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)

Factor XI (FXI) is the zymogen of a plasma serine protease (FXIa) that contributes to hemostasis by activating factor IX (FIX). This reaction appears to be important for sustaining thrombin production after initial fibrin formation, to consolidate and protect fibrin clots from degradation by fibrinolysis. Humans with congenital FXI deficiency have a variable propensity to bleed after trauma or surgery, but do not experience the "spontaneous" hemorrhage in joints and soft tissue characteristic of hemophilia (FVIII or FIX deficiency). Mice homozygous for a disruption of the FXI gene (FXI-/-) have prolonged activated partial thromboplastin times and no detectable plasma FXI activity. Like their human counterparts, FXI-/- animals are generally healthy, reproduce normally, and do not develop spontaneous hemorrhage. In tail bleeding time assays, FXI-/- animals may have slightly prolonged bleeding compared to FXI+/+ and FXI+/- animals, however, a consistent hemostatic deficit has not been identified. More impressive results are obtained when FXI-/- mice are crossed with protein C deficient mice. Severe FXI deficiency partially ameliorates the devastating hypercoagulable state associated with severe protein C deficiency, indicating that FXI plays a role in certain thrombotic conditions.
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PMID:Gene targeting in hemostasis. factor XI. 1117 49

Blood coagulation parameters (thromboplastin time. PT; activated partial thromboplastin time, aPTT; fibrinogen; antithrombin III, ATIII; von Willebrand factor-concentration, vWF; factor VIII-activity, FVIII) and fibrinolytic parameters (plasminogen; (alpha-antiplasmin; euglobulin-lysis-time, Elt; tissue plasminogenactivator-antigen, tPA-antigen; plasminogenactivator-1-antigen, PAI-1-antigen) were evaluated in 34 women on low-dose oral contraceptives (OC) twice at intervals of 12 weeks each time before and after maximal exercise. During the 12 weeks, 24 women took part in an aerobic conditioning program and 10 women were requested to avoid any kind of sports activity for this period. Blood samples were taken before training and before and after maximal treadmill exercise. This procedure was repeated after the training program. After maximal exercise we found a significant reduction of aPTT and PT (increase in %), a decrease in ATIII, vWF, fibrinogen, plasminogen and alpha2-antiplasmin but an increase in fibrinolytic activity (all p<0.05). Maximal exercise is associated with an increase in blood coagulation and fibrinolysis also in women taking OC. After the physical conditioning program an increase in fibrinolytic activity at rest was noted in the training group. Opposed to that the fibrinolytic activity at rest decreased in the control group after abstinence of sports activity over this period (p<0.05, MANOVA).
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PMID:Changes in blood coagulation and fibrinolysis associated with maximal exercise and physical conditioning in women taking low dose oral contraceptives. 1123 4

Large potency discrepancies between the chromogenic and one-stage clotting methods have been reported for patients' plasma samples following the infusion of recombinant factor VIII (rFVIII) concentrates. We have investigated the potency estimation of two different full-length rFVIII concentrates using both assay methods relative to both plasma and concentrate standards. Potencies by the chromogenic method were significantly higher (53% and 45%) than potencies by the one-stage clotting method when a plasma standard was used. In contrast, there was no significant potency difference between methods when a concentrate standard was used. Time-course studies into thrombin and activated factor X (FXa) generation, in modified clotting and chromogenic methods, respectively, revealed that the two rFVIII concentrates behaved very similarly to the concentrate standard, whereas the plasma standard showed slightly more rapid thrombin generation and markedly slower FXa generation. The different behaviour of rFVIII and plasma FVIII in the chromogenic method is proposed as the main cause of the methods-based potency discrepancy. The results support the use of a concentrate standard to measure rFVIII in post-infusion plasma.
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PMID:Potency estimation of recombinant factor VIII: effect of assay method and standard. 1138 Apr 27

