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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]

Overview

Heparin-induced thrombocytopenia is diagnosed when the platelet count falls by > 50% typically after 5-10 days of heparin therapy. 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.

Lab tests

The most specific tests are:

  • The serotonin release assay (SRA)
  • The heparin induce platelet aggregation (HIPA) assays and
  • Sthe solid-phase immunoassay (SPI) (H-PF4 enzyme-linked immunosorbent assay [ELISA]), and
  • Particle gel immunoassay (PIFA)
  • The sensitivity of these tests is 94% at best.

The serotonin release assay (SRA)

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

The heparin induce platelet aggregation (HIPA) assays

  • The HIPA looks for platelet aggregation that is present with heparin, platelets and patient serum but does not occur in the absence of heparin.
  • It has a >90% specificity but is limited by low sensitivity.

The 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. [1] [2] [3] [4]

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. If there is a major diagnostic doubt then there is a "4T" system for identifying patients at risk for HIT. It is defined as follows; 0-3 points; low probability 4-5 points; intermediate probability 6-8 points; high probability If the probability is high then discontinue the heparin and begin an alternative anticoagulant; some references recommend the same for those of intermediate risk too.

1) Thrombocytopenia;

  • 0 points for <30% fall or a nadir <10,000
  • 1 point for a 30-50% fall or a nadir of 10-19,000
  • 2 points for a >50% fall or a nadir greater than or equal to 20,000

2) Timing of the decrease in platelet count;

  • 0 points for less than a day
  • 1 point for greater than day 10 or timing unclear or less than day 1 if heparin exposure was within the past 30-100 days.
  • 2 points for day 5-10 or less than or equal to day 1 with recent heparin use (past 30 days)

3) Thrombosis or other sequelae;

  • 0 points for no thrombosis
  • 1 point for progressive, recurrent or silent thrombosis; erythematous skin lesions.
  • 2 points for a proven thrombosis, skin necrosis or acute systemic reaction after heparin bolus.

4) Other causes of thrombocytopenia;

  • 0 points if a definitive concurrent cause.
  • 1 point if there is a possible other reason for thrombocytopenia.
  • 2 points if there are no other possible reasons for thrombocytopenia.

Isolated HIT: This entity occurs when there is a decreased platelet count but without evidence of thrombosis. It is recommended to stop the heparin and use alternative anticoagulation. It is also recommended to screen for subclinical deep venous thrombosis with a compression ultrasound (~50% of patients show a DVT with this check).

References

  1. 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..
  2. 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
  3. 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
  4. 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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