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==Overview==
==Overview==
[[Heparin-induced thrombocytopenia]] is diagnosed when the [[platelet]] count falls by > 50% typically after 5-10 days of [[heparin]] therapy. The development of mild to moderate thrombocytopenia (platelet counts of 50-70,000) in the context of heparin exposure is suggestive of a possible diagnosis of HIT while severe thrombocytopenia and platelet counts less than 20,000 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 the nadirs in the platelet count, clinically significant bleeding associated with the thrombocoytopenia is quite rare. On the contrary, heparin induced thrombocytopenia is primarily a [[thrombosis|thrombotic]] disorder, with very high rates of [[thrombosis]], in the [[artery|arteries]] with or without [[vein|venous]] complications.
[[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.


==Historical Perspective==
==Historical Perspective==

Revision as of 18:07, 6 July 2017

Heparin-induced thrombocytopenia

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Heparin-induced thrombocytopenia from other Diseases

Epidemiology and Demographics

Risk Factors

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Diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2] Shyam Patel [3]

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.[1] Typical manifestations include thrombocytopenia with > 50% drop in platelet count after 5-14 days of receiving heparin.[1] Though there is a large reduction in the platelet count, platelet counts less than 20,000 per microliter are quite unusual for the syndrome.[2] 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 arteries with or without venous complications.

Historical Perspective

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.

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.

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.

Differentiating Heparin-induced thrombocytopenia from other Diseases

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.

Risk Factors

Screening

Natural History, Complications, and Prognosis

Natural History

Complications

Prognosis

Diagnosis

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.[3]

Physical Examination

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.

Imaging Findings

Other Diagnostic Studies

Treatment

=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 inhibitors are used to treat the thrombotic state. Out of these lepirudin and argatroban are available for use in USA.

Prevention

Patients with HIT should be treated with Bivalirudin, a direct thrombin inhibitor to support future procedures.

References

  1. 1.0 1.1 Lee GM, Arepally GM (2013). "Diagnosis and management of heparin-induced thrombocytopenia". Hematol Oncol Clin North Am. 27 (3): 541–63. doi:10.1016/j.hoc.2013.02.001. PMC 3668315. PMID 23714311.
  2. Arepally GM, Ortel TL (2010). "Heparin-induced thrombocytopenia". Annu. Rev. Med. 61: 77–90. doi:10.1146/annurev.med.042808.171814. PMID 20059332.
  3. Arepally GM, Ortel TL (2006). "Clinical practice. Heparin-induced thrombocytopenia". N. Engl. J. Med. 355 (8): 809–17. doi:10.1056/NEJMcp052967. PMID 16928996. Unknown parameter |month= ignored (help)

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