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)

Factors and inhibitors of coagulation and fibrinolysis were investigated on admission in 57 patients with acute leukaemia and they were correlated to the occurrence of haemorrhage. Coagulation disturbances were found in 98%. Seventeen of the patients with haemorrhagic symptoms had major bleeding. Severe thrombocytopenia (< 20 x 10(9)/l) was found in 16%. Patients with major bleedings had significantly lower concentrations of prothrombin complex, fibrinogen, protein C and platelets. Low levels of antiplasmin and fibrinogen were characteristic of 'bleeders' with promyelocytic and lymphoblastic leukaemia. We found a positive correlation between vWF:Ag and leukaemic cell count especially in lymphoblastic leukaemia (ks = 0.72). Reduced levels of antithrombin indicated a poorer prognosis.
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PMID:Bleeding complications and coagulopathy in acute leukaemia. 140 6

Patients with acute leukemia undergoing remission induction chemotherapy occasionally develop venous thrombosis despite severe thrombocytopenia and in the absence of disseminated intravascular coagulation. This observation prompted us to study the levels of the naturally occurring anticoagulant proteins C and S prospectively in patients undergoing remission induction chemotherapy for acute leukemia. Plasma samples from 50 adult patients with acute leukemia (34 AML, 16 ALL) were analyzed for protein C antigen, functional protein C, immunologic total and free protein S as well as levels of C4b binding protein (C4bBP). Plasma levels of immunologic protein C were significantly lower in patients with active acute myelocytic leukemia (mean = 77.9) than in controls (mean = 123.6) or patients in remission (mean = 132). Functional protein C levels were also significantly lower in AML patients with active disease (mean = 58.5) than controls (mean = 95.5) or patients in remission (mean = 98.5). Patients with acute lymphocytic leukemia (ALL) had normal levels of immunologic and functional protein C. Although total protein S levels were normal in all patients studied, levels of free protein S were significantly decreased in patients with active AML (mean = 29.3) compared with patients in remission (mean = 42.0) or controls (mean = 42.4). In contrast, patients with ALL, both with active disease and in remission had normal free protein S levels. This decrease in free protein S seen in active AML was not associated with liver disease, white cell count or an increase in C4bBP. These findings provide a possible explanation for the occasional occurrence of venous thrombosis in patients with acute myelocytic leukemia.
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PMID:Protein C and S levels in acute leukemia. 183 Apr 52

Eight pts with acute myeloid leukemia were studied to assess coagulation and fibrinolysis disturbances as a cause of hemorrhages associated to thrombopenia. Fibrinogen, products of fibrinogen to fibrin degradation, D-dimer, antithrombin III, protein C, plasminogen and alpha-2 antiplasmin determinations were performed at admission, during and after chemotherapy. All pts were on heparin during induction chemotherapy. Coagulation activation, which increased with the onset of chemotherapy (increases in D-dimer) and a decreasing trend at the end of the antileukemic therapy (normalization of fibrinogen levels) was observed. During the whole observation period alpha-2 antiplasmin levels remained very low. No significant changes were observed in antithrombin III or protein C levels. In conclusion, disseminated intravascular coagulation with associated thrombopenia is an important event in acute leukemia and an increased fibrinolytic activity due to low alpha-2 antiplasmin levels may take part in the genesis of hemorrhage. These data suggest that both heparin administration and the use of antifibrinolytic drugs may have a therapeutic effect.
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PMID:[Intravascular coagulation in acute promyelocytic leukemia: analysis of coagulation and fibrinolysis parameters]. 184 6

Immunotherapy with Interleukin-2 (IL-2) and LAK cells has shown antitumoral activity in metastatic cancer patients. So far, thrombocytopenia is the major side effect reported in hemostasis. We have studied coagulation parameters in 6 patients treated with r-Met Hu IL-2 [ala-125]. In each case, we have observed a significant fall in prothrombin time, fibrinogen, protein C, anti-thrombin III, plasminogen, alpha 2-antiplasmin and all of the clotting factors except factor VIII. There was a significant increase in the activated thromboplastin time. No significant modifications of the D-Dimer test, fibrin-fibrinogen degradation products (FDP) and thrombin time were observed. Our data suggest that r-Met Hu IL-2 [ala-125] could interfere with the hepatic synthesis of the clotting factors and their inhibitors.
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PMID:Blood coagulation abnormalities during adoptive immunotherapy with interleukin-2 (r-Met Hu IL-2 [ala 125]). 200 36

