Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of 5 years' use of Norplant on blood clotting factors was assessed in 97 Singaporean women. The subjects were healthy, non-smoking non-alcohol drinking and non-lactating. Blood was sampled at 6, 12, 18, 24, 36, 48 and 60 months, after an overnight fast, and resting 30 minutes before venipuncture. Hemoglobin and hematocrit increased 10% in the 1st year (p0.001), fell for the next 2 years, reaching pre-insertion levels by 3 years, then increased 10% for the last 2 years. There was a significant shortening of the prothrombin time (PT) throughout the 5 years, and of activated partial thromboplastin time (APTT) for 3 years. Vitamin K-dependent Factors II, V, VII, decreased throughout the 5 years, and fibrinolytic activity decreased at 2 and 4 years of use. Fibrinogen increased at the end of the 1st year only. Platelet numbers rose 25.6% to 43.4%, and platelet aggregation to both ADP and collagen increased throughout the 5 year period. Alpha2-macroglobulin and antithrombin III antigen levels were heightened for 4 years. Most of the observed changes were different from those seen in oral contraceptive users, except for alterations in platelet function. While some of the measured clotting factors were significantly different, none were of any clinical significance, nor were these women in a state of hypercoagulation.
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PMID:Effect of long-term use of Norplant implants on haemostatic function. 138 Sep 4

This study aimed to determine the kinetics of albumin resorption from and the healing of two types of albumin impregnated Vasculour II (Bard Cardiovascular) Dacron grafts (ACG-A and ACG-B) using whole blood preclotted Vasculour II Dacron grafts (without albumin) as controls (PCC). Prostheses measuring 4 mm ID x 50 mm length were implanted in the aortoiliac position in 24 dogs (ACG-A n = 12, ACG-B n = 24, PCC n = 12) and explanted after 1, 2 4, and 6 months. Platelet count, platelet aggregometry to 10(-5) M ADP, prothrombin time (PT), and partial thromboplastin time (PTT) were determined preoperatively and at explantation. Sections of the explanted grafts were assayed for human albumin by immunohistochemical techniques utilizing a rabbit polyclonal mono-specific antibody for human albumin followed by the addition of a biotinylated goat anti-rabbit IgG. Immunoperoxidase staining was then performed using Avidin D horse-radish peroxidase. Histology of the grafts (light microscopy, scanning electron microscopy, and transmission electron microscopy) as well as percent thrombus free surface area (TFSA) by computerized planimetry were also determined. Seven of 48 grafts were occluded (85.4% patency) with no difference among the three groups. Platelet aggregometry was not predictive of graft patency. No change in PT or PTT occurred nor was there any difference among the three groups. Retained albumin was detected in every one-month explant but not beyond that time, with the sensitivity for detecting human albumin in this assay being 20 mg albumin per gram of Dacron. All ACG explants at one month revealed inner capsular fibrin coagula not present in PCC specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Albumin impregnated vascular grafts: albumin resorption and tissue reactions. 138 74

Although it is reported that postoperative bleeding is reduced by reinfusing autologous platelet-rich plasma (PRP) after cardiopulmonary bypass (CPB), the effect of PRP on hemostasis is not reported in detail. We prepared PRP and fresh whole blood (WB) from the blood of seven patients each prior to their undergoing CPB, and reinfused them autologously to the patients intravenously after the CPB was terminated. In this article, the effect on hemostasis of autologous PRP and WB was described. Platelet aggregation rates and blood coagulation factors were examined before, during and after bypass. Platelet counts, ADP-induced platelet aggregation and the activities of coagulation factors II, V and VII-X were significantly greater in prepared PRP than in WB (p less than 0.01 or p less than 0.05). A mean volume of 724 +/- 109 ml of PRP or 401 +/- 63 ml of WB was reinfused within about 30 minutes after heparin was neutralized by protamine sulfate. The platelet counts increased from 4.3 +/- 1.4 x 10(4)/mm3 to 14.1 +/- 1.6 x 10(4)/mm3 after PRP reinfusion and the platelet aggregation rates increased significantly (p less than 0.01) after PRP reinfusion compared to WB transfusion. The activities of coagulation factors VII-X also increased significantly (p less than 0.05) after reinfusion of PRP when compared to transfusion of WB. The activated partial thromboplastin time decreased to 1.2 times the baseline in the PRP group but remained 1.5 times the baseline in the WB group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Reinfusion of autologous platelet-rich plasma improves hemostasis after cardiopulmonary bypass]. 140 62

