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 biocompatibility of modified and urease-immobilized poly(ethyleneglycol dimethacrylate/2-hydroxyethylmetacrylate) [poly(EGDMA/HEMA)] microbeads was tested through blood compatibility tests. Twelve percent HEMA incorporated nonporous particles of 105-125 microm were used in the research. Hydroxyl groups on microbeads were chemically modified by following a three-step procedure that is composed of activation, spacer-arm incorporation (hexamethylene diamine) and, finally, glutaraldehyde bounding. Enzyme urease was immobilized on microbead surfaces, and adsorption of blood proteins in serum and plasma, blood coagulation time, and leukocyte and platelet adhesion were tested. Incubation of 1.5 cc of biological fluid with 100 mg of urease-immobilized poly(EGDMA/HEMA) microbeads at room temperature shows that protein adsorption on surfaces occurs, but protein content after treatment was in the range of healthy people. Adsorbed albumin and total globulin amounts per gram of microbeads is much greater than fibrinogen. Immobilization of urease reduced the protein adsorption and blood coagulation times compared with those of modified microbeads. Prothrombin time (PT) was not altered much, whereas poly(EGDMA/HEMA) microbeads induced a significant increase of activated partial thromboplastin time (APTT). The platelet and leukocyte adhesion slightly increased with the modification of poly(EGDMA/HEMA) and decreased with the introduction of urease. When blood samples were treated with urease-immobilized microbeads, BUN values of patients were lowered to almost acceptable amounts.
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PMID:Biocompatibility investigation and urea removal from blood by urease-immobilized HEMA incorporated poly(ethyleneglycol dimethacrylate) microbeads. 1247 42

Multicentric Castleman's Disease (MCD) is an atypical lymphoproliferative disorder, related to human herpesvirus 8 (HHV-8) infection and often associated with autoimmune diseases such as haemolytic anaemia and thrombocytopenia. Acquired haemophilia (AH) is a rare, life-threatening disease, which can occur in association with lymphoproliferative disorders, although only one case of AH in MCD has been described so far. We report the case of a human immuno deficiency virus negative 71-yr-old woman referred to our hospital for prolonged bleeding on surgical site following a lymph node biopsy. Lymph node histology revealed MCD, while the screening for the bleeding disorder showed prolonged activated partial thromboplastin time (APTT) (ratio: 1.89, normal value <1.24), low factor VIII (FVIII:C) levels (6%) with anti-factor VIII antibodies (2.3 Bethesda units), leading to a diagnosis of AH. Virological studies on plasma, lymphocyte and bronchoalveolar wash showed positivity for HHV-8 infection. Treatment with steroids (metilprednisolone 1-1.5 mg/kg/d) and cyclophosphamide (100 mg/d orally) was unsuccessful, and then antiviral therapy with cidofovir (5 mg/kg/wk) was started. A transient normalisation of APTT was seen after two administrations of cidofovir, but then coagulation parameters worsened and a large haematoma of the arm appeared. Bleeding was successfully stopped with two boluses of recombinant activated factor VII (Novoseven 90 microg/kg). Therapy with anti-CD 20 monoclonal antibody rituximab (Mabthera 375 mg/m2 once a week for 4 wk) was started, and following two administrations APTT normalised once again. Cardiological and neurological complications arose before the third dose of rituximab and the patient died shortly afterwards.
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PMID:Acquired haemophilia in HIV negative, HHV-8 positive multicentric Castleman's disease: a case report. 1260 62

The hemostatic process initiated by the exposure of tissue factor to blood is a threshold limited reaction which occurs in two distinct phases. During an initiation phase, small amounts of factor (F)Xa, FIXa and thrombin are generated. The latter activates the procofactors FV and FVIII to the activated cofactors which together with their companion serine proteases form the intrinsic FX activator (FVIIIa-FIXa) and prothrombinase (FVa-FXa) which generate the bulk of FXa and thrombin during a propagation phase. The clotting process (fibrin formation) occurs at the inception of the propagation phase when only 5-10 nM thrombin has been produced. Consequently, the vast majority (greater than 95%) of thrombin is produced after clotting during the propagation phase of thrombin generation. The blood of individuals with either hemophilia A or hemophilia B has no ability to generate the intrinsic FXase, and hence is unable to support the propagation phase of the reaction. Since clot based assays conclude before the propagation phase they are not sensitive to hemophilia A and B. The inception and magnitude of the propagation phase of thrombin generation is influenced by genetic polymorphisms associated with thrombotic and hemorrhagic disease, by the natural abundance of pro- and anticoagulants in healthy individuals and by pharmacologic interventions which influence thrombotic pathology. Therefore, it is our suspicion that the performance of the entire process of thrombin generation from initiation through propagation and termination phases of the reaction are relevant with respect to both hemorrhagic and thrombotic pathology.
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PMID:What is all that thrombin for? 1287 Dec 86

