Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desmopressin (DDAVP) 0.3 micrograms/kg was administered intravenously to three normal volunteers and 12 patients with von Willebrand's disease (vWD), congenital or acquired platelet function defect, or uremic bleeding to assess its effects and side effects. DDAVP significantly shortened the bleeding time as compared with basal values. The mean peak post-DDAVP level of factor VIII coagulant activity increased 5.9 +/- 0.5 (mean +/- SEM) fold, von Willebrand factor antigen increased 3.7 +/- 0.3 fold, von Willebrand factor ristocetin cofactor activity increased 4.6 +/- 0.6 fold and the tissue-type plasminogen activator antigen increased 3.4 +/- 0.6 fold. Analysis of the multimeric structure of the von Willebrand factor revealed that type I vWD had complete correction after DDAVP infusion transiently. Except for a mild drop in both systolic and diastolic blood pressures, few side effects were noted. By concomitant intravenous infusion of DDAVP and oral administration of tranexamic acid, we successfully treated two cases of type I vWD undergoing tooth extraction, and one case of acquired bleeding disorder undergoing a biopsy of a mandibular mass, and a uremic patient complicated by intractable traumatic hematuria. Our experiences confirmed that most patients with vWD and some patients with congenital or acquired bleeding disorders can be treated effectively by DDAVP infusion without the need for plasma product replacement. In this study we found that a patient with a variant form of type I vWD had prolongation of the bleeding time, thrombocytopenia and platelet aggregation after DDAVP infusion.
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PMID:Experience of desmopressin (DDAVP) administration in patients with congenital and acquired bleeding disorders. 136 75

We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor. 145 98

Hypoxia-induced stimulation of the rate of von Willebrand factor (vWF) release from human umbilical vein endothelial cells in culture, and the influence of the calcium antagonist verapamil, was studied using a system in which a pO2 of 20 mm Hg was achieved over 60 min. The mean +/- SEM rate of vWF release over 60 min in normoxia was 0.42 +/- 0.07% pooled plasma standard. The addition of verapamil did not alter the basal rate of vWF release, but after 60 min of hypoxia, the rate was increased to 0.71 +/- 0.03% plasma standard (p < 0.01). Verapamil at a concentration of 0.1 microgram/ml of media had no influence on the stimulated rate of release (0.78 +/- 0.07%), but increasing concentrations of verapamil up to a maximum of 1 microgram/ml attenuated the hypoxia induced stimulation (0.48 +/- 0.07%; p = 0.04 vs. hypoxic control). Thus, verapamil at this concentration completely blocked the hypoxia-induced stimulation.
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PMID:Hypoxia-induced von Willebrand factor release is blocked by verapamil. 146 48

Hemodialysis induces thrombocytopenia and activation of coagulation. The severity of this reaction depends on the kind of membrane. In this study, we present the results of determination of platelet count, and of different factors of coagulation in 10 stable dialysis patients. Measurements were performed at the start and after 15 and 45 min of dialysis. Samples were taken before and after the dialyzer. All 10 patients were treated consecutively and in a random order during 14 days with the following membranes: polyacrylonitrile (Filtral 12, Hospal), hemophan (GFS 120 Plus, Gambro, and Bio-Nephros HF Andante, Organon), polysulfone (F6, Fresenius), cuprammonium (AM50-BIO, Asahi) and cellulose acetate (Duo-Flux, Cordis-Dow). The cellulose acetate membrane induced a small but significant drop of mean platelet count [results are mean (SEM)]: from 245,000 (17,000) to 224,000 (16,000)/microliters after 15 min. With the same membrane a dramatic increase after 15 min was noted of 6-keto-PGF1 alpha from 56.3 (9) to 146.7 (35.7) pg/ml. The other membranes did not influence significantly prostanoid levels and platelet count. During dialysis no significant changes of fibrinopeptide A (FPA) and von Willebrand factor (VWF) were observed. Nevertheless, predialysis FPA and beta-thromboglobulin (beta TG) concentrations were lowest after 14 days of treatment with cellulose acetate and polyacrylonitrile membranes. It is concluded that the activation of coagulation depends on the membrane used. The activation may be dominated by one single system (e.g. prostanoids). The different predialysis concentration of some of the factors suggests interference of the dialysis membrane with the activation of coagulation during the interdialytic period.
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PMID:Evaluation of platelets and hemostasis during hemodialysis with six different membranes. 176 95

