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| ==Overview== | | ==Overview== |
| [[Heparin-induced thrombocytopenia]], or [[HIT]], is a transient yet potentially life-threatening thrombotic disease characterized by low platelet count and paradoxical blood clot formation after exposure to the anticoagulant heparin or its derivatives.<ref name="pmid23714311">{{cite journal| author=Lee GM, Arepally GM| title=Diagnosis and management of heparin-induced thrombocytopenia. | journal=Hematol Oncol Clin North Am | year= 2013 | volume= 27 | issue= 3 | pages= 541-63 | pmid=23714311 | doi=10.1016/j.hoc.2013.02.001 | pmc=3668315 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23714311 }} </ref> Typical manifestations include [[thrombocytopenia]] with > 50% drop in [[platelet]] count after 5-14 days of receiving heparin.<ref name="pmid23714311">{{cite journal| author=Lee GM, Arepally GM| title=Diagnosis and management of heparin-induced thrombocytopenia. | journal=Hematol Oncol Clin North Am | year= 2013 | volume= 27 | issue= 3 | pages= 541-63 | pmid=23714311 | doi=10.1016/j.hoc.2013.02.001 | pmc=3668315 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23714311 }} </ref> Though there is a large reduction in the [[platelet]] count, platelet counts less than 20,000 per [[microliter]] are quite unusual for the syndrome.<ref name="pmid20059332">{{cite journal |author=Arepally GM, Ortel TL |title=Heparin-induced thrombocytopenia |journal=Annu. Rev. Med. |volume=61 |issue= |pages=77–90 |year=2010 |pmid=20059332 |doi=10.1146/annurev.med.042808.171814 |url=}}</ref> Given that the nadir in the platelet count is not extremely low, clinically significant bleeding is rarely associated with HIT. On the contrary, HIT is primarily a [[thrombotic]] disorder, with very high rates of [[thrombosis]] in the [[artery|arteries]] with or without [[vein|venous]] complications.
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| ==Historical Perspective== | | ==Historical Perspective== |
| In the 1950s, Rodger Weissman and Richard Tobin of Hitchcock Memorial Hospital and Dartmouth Medical School describes the phenomenon of HIT.<ref name="pmidPMID13497418">{{cite journal| author=WEISMANN RE, TOBIN RW| title=Arterial embolism occurring during systemic heparin therapy. | journal=AMA Arch Surg | year= 1958 | volume= 76 | issue= 2 | pages= 219-25; discussion 225-7 | pmid=PMID13497418 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13497418 }} </ref> <ref name="pmid23714311">{{cite journal| author=Lee GM, Arepally GM| title=Diagnosis and management of heparin-induced thrombocytopenia. | journal=Hematol Oncol Clin North Am | year= 2013 | volume= 27 | issue= 3 | pages= 541-63 | pmid=23714311 | doi=10.1016/j.hoc.2013.02.001 | pmc=3668315 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23714311 }} </ref> They noted an alarming increase in the incidence of peripheral arterial embolism after systemic heparin therapy.<ref name="pmidPMID13497418">{{cite journal| author=WEISMANN RE, TOBIN RW| title=Arterial embolism occurring during systemic heparin therapy. | journal=AMA Arch Surg | year= 1958 | volume= 76 | issue= 2 | pages= 219-25; discussion 225-7 | pmid=PMID13497418 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13497418 }} </ref> They reported 10 cases of embolism and thrombotic complications after heparin. <ref name="pmidPMID13497418">{{cite journal| author=WEISMANN RE, TOBIN RW| title=Arterial embolism occurring during systemic heparin therapy. | journal=AMA Arch Surg | year= 1958 | volume= 76 | issue= 2 | pages= 219-25; discussion 225-7 | pmid=PMID13497418 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13497418 }} </ref> Emboli were noted in the femoral, popliteal, and cerebral circulation. This seminal study paved the way for future investigations into the pathophysiology of HIT.
