Heparin-induced thrombocytopenia pathophysiology: Difference between revisions
Jump to navigation
Jump to search
mNo edit summary |
Shyam Patel (talk | contribs) |
||
| Line 7: | Line 7: | ||
==Pathophysiology== | ==Pathophysiology== | ||
An understanding of the pathophysiology of HIT requires an understanding of normal physiology: | |||
* Under normal circumstances, [[platelet factor 4]] (PF4) is found in the alpha granules of platelets. It is a positively charged protein that functions to antagonize the effects of heparin-like proteins like heparin sulfate and chondroitin sulfate on the cell surface.<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> PF4 is located intracellularly, but upon platelet activation, PF4 is released, and it contributes to the release of antithrombin from the cell surface, promoting clotting (platelet plugging). | |||
* Under normal circumstances, there are no endogenous antibodies to PF4. | |||
* | The pathophysiology of HIT begins with heparin or heparinoid exposure: | ||
* Heparin exposure can trigger the release of PF4 from endothelial surfaces. Heparin can then form ultra-large complexes with PF4 via electrostatic forces. | |||
* | * These complexes of heparin and PF4 can induce production of antibodies, and this large complex serves as an unfamiliar antigen to the body.<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> IgG antibodies are typically produced. | ||
* | * Immune complexes eventually form, consisting of heparin, PF4 and IgG.<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> The [[crystallized fragment]] domain, or ([[Fc]]) domain of IgG can bind to Fc receptors, such as FC gamma R II, on the surface of a variety of immune cells, including platelets, neutrophils, and monocytes. | ||
* Binding of IgG from the large complexes triggers activation of the target cells and eventual production of thrombin, which is highly thrombogenic and contributes to clot formation.<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> | |||
* Widespread systemic thrombosis can lead to significant morbidity and mortality. | |||
==Reference== | ==Reference== | ||
Revision as of 19:13, 6 July 2017
|
Heparin-induced thrombocytopenia |
|
Differentiating Heparin-induced thrombocytopenia from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Heparin-induced thrombocytopenia pathophysiology On the Web |
|
American Roentgen Ray Society Images of Heparin-induced thrombocytopenia pathophysiology |
|
Heparin-induced thrombocytopenia pathophysiology in the news |
|
Directions to Hospitals Treating Heparin-induced thrombocytopenia |
|
Risk calculators and risk factors for Heparin-induced thrombocytopenia pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]
Overview
Heparin-induced thrombocytopenia is diagnosed when the platelet count falls by > 50% typically after 5-10 days of heparin therapy. 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.
Pathophysiology
An understanding of the pathophysiology of HIT requires an understanding of normal physiology:
- Under normal circumstances, platelet factor 4 (PF4) is found in the alpha granules of platelets. It is a positively charged protein that functions to antagonize the effects of heparin-like proteins like heparin sulfate and chondroitin sulfate on the cell surface.[1] PF4 is located intracellularly, but upon platelet activation, PF4 is released, and it contributes to the release of antithrombin from the cell surface, promoting clotting (platelet plugging).
- Under normal circumstances, there are no endogenous antibodies to PF4.
The pathophysiology of HIT begins with heparin or heparinoid exposure:
- Heparin exposure can trigger the release of PF4 from endothelial surfaces. Heparin can then form ultra-large complexes with PF4 via electrostatic forces.
- These complexes of heparin and PF4 can induce production of antibodies, and this large complex serves as an unfamiliar antigen to the body.[1] IgG antibodies are typically produced.
- Immune complexes eventually form, consisting of heparin, PF4 and IgG.[1] The crystallized fragment domain, or (Fc) domain of IgG can bind to Fc receptors, such as FC gamma R II, on the surface of a variety of immune cells, including platelets, neutrophils, and monocytes.
- Binding of IgG from the large complexes triggers activation of the target cells and eventual production of thrombin, which is highly thrombogenic and contributes to clot formation.[1]
- Widespread systemic thrombosis can lead to significant morbidity and mortality.