Journal of Thrombosis and Thrombolysis

, Volume 39, Issue 1, pp 60–67 | Cite as

Prevalence and clinical implications of anti-PF4/heparin antibodies in intensive care patients: a prospective observational study

  • Sixten SellengEmail author
  • Kathleen Selleng
  • Sigrun Friesecke
  • Matthias Gründling
  • Sven-Olaf Kuhn
  • Ricarda Raschke
  • Olivia J. Heidecke
  • Carsten Hinz
  • Gregor Hron
  • Theodore E. Warkentin
  • Andreas Greinacher


Data on the frequency of anti-platelet factor 4/heparin (PF4/H) antibodies and their association with outcomes in intensive care unit (ICU) patients are sparse. In this prospective, observational study we screened 320 consecutive surgical/medical ICU patients for anti-PF4/H antibodies by enzyme-immunoassay (EIA) for immunoglobulin (Ig)G/A/M separately and heparin-induced platelet activation assay (HIPA) at ICU admission (=baseline), day 6, and day 10. HIPA-positive patients were additionally tested by serotonin-release assay (SRA). Patients tested positive by day 10: for anti-PF4/H-IgG = 17.2 % and for anti-PF4/H-IgM = 42.1 %. Within the first 10 ICU days, platelet counts decreased to <100 Gpt/L in 27.8 % patients. However, only seven patients (2.2 %) experienced a drop in the platelet count ≥50 % beginning after the fourth ICU day. These included the only two patients (0.6 %; 95 % confidence interval 0.08–2.2 %) with heparin-induced thrombocytopenia (HIT). Only strong reactions in the HIPA were reproducible by SRA. This study confirms that testing for anti-PF4/H IgG antibodies should be restricted to ICU-patients who develop a platelet count decrease of >50 % that begins after day four of heparin treatment (which may have started before ICU admission). Among patients testing positive by IgG-specific EIA a functional platelet activation assay should be performed (regarding only strong reactions as positive).


Heparin-induced thrombocytopenia Laboratory testing Platelet 4/heparin antibodies Critical care Intensive care 



This study was supported by the German Federal Ministry for Education and Research (ZIK-HIKE 03Z2CK1) and was performed within the Department of Cardiovascular Medicine at the Medical Faculty, Ernst-Moritz-Arndt-Universität, Greifswald.

Conflict of interests

All authors state that they have no conflict of interests.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sixten Selleng
    • 1
    Email author
  • Kathleen Selleng
    • 2
  • Sigrun Friesecke
    • 3
  • Matthias Gründling
    • 1
  • Sven-Olaf Kuhn
    • 1
  • Ricarda Raschke
    • 2
  • Olivia J. Heidecke
    • 2
  • Carsten Hinz
    • 2
  • Gregor Hron
    • 2
  • Theodore E. Warkentin
    • 4
  • Andreas Greinacher
    • 2
  1. 1.Department of Anaesthesiology and Intensive CareUniversity Medicine GreifswaldGreifswaldGermany
  2. 2.Institute for Immunology and Transfusion MedicineUniversity Medicine GreifswaldGreifswaldGermany
  3. 3.Department of Internal Medicine BUniversity Medicine GreifswaldGreifswaldGermany
  4. 4.Hamilton Regional Laboratory Medicine Program, Department of Pathology and Molecular Medicine, Hamilton General Hospital, Hamilton Health SciencesMcMaster UniversityHamiltonCanada

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