Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A quantitative and non-occlusive deep vein thrombosis model was developed in rabbits. We used this model to test the antithrombotic activity of the prothrombinase complex inhibitors factor rXai and its chemical analog glutamyl-glycyl-arginyl chloromethyl ketone inactivated human factor Xa (EGR-Xai), along with the thrombin inhibitors D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) and heparin. Dose dependent effects of the inhibitors during constant infusion were monitored. Measurements included thrombus weights, hemostatic parameters and both cuticle and ear bleeding times. In this model, factor rXai and EGR-Xai had comparable in-vivo efficacy, and showed 80%-93% inhibition at plasma levels of 6.5 nM (rXai) and 8 nM (EGR-Xai). Effects on ex-vivo clotting times varied among the inhibitors. At 80-100% thrombus inhibition, factor rXai and EGR-Xai had no statistically significant effect, while PPACK extended thrombin clotting time (TCT) times 2.3-fold, and heparin prolonged both activated partial thromboplastin time (APTT), prothrombin time (PT) and TCT ex-vivo clotting times 6.9-, 1.2-, and 7-fold respectively. At these dosages, cuticle and ear bleeding times were prolonged for all inhibitors and showed increases of 177%-389% (cuticle) and 45%-129% (ear). Our results demonstrate that direct inhibition of prothrombinase complex assembly is effective in arresting venous thrombosis.
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PMID:A comparative study of prothrombinase and thrombin inhibitors in a novel rabbit model of non-occlusive deep vein thrombosis. 802 1

Prevention of deep venous thrombosis is fundamental in the prevention of pulmonary embolism. Deep venous thrombosis is common after all surgical procedures, but the frequency differs, as does the effectiveness of various methods of prevention. Low-dose heparin, low molecular weight heparin, graduated compression elastic stockings, intermittent pneumatic compression, and oral anticoagulants have a role in the prevention of deep venous thrombosis, depending on the risks of deep venous thrombosis and their demonstrated effectiveness (or lack of effectiveness) in the particular circumstance. The optimal method of prophylaxis is specific to the predisposing condition. Heparin continues to be a mainstay of anticoagulant therapy. Major bleeding is rare in patients treated with low doses of heparin to prevent deep venous thrombosis. With therapeutic doses, however, major bleeding occurs in about 5% of patients. The optimal dose of warfarin and the method of evaluating the anticoagulant effect of warfarin have undergone modifications in recent years. It is now recognized that the prothrombin time ratio depends on the activity of the thromboplastin used for measuring the prothrombin time. An International Normalized Ratio, which relates to a standardized thromboplastin, has been developed, thus avoiding differences of the prothrombin time ratio that occur from batch to batch of thromboplastin reagent from the same manufacturer and that occur with different thromboplastin reagents from different animal sources and different manufacturers. The bedside diagnosis of pulmonary embolism is useful in helping a physician determine the extent to which diagnostic tests should be pursued. A sound bedside impression also contributes strongly to the formulation of a noninvasive diagnosis of pulmonary embolism. The clinical manifestations of pulmonary embolism form a recognizable constellation of findings that often lead to a correct diagnosis or exclusion of pulmonary embolism. Important clues to the diagnosis of pulmonary embolism relate to the initial syndrome. The presentation of pulmonary embolism is most often in the form of the pulmonary hemorrhage-pulmonary infarction syndrome. The next most common presentation is unexplained dyspnea, unaccompanied by pulmonary hemorrhage or infarction. Least common, but most severe, is the syndrome of circulatory collapse. Immobilization, usually caused by surgery, is the most frequent predisposing factor. Most patients with clinically recognizable pulmonary embolism have dyspnea or tachypnea. Dyspnea or tachypnea or pleuritic pain occurs in nearly all patients who have clinically apparent pulmonary embolism (97%). Ordinary tests such as the electrocardiogram and chest radiograph are helpful if the physician is attentive to nonspecific abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute pulmonary embolism. 807

Lysis block treatment (LBT) is a new form of fibrinolytic therapy for deep vein thrombosis and arterial occlusion in the distal parts of the limbs. Strictly local lysis was achieved by placing a cuff around the thigh or the upper arm, inflating the cuff to a pressure of 500 mmHg ("Bier's blockade"), and giving heparin and tissue plasminogen activator (rt-PA) by intravenous injection into the dorsal pedis or antecubital veins. Occlusion lasted for one hour. This new technique was demonstrated in 22 patients. Six patients presented with popliteal vein thromboses and 1 patient with a distal femoral vein thrombosis. In addition, 15 arterial occlusions were treated comprising 3 calf, 6 popliteal, 3 distal femoral, and 2 digital sites and 1 brachial site. Five of 7 venous and 9 of 15 arterial occlusions were partially or totally removed. The activated partial thromboplastin time remained nearly unchanged during LBT and only a limited and short-term lengthening was recorded after restoration of blood flow. This was of importance for patients with bleeding tendencies, which are normally a contraindication for systemic lysis. LBT may therefore be considered as a useful alternative to systemic fibrinolytic treatment.
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PMID:Lysis block treatment: a new form of local thrombolysis. 812 90

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heparin therapy in pediatric patients: a prospective cohort study. 813 3

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

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


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