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)

Resistance to activated protein C (RAPC) has been described recently as a cause of trombophilia; this may justify up to 50% of thromboembolic disease without predisposing cause in patients under 45 years. A 29 years-old male with a previous deep venous thrombosis (DVT) in the lower left limb three years earlier, developed a DVT in the right lower limb after a trauma of the knee that required immobilization, was associated to pulmonary thromboembolism diagnosed by gammagraphic methods. The phlebographic study showed femoro-iliaco-caval venous thrombosis. The proband's father and a younger brother had a previous history of thrombotic episodes. The following tests, were performed in the proband and relatives: prothrombin time, aPTT, thrombin time, fibrinogen, (Von Clauss), antithrombin III (chromogenic), protein C and protein S (coagulometry and ELISA), plasminogen (chromogenic) and lupus anticoagulant (ITT, dRVVT, aCL). RAPC was evaluated in two different samples. The proband study was performed under oral anticoagulation treatment (OAT). Control groups were: 21 blood donors and 12 OAT patients. The results showed a decreased response to APC in the proband (ratio 1.5) and relatives: father (1.4), brothers (1.5 and 1.5), while the mother was within the normal range (> or = 2). In normal controls and OAT patients the ratio was over 2. No other abnormalities were detected in the assays performed. It is concluded that RAPC is the cause of this familial trombophilia. RAPC should be included in the evaluation study of trombophilia.
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PMID:[Familial thrombophilia due to resistance to activated protein C]. 798 58

Anticoagulants are generally prescribed for the treatment of thrombosis occurring in deep veins. Recent progress in both heparin therapy and in antivitamin K agents require a new look at the therapeutic choice. Due to its immediate anticoagulant action heparin is essential as first intention therapy. Indeed, initial oral anticoagulants are less effective, both in terms of clinical extension and in radiological outcome, than an initial heparin/antivitamin K combination. Non-fractionated heparin administered with an automatic syringe after a priming bolus is the reference treatment for venous thrombosis since it has now been established that 2 subcutaneous injections of heparin are less effective than the intravenous route. Both the effect and safety of low molecular weight heparin have been shown to be comparable with that of non-fractionated heparin. When the dose is adapted to patient weight, 70% are within therapeutic limits after the first injection. Two daily injections of 100 IU per kg body weight can be recommended as initial treatment for deep vein thrombosis. Anticoagulation must be continued for several days but the risk of induced thrombocytopenia persists with low molecular weight heparin. Long-term use should be retained essentially for pregnant women with deep vein thrombosis due to the foetal risk of oral antivitamin K. Antivitamin K oral agents may be initiated early without hindering the anticoagulant effect of heparin. With oral agents, anticoagulant equilibrium is reached, on the average, after 6 days and is a function of vitamin K-dependent half-lives. Since antivitamin K agents affect the stability of prothrombin times during the day/night cycle, it has been recommended to favour long half-life molecules. Standardized prescription protocols can improve safety and anticoagulant equilibrium. To date, the recommended management of deep vein thrombosis includes combining low molecular weight heparin and long half-life antivitamin K. Further progress may be forthcoming with the development of new antithrombotic agents such as hirudine or sulfated heparanes.
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PMID:[Which antithrombotic agents should be prescribed in deep venous thrombosis of the limbs?]. 802 37

