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Assist in the diagnosis of heparin-induced thrombocytopenia.
HIPA results should not be the sole basis for establishing the diagnosis of heparin-induced thrombocytopenia. Some patients with HIPA will not develop symptoms of heparin-induced thrombocytopenia (HIT). Microbial contamination, lipemia, icterus, or hemolysis may interfere with this test and immune complexes or immunoglobulin aggregates in the patient sample can produce false-positive results. Heparin in the sample (>1 unit/mL) can produce false-negative results.
HIT, also referred to as heparin-associated thrombocytopenia (HAT), occurs in 1% to 5% of patients treated with standard unfractionated heparin.1-3 The most common form of HIT presents as a mild thrombocytopenia one to five days after initiation of heparin therapy. Type I HIT is not thought to be immune in etiology and may be mediated by a direct interaction between heparin and circulating platelets, causing platelet clumping or sequestration. This type of heparin-associated thrombocytopenia often occurs in patients on their first exposure to heparin.1 In this condition, platelet counts typically normalize within a few days, regardless of whether or not heparin therapy is continued.
Type II HIT is a much more clinically-significant, immune-mediated response to heparin that is frequently associated with the production of HIPA. Type II HIT can be associated with severe thrombosis, with the platelet count decreasing typically by 50%. The thrombocytopenia typically begins later than that of type I HIT, usually occurring some 5 to 10 days after the initiation of heparin therapy in patients who had never been previously exposed to heparin. Patients with prior exposure to heparin can develop thrombocytopenia more quickly on re-exposure due to earlier sensitization. In type II HIT, heparin is thought to bind to platelet factor 4, be found on platelets and endothelial cells, and to produce a conformational change, exposing antigenic sites for antibody formation.2 These antibodies bind to the heparin-PF4 complex and can activate platelets, resulting in the formation of microparticles and thrombin generation, with subsequent production of potentially severe venous or arterial thrombosis. Heparin treatment should be stopped and alternative anticoagulation considered in patients who develop type II HIT.1,2
Like other serologic (EIA based) assays, this assay has a high negative predictive value and only a moderate positive predictive value for HIT.4 Recent studies have shown that the magnitude (optical density, OD) of the result relative to the cutoff of 0.4 OD can provide useful information regarding the probability of developing HIT.4-8 The likelihood of developing HIT is significantly higher when the OD is >2.0 than when the OD is closer to the cutoff.4-8 One recent study revealed that patients with negative results just below the cutoff of 0.4 OD have a high probability of having positive results on repeat testing a few days later.9
1. Adcock DM, Bethel MA, Macy PA. Coagulation Handbook.Aurora, Colo: Esoterix-Colorado Coagulation; 2006.
2. Warkentin TE. Heparin-induced thrombocytopenia. In Kitchens CS, Alving BM, Kessler CM, eds. Consultative Hemostasis and Thrombosis. Philadelphia, Pa: WB Saunders Co; 2002:355-372.
3. Fabris F, Ahmad S, Cella G, Jeske WP, Walenga JM, Fareed J. Pathophysiology of heparin-induced thrombocytopenia. Clinical and diagnostic implications-A review. Arch Pathol Lab Med. 2000 Nov; 124(11):1657-1566. PubMed 11079020
4. Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep, 126(3 Suppl):311S-337S [published erratum: Chest. 2005 Jan; 127(1):416]. PubMed 15383477
5. Warkentin TE, Sheppard JA, Horsewood P, Simpson PJ, Moore JC, Kelton JG. Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood. 2000 Sep 1; 96(5):1703-1708. PubMed 10961867
6. Warkentin TE, Heddle NM. Laboratory diagnosis of immune heparin-induced thrombocytopenia. Curr Hematol Rep. 2003 Mar; 2(2):148-157 (review). PubMed 12901146
7. Fabris F, Luzzatto G, Soini B, et al. Risk factors for thrombosis in patients with immune mediated heparin-induced thrombocytopenia. J Intern Med. 2002 Aug; 252(2):149-154. PubMed 12190890
8. Zwicker JI, Uhl L, Huang WY, Shaz BH, Bauer KA.. Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia. J Thromb Haemost. 2004 Dec, 2(12):2133-2137. PubMed 15613017
9. Refaai MA, Laposata M, Van Cott EM. Clinical significance of a borderline titer in a negative ELISA test for heparin-induced thrombocytopenia. Am J Clin Pathol. 2003 Jan; 119(1):61-65. PubMed 12520698
