Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four hemodialysis patients (1 male and 3 females, aged 29-40 years) with unusual recurrent vascular access or dialyzer thrombosis were studied to find out whether a hypercoagulable state exists. Measurements of euglobulin clot lysis time (ELT), fibrinogen, antithrombin III (AT III), protein C (PC), protein S (PS), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) were done. Results indicated that all patients had prolonged ELT, low tPA, elevated PAI, normal AT III, and PS. Three patients had elevated fibrinogen level and two had low PC. Danazol 200 mg orally once a day effectively prevented any further thrombosis. In 4 weeks' time, all the abnormal coagulation studies normalized in addition to elevation of AT III, PC and PS. Only 1 female patient had a prolonged menstrual period, which was reversed by lowering the daily dose of danazol to 100 mg. No other side effects were encountered. These data indicate that hypofibrinolysis may play a major role in vascular access or dialyzer thrombosis and that low-dose danazol may provide an effective prophylaxis and treatment. Larger controlled studies are needed to confirm these findings.
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PMID:Low-dose danazol for vascular access and dialyzer thrombosis in hemodialysis patients. 152 23

The lupus anticoagulant may be accompanied by an acquired factor II deficiency and bleeding. We report on a patient with a lupus anticoagulant and factor II (Fll) deficiency responsive to Danazol. Acquired hypoprothrombinemia (FII) with the lupus anticoagulant (LA) may be accompanied by a hemorrhagic diathesis. A 64-year-old male with discoid lupus erythematosis bled after an intestinal polypectomy. His FII level was 18%, and his FII antigen level was 20%. Danazol (D) (600 mg per day) administration was associated with a rise in FII activity and antigen to 50% within 10 days. The patient underwent abdominal surgery. We studied the effect(s) of D on the FII level and on other coagulation factors in this patient. The patient's plasma FII antigen had a single precipitin arc compared to the two peaks of normal plasma on counterimmunoelectrophoresis with Ca++. The samples pre- and during D therapy had the same positively charged arc as normal samples, although they were quantitatively different. Neuraminidase treatment demonstrated a decrease in the positively charged migration of normal and the patient's FII antigen. Affinity chromatography of normal and patient plasma on a Sepharose protein A column revealed FII antigen present in the patient's bound fraction. The relative percentages of bound FII before and during D treatment were similar. During D therapy, levels of FIX and X rose 50-100%, and protein C rose 20-25%, while free protein S did not change. D is an effective therapy for acquired FII deficiency associated with LA. D does not affect the binding of Ig to FII, but D raises FII levels by increasing synthesis of the FII protein.
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PMID:Acquired hypoprothrombinemia: effects of danazol treatment. 894 70

Danazol, a synthetic attenuated anabolic steroid, has been administered for 36 months to a 32 year old male with hereditary Protein S (PS) deficiency who had become non-compliant for warfarin therapy. The patient has an eleven year history of venous thrombosis. Since danazol therapy was initiated, the patient has not experienced a thrombotic event or adverse side-effects. Levels of PS, other inhibitors, fibrinolytic components, and markers for thrombin and platelet activation were measured prior and subsequent to therapy. Following danazol administration, marked and sustained increases were noted in Free Protein S, Antithrombin, and Protein C. Platelet CD62 (P-selectin) positivity which was elevated before therapy, decreased to assay threshold limits within five weeks. Both Prothrombin Fragment 1.2 and thrombin-antithrombin complexes were elevated post danazol therapy indicating continued clearance of generated thrombin. These data suggest that the protective effect provided by danazol in this patient with hereditary PS deficiency, may in large part be due to suppression of platelet activation by thrombin inhibition than simply through elevation of PS.
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PMID:Efficacy of danazol in a patient with congenital protein-S deficiency: paradoxical evidence for decreased platelet activation with increased thrombin generation. 930 21