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

The important roles of thrombin in the development and propagation of thrombosis are well recognized. In addition to being the enzyme for clotting fibrinogen (the major protein component of blood clots), thrombin accelerates its own generation by activating factor V, factor VIII, factor XI and platelets. It accelerates the stabilization of clots by activating factor XIII to factor XIIIa, the enzyme which crosslinks fibrin. There are probably two major pathways for regulating the availability of thrombin in vivo: inactivation of thrombin (by antithrombin III/vessel wall heparan sulfate and perhaps by other endogenous antithrombins) and the inactivation of factor Va and factor VIIIa by activated protein C. Factor Va and factor VIIIa accelerate the production of thrombin. However, when thrombin becomes bound to fibrin (in clots or possibly on cell surfaces), the ability of antithrombin III/heparin to inactivate thrombin is then reduced significantly. Impairment by fibrin of thrombin inhibition by antithrombin III may account in part for the inability of unfractionated heparin to prevent post-operative deep vein thrombosis in up to 20% of patients who undergo major elective orthopaedic surgery, and may also explain the need for oral anticoagulants after unfractionated and low molecular weight heparins are used to initiate the treatment of established deep vein thrombi. The ineffectiveness of the antithrombin III/heparin pathway for inhibiting thrombin under some circumstances has been a contributory factor for the development, evaluation and identification of other inhibitors of thrombin which are more able than antithrombin III/heparin to inactivate thrombin when the enzyme is bound to fibrin. The focus of this review is to detail how these synthetic agents, by directly or indirectly inactivating thrombin, can also effectively inhibit prothrombin activation in vitro.
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PMID:Mechanisms for the anticoagulant effects of synthetic antithrombins. 815 38

Fibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects. At presentation, D-Di, F 1+2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1+2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 micrograms/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1+2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Markers of hemostatic system activation in acute deep venous thrombosis-evolution during the first days of heparin treatment. The DVTENOX Study Group. 816 10

Three patients are presented with traumatic spinal cord injury (SCI) complicated by acute heterotopic ossification (HO), and concurrent deep vein thrombosis 15 months, 18 months and 22 years after SCI, accompanied by persistent hypercoagulation. The diagnosis of HO preceded deep vein thrombosis in all three patients. All were treated with etidronate disodium and therapeutic heparin followed by oral anticoagulation. As these patients were not acutely injured, the questions arose as to what predisposed them to deep vein thrombosis and when was the appropriate time to discontinue anticoagulation. Over a course of 3 years following deep vein thrombosis, these patients were monitored for evidence of hypercoagulation by D-dimer assay, plasma fibrinogen estimation, and rate of whole blood clotting by Sonoclot coagulation analyzer. The activity of acute HO was assessed by three-phase bone scan. A steady state of hypercoagulation, reflected by an increase in all three parameters, ran parallel to the extent of acute HO for the entire observation period. Moreover, hypercoagulation was persistently greater during increased acute HO activity even when the warfarin-induced prothrombin time ratio was 1.2-1.5. In addition, as acute heterotopic ossification activity decreased, the test values returned to near normal during warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistent hypercoagulation associated with heterotopic ossification in patients with spinal cord injury long after injury has occurred. 825 28

The increased incidence of intravascular thrombosis and thromboembolic episodes in patients with malignant disease is well documented. There have, however, been only two reports of covert malignancy in patients who continue to extend their deep vein thrombosis despite apparently adequate anticoagulation. Three patients are described in whom venous thrombosis steadily worsened despite a prothrombin time of at least twice normal. None had either obvious predisposing factors to thromboembolism or a family history of thrombotic disease. Recognition of this phenomenon can be helpful in avoiding delay in diagnosing malignancy in young patients.
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PMID:Occult malignancy is associated with venous thrombosis unresponsive to adequate anticoagulation. 826 Mar 36

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

Hip joint replacement surgery, using acrylic cement for prosthesis fixation, is associated with intraoperative cardiorespiratory dysfunction, and a high frequency of postoperative proximal deep vein thrombosis (DVT). Levels of prothrombin fragments 1+2 (F1+2), tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), D-dimer and interleukin 6 (IL-6) were measured in arterial (AB) and mixed venous blood (MVB) in five patients during and after total hip replacement operation with acrylic cement prosthesis fixation. Sequential peaks of F1+2, t-PA, PAI-1 and IL-6 appeared, starting with activation of coagulation during preparation of bone, closely followed by activation of fibrinolysis. Later, this was counteracted by an antifibrinolytic response and increase of IL-6. After a fibrinolytic shutdown on the third postoperative day as evidenced by a drop in t-PA and D-dimer concentrations, a second wave of coagulation was seen at the end of the first week. The present model, with frequent sampling of blood entering and leaving the lungs, confirms our earlier findings of the lung as a key organ in promoting coagulation following traumatic activation.
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PMID:Sequential intrapulmonary and systemic activation of coagulation and fibrinolysis during and after total hip replacement surgery. 836 70


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