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)

During late seventies it became apparent that the appearance of antiphospholipid antibodies is associated with thromboembolic manifestations, such as cerebral or myocardial infarction, pulmonary thromboembolism, deep vein thrombosis, intrauterine fetal losses and thrombocytopenia. The term antiphospholipid syndrome has been used to define this set of pathologic features. Recognition of this syndrome has spread worldwide as its clinical implications have become appreciated. Recent studies showed that cofactor, beta 2-glycoprotein I (beta 2-GPI) is required for binding of anticardiolipin antibodies (aCL) raised in the patients with SLE and related other autoimmune disorders. However, this finding has generated considerable controversy. Four different hypotheses have been proposed to explain the specificity of aCL: (1) CL is directly recognized by aCL; (2) the beta 2-GPI-CL complex is the structure recognized by aCL; (3) the beta 2-GPI is the actual target antigen for aCL but is cryptic in the absence of CL; and (4) the actual epitope for aCL appears on the native structure of beta 2-GPI. We showed that aCL bound to beta 2-GPI interacting with poly-oxygenated plates and in the absence of CL, an interaction which depends on introduction of oxygen atoms on the polystyrene surface. We also showed that the beta 2-GPI bound to CL via a particular region on the fifth domain, namely C281KNKEKKC288, and the tertiary structure of the region is involved in binding to phospholipid. Several mechanisms to explain the vascular injury and thrombosis associated with aCL have been proposed, primarily based on their phospholipid reactivity to activated platelets. Whether aCL-through binding to complex of beta 2-GPI and negatively charged phospholipid in the phospholipid-dependent coagulation reactions of hemostasis contribute to the increased risk of thrombosis in patients with aCL is an important question in need of an answer. We have demonstrated the possibility that not only activated platelets but also oxidized lipoproteins, e.g., low-density lipoprotein (LDL), may be thrombogenic targets of aCL which recognize the altered beta 2-GPI structure.
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PMID:[Autoantibodies and thrombosis]. 936 65

To determine whether factor V Leiden is associated with thrombotic events in patients with heparin-induced thrombocytopenia (HIT), we evaluated 165 patients with serologically confirmed HIT for the presence of factor V Leiden and determined the incidence of venous or arterial thrombosis during the period of HIT. Factor V Leiden was detected in 16 of 165 HIT patients (9.7%). HIT-associated venous thrombosis occurred in 11 of 16 factor V Leiden positive subjects and 94 of 149 factor V Leiden negative subjects (69% vs. 63%; p = 0.79). Arterial thrombosis occurred in 1 of 16 factor V Leiden positive subjects and 21 of 149 factor V Leiden negative subjects (6% vs. 14%; p = 0.70). There was no difference in the incidence of proximal limb DVT, pulmonary embolism, venous limb gangrene, local skin reactions, hemorrhagic adrenal infarction, stroke, or myocardial infarction between the groups. No difference in the severity of venous thrombosis between Leiden positive and negative subjects was detected. Our data suggest that in the acute prothrombotic milieu of HIT, heterozygous factor V Leiden is not an important additional risk factor for thrombosis.
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PMID:Factor V Leiden and thrombotic complications in heparin-induced thrombocytopenia. 945 22

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is an immune-mediated response to the administration of heparin that results in life-threatening thrombosis. The pathophysiology of HITTS remains controversial. The onset of clinical symptoms and laboratory changes is usually delayed 1-2 weeks after exposure to heparin. Thrombosis occurs in both the arterial and venous circulation with significant morbidity and mortality. Complications include deep venous thrombosis, pulmonary embolus, stroke, myocardial infarction, chronic venous insufficiency, extremity ischemia, gangrene, and death. Diagnostic criteria for HITTS include thrombocytopenia during heparin exposure, exclusion of other causes such as sepsis or medications, resolution of thrombocytopenia after withdrawal of heparin, demonstration of in vitro heparin-dependent platelet antibodies, and development of vascular thrombosis. Despite having several disadvantages, the carbon-14-serotonin release assay is the most sensitive and specific test for HITTS. Angiography as an adjunct to other imaging modalities can document the presence, location, and extent of thrombus. Optimal treatment has not yet been defined but should include immediate discontinuation of use of all heparin products and heparin-coated catheters. In addition, alternate methods of antithrombotic therapy should be considered. In severe cases, thrombolysis or thrombectomy may be warranted. Familiarity with the pathophysiology, clinical manifestations, complications, diagnostic criteria, and treatment options associated with HITTS will enable timely recognition and facilitate prompt and effective treatment.
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PMID:Heparin-induced thrombocytopenia and thrombosis syndrome. 946 Jan 12

