissue thromboplastin, the warfarin regimen produced an antithrombotic effect by the sixth hour, which increased to significance by day 2 and was further significantly increased by day 10. These three stages correspond to the initial depletion of the vitamin K-dependent clotting factors, the maximal depletion of these proteins, and the maximal increase in Xa inhibitory activity, respectively. Thus these experiments separate the antithrombotic potential of warfarin into two components: an early effect related to the decrease in factor VII and a delayed augmentation of Xa inhibitory acticity. Intravenous heparin alone (5 U/kg) did not protect against infusions of 60 micrograms of tissue thromboplastin but did provide an antithrombotic effect against 45 micrograms of the same infusate. Higher doses of heparin, however, did protect against infusion of 60 micrograms of tissue thromboplastin. After 48 hr of warfarin treatment, 5 U/kg heparin increased protection against 60 micrograms of tissue thromboplastin to a degree equivalent to that provided after 10 days of warfarin therapy alone.
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Estrogen-containing compounds are thrombogenic in man. The extent of thrombosis is dose-related, but a measure of this thrombogenicity is not currently available. Evidence is presented, using an animal model of venous thrombosis, that impaired Xa inhibitory activity (the rate of reaction between Xa and antithrombin III) correlates with the development of thrombosis initiated by thrombin in rabbits receiving an oral contraceptive compound. The responses in the clotting assay and in the extent of thrombosis are dose-related. The hypercoagulable state induced by oral contraceptives can be completely reversed by trace amounts of heparin.