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)

In a 14-years old girl, suffering from deep venous thrombosis protein C deficiency (activity: 55-58%) was diagnosed. Following rethrombosis oral anticoagulant therapy (OAT) with Phenprocoumon (Marcumar) was started. To find the required dosage for OAT the concentrations of prothrombin fragment (F1+2; < 0.5 nM/l) and fibrin monomers (< 2.5 mg/l) were measured. With this procedure an unusually high thromboplastin time (40-45%) was found to be safe.
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PMID:[Prevention of thrombosis in protein C deficiency]. 833 42

Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder manifested by recurrent thrombosis in the venous and arterial system. We report a group of seven patients with lower limb ischaemia associated with PAPS. Four were male patients and three were females, with a mean age of 37 years. All had a previous deep vein thrombosis and the majority, five out of seven, had a prior cerebrovascular accident (CVA). Prolonged activated thromboplastin time was demonstrated in all our patients and PAPS was established by positive thromboplastin titration index, circulating anticoagulant index and increased anticardiolipin levels. Symptoms included claudication in three, rest pain in four and gangrene in five patients. Angiography demonstrated thrombosis of various segments of the arterial tree including: aorta, iliac, femoral and popliteal arteries. Two patients were treated conservatively and one by percutaneous transluminal angioplasty (PTA) of the distal aorta. A total of eleven vascular surgical procedures were performed in four patients resulting in early postoperative thrombosis (2h-30 days) in 10 cases. Only one graft remained patent, when full heparinisation (1000 units/h) was used perioperatively. We conclude that PAPS patients are at high risk for graft thrombosis and should only be operated upon on full anticoagulation, starting at operation and proceeding indefinitely.
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PMID:Lower limb ischaemia in primary antiphospholipid syndrome. 835 98

The biological response to 4 different heparins after successive subcutaneous administration once daily for 5 days at a dose used for primary prophylaxis of deep vein thrombosis was investigated in a randomized cross-over study in 12 volunteers. Three different preparations of low molecular weight heparins (LMWH) were administered, 10,000 U unfractionated heparin (UFH) was used as a control. The anticoagulant properties in terms of anti-Xa activities, as measured by a chromogenic substrate assay or Heptest, showed high interindividual variations with peak levels 2 to 4 h following injections. There was a significantly higher increase of anti-Xa activities 3 h after administration at day 5, when compared with day 1, for two LMWH's, suggesting an accumulation of the anticoagulatory effect. The anticoagulant activity, especially when measured by Heptest, was significantly influenced by the body weight. This could be observed for all LMWH's. For the assessment of anticoagulant activity in LMWH-treated individuals, the chromogenic substrate assay and Heptest revealed maximal correlation (r = 0.51), while in UFH-treated individuals, peak correlation (r = 0.75) was observed between the partial thromboplastin time and thrombin clotting time. The chromogenic substrate method was the most sensitive anti-Xa assay, showing also the smallest interindividual variation. No significant influence of heparins neither on platelet count and function nor on fibrinolysis were recognized. Enhanced lipolytic activities were not observed. There was an increase of alanine aminotransferases induced by UFH as well as LMWH's, which, however, was most pronounced after UFH.
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PMID:Comparison of low molecular weight heparins and unfractionated heparin after successive subcutaneous administration. A randomized controlled study in healthy volunteers. 839 45

Antiphospholipid antibodies (APL) are associated with venous and arterial thrombosis in SLE patients. Various thrombotic and non-thrombotic neurological manifestations have been reported in SLE but whether or not they are related to the presence of APL antibodies remains uncertain. To assess the possible association between neurological involvement in SLE and APL antibodies, IgG anticardiolipin antibodies (IgG ACL) were looked for using an ELISA technique in 92 consecutive SLE patients seen over a one-year period. Other APL determinations included VDRL and lupus anticoagulant (LAC) testing using APTT and the diluted thromboplastin time. Twenty-four SLE patients presented with neurological manifestations (40 episodes): 15/24 (62.5%) were found positive for APL antibodies (11 VDRL, 8 LAC, 7 ACL antibodies) versus 22/68 patients (32%) without neurological symptoms (p < 0.01). APL antibodies antedated neurological symptoms in 13/16 cases. Neurological manifestations were subsequently divided into 3 groups: thrombotic (n = 14), psychosis and convulsions (n = 15), miscellaneous (n = 10). No correlation was found between APL antibodies and any of the 3 subgroups. Among patients with neurological SLE, APL antibodies were present in two with valvular heart disease, as well as in seven with a history of either deep vein thrombosis, livedo reticularis or miscarriage. Among 7 patients with thrombocytopenia and neurological symptoms, 6 had APL antibodies. These data suggest that APL syndrome is associated with neuro-ophthalmological manifestations of SLE regardless of whether or not the mechanism of neurological involvement is thrombotic. SLE patients with APL antibodies may be at risk for future neurological manifestations. However, it is still questionable that APL positivity has definite therapeutic consequences.
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PMID:Neurological manifestations of systemic lupus erythematosus: role of antiphospholipid antibodies. 840 81

