Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is postulated that ADP secreted by platelets is the physiological thromboplastin which initiates the conversion of prothrombin to thrombin and hence brings about the coagulation of the blood. The experiments which led to the formulation of the hypothesis are described. Experimental work compatible with the hypothesis is outlined. The implications of the hypothesis with regard to the modern cascade theory of coagulation are discussed.
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PMID:On the coagulation of the blood: an elaboration of Lord Lister's hypothesis and the four-factor model of Morawitz. 225 76

The purpose of this study was to correlate bleeding complications during and after treatment with recombinant tissue-type plasminogen activator (rt-PA) with serial template bleeding time measurements, with ADP-induced platelet aggregation, with clinical characteristics, and with hemostatic parameters. Fifty-two of 55 consecutive patients with acute myocardial infarction and template bleeding times (Ivy method) of less than 9.5 minutes were treated with rt-PA in a total dose of 55-212 mg (mean, 109 mg) over 90 to 360 minutes (median, 240 minutes) combined with heparin. The mean bleeding time was significantly prolonged at 90 minutes (from 5.0 +/- 1.9 to 8.2 +/- 4.3 minutes, p less than 0.0001) but returned toward baseline after 4 hours (from a median of 8.0 to 7.0 minutes, p less than 0.05). Thirteen patients (25%) suffered relatively minor but spontaneous bleeding that did not correlate with age, hypertension, smoking, partial thromboplastin time, platelet count, ADP-induced platelet aggregation, steady-state rt-PA level, or extent of fibrinogen degradation. In multivariate analysis, only the 90-minute bleeding time correlated with spontaneous bleeding (p = 0.01). Prolongation of the 90-minute bleeding time to greater than or equal to 9 minutes, which occurred in 21 patients, correlated with spontaneous bleeding with a sensitivity of 69% (95% confidence interval, 39-90%) and a specificity of 69% (95% confidence interval, 52-83%). Retrospective analysis revealed that in 14 patients taking aspirin, the bleeding time at 90 minutes was significantly more prolonged (p less than 0.05) and spontaneous bleeding significantly more frequent (p less than 0.01) than in patients not taking aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between template bleeding times and spontaneous bleeding during treatment of acute myocardial infarction with recombinant tissue-type plasminogen activator. 250 11

A four-year-old Standardbred gelding presented with a 3.5 year history of intermittent epistaxis and spontaneous submucosal petechiae and ecchymoses in the nares and the mouth. Routine haematological and biochemical examinations were unremarkable. A thrombocytopathy was suspected when activated partial thromboplastin time, one stage prothrombin time, plasma fibrinogen and the platelet count were all normal. The patient's platelets failed to aggregate with serotonin, adenosine diphosphate, collagen (at 20 micrograms/ml) or the endoperoxide analogue U46619. Very high levels of collagen (100 micrograms/ml) did cause aggregation. The response to the calcium ionophore A23187 was reduced and although complete degranulation occurred the resulting aggregates were unstable. Thromboxane generation in response to collagen and ADP was inferred from the concentration of its stable metabolite thromboxane B2 and was reduced. A diagnosis of a thrombasthenia-like syndrome possibly equivalent to Type II Glanzmann's thrombasthenia in people was made.
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PMID:Functional and morphological studies on blood platelets in a thrombasthenic horse. 251 43

A left ventricular assist device (VAD) with a smooth surface of segmented polyurethane was implanted in five goats for 10-55 days, and plasma levels of fibrinogen (Fg), prekallikrein (PK), fibrinogen, fibrin degradation products (FDP), antithrombin III (AT III), prothrombin time (PT), partial thromboplastin time (PTT), platelet (Pl) count, and platelet aggregation (PlAg) induced by adenosine diphosphate were measured during the experiment. Heparin was administered during surgery and no systemic antithrombotic therapy was given thereafter. Before the third postoperative day (POD), plasma levels of Fg and PK were at their lowest, and increased afterward. Between the second and fifth POD PT and PTT increased to 130-160%, and returned to normal gradually. Plasma FDP appeared on the second POD and reached peak values of 10-40 micrograms/ml on the sixth POD. Platelet and AT III levels showed no uniform tendency, but the rate of PlAg decreased to levels of 6-77% before the fifth POD and remained low at approximately 80%, influenced by the pumping even after the 25th POD. In summary, VADs themselves activated coagulation and induced consumption coagulopathy to some degree. However, most of the parameters returned to normal within 2 weeks.
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PMID:Influences of ventricular assist device pumping on blood coagulation. 259 87

The synthetic inhibitors of plasma kallikrein (PK) were found, which are called PKSI-1007, PKSI-0180 and PKSI-0527 in our laboratories. (1) The inhibitors inhibited PK competitively with D-Pro-Phe-Arg-pNA and the Ki values obtained were considerably small, 10(-6) M-10(-7) M. However, the Ki values for glandular kallikrein (GK), plasmin (PL), thrombin (TH) and factor Xa (FXa) were larger. In particular, a selectivity of PKSI-0527 towards PK was very high and the toxicity was weak (i.v. LD50 for mice is over 100 mg/kg). (2) The inhibitors were effective (a) to prevent the bradykinin formation in the kaolin-activated human plasma and the acid-treated ascites taken from the mice bearing Sarcoma 180, (b) to prolong the coagulation time by contact activation, and (c) to inhibit the enhancement of ADP-platelet aggregation by PK. The results indicated that the some PKSI-inhibitors will be much useful for the basic studies, furthermore they deem to be even promising towards the clinical application.
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PMID:Highly selective synthetic inhibitors with regard to plasma-kallikrein activities. 261 76