1. The effects of acute hypoglycaemia on haemostasis, fibrinolysis, blood viscosity and erythrocyte aggregation were examined after acute insulin-induced hypoglycaemia in six normal male subjects and in six male patients with poorly controlled insulin-dependent diabetes. In the control subjects hypoglycaemia caused a significant increase in the concentration of von Willebrand factor, with no change in the concentrations of fibrinogen and cross-linked fibrin degradation products. Fibrinolysis was enhanced, as indicated by significant increases in tissue plasminogen activator concentration and the fibrin plate lysis area, with a fall in plasminogen-activator inhibitor activity, suggesting complex formation. Whole-blood and plasma viscosity increased significantly after hypoglycaemia, but there was no significant change in erythrocyte aggregation tendency. 2. In diabetic patients the increase in the concentration of von Willebrand factor was significantly greater than in the control group (analysis of variance, P less than 0.02). The basal concentration of tissue plasminogen activator was reduced at 3.7 +/- 0.7 mg/l (mean +/- SEM) in the diabetic group compared with 8.5 +/- 1.3 mg/l in the control group (Student's t-test, P less than 0.01), but thereafter the increase in response to hypoglycaemia was similar. The changes in the other variables were not significantly different from the changes in the control group. 3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes.
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PMID:Effects of acute insulin-induced hypoglycaemia on haemostasis, fibrinolysis and haemorheology in insulin-dependent diabetic patients and control subjects. 185 95

In this study, the question of whether glycoprotein Ib (GPIb) mediates both high and moderate affinity pathways of alpha-thrombin-induced platelet activation was examined. Flow cytometric studies, using a panel of monoclonal antibodies (MoAbs), showed that Serratia marcescens protease treatment removed greater than 97% of the glycocalicin portion of GPIb but did not affect the changes in the expression of GPIX or GMP-140 that were induced by high concentrations of alpha-thrombin (10 nmol/L). However, Serratia treatment almost completely abolished the increase in platelet surface GMP-140 induced by low concentrations of alpha-thrombin (0.5 nmol/L) and diminished the downregulation of platelet surface GPIX by 60.9% +/- 5.6% (mean +/- SEM, n = 3). When present in 20-fold molar excess, an MoAb directed against the alpha-thrombin/von Willebrand factor (vWf) binding domains of GPIb completely blocked the ristocetin-dependent binding of vWf to platelets but inhibited only to about 50% the binding of alpha-thrombin and the activation-dependent binding of vWf. In platelets treated with Serratia marcescens protease to remove GPIb, a concentration of this MoAb 16,000-fold in excess of the maximum possible remaining copies of GPIb failed to inhibit platelet activation by alpha-thrombin. These studies demonstrate that activation of intact platelets by alpha-thrombin proceeds by both GPIb-dependent and GPIb-independent mechanisms.
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PMID:Glycoprotein Ib (GPIb)-dependent and GPIb-independent pathways of thrombin-induced platelet activation. 201

Plasma von Willebrand factor antigen concentration was determined in 15 dogs with suspected hypothyroidism, in 1 dog with hyperthyroidism, and in 14 euthyroid dogs. The mean +/- SEM von Willebrand factor:antigen concentration in hypothyroid dogs (47.1% +/- 12.6%) was significantly decreased (P less than 0.0005), compared with that in euthyroid dogs (94.7 +/- 5.6%). Four hypothyroid dogs were given thyroxine for 1 month and all 4 had an increase in von Willebrand factor:antigen concentration. The plasma von Willebrand factor:antigen concentration was 200% in the hyperthyroid dog. Seemingly, reduced concentrations of plasma von Willebrand factor:antigen can be found in dogs in association with congenital von Willebrand disease or with von Willebrand disease acquired through hypothyroidism.
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PMID:Plasma von Willebrand factor concentration and thyroid function in dogs. 210 58