Deep vein thrombosis (DVT) has a high social and economic cost disease being its prevalence in the general population elevated and producing possibly fatal (pulmonary embolism) or disabling (post-thrombotic syndrome) complications. Thus, it appears of great importance to know the epidemiological and clinical characteristics of DVT in order to perform the best diagnosis, therapy and prophylaxis. The study population is composed by 146 patients (84 males and 62 females, mean age 60.9 +/- 15.3 years, range 19.92 years), arrived in our Vascular Echography Laboratory with the clinical suspect of DVT confirmed by means of echo color Doppler. The most frequent clinical signs were skin hyperthermia in 118 patients (80.8%) and edema in 116 patients (79.5%), while the most common symptom was pain, 89 patients (61.0%). Eleven patients (7.5%) were asymptomatic. The echo criteria utilized were direct thrombus visualization, vessel diameter higher than the contralateral, reduced or absent vessel wall ability to be compressed, reduced or absent color Doppler venous flow, lack or reduction of respiratory flow modulation, visualization of collateral circulation. DVT was located in 131 patients (89.7%) in inferior limbs (proximal in 122 patients, isolated distal in 9 patients), in 14 patients (9.6%) in superior limbs and in 3 patients (2.1%) in the internal jugular vein. In 130 patients a risk factor or a predisposing condition was identified: secondary DVT; in 16 patients the DVT was considered idiopathic. The most frequent risk factors were: previous surgery 28.1%, immobilization 19.9% trauma 17.1%, tumors 9.6%. A hypercoagulation was detected in 4 patients: antithrombin III deficit in 2, post-splenectomy thrombocytosis in 1 and antiphospholipid antibodies syndrome in the last one. The Pisa territory epidemiologic data showed a male 0.51 and female 0.38/1000 subject/year DVT incidence, with significantly higher values in older than 45-54 males and 55-64 females. One hundred and thirty one patients were treated with 5-11 day heparin infusion and thereafter with warfarin at least for 6 months, 1 year or indefinitely depending on thromboembolic risk. Six patients with distal DVT and 9 patients with hemorrhagic risk were treated with subcutaneous calcic or low weight heparin. In 1 patient with a mobile thrombus judged as at very high risk of embolization, a caval filter was positioned. Anticoagulant therapy complications were: 2 minor bleedings, 1 alopecia, 1 thrombocytopenia. Two patients died for neoplastic complications. Fifty-seven patients completed a 6-month follow-up and were submitted to a control each study that evidenced: total recanalization in 15 (26.3%), partial recanalization in 25 (43.9%) and no recanalization in 17 patients (29.8%). In 6 patients there was a DVT relapse and in 9 pulmonary embolization: almost all these patients were in the partial recanalization group.
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PMID:[Deep venous thrombosis: epidemiologic, diagnostic and therapeutic aspects]. 967 60

Low-molecular-weight heparin has been studied for the treatment of deep vein thrombosis in the inpatient setting and more recently in the outpatient setting. It is as safe and effective as unfractionated heparin and is effective when administered subcutaneously once or twice a day. Its bioavailability nears 100% and it has a longer half-life than unfractionated heparin, resulting in a prolonged anticoagulant effect. A reduction in thrombocytopenia and bleeding complications with low-molecular-weight heparin has been reported. Laboratory monitoring is unnecessary. Low-molecular-weight heparin provides the opportunity for home therapy.
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PMID:Low-molecular-weight heparin for the treatment of deep vein thrombosis. 969 49

Anticoagulation with heparin has a valuable place in prevention and management of deep venous thrombosis. However, the benefit of heparin in acute ischemic stroke and transient ischemic attack remains unclear despite its widespread use for these indications. Heparin also carries several risks, including unpredictable anticoagulation effects, bleeding, and thrombocytopenia. Low-molecular-weight heparins (LMWHs) and heparinoids have several advantages over heparin, such as higher bioavailability, more predictable anticoagulant effects, and less interaction with platelets. Heparin, LMWHs, and heparinoids have been studied in acute ischemic stroke with variable results. Of three recent, large, controlled clinical trials, only one documented a net benefit of treatment. Fewer patients treated with an LMWH within 48 hours of stroke were dead or disabled at 6 months compared with placebo-treated patients. The largest randomized clinical trial of heparin in acute stroke (the International Stroke Trial) showed that heparin was associated with a significant excess in bleeding complications but no clinical benefit at 6 months. Interim analysis of the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) study also showed an excess number of bleeding complications in the treated group without a corresponding benefit on stroke outcome at 3 months. Therefore, although heparin, LMWHs, and heparinoids continue to be used in the management of patients with acute ischemic stroke, their value in recurrent stroke prevention and in the treatment of stroke-in-progress remains unsettled. Ongoing studies may help to clarify the use of LMWHs and heparinoids in these patients.
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PMID:Heparin and heparinoids in stroke. 974 37