The authors studied the influence of adenine and pyridine nucleotides on platelet aggregation and on the time of calcium-induced coagulation of citrate plasma, rich or poor in platelets, with deficiency of membrane fragments and its compensation with exogenous small-dispersed tissue thromboplastin. Calcium ions stimulated the conversion of small-dispersed inactive thromboplastin into a larger and more active substance. The antiaggregation agents AMP and NAD+ inhibited inclusion of phospholipid membrane fragments into the process of recalcified plasma coagulation, i.e. expressed an anticoagulant effect, while the aggregation agents (ADP, NADH) intensified their procoagulant action.
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PMID:[Effect of nucleotide aggregants and anti-aggregants on the coagulation potential of blood plasma]. 270 62

Activation of human platelets by complement proteins C5b-9 is accompanied by the release of small plasma membrane vesicles (microparticles) that are highly enriched in binding sites for coagulation factor Va and exhibit prothrombinase activity. We have now examined whether assembly of the prothrombinase enzyme complex (factors VaXa) is directly linked to the process of microparticle formation. Gel-filtered platelets were incubated without stirring with various agonists at 37 degrees C, and the functional expression of cell surface receptors on platelets and on shed microparticles was analyzed using specific monoclonal antibodies and fluorescence-gated flow cytometry. In addition to the C5b-9 proteins, thrombin, collagen, and the calcium ionophore A23187 were each found to induce formation of platelet microparticles that incorporated plasma membrane glycoproteins GP Ib, IIb, and IIIa. These microparticles were enriched in binding sites for factor Va, and their formation paralleled the expression of catalytic surface for the prothrombinase enzyme complex. Little or no microparticle release or prothrombinase activity were observed when platelets were stimulated with epinephrine and ADP, despite exposure of platelet fibrinogen receptors by these agonists. When platelets were exposed to thrombin plus collagen, the shed microparticles contained activated GP IIb-IIIa complexes that bound fibrinogen. By contrast, GP IIb-IIIa incorporated into C5b-9 induced microparticles did not express fibrinogen receptor function. Platelets from a patient with an isolated defect in inducible procoagulant activity (Scott syndrome) were found to be markedly impaired in their capacity to generate microparticles in response to all platelet activators, and this was accompanied by a comparable decrease in the number and function of inducible factor Va receptors. Taken together, these data indicate that the exposure of the platelet factor Va receptor is directly coupled to plasma membrane vesiculation and that this event can be dissociated from other activation-dependent platelet responses. Since a catalytic membrane surface is required for optimal thrombin generation, platelet microparticle formation may play a role in the normal hemostatic response to vascular injury.
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PMID:Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. 279 43

Middle-weight molecules exert a marked anticoagulant effect, inhibit fibrinolysis and promote disaggregation of spontaneously aggregated blood platelets, decrease the degree of ADP-induced aggregation of blood platelets, and raise vascular permeability thus influencing the hemostatic potential of the blood. The types of the activity established are mainly detectable in the dialysed fraction of middle-weight molecules. After purification by means of dialysis the middle-weight molecule fraction promotes the formation of an active prothrombin-transforming complex without Ca++ in the presence of the matrix (tissue thromboplastin). On storage of the conserved donor's blood and plasma there occurs an accumulation of middle-weight molecule substances. This process is of moderate character, being two times more pronounced in the blood than in the plasma.
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PMID:[Effects of middle-weight molecules on the mechanism of hemostasis]. 280 67

Blood from adult male Wistar rats clotted rapidly in glass or siliconized tubes; the clots retracted and did not lyse. The serum prothrombin, plasma prothrombin and activated partial thromboplastin times were shorter than those of normal humans. In contrast, the thrombin and reptilase times were longer than those of normal human plasma, due apparently to the presence of a low-grade thrombin inhibitor in rat plasma. Coagulation factors, X, VIIIR:vW and IX assayed lower in rat than human plasma, while factors VIII:C and anti-thrombin III were higher. Values for other coagulation factors (II, V, VII, XI, XII and Fletcher) fell within the human range. Platelets were small and numerous. They aggregated well with ADP but poorly or not at all with collagen, ristocetin, thrombin, epinephrine, arachidonic acid and pig or bovine plasmas. Leukocytes numbered 4-8 X 10(3) cells/mm3, a near human range and were predominantly lymphocytic. Erythrocytes were small (MCV = 56-60 fl) and numerous (5.5-6.4 X 10(6) cells/mm3).
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PMID:Comparative hematology and coagulation: studies on rodentia (rats). 286 3

The effects of intravenous latamoxef therapy at two doses of 3g and 6g daily for 7 days was assessed by various haemostatic parameters. With both doses, the prothrombin time, thrombin time and activated partial thromboplastin time remained within the normal range throughout the study. However, with the 6g day-1 dose there was a marked prolongation of the bleeding time associated with defective platelet aggregation to adenosine diphosphate and low dose collagen after 7 days therapy. With the 3g day-1 dose of latamoxef, there was no prolongation of the bleeding time and only minor changes in platelet aggregation responses.
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PMID:Effects of various doses of latamoxef (moxalactam) on haemostasis. 287 35


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