Vitamin B6 has an antithrombotic effect. This, based on the results of in vitro studies, has been attributed to an antiplatelet effect. We assessed the in vivo effect of vitamin B6 by measuring the effect of long-term administration of vitamin B6 on platelet function and blood coagulation. Vitamin B6 (pyridoxine hydrochloride), 100mg twice daily p.o. for fifteen days, was administered to 10 healthy volunteers. The bleeding time was measured before the first dose and 15 days after. A baseline value, the acute effect, chronic effect, and the acute-on-chronic effect of vitamin B6 was estimated by measuring platelet function. The following tests were performed: platelet aggregation induced by collagen, ADP and epinephrine; thromboxane A2 (TxA2)-production and prostacyclin inhibition of ADP-induced aggregation. The effects on the coagulation system were monitored by measuring: the prothrombin time, activated partial thromboplastin time and levels of coagulation factor. Vitamin B6 significantly prolonged the bleeding time from 4.1 +/- 1.1 minutes to 6.8 +/- 1.0 minutes (p = 0.0063). Aggregation of platelets with collagen was slightly but not significantly inhibited. Platelet aggregation induced with the agonists ADP or epinephrine was significantly inhibited by vitamin B6, and the platelets tended to aggregate at a slightly decreased rate. The mean TxA2-production was slightly, but not significantly, decreased. Vitamin B6 had no effect on the sensitivity of platelets to prostacyclin, or on the coagulation system. Our results indicate that the antithrombotic effects of vitamin B6 is limited to inhibition of platelet function; there was no measurable influence on coagulation. The results of this in vivo study are however such that clinical trials are warranted to further assess the efficacy of vitamin B6 as an antiplatelet drug.
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PMID:The in vivo effect in humans of pyridoxal-5'-phosphate on platelet function and blood coagulation. 151 26

The coagulation-fibrinolysis system has been studied in two groups of 16 patients classified ASA 1 undergoing radical mastectomy during controlled hypotensive anesthesia induced by prostaglandin E1 (PGE1) or by trimethaphan (TMP) under enflurane anesthesia. Thrombelastography (TEG) was used to evaluate both coagulation and fibrinolysis systems, while simultaneously measuring platelet aggregation in response to ADP and collagen, prothrombin time (PT), activated partial thromboplastin time (APTT), serum concentrations of fibrinogen, and platelet counts. In the PGE1 group, APTT was significantly shortened (P less than 0.05) while the drug was being infused, but there was no statistically significant difference between the two groups, which was considered due to the effect of enflurane. Also, no statistically significant changes were noted in the other measured parameters. These results suggest that controlled hypotensive anesthesia using either PGE1 or TMP under enflurane anesthesia produces no significant changes in the blood coagulation-fibrinolysis system and that both are useful for the management of bleeding during surgery. Further, TEG was found to reflect other parameters properly. It is therefore useful for monitoring the blood coagulation-fibrinolysis system during anesthesia.
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PMID:[Effects of induced hypotensive anesthesia on the blood coagulation-fibrinolysis system measured by thrombelastography--comparison between prostaglandin E1 and trimethaphan]. 154 7

We have shown recently that the calcium-dependent phospholipid-binding protein annexin V (placental anticoagulant protein I) can be used to study the exposure of anionic phospholipid after platelet activation. In this study we have further examined the mechanism of this process. Collagen-induced exposure of annexin V binding sites correlated directly with increased ability to support activity of the reconstituted prothrombinase complex. The potency of annexin V as an inhibitor of platelet prothrombinase was the same as its Kd for platelets. Prior incubation of platelets with 5'-p-fluorosulfonylbenzoyladenosine or p-chloromercuribenzenesulfonate had no significant effect on annexin V binding. Similarly, inhibition of platelet cyclic endoperoxide synthesis by acetylsalicylic acid or indomethacin did not inhibit annexin V binding. Staurosporine inhibited collagen-induced, but not A23187-induced, annexin V binding. Agents that increase intraplatelet cyclic nucleotides partially inhibited collagen-induced annexin V binding. Thus, collagen-induced exposure of anionic phospholipid appears to depend primarily on increases in intraplatelet free calcium and may be independent of ADP- or endoperoxide-mediated pathways. Binding sites for annexin V on microparticles derived from collagen-stimulated platelets were demonstrated by flow cytometry and gel filtration. In addition, prior incubation of platelets with 100 nM annexin V inhibited factor Va binding to both platelets and platelet-derived microparticles. These results support the concept that the procoagulant effect of platelets and platelet-derived microparticles is mediated by calcium-induced exposure of anionic phospholipids.
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PMID:Collagen-induced exposure of anionic phospholipid in platelets and platelet-derived microparticles. 166 6