von Willebrand factor (vWF) is synthesized in endothelial cells (EC) and may be either secreted constitutively or stored in Weibel-Palade bodies (WPB) for regulated release. Because fibrin stimulates rapid vWF release from EC, we examined the binding of EC synthesized vWF to fibrin. Culture medium containing constitutively secreted vWF was removed from metabolically labeled primary cultures of human umbilical vein EC, and vWF released from WPB was obtained after stimulation by A23187. vWF-deficient fibrinogen with or without factor XIII was added to releasate or media and clotted with thrombin to form crosslinked or noncrosslinked fibrin. vWF was immunopurified from releasate or media before and after clotting, and the amount and multimeric pattern of vWF bound was determined after sodium dodecyl sulfate agarose gel electrophoresis. High molecular weight multimers of vWF, whether secreted constitutively or released from WPB, bound preferentially to fibrin. Multimers of greater than 20 subunits represented 60% +/- 4% (SEM) of A23187 released vWF and 11% +/- 5% of media vWF, but binding to fibrin was similar, 96% +/- 1% and 94% +/- 2%, respectively. A progressively smaller proportion of vWF bound as multimer size decreased, and dimeric vWF binding was least, with 34% +/- 5% binding from A23187 releasate and 51% +/- 4% from media. The amount of vWF binding to crosslinked or noncrosslinked fibrin was similar, and preferential binding of high molecular weight multimers occurred with both. As measured by enzyme-linked immunosorbent assay, 45% +/- 2% of constitutively secreted vWF bound to crosslinked fibrin and 50% +/- 2% to noncrosslinked fibrin. The propolypeptide of vWF did not bind to fibrin. These findings indicate that binding of EC secreted vWF binding to fibrin depends on multimeric size but not on factor XIII crosslinking. This suggests that vWF released from EC in the presence of fibrin will bind locally, thereby facilitating platelet adhesion to the hemostatic plug or thrombus.
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PMID:Multimer size dependence of von Willebrand factor binding to crosslinked or noncrosslinked fibrin. 210 83

To determine whether the clinical, immunological and serological features of patients with silica-associated systemic sclerosis are different from patients with the 'idiopathic' form of systemic sclerosis (SS) we studied 22 underground coal miners who were exposed to silica dust (SD), 30 mine workers who later developed silicosis (S) and 17 mine workers exposed to silica dust who subsequently developed a systemic sclerosis-like disease (SA-SS). The patients with SA-SS had features clinically indistinguishable from individual patients with SS. They all had Raynaud's phenomenon, 14 had cutaneous sclerosis identical to that seen in acrosclerosis and three had a generalized cutaneous sclerosis. Sixteen patients had bibasilar pulmonary fibrosis, 10 had necrosis of the fingertip pulps, nine had oesophageal involvement and only one patient had renal involvement. Antinuclear antibodies and circulating immune complexes were detected in three and eight patients with SD, 14 and five patients with S and in 16 and nine patients with SA-SS, respectively. Anti-Scl-70 antibody was detected in eight of the 17 patients with SA-SS. Evidence for in vivo endothelial cell damage, as determined by elevated levels of von Willebrand factor, was found in nine patients with SD, 14 patients with S and in 10 patients with SA-SS. Following incubation of the patient's serum with confluent cultures of human umbilical vein endothelial cells there was only a significant reduction in calcium ionophore-induced release of prostacyclin with the serum from SA-SS patients compared to that with control serum (NC). The mean +/- SEM release of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin expressed as ng/10(4) cells) decreased from 2.90 +/- 0.27 to 2.01 +/- 0.33 (SD), 3.34 +/- 0.42 to 1.76 +/- 0.31 (S), 1.98 +/- 0.12 to 0.64 +/- 0.07 (SA-SS) and 2.28 +/- 0.33 to 1.36 +/- 0.21 (NC) with 1 and 20% serum, respectively. This study demonstrates that immune complex and antinuclear antibody formation and in vivo endothelial cell damage occurs following occupational exposure to silica. The patients who subsequently develop a systemic sclerosis-like disease have clinical, immunological and serological features which are indistinguishable from the idiopathic form of the disease although as a group the SA-SS patients have a higher prevalence of pulmonary involvement and the anti-Scl-70 antibody.
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PMID:Silica-associated systemic sclerosis is clinically, serologically and immunologically indistinguishable from idiopathic systemic sclerosis. 217 91

The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.
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PMID:Bleeding time prolongation with streptokinase and its reduction with 1-desamino-8-D-arginine vasopressin. 224 38


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