Protein C (PC) is the central component of a major antithrombotic regulatory system with both anticoagulant and profibrinolytic properties. A deficiency of PC is one of several hereditary abnormalities of haemostatic proteins that have been described in patients with a propensity for thromboembolic complications. Major morbidity is often seen in these patients. The various aspects of hereditary PC deficiency in terms of clinical presentation, genetics, diagnosis and treatment of both homozygous and heterozygous states will be presented. In heterozygous deficiency, the levels of plasma PC are usually between 35% and 65% of normal, whereas the majority of normal individuals have levels between 70% and 130%. PC-deficient patients usually develop venous thrombotic complications between the ages of 15 and 40 years with a high incidence of DVT and pulmonary embolism. The majority of thrombotic lesions appear to develop spontaneously; others are associated with trauma, surgery or pregnancy. Treatment of symptomatic patients is initial heparin therapy followed by coumadin. After multiple thrombotic events, lifelong oral anticoagulant therapy is necessary. The potential complications of treatment are coumadin-induced skin necrosis, heparin-induced thrombocytopenia and bleeding. Homozygous PC deficiency, a rare but fatal hereditary condition, manifests itself with massive DIC and purpura fulminans in the newborn period. Effective treatment for these infants can be instituted with either oral anticoagulant therapy or PC replacement. The heterozygous deficiency of PC is similar to that found in other inherited disorders in that several genetic mechanisms are responsible for the expression of the disease. Both quantitative and qualitative decreases in PC exist, the former being type I deficiency and the latter, type II. The best initial diagnosis of either form involves a clotting (functional) assay while differentiation between the two also requires an antigenic (immunological) assay. Autosomal inheritance with significant variable penetrance is found with profound clinical implications. In summary, PC deficiency is one of a group of inherited disorders termed hereditary thrombotic disease, which may have serious implications for patient morbidity and mortality.
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PMID:Hereditary protein C deficiency: a review of the genetics, clinical presentation, diagnosis and treatment. 210 16

A patient with microvascular thrombosis and thrombocytopenia was found to have a high-titre lupus anticoagulant. The biological effects of the patient's lupus anticoagulant were studied using whole patient serum and plasma. Staph Protein A eluate, and affinity-purified lupus anticoagulant. The latter was isolated by immunoadsorption of serum onto cardiolipin/phosphatidylserine/cholesterol liposomes. Each source of lupus anticoagulant demonstrated 'anticoagulant' activity, defined as prolongation of a modified kaolin clotting time, and contained antibody which bound to endothelial monolayers. Each interfered with thrombin-mediated prostacyclin release from endothelial cells, but had no effect on arachidonate-induced prostacyclin release. In addition, the lupus anticoagulant selectively blocked platelet aggregation in response to thrombin, but not in response to arachidonate, ADP or epinephrine. Lupus anticoagulant also reduced thrombin-stimulated shifts in cytosolic calcium. Thrombin-mediated membrane inositol metabolism and total thrombin binding to endothelium were unaffected by lupus anticoagulant, and another endothelial anticoagulant function related thrombin binding. Protein C activation by thrombomodulin, was not altered. We conclude that the binding of lupus anticoagulant to endothelial cells and platelets does not prevent all thrombin signalling events, but does interrupt prostacyclin production.
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PMID:Lupus anticoagulant induces a selective defect in thrombin-mediated endothelial prostacyclin release and platelet aggregation. 249 19

In a family of four the whole spectrum of antiphospholipid and associated antibodies was present but without evidence of connective tissue disease. All four members had anticardiolipin antibodies; two had a confirmed lupus anticoagulant. Thrombocytopenia was severe in one and associated with a high titre of antiplatelet antibody, while another member was found to have a positive antiglobulin test. One member also had a low protein C concentration while two had decreased concentration of protein S. Factors that predispose to these antibodies may be environmental as well as genetic. In view of the well known association of spontaneous thrombotic events with some of these antibodies the prognosis for the family members must be guarded.
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PMID:Familial occurrence of the antiphospholipid syndrome. 211 Jan 95

