Heparin-induced thrombocytopenia classification
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Heparin-induced thrombocytopenia |
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Differentiating Heparin-induced thrombocytopenia from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Aric C. Hall, M.D., [3], Shyam Patel [4]
Overview
Heparin-induced thrombocytopenia is diagnosed when the platelet count falls by > 50% typically after 5-10 days of heparin therapy. There are two forms of HIT: type I and type 2. Type II HIT is the main adverse effect of heparin use.
Classification
A diagnosis of HIT requires the presence of heparin exposure and the subsequent development of antibodies to heparin-PF4 complex. It is typically accompanied by thrombocytopenia (platelet count < 150,000 per microliter). Thrombosis is a common complication but is not required for a diagnosis of HIT.[1] In 10-15% of patients, a decrease in platelet count does not occur. In some cases, the platelet count can decrease by 30-50% and the nadir remains above 150,000 per microliter.[1] The time course for thrombocytopenia is usually 5-14 days after heparin exposure.[2]
Type I
- Type I HIT occurs in 10-20% of all patients on heparin. In this form patients characteristically have a transient decrease in platelet count (rarely <100,000 per microliter) without any further symptoms.
- thrombocytopenia recovers even if heparin is continued to be administered. It is not due to an immune reaction, and antibodies are not found upon investigation.
- It is due to heparin-induced platelet clumping; it is innocuous.[3]
Type II
- Type II HIT is more classic form of HIT. It is due to an autoimmune reaction with antibodies formed against the heparin-platelet factor 4 (PF4) complex. Antibodies can also develop against neutrophil-activating peptide 2 (NAP-2) and interleukin 8 (IL-8) which form complexes with heparin.
- Heparin binding to PF4 causes a conformational change in the protein, rendering it antigenic. Antibodies bind to these complexes, activate the surrounding platelets and generate thrombin. Type II HIT develops in about 3% of all patients on unfractionated heparin (UFH) and in 0.1% of patients on low-molecular weight heparin (LMWH) and causes thrombosis in 30% to 40% of these patients. The other patients are able to compensate for the activation of hemostasis that leads to thrombosis.
- Clot formation is mainly arterial, and most thrombotic events are in the lower limbs. Skin lesions and necrosis may also occur at the site of the heparin infusion. Rapid-onset HIT can result in life-threatening acute systemic reactions (i.e. rigors, fever, hypertension, tachycardia) and cardiopulmonary collapse. Single or trivial doses of heparin, such as catheter flushes, can cause type II HIT.
- The onset of thrombocytopenia is independent of the type of heparin, dose and route of administration, and antibodies can persist for 4-6 weeks but disappear after 3 months. The presence of HIT antibodies, even at higher titer, does not predict an increase in complications. An increase in the titers of the antibodies do, however, result in an increase in the in-vitro activation of the coagulation system.
- The ELISA test, though not ideal, is the best predictive diagnostic test of type II HIT. It has been suggested that type II HIT only occurs with high antibody titers and after persistent exposure to heparin; also it suggests that antigens different from the heparin-PF4 complex can be involved. There may be a HIT antibody active in a non-heparin dependent manner. Data exists suggesting that there are "superactive" HIT antibodies capable of activating platelets without heparin.[4]
Isolated HIT
- Isolated HIT refers to the presence of HIT but absence of thrombosis. Diagnostic criteria are thrombocytopenia after heparin exposure and presence of antibodies to the heparin-PF4 complex, without evidence of clot formation.[5]
Rapid-Onset HIT
- This is characterized by a sudden development of thrombocytopenia within 24 hours in the setting of pre-formed antibodies to heparin-PF4.[1] The presence of pre-formed circulating antibodies is due to exposure to heparin within the past 30 days.
Delayed-Onset HIT
- This is characterized by development of thrombocytopenia after 3 weeks from heparin cessation. This is in contrast with rapid-onset HIT in which the thrombocytopenia occurs abruptly.[1]
Reference
- ↑ 1.0 1.1 1.2 1.3 Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S; et al. (2012). "Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e495S–e530S. doi:10.1378/chest.11-2303. PMC 3278058. PMID 22315270.
- ↑ Greinacher A, Selleng K, Warkentin TE (November 2017). "Autoimmune heparin-induced thrombocytopenia". J. Thromb. Haemost. 15 (11): 2099–2114. doi:10.1111/jth.13813. PMID 28846826.
- ↑ Ahmed I, Majeed A, Powell R (September 2007). "Heparin induced thrombocytopenia: diagnosis and management update". Postgrad Med J. 83 (983): 575–82. doi:10.1136/pgmj.2007.059188. PMC 2600013. PMID 17823223.
- ↑ Franchini, Massimo (2005). Thrombosis Journal. 3 (1): 14. doi:10.1186/1477-9560-3-14. ISSN 1477-9560. Missing or empty
|title=(help) - ↑ Lee GM, Arepally GM (2013). "Heparin-induced thrombocytopenia". Hematology Am Soc Hematol Educ Program. 2013: 668–74. doi:10.1182/asheducation-2013.1.668. PMC 4153428. PMID 24319250.