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)

We report a truck driver with severe soft tissue contusion of both legs who developed atypical heparin-induced thrombocytopenia (HIT) after a thrombosis prophylaxis with unfractionated heparin; despite a thrombosis the patient showed a systemic allergic reaction to heparin in combination with elevation of thrombocytes and positive heparin-dependent antibodies. Six days after the initial trauma deep vein thrombosis of the left lower leg was diagnosed and fasciotomy was performed, preventing an imminent compartment syndrome. Another 5 days later the patient developed exanthema of the trunk and upper extremities and urticaria on his face, as well as severe headache. His platelet count increased from 134,000/microliter to 258,000/microliter. After exclusion of other causes for these symptoms, a reaction to heparin-dependent antibodies (heparin-platelet-factor 4 complex) was demonstrated 2 days later. Thrombosis prophylaxis was changed to hirudin (Refludan) and elevation of thrombocytes to 445,000/microliter was noted. Shortly after rinsing of an intravenous line with less than 50 IE unfractionated heparin at day 36 after trauma the patient developed an anaphylactic shock, which could be managed with cortisone. We suggest that in HIT the thrombocytopenia may represent only one form of an allergic reaction to heparin. The cause of the thromboembolic event is an antigen-antibody reaction to heparin taking place on the surface of the thrombocyte. This is similar in all forms of systemic reaction to heparin application, even though the symptoms may vary. As thrombocytopenia may not be the main symptom of a heparin-induced antibody reaction--in our hospital only 5 of 10 patients with HIT--the disease should rather be named "heparin allergy". We suggest a new classification of different pattern of heparin allergy types I-IV. The new types I and II are similar to HIT types I and II. Type III is the reaction of antibodies without decrease of thrombocytes, and type IV the reaction of antibodies associated with systemic allergic symptoms.
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PMID:[Atypical heparin-induced thrombocytopenia (HIT)--"heparin allergy" with thrombocytosis]. 1041 4

Antithrombin drugs represent a wide group of natural agents, recombinant agents equivalent to some of the naturally occurring proteins, and synthetic agents. This group of drugs is characterized by marked structural and functional heterogeneity. Several of these drugs are currently in various phases of development. Argatroban represents the first clinically approved antithrombin agent, which was made available in Japan several years ago. Two recombinant hirudin preparations, Revasc (Novartis) and Refludan (Aventis), are available for postsurgical DVT prophylaxis and alternate anticoagulant use in patients with heparin-induced thrombocytopenia. A synthetic antithrombin agent based on the combined structures of hirudin and antithrombin peptides, hirulog (Bivalirudin), is undergoing clinical trials in cardiovascular indications. Additional studies on the hirudins are being carried out to test their efficacy as surgical and interventional anticoagulants as replacements for heparin. However, the need for a proper antagonist is one of the limiting factors for the optimal development of hirudin in this indication. Several of the synthetic thrombin inhibitors are also being developed for oral use for the prophylaxis of DVT in surgical patients. Since the therapeutic index of thrombin inhibitors is narrower than that of heparin, this route may not be an optimal approach for the development of these agents. Despite several unresolved developmental issues, the thrombin inhibitors provide a useful alternative to heparin anticoagulation and may prove to be useful in validated clinical use.
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PMID:Antithrombin agents: the new class of anticoagulant and antithrombotic drugs. 1072 36

