Prospective Evaluation of a Rapid Functional Assay for Heparin-Induced Thrombocytopenia Diagnosis in Critically Ill Patients

Crit Care Med. 2019 Mar;47(3):353-359. doi: 10.1097/CCM.0000000000003574.


Objectives: Overdiagnosis of heparin-induced thrombocytopenia remains an unresolved issue in the ICU leading to the unjustified switch from heparin to alternative anticoagulants or delays in anticoagulation. Platelet function assays significantly improve the specificity of heparin-induced thrombocytopenia diagnosis, but they are not readily available, involve technical difficulties and have a long turnaround time. We evaluated the performance of a rapid and easy to perform functional assay for heparin-induced thrombocytopenia diagnosis in ICU patients, known as "heparin-induced multiple electrode aggregometry."

Design: In this observational prospective study patients were tested with the immunoglobulin G enzyme-linked immunosorbent assay, the serotonin release assay and heparin-induced multiple electrode aggregometry. Heparin-induced multiple electrode aggregometry was assessed against heparin-induced thrombocytopenia diagnosis (clinical picture in favor, serotonin release assay, and immunoglobulin G enzyme-linked immunosorbent assay positive) and serotonin release assay.

Setting: Medical or surgical ICU of 35 medical centers.

Patients: Patients suspected for heparin-induced thrombocytopenia hospitalized in medical or surgical ICU from January 2013 to May 2013.

Interventions: None.

Measurements and main results: Heparin-induced thrombocytopenia diagnosis was retained in 12 patients (14%). Using heparin-induced thrombocytopenia diagnosis as reference, heparin-induced multiple electrode aggregometry showed an excellent negative predictive value and sensitivity, at 98% and 92% respectively. Its positive predictive value and specificity were 100%. Receiver operating characteristic analysis with the serotonin release assay as reference showed an optimal heparin-induced multiple electrode aggregometry cut-off at 1,300 AU × minutes (specificity, 100%; sensitivity, 90%; area under the curve, 0.98; 95% CI, 0.95-1.0). The Kappa coefficient between heparin-induced multiple electrode aggregometry and the serotonin release assay was at 0.90%.

Conclusions: Heparin-induced multiple electrode aggregometry performed very well in heparin-induced thrombocytopenia diagnosis in ICU patients and agreed with the gold standard test for heparin-induced thrombocytopenia diagnosis, the serotonin release assay. Heparin-induced multiple electrode aggregometry is a reliable and rapid platelet functional assay that could decrease heparin-induced thrombocytopenia overdiagnosis in the ICU setting.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Critical Illness
  • Electric Impedance
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heparin / adverse effects*
  • Humans
  • Male
  • Platelet Aggregation
  • Platelet Function Tests / methods*
  • Prospective Studies
  • Sensitivity and Specificity
  • Thrombocytopenia / diagnosis*
  • Thrombocytopenia / etiology


  • Heparin