The monitoring of coagulation-inhibitor bypassing agents, including recombinant factor VIIa (rFVIIa), remains a major issue in the management of clinical hemophilia. Clotting assays using prothrombin time (PT) and measurements of factor VII (FVII) activity do not always reflect the hemostatic effects of treatment. Thrombelastography can be used to observe the global effects of treatment on the overall coagulation process and is especially useful for observing the effects of hemostatic treatment in hemophilia patients with inhibitors. Waveform analysis is another technique for evaluating global hemostatic condition where changes in light transmission during routine clotting assays, such as the activated partial thromboplastin time (aPTT), are measured. We found that waveforms differed between individual patients with severe hemophilia A (FVIII:C < 1.0 IU/dL) with levels of sensitivity at below FVIII:C 1.0 IU/dL. Clot waveforms indicated dose-dependent improvements in clot formation after the addition of rFVIIa to both FVIII-deficient and factor IX (FIX)-deficient plasma. The improvements were further enhanced in the presence of both platelets and synthetic phospholipids, and were more pronounced with FVIII-deficient plasma than with FIX-deficient plasma. It appears that clot waveform analysis provides a very useful means for monitoring hemostasis in hemophilia A patients with inhibitors.
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PMID:Understanding the hemostatic effects of recombinant factor VIIa by clot wave form analysis. 1487 33

von Willebrand disease (vWD) is the most common congenital bleeding disorder in the USA, affecting 1-3% of the population. Previously characterizing the bleeding symptoms in females with type 1 vWD, we evaluated 42 males with type 1 vWD, mean age 16 years (1-64), of whom 24 (57%) presented with bleeding symptoms. The most common initial symptom was postoperative bleeding (26%). The most common bleeding symptoms ever were epistaxis (53%), bruising (50%), postoperative bleeding (47%), haematomas (29%) and oral bleeding (29%). Of postoperative bleeding, ear/nose/throat (44%), dental (17%) and circumcision bleeding (22%) occurred at a median 10 years of age, despite a previous bleeding or family history in 89%. Complications included anaemia in five (12%), neurological sequelae after subdural haematoma and tonsillectomy in two (5%), transfusion-associated hepatitis C in two (5%) and degenerative joint disease after traumatic haemarthroses in one (2%). The bleeding time (BT) was prolonged in 83%, and the ristocetin cofactor (vW:RCoF) and factor VIII (FVIII:C) decreased in 64% and 43%, respectively. Haemarthroses and haematoma formation were associated with a longer activated partial thromboplastin time (APTT) (P < 0.05), and anaemia with a lower FVIII:C (P < 0.05). In 81%, a haemostatic response occurred with 1-8 deamino-d-arginine vasopressin (DDAVP), although, in 13%, surgical intervention was also required to achieve haemostasis. Postoperative bleeding could have been avoided in 89%, if a preoperative past bleeding history or family history had been obtained, and, in at least 94%, if a preoperative BT and APTT had also been performed. The failure to avoid postoperative bleeding and related complications in patients with vWD by taking a personal and family bleeding history constitutes a major public health problem.
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PMID:Bleeding manifestations in males with von Willebrand disease. 1496 5

Using a cell-based model system of coagulation, we performed a systematic examination of the effect of varying individual procoagulant proteins (over the range of 0-200% of pooled plasma levels) on the characteristics of thrombin generation. The results revealed a number of features unique to the different coagulation factors, as well as common features allowing them to be grouped according to the patterns observed. Variation of those factors contributing to formation of the tenase complex, factor (F)VIII, factor (F)IX and factor (F)XI, primarily affected the rate and peak of thrombin production, but had little to no effect on total thrombin production. The effect of decreased FXI was milder than seen with decreased FVIII or FIX, and more variable between platelet donors. In contrast, varying the concentration of factors that contribute to formation of the prothrombinase complex, prothrombin or factor (F)V (with FV-deficient platelets), significantly affected all three measures of thrombin production: rate, peak and total. Additionally, while no thrombin generation was observed with no factor X, only very small amounts (between 1% and < 10% of normal plasma levels) were required to normalize the measured parameters. Finally, our results with this cell-based system highlight differences in thrombin generation on cell surfaces (platelets) compared with phospholipids, and suggest that platelets contribute more than simply a surface for the generation of thrombin.
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PMID:Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system. 1500 54

This study assessed the effect on coagulation tests of fresh frozen plasma (FFP), given according to guidelines compared with higher doses in critically ill patients. Group 1 (10 patients) received 12.2 ml/kg and group 2 (12 patients) 33.5 ml/kg FFP. Prothrombin time, activated partial thromboplastin time and factors I-XII were measured before and after FFP infusion. Factor levels of 30 IU/dl (1 g/l for fibrinogen) were considered haemostatic. A retrospective review showed 10 of 22 (five in group 1 and five in group 2) patients had not required FFP. Of those that needed FFP, one of five in group 1 and seven of seven in group 2 had coagulation factor levels above the target post-FFP. Increments for group 1 versus 2 were: fibrinogen 0.4 vs. 1.0 g/l, FII 16 vs. 41*, FV 10 vs. 28*, FVII 11 vs. 38*, FVIII 10 vs. 17, FIX 8 vs. 28*, FX 15 vs. 37*, FXI 9 vs. 23 and FXII 30 vs. 44 IU/dl* (*P < 0.01). In vivo recovery of coagulation factors was the same for both groups and the observed increments correlated with the dose of FFP. In conclusion, coagulation screens were poor predictors of coagulation factor levels and current guidelines on the use of FFP result in predictably small increments in coagulation factors in critically ill patients and should be reviewed.
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PMID:Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. 1501 71