Lupus anticoagulant, concentrations of anticardiolipin antibodies, antithrombin III, plasminogen, (free) protein S, protein C, prothrombin, platelet counts, and bleeding times were determined in 74 lupus patients (58 with systemic lupus erythematosus; 16 with lupus-like disease) to establish the presence of risk factors for thrombosis in these patients. Of the variables evaluated, lupus anticoagulant had the strongest association with a history of thrombosis. Both positive anticardiolipin antibody concentrations and the presence of (mild) thrombocytopenia were significantly associated with a history of thrombosis and the presence of lupus anticoagulant. Reduced concentrations of antithrombin III, plasminogen, (free) protein S, and protein C were found in some patients but were not associated with either thrombosis or lupus anticoagulant. Mean concentrations of total protein S were significantly lower in patients with thrombosis than in those without and in patients with lupus anticoagulant than in those without. The antigenic concentration of prothrombin was reduced in 3/74 (4%) lupus patients. These three patients had lupus anticoagulant but no history of thrombosis, which suggests that a low prothrombin concentration protects patients with lupus anticoagulant from the development of thrombosis. A prolonged bleeding time was associated with the presence of lupus anticoagulant but not with a history of thrombosis. Analysis by stepwise logistic regression did not disclose additional risk factors for thrombosis in lupus patients with lupus anticoagulant. Increased antithrombin III concentrations and decreased free protein S concentrations are often found in lupus patients, unrelated to lupus anticoagulant or thrombosis.
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PMID:Risk factors for thrombosis in lupus patients. 251 63

A 16-year-old boy had recurrent venous thromboses and pulmonary thromboembolism that caused him pulmonary hypertension. He also had livedo reticularis, thrombocytopenia and high titer IgG antiphospholipid (cardiolipin) antibodies. In the absence of clinical and laboratory evidence of SLE, he was considered to have a primary antiphospholipid syndrome. Coagulation studies revealed a functional deficiency of protein C although it was present in normal antigenic amounts. Since both his parents had normal functional and antigenic protein C findings, his deficiency was considered acquired. The reactivity of the anticardiolipin antibodies could be decreased in a dose dependent fashion when preincubated with increasing amounts of thrombomodulin, a protein required for protein C activation at the endothelial cell membrane. This interaction of antiphospholipid antibodies with thrombomodulin may help explain the occurrence of thrombosis in some patients with antiphospholipid antibodies, despite the behavior in vitro of these antibodies as circulating anticoagulants.
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PMID:Acquired protein C deficiency in a patient with primary antiphospholipid syndrome. Relationship to reactivity of anticardiolipin antibody with thrombomodulin. 254 43

Post-operative thrombo-embolic disease remains a frequent occurrence in spite of advances in their prophylaxis. Evaluation of 60 case-reports of this disease which often includes peripheral manifestations and always pulmonary manifestations, enables to specify the role of the procedure itself (mostly orthopaedic surgery 60%), pelvic surgery 20%, the chronology of events (possibility of early embolism between D1 and D3 and usual occurrence of manifestations between D8 and D18, and the importance of the background, whether investigated or not: deficiencies in anti-thrombin III, protein C and S: 4 cases. The diagnosis is based on clinical signs (non-specific) and the laboratory tests, especially scintigraphy (screening) and angiography, absolutely necessary for the diagnosis and evaluation of the amputation coefficient (Miller index). With a diagnosis of pulmonary embolism, it is always necessary to look for a proximal venous thrombosis. The treatment, calls for heparin (quite seldom), thrombolytics (Urokinase, Plasminogen in our experience), the indication of which must take into consideration the delays and the nature of the previous procedure, and finally surgery (massive forms where thrombolytics are contraindicated). The thrombo-embolic manifestations with thrombogenic thrombopenia secondary to heparin are quite frequent, in a surgical environment (10 cases) and difficult to treat.
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PMID:[Postoperative pulmonary embolism]. 266 1


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