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)

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

Argatroban, a synthetic peptidomimetic antithrombin agent, is the first clinical anticoagulant solely to target thrombin. For some time, this drug has been used in Japan for the management of thromboembolic disorders. Recently, it has been approved in Japan for use in thrombotic and ischaemic stroke. Despite a large number of preclinical studies on the pharmacology of this agent, clinical trials in Europe and North America were only initiated in 1996. Argatroban produces anticoagulant effects comparable to therapeutic heparinisation at concentrations of approximately 1 microg/ml. At concentrations of 5-10 microg/ml, this agent produces adequate anticoagulation for inteventional cardiovascular procedures and prolongs the activated clotting time (ACT) to 400-600 s. The predictable anticoagulant effect of this agent is relatively short lasting, and may not warrant pharmacologic neutralisation in the majority of patients. However, patients with hepatic dysfunction may need some means of neutralisation. Unlike heparin, this drug produces its anticoagulant effects by direct inhibition of thrombin and thrombin-mediated processes. This agent is not influenced by endogenous factors such as platelet factor 4 and other proteins which bind heparin. Argatroban's use does not lead to the formation of antiplatelet antibodies. Thus, this drug is useful in the management of heparin induced thrombocytopenic (HIT) patients. Although argatroban was initially developed for the management of deep vein thrombosis (DVT), based on its pharmacologic properties, it can be developed for safer anticoagulation in such indications as acute coronary syndromes, as an adjunct to thrombolytics, thrombotic and ischaemic stroke and inflammatory diseases resulting in thrombotic complications.
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PMID:Pharmacology of argatroban. 1599 20

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

Unfractionated heparin and low-molecular-weight heparin are currently the anticoagulants of choice for the prevention of recurrent thromboembolic disease during pregnancy. However, heparin-induced thrombocytopenia contraindicates the use of unfractionated heparin and low-molecular-weight heparin. We describe a patient who was admitted to our hospital with deep vein thrombosis at 18 weeks of gestation and who developed heparin-induced thrombocytopenia during her antenatal care. Therapeutic anticoagulation was initially achieved with argatroban, then changed to fondaparinux. During early labor, fondaparinux was discontinued and intravenous argatroban was substituted. Argatroban was discontinued during transition to active labor. After return of a normal partial thromboplastin time, combined spinal-epidural analgesia was induced for routine completion of labor and vaginal delivery. We discuss the decisions made in the maintenance of this patient's anticoagulation during the peripartum period as well as timing of her neuraxial labor analgesia.
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PMID:Anticoagulation with argatroban in a parturient with heparin-induced thrombocytopenia. 1962 81

A 60-years old patient was admitted to a community hospital with septic arthritis. He was treated with antibiotics and subcutaneous unfractionated heparin (UH) was used for venous thromboprophylaxis. After three days, he developed leg deep venous thrombosis and was treated with IV heparin. One day later, the patient developed pulmonary emboli, which was found using ventilation/perfusion scan. He was transferred to the University Hospital for further management. Upon arrival, antibiotic and intravenous UH were continued. Trans-Esophageal Echocardiogram showed a thrombus in the right atrium, a small portion of which extended to the left atrium through a patent foramen ovale. Another large thrombus was noted in the right ventricle, which extended to the pulmonary artery. Review of the patient's medical records revealed a halving of his platelet count three days following the heparin administration. Therefore, HIT seemed very likely. Intravenous UH was stopped and an emergency thrombectomy was performed. ELISA testing of HIT antibodies came negative. This made HIT diagnosis unlikely and the patient received dalteparin. A week later, as the platelet count declined again, HIT antibodies' testing using ELISA and C-14 serotonin release was repeated, and both assays were positive. Argatroban was restarted and the platelet count normalized.
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PMID:Heparin-induced thrombocytopenia associated with massive intracardiac thrombosis: a case report. 2293 22

Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.
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PMID:Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor. 2363 77

We present a case of a dialysis-dependent end-stage renal disease patient who originally presented with sepsis and later developed heparin-induced thrombocytopenia-related upper extremity deep venous thrombosis that rapidly progressed to phlegmasia. Argatroban, a direct thrombin inhibitor, was initiated without delay. Argatroban restored the venous patency completely but did not reverse his two gangrenous fingers. The patient finally underwent digital amputation. The management of this uncommon, but life-threatening, situation of upper limb phlegmasia cerulea dolens secondary to heparin-induced thrombocytopenia leading to gangrene is discussed in this case report.
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PMID:Upper Limb Phlegmasia Cerulea Dolens Secondary to Heparin-induced Thrombocytopenia Leading to Gangrene. 3014 6

BACKGROUND Autoimmune heparin-induced thrombocytopenia (aHIT) refers to a condition, in which antiplatelet factor-4 (PF4) antibodies activate platelets even in the absence of heparin (heparin independent platelet activation). This is a severe hypercoagulable state triggering massive thrombin storm needing additional therapies and aggressive anticoagulation apart from stopping heparin. Thrombocytopenia in these cases seems to be very severe and prolonged compared to classic HIT and poses additional clinical challenges in terms of anticoagulation management. Recently, direct oral anticoagulants (DOACs) seem to be an attractive option in the management of HIT as an alternative to vitamin K antagonists (VKA). CASE REPORT We describe a case of a 55-year African American male who presented with pleuritic chest pain and was found to have worsening kidney disease. Clinical and electrocardiogram findings suggested uremic pericarditis, and dialysis was warranted. After 5 days of exposure to heparin flushes during dialysis, the patient developed thrombocytopenia, and subsequently HIT was diagnosed. Argatroban was started initially, however, his platelets count continued to drop, and he developed acute deep venous thrombosis of the right lower leg. IVIG (intravenous immunoglobulin) was started and his platelet count started to improve after several days. The patient was discharged on Eliquis and his platelet count returned to normal levels after 3 months. CONCLUSIONS This case emphasizes the challenge managing HIT, a condition that has a high rate of complications. Several studies have reported platelet recovery with IV immunoglobulin when standard therapies fail. Recent evidence also supports the safety and efficacy of DOACs in offering a simplified way of managing these patients, especially in outpatient settings.
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PMID:Autoimmune Heparin-Induced Thrombocytopenia: Treatment Obstacles and Challenging Length of Stay. 3085 May 76