The effects of low molecular weight heparin (LHG) on the blood coagulation system, hemorrhage, lipolytic activity and bone metabolism were compared with those of conventional sodium heparin (Heparin). The anti-thrombin activity of LHG measured by the prolongation of activated partial thromboplastin time and thrombin time and measured by the suppressive effect on thrombin-induced mortality was approximately 4 times weaker than those of Heparin on a weight basis, while the anti-Xa activity of LHG measured by the chromogenic method was approximately half of that of Heparin. Heparin caused a marked and dose-dependent increase in the rat-tail bleeding time, while the effect of LHG was almost 4 times weaker than that of Heparin. These results indicate that the prolongation of bleeding time is mainly due to the inhibition of thrombin. At low doses, LHG showed lower lipolytic activity than Heparin, while at high dosage, LHG and Heparin showed similar activity. Heparin enhanced the ADP-induced platelet aggregation in vitro, but LHG showed no effects. LHG and Heparin had no effects on bone resorption nor bone formation in the rat cultured calvaria. The results of our study suggest that alternate use of LHG may reduce the known adverse effects of conventional heparin.
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PMID:[Pharmacological studies of low molecular weight heparin (LHG)]. 166 91

The authors evaluated the potential for thrombotic complications arising from implantation of a ventricular assist device (Sarns/3M-VAD) in four calves. Coagulation screening tests (prothrombin time [PT], partial thromboplastin time [PTT], thrombin time [TT]), fibrinogen levels, and antithrombin III functional activity were found to be of little value as predictors of the degree of activation of the hemostatic system. However, platelet counts, adenosine diphosphate (ADP)- and collagen-induced platelet aggregation, and thromboxane (TXB2) levels were good indicators of changes in platelet reactivity. Platelet counts (initial value 6 x 10(5) rose, and were associated with increased rate and extent of ADP- and collagen-induced platelet aggregation, which remained elevated during the entire 25 day postimplantation period. The first 5 days postimplantation revealed a typical acute inflammatory response, with increased platelet levels, but with TXB2 levels significantly decreased during this period. A monoclonal antibody based bovine D-dimer assay and Western blot studies indicated a small but significant increase in circulating bovine D-dimer, indicating localized fibrin formation and its dissolution.
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PMID:Hemostatic evaluation of Sarns/3M-VAD implantation in calves. 175 Nov 63

The effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.
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PMID:Effect of flomoxef on blood coagulation and alcohol metabolism. 178 45

The in vitro effects of zinc and magnesium salts on blood coagulation mechanism and platelet aggregation were studied on rat plasma. Addition of zinc sulphate to pooled rat plasma in a range of concentrations (0.3-1 mg/ml) caused a dose dependent significant prolongation of recalcification, prothrombin and partial thromboplastin times. These effects reached a peak after 30 minutes while the thrombin clotting time was not significantly altered and was even shortened in the presence of highest concentration of zinc tested (1 mg/ml). Incubation of thrombin with zinc sulphate (150 micrograms/ml) for up to 30 minutes did not affect significantly the action of thrombin. Incubation of the same concentrations of zinc sulphate with fibrinogen produced non clotting of fibrinogen after 0-minutes. Addition of rising concentrations of zinc sulphate to rat PRP produced inhibition of ADP-induced platelet aggregation. On the other hand, collagen-induced aggregation was insignificantly inhibited in the presence of zinc. In contrast, in vitro additions of rising concentrations of magnesium sulphate (2-5 mg/ml) to pooled rat plasma exerted no effect on recalcification time immediately after addition (0-minutes), but after 5 minutes following incubation it produced significant shortening of recalcification time in all the doses tested. The prothrombin time showed a general trend of shortening, maximal after 5-minutes incubation. The results of partial thromboplastin times revealed clotting before addition of calcium chloride. The thromboplastin time also showed progressive shortening with rising concentrations of magnesium sulphate. When thrombin solution was exposed to magnesium sulphate (2.5 mg/ml) no effect on the activity of thrombin was seen for up to 30 minutes. Fibrinogen solution similarly exposed to the same concentration of magnesium sulphate did not show any significant effect on its clottability with thrombin for up to 30 minutes. Magnesium sulphate in the range of doses tested significantly enhanced platelet aggregation of PRP in response to both ADP and collagen, and the responses observed were not dose dependent. The mechanisms underlying the effects of these two metals on blood clotting and platelet aggregation are discussed.
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PMID:In vitro effects of trace elements on blood clotting and platelet function. B--Zinc and magnesium. 180 Jun 25


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