Traditionally, acute deep venous thrombosis (DVT) is treated with intravenous heparin followed by oral anticoagulants. With the advent of the low-molecular-weight heparins (LMWHs), this strategy is changing dramatically. LMWHs are compounds derived from standard unfractionated heparin that offer distinct clinical advantages over unfractionated heparin, including better bioavailability, longer half-life, and a more predictable anticoagulant response that obviates the need for laboratory monitoring. The common side effects of unfractionated heparin, including bleeding, thrombocytopenia, and osteoporosis, may be less common with LMWH. For the treatment of established venous thromboembolism, LMWH is at least as safe and effective as unfractionated heparin. Recent studies demonstrate that home therapy of DVT with LMWH, compared with inpatient therapy with unfractionated heparin, produces comparable clinical outcomes and patient satisfaction, with dramatic cost savings. With careful patient selection, home therapy of venous thromboembolism is quickly becoming the new standard of care.
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PMID:Low-molecular-weight heparin in the treatment of deep venous thrombosis. 979 94

Thrombosis is a common and potentially serious complication of immune-mediated heparin-induced thrombocytopenia (HIT). Discontinuation of heparin is a simple and important maneuver in patients with suspected HIT. Unfortunately, thrombosis often occurs even in those patients in whom heparin was discontinued because of thrombocytopenia alone ("isolated" HIT). It therefore is reasonable to consider prophylactic anticoagulation with an alternate anticoagulant in patients with suspected HIT, especially if their initial indication for anticoagulation persists. For patients with thrombosis complicating HIT, conventional treatment options often have important limitations. Warfarin has a slow onset of action, and its use in patients with acute HIT and deep venous thrombosis has been associated with the devastating syndrome of venous limb gangrene. Ancrod, a defibrinogenating snake venom with thrombin-like activity, has also been used to treat HIT. However, this agent does not inhibit thrombin generation in HIT, which could explain why some patients who have been treated with this agent have developed certain adverse clinical events, such as warfarin-associated venous limb gangrene. The use of low-molecular-weight heparin (LMWH) to treat patients with HIT is limited by their high rate (up to 100%) of in vitro cross-reactivity with HIT sera, and the relatively frequent occurrence of new or recurrent thrombocytopenia or thrombosis during treatment of HIT with this class of agents. In contrast, the mixture of anticoagulant glycosamingoglycans known as danaparoid sodium has a much lower frequency of in vitro cross-reactivity with HIT sera (10% to 40%, depending upon the sensitivity of the assay). Moreover, clinically significant cross-reactivity during treatment with danaparoid appears to be uncommon, even in patients in whom in vitro cross-reactivity is demonstrable.
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PMID:Limitations of conventional treatment options for heparin-induced thrombocytopenia. 985 80

It is clear that patients with malignancy, particularly adenocarcinomas, have an increased propensity to thrombosis. It also appears that patients with malignancy and thrombosis are relatively refractory to warfarin therapy and some may not respond ideally to heparin preparations. Occult malignancy in patients with unexplained thrombosis is of concern; however, the incidence varies with the age of the patient approaching 10% in those over 50 years of age. The extent of the evaluation for an underlying occult malignancy should be dictated by clinical judgment. Recurrent unexplained DVT, resistance to warfarin, and thrombosis of unusual sites are the major clues to significantly enhance the suspicion of an occult malignancy. In general, patients with thrombosis and malignancy need not be evaluated for hereditary or acquired hemostasis defects; finding one of these defects is both unlikely and will probably not alter antithrombotic therapy. Hemorrhage in cancer patients is usually due to thrombocytopenia related to chemotherapy (particularly solid tumors) or bone marrow failure (usually leukemias), or disseminated intravascular coagulation (DIC). DIC is usually seen in M-3 and M-4 leukemia or in septic patients with solid tumors. Finally, catheter thrombosis is a common problem in patients with cancer and can be significantly decreased with the routine use of low-dose warfarin therapy.
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PMID:Issues of thrombosis and hemorrhagic events in patients with cancer. 989 Dec 25

Inspired by the high response rates achieved with the DBCT regimen (dacarbazine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sampling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response rate of 22.7% (95% confidence interval 12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocytopenia, protracted nausea/vomiting and ototoxicity. Renal toxicity was generally mild, but possibly contributed to two deaths. Seven patients experienced deep venous thrombosis during the study. TAM had no influence on the pharmacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment. However, a recent publication concludes that the latter achieves a considerably lower response rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered routinely to unselected patients. Considering the number of potentially serious side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients.
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PMID:Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma. 991 19


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