Blood coagulation has been thought to be composed of both intrinsic and extrinsic pathways. Recent evidence strongly supports the critical role of the extrinsic pathway in the initiation of blood coagulation. This investigation established an assay that examines the role of FXI in the thromboplastin-initiated (extrinsic) coagulation based on this new concept. Plasma clotting times were measured at different concentrations of thromboplastin with activated FXII inhibited (FXIIa-inhibited Diluted Thromboplastin Time, FXIIaiDTT). Only at low concentrations of thromboplastin was FXIIaiDTT of FXI-deficient plasma significantly prolonged than that of normal plasma. Depletion of FXI from normal plasma prolonged its FXIIaiDTT and replenishment of FXI shortened it. FXIIaiDTTs of both FVIII-deficient and FIX-deficient plasma were remarkably prolonged, and addition of normal plasma dose-dependently shortened it. Furthermore, earlier alpha-thrombin inhibition was directly correlated with decreasing FXa generation. The amount of FXa production was: platelet-rich plasma > platelet-poor plasma > FXI-deficient plasma. Therefore, our findings from the FXIIaiDTT assays not only support the critical role of extrinsic pathway in blood coagulation initiation, but also demonstrate the importance of FXI as an amplifier of thrombin generation in thromboplastin-initiated coagulation.
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PMID:The role of factor XI in a dilute thromboplastin assay of extrinsic coagulation pathway. 1143 84

Acquired inhibitors to FVIII (anti-FVIII) are uncommon in children. An acquired anti-FVIII developed in a previously healthy 4-year-old boy treated with penicillin for streptococcal pharyngitis. Aspirin prophylaxis begun for suspected rheumatic fever led to compartment syndromes of all four extremities, which resolved with high-dose FVIII and surgical decompression. Anti-FVIII in this patient, and the five additional cases identified in a survey of 160 haemophilia treatment centres, occurred at a median age of 8 years, with median initial and peak titres of 4.6 and 6.9 Bethesda Units (BU), respectively. All six presented with bleeding, including haematomas (three intramuscular, one intracranial), and ecchymoses in three. The median baseline FVIII was 0.05 U mL(-1), and the median baseline activated partial thromboplastin time (APTT) was 79.8 s. The inhibitor resolved completely in five patients (83%) within a median 5 months, after treatment with FVIII concentrate, steroids, cytoxan, methotrexate, and no treatment. The inhibitor persisted in the patient with Goodpasture's disease, despite steroids, cytoxan, cyclosporin, and intravenous gamma globulin. Aspirin therapy, in two, worsened ongoing bleeding. The association of penicillin-like drugs in this and three other cases in the literature suggest that to avoid potential catastrophic bleeding, it is prudent to obtain an APTT prior to initiating aspirin for suspected rheumatic fever. In conclusion, acquired anti-FVIII inhibitors in children may cause severe bleeding, and remit in the majority after FVIII and/or immunosuppressive therapy.
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PMID:Acquired anti-FVIII inhibitors in children. 1188 62

Persons who have been in contact with Lonomia achelous or Lonomia obliqua caterpillars present external and internal bleeding and opening of recently healed wounds. Hematological tests show normal platelet count, prolonged prothrombin time, activated partial thromboplastin time and thrombin time, totally corrected by normal plasma. Decreased fibrinogen (Fg), factor (F) V, FXIII, plasminogen and alpha(2)-antiplasmin with increased FVIII: C, von Willebrand factor, Fg degradation products and D dimers. Tissue plasminogen activator, plasminogen activator inhibitor and protein C varied. In L. achelous biological fluids, compounds with anticoagulant or procoagulant properties have been identified. In L. obliqua bristle extracts, mainly procoagulant activities have been identified. Subcutaneous injections of L. achelous crude extracts and a semipurified fraction reduce Fg, plasminogen and FXIII in rabbits. Intravenous injections of a very purified fraction of L. achelous in rabbits produce lysis of preformed thrombi, a decrease of Fg, plasminogen, alpha(2)-antiplasmin, FXIII and inhibition of postthrombolytic thrombus growth. Subcutaneous injections of L. obliqua bristle extracts prolong prothrombin time and activated partial thromboplastin time and reduce FXIII. Intravenous injections of crude bristle extract and a purified fraction of L. obliqua induce disseminated intravascular coagulation.
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PMID:Lonomia genus caterpillar envenomation: clinical and biological aspects. 1191 Jan 97