The incidence of postoperative deep vein thrombosis (PDVT) after aortic surgery and lower limb revascularisation has not been assessed by a large prospective study. In a prospective randomised trial the effect of a low-molecular-weight heparin fragment, Enoxaparin (ENX) 4200 anti factor Xa IU once daily was compared to that of unfractionated heparin (UFH) 7500 IU twice daily. Two hundred and thirty-three consecutive patients were classified into three groups, aortic or aortoiliac and aneurysmectomy (n = 75), aorto-femoral bypass for atherosclerotic disease (n = 71), and femoropopliteal or femorodistal bypass (n = 87). Patients were analysed for development of deep vein thrombosis by Duplex scanning and, if positive, by venography between the seventh and tenth postoperative day. PDVT was present in 10 patients in the ENX group and in four patients in the UFH group (8.2 and 3.6% respectively, NS). The incidence of PDVT was 8% after aortic or aortoiliac aneurysmectomy, 7% after aortofemoral revascularisation, and 3.4% after femoropopliteal or femorodistal bypass. The overall incidence of PDVT after aortic surgery was 7.5% (95% CI 5.4-9.7). There was no pulmonary embolism. Intra-operative blood loss and postoperative bleeding events did not differ significantly between the ENX and UFH groups. After 1 month follow-up, no clinical event or death could be related to PDVT or pulmonary embolism. In conclusion, in vascular surgery ENX is as safe and effective in the prevention of PDVT as is UFH.
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PMID:A randomised controlled trial of a low-molecular-weight heparin (Enoxaparin) to prevent deep-vein thrombosis in patients undergoing vascular surgery. 840 1

Native hirudin is a heterogenous polypeptide obtained from the medicinal leech, Hirudo medicinalis. Recent advances in molecular biological techniques have led to the availability of large amounts of hirudin in the recombinant form. Recombinant hirudins (rH) are currently being investigated for potential use in the prophylaxis and treatment of deep venous thrombosis (DVT), in disseminated intravascular coagulation (DIC) and during cardiovascular bypass surgery. In this study, one specific variant of rH with a lysine residue in position 47 (rHV2-Lys 47) was administered in dogs in a multiple dose regimen of 2 mg/kg (i.v. bolus) for three weeks with a dosing interval of one week. After each dose, blood samples were collected at regular time intervals, plasma separated and stored at -4 degrees C. Concentrations of rHV2-Lys 47 in each sample were determined using an enzyme-linked immunosorbent assay (ELISA). Ex vivo antithrombin responses measured included activated partial thromboplastin time (APTT), calcium-thrombin time (Ca++TT-10 NIH units/ml) and a chromogenic anti-IIa assay. It was the purpose of this study to detect any sensitization or desensitization of antithrombin responses when rHV2-Lys 47 is used in a repeated fashion such as would be expected in the prophylaxis of DVT. The results indicated that there was no attenuation in the responses; however, there was a sensitization of response as measured by the Ca++TT (10 NIH units/ml). These findings could have major implications in the clinical use of rH where this drug is expected to be used in a multiple dose regimen.
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PMID:Alteration of pharmacokinetics and pharmacodynamics of recombinant hirudin (rHV2-Lys 47) after repeated intravenous administration in dogs. 846 75

The incidence of thromboembolic complications in patients with multiple injuries was reviewed as well with respect to our own prospective investigation (141 patients with a mean injury severity score of 37 points). The rate of deep venous thrombosis (DVT) in severely injured patients is reported to vary from 20 to 90% if invasive diagnostic procedures are used, whereas the rate of clinically relevant manifestations of DVT seems to be much lower. Although 96% of the patient population in our study were thought to be at high risk of having DVT (applying generally accepted risk factors), only 1.4% of the subjects actually developed clinically relevant DVT. The analysis of several parameters of the coagulation and fibrinolytic systems (platelet count, prothrombin time, partial thromboplastin time, antithrombin III, prothrombin, plasminogen, tissue-plasminogen-activator and its inhibitor) showed simultaneous activation of both systems in these severely injured patients. Thus, increased coagulation seems to be counteracted by increased fibrinolysis. In addition, fluid resuscitation with crystalloid and colloid infusions in the prehospital period (1970 ml and 573 ml, respectively) can be viewed as early prophylaxis of thromboembolic complications. Thus, the low DVT rate in a high-risk patient group with multiple injuries might be at least partially explained.
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PMID:[Venous thrombosis following severe multiple trauma]. 849 93

