Heparin-induced thrombocytopenia laboratory findings

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Heparin-induced thrombocytopenia

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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

A variety of laboratory tests can be used to aid in the diagnosis of HIT. A complete blood count is always necessary and will show low platelet count. A high value of the PF4 IgG optical density can suggest HIT. Confirmatory testing is done with the serotonin release assay (SRA), heparin-induced platelet aggregation (HIPA) assay, or other functional assay. These confirmatory tests have high specificity.

Lab tests

The most sensitive lab tests are:

  • Complete blood count (CBC): This will show a low platelet count, (also known as thrombocytopenia). There is no specific threshold below which HIT is diagnosed, but the typical standard is a decrease in platelet count by approximately 50% or more.
  • Anti-heparin-PF4 IgG: This is a test that employs enzyme-linked immunosorbent assay (ELISA) to detect antibodies against the heparin-PF4 complex. The higher the optical density (OD), the stronger the antibody titer and the higher the likelihood of HIT.

The most specific tests are:

  • Serotonin release assay (SRA)
  • Heparin induce platelet aggregation (HIPA) assays
  • Solid-phase immunoassay (SPI) (H-PF4 enzyme-linked immunosorbent assay [ELISA])
  • Particle gel immunoassay (PIFA)

These specific tests are used for confirmatory testing for HIT after the initial PF4-IgG test is found to be high. The sensitivity of these confirmatory tests, however, is 94% at best.

Serotonin release assay (SRA)

  • The gold standard is the serotonin release assay (SRA) where antibodies from the patient’s serum result in release of carbon-14 radiolabeled serotonin attached to platelets from a normal patient.

Heparin-induced platelet aggregation (HIPA) assay

  • The HIPA assay is done via a light transmission aggregometer.[1] It is performed by mixing platelet-poor plasma from a patient with suspected HIT with platelet-rich plasma from donors.
  • It has a >90% specificity but is limited by low sensitivity.

Solid-phase immunoassay (SPI)

  • The SPI is an enzyme-linked immunosorbent assay (ELISA) that tests for the presence or absence of heparin-PF4 complexes.
  • As it does not determine whether the antibodies are functionally significant, it is best used in conjunction with one of the two prior tests. [2] [3] [4] [5]

If HIT is suspected it may take hours to days to obtain the laboratory back. In the meantime it may simply be a safer approach to substitute another agent (eg agatroban) for heparin.

Reference

  1. Harenberg J, Marx S, Krejczy M, Wehling M (2012). "New anticoagulants - promising and failed developments". Br J Pharmacol. 165 (2): 363–72. doi:10.1111/j.1476-5381.2011.01578.x. PMC 3268190. PMID 21740405.
  2. Harenberg J, Huhle G, Giese C, Wang L, Feuring M, Song X, Hoffmann U (2000). "Determination of serotonin release from platelets by enzyme immunoassay in the diagnosis of heparin-induced thrombocytopenia". Br J Haematol. 109 (1): 182–6. PMID 10848798..
  3. Hirsh J, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1992; 102:337S-351S. PMID 1327666
  4. Walenga JM, Bick RL. Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy. Med Clin North Am 1998; 82:635-58. PMID 9646784
  5. Fabris F, Luzzatto G, Stefani PM, Girolami B, Cella G, Girolami A. Heparin-induced thrombocytopenia. Haematologica 2000 Jan; 85:72-81. PMID 10629596

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