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| ==Classification== | | ==Classification== |
| There are two types of [[HIT]], type I and type II. Type I HIT patients characteristically have a transient decrease in platelet count (rarely <100,000) without any further symptoms and can recover even if heparin is continued to be administered. It occurs in 10-20% of all patients on heparin and is not due to an immune reaction and antibodies are not found upon investigation. HIT-1 is due to heparin-induced platelet clumping; it is innocuous. Type II is due to an autoimmune reaction with antibodies formed against platelet factor 4 (PF4), neutrophil-activating peptide 2 (NAP-2) and interleukin 8 (IL8) which form complexes with heparin.
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| ==Pathophysiology== | | ==Pathophysiology== |
| It is caused by antibodies to complexes between [[heparin]] and [[platelet factor 4]] (PF4). These antibody complexes stimulates the procoagulant pathways due to activation of [[platelet]] and [[endothelium]].
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| ==Causes== | | ==Causes== |
| '''Heparin-induced thrombocytopenia''' ([[HIT]]) with or without '''[[thrombosis]]''' (HITT) is [[thrombocytopenia]] (low [[platelet]] counts) due to the administration of [[heparin]]. While it is mainly associated with [[unfractionated heparin]] ([[UFH]]), it can also occur with exposure to [[low-molecular weight heparin]] (LMWH), but at significantly lower rates.
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| ==Differentiating Heparin-induced thrombocytopenia from other Diseases== | | ==Differentiating Heparin-induced thrombocytopenia from other Diseases== |
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| ==Epidemiology and Demographics== | | ==Epidemiology and Demographics== |
| It has been found to occur with increased frequencies in females, white population and patients over age of 60 years. An episode of [[Heparin-induced thrombocytopenia]] increases risks for other future thrombo-embolic events.
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| ==Risk Factors== | | ==Risk Factors== |
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| ==Diagnosis== | | ==Diagnosis== |
| ===History and symptoms=== | | ===History and symptoms=== |
| HIT typically develops 4-14 days after the administration of [[heparin]]. The onset of thrombocytopenia in less than 4-5 days after the initiation of heparin treatment is extremely rare due to the time required for antibody production, and alternative explanations should be sought for the development of thrombocytopenia this early in therapy. The primary exception to this is in the case of recent heparin exposures (<100 days) where the patient may have pre-existing antibodies against the heparin-PF4 complex.<ref name="pmid16928996">{{cite journal |author=Arepally GM, Ortel TL |title=Clinical practice. Heparin-induced thrombocytopenia |journal=N. Engl. J. Med. |volume=355 |issue=8 |pages=809–17 |year=2006 |month=August |pmid=16928996 |doi=10.1056/NEJMcp052967 |url=}}</ref>
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| ===Physical Examination=== | | ===Physical Examination=== |
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| ===Laboratory Findings=== | | ===Laboratory Findings=== |
| The four commonest diagnostic tests used for heparin-induced thrombocytopenia (HIT) are Serotonin release assay, heparin-induced platelet aggregation assay, solid phase immunoassay (enzyme-linked immunosorbent assay), and particle gel immunoassay.
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| ===Imaging Findings=== | | ===Imaging Findings=== |
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| ==Treatment== | | ==Treatment== |
| ===Medical Therapy== | | ===Medical Therapy== |
| Treatment is by prompt withdrawal of [[heparin]] and replacement with a suitable alternative anticoagulant. [[Lepirudin]], [[fondaparinux]], [[bivalirudin]], [[argatroban]], [[danaparoid]] or other [[direct thrombin inhibitor]]s are used to treat the thrombotic state. Out of these lepirudin and argatroban are available for use in USA.
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| ==Prevention== | | ==Prevention== |
| Patients with HIT should be treated with [[Bivalirudin]], a direct thrombin inhibitor to support future procedures.
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| ==References== | | ==References== |