We identified 100 patients (51 males and 49 females) as having the lupus anticoagulant. The following diagnoses were found in the patient population: human immunodeficiency virus positivity, 20%; systemic lupus erythematosus, 10%; prolonged preoperative activated partial thromboplastin time (APTT), 10%; procainamide hydrochloride-induced inhibitor, 9%; deep vein thrombosis, 6%; seizure disorders/epilepsy, 5%; and miscellaneous conditions, 40%. Identification was based on a prolonged APTT (> 40 seconds) that normalized with increased phospholipid concentrations and/or a prolonged Russell viper venom clotting time patient-control ratio of 1.20 or greater. In 68 cases (group 1), patient plasma prolonged the APTT of normal plasma in a 1:1 mixing study. However, in 32 cases (group 2), no such prolongation was observed. There was a significant difference between presenting APTTs in patients from group 1 (mean +/- SD, 58.29 +/- 13.30 seconds) compared with that in group 2 (mean +/- SD, 47.93 +/- 5.09 seconds). Furthermore, 66% of group 1 patients had elevated anticardiolipin antibody titers compared with only 41% in group 2. Of the 32 patients in group 2, 16 (50%) were positive for human immunodeficiency virus. We concluded that the investigation of a lupus anticoagulant should not be abandoned because patient plasma does not prolong the APTT of normal plasma in a mixing study, especially in a human immunodeficiency virus-positive population.
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PMID:The lupus anticoagulant. High incidence of 'negative' mixing studies in a human immunodeficiency virus-positive population. 850 27

The objective was to retrospectively study the initiation of anticoagulant therapy in inpatients of the two major teaching hospitals in Tasmania, Australia. The medical records of a random sample of patients with an admission diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE) during the period February 1992 to June 1994 were studied, to examine therapeutic issues including (i) the time taken after commencing heparin to achieve a therapeutic activated partial thromboplastin time (APTT), (ii) when warfarin was commenced, (iii) the time taken after commencing warfarin to achieve a therapeutic International Normalized Ratio (INR), and (iv) the degree of anticoagulant control at the time of discharge from hospital. The medical records of 99 patients (median age: 65 years and range: 16-93 years; 52 females) were studied. Heparin was generally commenced within 4 h of admission to hospital. The median duration of heparin therapy was 5 days (range: 2-26 days). The median number of APTTs performed per patient was 6 (range: 1-24), with most results (60%) being below the optimum range. Warfarin was commenced from day 1 of hospitalization in only 34% of patients. The INR was within the therapeutic range in only 29% of cases when heparin was ceased. The median time taken to achieve a therapeutic INR after starting warfarin was 3 days (range: 1-15 days).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Review of the initiation of anticoagulant therapy. 855 86

The potential value of measurements of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer for the assessment of antithrombotic efficacy of heparin in acute deep venous thrombosis (DVT) was prospectively investigated. These variables were determined at presentation and subsequently once daily during a course of seven days heparin therapy. Heparin doses were adjusted according to the activated partial thromboplastin time (APTT). Compression ultrasonography was performed at presentation and on day 7 to determine the extent of thrombosis according to a predefined score. Out of a total of 50 patients accrued to the study 44 patients had reduced or unchanged extent of thrombosis, whereas in six patients an extension was documented. Although thrombin generation was significantly inhibited after initiation of heparin therapy as reflected by a decrease in F1 + 2 and TAT levels, these markers were not useful for the detection of patients with DVT extension. In contrast, anti-factor-Xa activities but not APTT measurements were significantly lower in the group of patients with propagation of DVT (median: 0.22 U/ml versus 0.38 U/ml, interquartile range: 0.1-0.33 U/ml versus 0.19-0.55 U/ml; P = 0.001). D-dimer decreased within the first days of heparin therapy but failed to indicate DVT progression. These data suggest that plasma anti-factor-Xa activity correlates better with the antithrombotic efficacy of heparin than APTT measurements and markers of coagulation or fibrinolysis activation.
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PMID:Markers of coagulation activation for evaluation of the antithrombotic efficacy of heparin: a prospective study in acute deep venous thrombosis. 856 38


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