Von Willebrand disease (vWD) is caused by quantitative or qualitative defects, or both, of the von Willebrand factor (vWF), a multimeric high-molecular glycoprotein (GP). Typically, it affects the primary hemostatic system, which is reflected by a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (1) by supporting platelet adhesion to the injured vessel wall under conditions of high shear forces and (2) by its carrier function for factor VIIIc (FVIIIc) in plasma. Because of the complexity of the disease, diagnosis of vWD is one of the most challenging of any coagulation disorder. The stepwise diagnosis of vWD includes patients and family history, screening procedures (bleeding time [BT], filter tests, platelet counts, activated partial thromboplastin time [aPTT]), confirmatory tests (vWF antigen [vWF:Ag], vWF ristocetin cofactor activity [vWF:RCo], vWF collagen-binding [vWF:CB] assay, ristocetin-induced platelet aggregation [RIPA], FVIIIc) and tests for final classification (multimeric analysis, FVIII binding capacity of vWF [vWF:FVIIIB], platelet vWF). In 1999, we classified 303 patients with congenital vWD as type 1 (n = 122), type 2 (n = 171), and type 3 (n = 10). Type 2 was further subdivided into type 2A (n = 126), type 2B (n = 17), type 2M (n = 22), and type 2N (n = 6). Type 2A showed a remarkable heterogeneity, with only 27.8% (n = 36) of the "classic" IIA pattern. The other high-frequency patterns were type IB (25.4% n = 32) and type IIE/F/H-like structural abnormalities (28.6% n = 36). The spectrum was completed with samples from patients with types 2D, 2C, 2C Miami, smeary structures, and other rare subtypes (together 18.9% n = 23).
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PMID:Laboratory diagnosis of congenital von Willebrand disease. 1199 41

Fourteen patients with different types of von Willebrand disease (vWD) having acute bleeds or elective surgery were treated with Immunate(sound recording copyright sign), a double-virus inactivated factor VIII/von Willebrand factor (FVIII/vWF) concentrate. The concentrate was applied as a bolus or via continuous infusion. FVIII activity (FVIIIc), vWF antigen (vWF:Ag), ristocetin cofactor activity (vWF:RCo), collagen binding activity (vWF:CB), activated partial thromboplastin time (aPTT), and von Willebrand multimers (vW-multimers) were monitored for 48 hours. Pharmacokinetic analyses were performed. The clinical efficacy was rated excellent or good. Bleeding complications occurred in 3 patients due to an additional FXIII deficiency in one patient, to a surgically induced bleed in another patient, and a rather short substitution period in the third patient. There were no serious adverse experiences. One patient showed a phlebitic reaction at the site of venous access after more than 100 hours of continuous infusion, requiring a change to application via bolus.
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PMID:Successful treatment of patients with von Willebrand disease using a high-purity double-virus inactivated factor VIII/von Willebrand factor concentrate (Immunate). 1199 43

We report the case of a 64-year-old man without hemorrhagic history experiencing epistaxis. The standard hemostasis assessment including prothrombin index, activated partial thromboplastin time (APTT) and platelet count found an isolated abnormal APTT (105 sec vs 33 sec). Therefore, coagulation factors were explored. An acquired factor VIII deficiency (5%) with anti-FVIII antibody (4.5 Bethesda unit.mL-1) was recognised. This anti-FVIII antibody was related to a Chlamydia pneumoniae pulmonary infection. Treatment consisted of: i) Four successive anterior packing and activated factor VII infusion (Novoseven); ii) steroids injection and bi-antibiotherapy. The time course of the epistaxis was favourable under treatment.
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PMID:[Autoantibodies and anti-factor VIII and Chlamydia pneumoniae infection]. 1219 96

Abnormally short activated partial thromboplastin times (APTTs) are associated with an increased risk of thrombotic disorders. We have examined the status of coagulation activity in subjects with short APTTs. In addition, the presence of the thrombotic risk factors G1691A-factor V, G20210A-prothrombin gene mutation and factor VIII coagulant activity (FVIII:C) was determined. Plasma levels of TAT, F1+2, D-dimer and FVIII:C were markedly higher in subjects with short APTTs compared with subjects with normal APTTs. APTTs were inversely related to TAT, F1+2, D-dimer and FVIII:C levels. The prevalence of G1691A-factor V and G20210A-prothrombin gene mutation between the group with short APTTs and the control group was not significantly different. Hence, these gene polymorphisms do not contribute to the increased risk of thrombosis associated with short APTTs. In conclusion, short APTTs are indicative of marked coagulation activity and elevated FVIII:C levels. Elevated FVIII:C levels may play a pathogenic role in the increased risk of thrombosis associated with abnormally short APTTs.
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PMID:Abnormally short activated partial thromboplastin times are related to elevated plasma levels of TAT, F1+2, D-dimer and FVIII:C. 1237 29


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