This study was designed to investigate the ability of long-term primary cultures of adult human hepatocytes to secrete the main haemostasis proteins. Factors II, V, VII, VIII, PIVKA-II (protein induced by vitamin K 1 absence or antagonist II), fibrinogen and antithrombin were quantified in culture medium by immunological methods and by measuring the coagulant activity of factors II, V and VII. All the haemostasis protein antigens except the factor VIII antigen (FVIII:Ag) were found in the culture medium throughout the culture period. The clotting activity of each factor correlated well with antigen level. In addition, fibrinogen and fibrin were detected in the fibrillar material following incubation of the culture medium with thromboplastin. Moreover, adding vitamin K 1 to the culture medium resulted in a significant increase of factors II and VII and a reciprocal decrease of the PIVKA-II, and adding von Willebrand factor resulted in a drastic increase of the level of FVIII:Ag. We conclude that, in our culture system, normal adult human hepatocytes retain their capacity to secrete haemostasis proteins for at least 30 days.
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PMID:Secretion of functional plasma haemostasis proteins in long-term primary cultures of human hepatocytes. 1514 80

Blood coagulation activation might be one mechanism linking acute mental stress with coronary events. We investigated the natural habituation of coagulation responses and recovery to short-term mental stress. Three times with one-week intervals, 24 men (mean age 47 +/- 7 years) underwent the same 13-min stressor (preparation, job interview, mental arithmetic). During each visit venous blood was obtained four times (baseline, immediately post-stress, 45 min of recovery, 105 min of recovery). Eight blood coagulation parameters were measured at weeks one and three. Acute stress provoked increases in von Willebrand factor antigen, fibrinogen, clotting factor FVII activity (FVII:C), FVIII:C, FXII:C (p's < or = 0.019), and D-dimer (N.S.). All coagulation parameters experienced full recovery except FVIII:C (p = 0.022). Stress did not significantly affect activated partial thromboplastin time and prothrombin time. At all time points FVIII:C and FXII:C levels were significantly higher at week one compared to week three (p's < or = 0.041). Before catheter insertion, systolic blood pressure (p = 0.001) and heart rate (p = 0.026) were relatively higher at week one. Unlike the magnitude of systolic blood pressure response to stress (p = 0.007) and of cortisol recovery from stress (p = 0.002), the magnitude of all coagulation responses to stress and the recovery from stress were similar in week one and week three. Sympathetic activation with anticipatory stress best explained increased baseline activity in FVIII and FXII at week one. An incapacity of the coagulation system to adapt to stress repeats is perhaps a consequence of evolution, but might also contribute to increased coronary risk in some individuals, particularly in those with cardiovascular diseases.
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PMID:The effect of natural habituation on coagulation responses to acute mental stress and recovery in men. 1558 41

Activated recombinant human factor VIIa (rFVIIa) has been used as a hemostatic agent in patients with hemophilia and acquired inhibitors. Other indications for rFVIIa may include liver disease, warfarin sodium (Coumadin) overdose, or trauma. Monitoring patients on this treatment with standard laboratory testing is problematic. Bleeding risk does not correlate well with the prothrombin time (PT) or the activated partial thromboplastin time (aPTT) during therapy with rFVIIa. In addition, there is no identifiable literature on the effect of rFVIIa on assays of inhibitors in this patient group. Monitoring inhibitors may be important during interventions aimed at acutely reducing inhibitor levels, such as during plasma exchange or protein adsorption. We performed factor assays and evaluated inhibitor levels in plasma from 3 patients with deficiencies in FVIII (2 patients) or FIX (1 patient) and inhibitors (titer range, 5.8-17.4 Bethesda units) before and after adding rFVIIa (range, 0.25-8 microg/mL) in vitro. Additionally, we performed assays of factors of both intrinsic and extrinsic systems to determine the impact of rFVIIa on these tests. We found that both factor levels and inhibitor titers from patients with hemophilia A or B could be measured accurately, even in the presence of suprapharmacologic doses of rFVIIa (8 microg/mL). We also obtained accurate measurements for other assays of the intrinsic coagulation system (FXI and FXII) based on the aPTT. Conversely, we found that assays of the extrinsic system based on the PT (FII, FV, and FX) produced results that were unreliable. FVII results were very high but reproducible. These results suggest that assays based on the PT are inaccurate and should be avoided during FVIIa treatment. Conversely, FVIII and FIX levels and inhibitor titers can be accurately monitored in hemophilia patients receiving rFVIIa according to results of aPTT-based coagulation tests.
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PMID:Effect of activated recombinant human factor 7 (Niastase) on laboratory testing of inhibitors of factors VIII and IX. 1602 35


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