Heparin-induced thrombocytopenia (HIT) is a transient hypercoagulability state initiated, paradoxically, by the anticoagulant, heparin. It is characterized by antibody-induced activation of platelets, leading to thrombin generation. Many patients with HIT develop thrombosis; even when heparin is stopped because of "isolated HIT" detected during routine platelet count monitoring, 25-50% of patients subsequently develop symptomatic thrombosis. Thus, an alternative anticoagulant should be substituted for heparin when HIT is strongly suspected. Two direct thrombin inhibitors (DTIs), lepirudin and argatroban, have been studied for prevention and treatment of thrombosis in HIT patients. Lepirudin is a polypeptide that binds irreversibly to the fibrin-binding and catalytic sites on thrombin (bivalent inhibitor). In contrast, argatroban is a synthetic, small-molecule DTI that binds reversibly to the catalytic site alone (univalent inhibitor). Results of historically controlled clinical trials suggest both agents are effective for preventing and treating thrombosis in HIT. However, these agents have not been compared directly, and important differences in study design limit conclusions from indirect comparison. For example, lepirudin was given for 12-14 days (mean) in treatment studies of thrombosis complicating HIT, whereas argatroban was given only for 6-7 days, a difference that could explain apparent lower thrombosis rates (and greater bleeding) with lepirudin. Recently, the transition from DTI therapy to oral anticoagulation in patients with deep venous thrombosis (DVT) complicating HIT has been identified as a risk period for coumarin-induced venous limb gangrene. Thus, the DTI should be given alone during acute HIT, with oral anticoagulants deferred until substantial resolution of the thrombocytopenia has occurred.
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PMID:Management of heparin-induced thrombocytopenia: a critical comparison of lepirudin and argatroban. 1289 20

We report the successful use of r-hirudin (lepirudin) for cardiopulmonary bypass in a 67-year-old man who developed heparin-induced thrombocytopenia type II during heparin treatment of an extensive deep venous thrombosis. Lepirudin was monitored by the modified ecarin clotting time in a "mobile laboratory" set up next to the cardiac theatre, aiming for lepirudin levels of 3.5 to 4.5 microg/ml during bypass.
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PMID:Heparin-induced thrombocytopenia and the use of r-hirudin during cardiopulmonary bypass. 1649 70

Heparin induced thrombocytopenia (HIT) is a serious and life endangering complication of heparin therapy. It usually occurs after 5-14 days of continuous heparin therapy. It is immune mediated. Heparin, in the affected individual binds with platelet factor 4 (PF-4) and forms a highly antigenic Heparin PF-4 complex which leads to the generation of specific IgG Heparin PF4 antibodies (also called HIT antibodies). HIT antibodies may activate the platelets via Fcy receptor causing the release of highly coagulable micro particles which promote thrombosis--both venous and arterial. However, all patients with HIT antibodies do not progress to HIT with thrombosis (HITT). HIT can present as asymptomatic thrombocytopenia. It can also present with alarming features of venous and/or arterial thromboembolism, for example, pulmonary embolism from deep vein thrombosis (DVT), limb gangrene warranting amputation, cerebrovascular attack (CVA) or myocardial infarction (MI). Rare manifestation of HIT includes necrotizing skin lesion, acute anaphylactoid reaction following IV heparin bolus and acute adrenal apoplexy due to massive adrenal vein thrombosis. The diagnosis is based upon the combination of unexplained thrombocytopenia, demonstration of HIT antibodies, clinical profile and outcome of the case following withdrawal of heparin and administration of non-heparin anticoagulant like Lepirudin, Argatroban or Danaparoid. The choice of alternative anticoagulant depends upon the availability, cost, monitoring facilities and administrative guidelines.
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PMID:Heparin induced thrombocytopenia. 1905 9

Vascular thrombosis is a common clinical feature of both essential thrombocythemia (ET) and heparin-induced thrombocytopenia (HIT). The development of HIT in a patient with ET is rare and underrecognized. We report the case of a 77-year-old woman with preexisting ET, who was admitted with acute coronary syndrome, and IV heparin was started. She was exposed to unfractionated heparin (UFH) 5 days prior to this admission. Decrease in platelet count was noted, and HIT panel was sent. Heparin was discontinued. Patient developed atrial fibrillation, and Dabigatran was started. On day three, patient also developed multiple tiny cerebral infarctions and acute right popliteal DVT. On day ten of admission, HIT panel was positive, and Dabigatran was changed to Lepirudin. Two days later, Lepirudin was also discontinued because patient developed pseudoaneurysm on the right common femoral artery at the site of cardiac catheterization access. A progressive increase in the platelet count was noted after discontinuing heparin. Physicians should be aware of the coexistence of HIT and ET, accompanied challenges of the prompt diagnosis, and initiation of appropriate treatment.
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PMID:Heparin-Induced Thrombocytopenia in a Patient with Essential Thrombocythemia: A Case Based Update. 2657 18