Log in | Register

Prevalence and outcome of heparin-induced thrombocytopenia diagnosed under veno-arterial extracorporeal membrane oxygenation: a retrospective nationwide study

Antoine Kimmoun| Walid Oulehri| Romain Sonneville| Paul-Henri Grisot| Elie Zogheib| Julien Amour| Nadia Aissaoui| Bruno Megarbane| Nicolas Mongardon| Amelie Renou| Matthieu Schmidt| Emmanuel Besnier| Clément Delmas| Geraldine Dessertaine| Catherine Guidon| Nicolas Nesseler| Guylaine Labro| Bertrand Rozec| Marc Pierrot| Julie Helms| David Bougon| Laurent Chardonnal| Anne Medard| Alexandre Ouattara|
Original
Volume 44, Issue 9 / September , 2018

Pages 1460 - 1469

Abstract

Purpose

Thrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO.

Methods

This retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3 days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT.

Results

A total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% [95% CI] [0.21–0.52]). Fourteen of 39 patients (35.9% [20.8–50.9]) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (p = 0.073). The platelet course was similar between Confirmed and Excluded HIT (p = 0.65). Mortality rate was 33.3% [13.2–53.5] in Confirmed and 50% [23.8–76.2] in Excluded HIT (p = 0.48).

Conclusions

Prevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.

Keywords

References

  1. Abrams D, Combes A, Brodie D (2014) Extracorporeal membrane oxygenation in cardiopulmonary disease in adults. J Am Coll Cardiol 63:2769–2778
    • View reference on publisher's website
    • View reference on PubMed
  2. Combes A, Brodie D, Chen YS, Fan E, Henriques JPS, Hodgson C, Lepper PM, Leprince P, Maekawa K, Muller T, Nuding S, Ouweneel DM, Roch A, Schmidt M, Takayama H, Vuylsteke A, Werdan K, Papazian L (2017) The ICM research agenda on extracorporeal life support. Intensive Care Med 43:1306–1318
  3. Abrams D, Baldwin MR, Champion M, Agerstrand C, Eisenberger A, Bacchetta M, Brodie D (2016) Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: a cohort study. Intensive Care Med 42:844–852
  4. Opfermann P, Bevilacqua M, Felli A, Mouhieddine M, Bachleda T, Pichler T, Hiesmayr M, Zuckermann A, Dworschak M, Steinlechner B (2016) Prognostic impact of persistent thrombocytopenia during extracorporeal membrane oxygenation: a retrospective analysis of prospectively collected data from a cohort of patients with left ventricular dysfunction after cardiac surgery. Crit Care Med 44:e1208–e1218
    • View reference on publisher's website
    • View reference on PubMed
  5. Millar JE, Fanning JP, McDonald CI, McAuley DF, Fraser JF (2016) The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology. Crit Care 20:387 (London, England)
    • View reference on publisher's website
    • View reference on PubMed
  6. Murphy DA, Hockings LE, Andrews RK, Aubron C, Gardiner EE, Pellegrino VA, Davis AK (2015) Extracorporeal membrane oxygenation-hemostatic complications. Transfus Med Rev 29:90–101
    • View reference on publisher's website
    • View reference on PubMed
  7. Pouplard C, May MA, Iochmann S, Amiral J, Vissac AM, Marchand M, Gruel Y (1999) Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin: clinical implications for heparin-induced thrombocytopenia. Circ 99:2530–2536
    • View reference on publisher's website
  8. Selleng S, Malowsky B, Strobel U, Wessel A, Ittermann T, Wollert HG, Warkentin TE, Greinacher A (2010) Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positive. J Thromb Haemost 8:30–36
    • View reference on publisher's website
    • View reference on PubMed
  9. Sakr Y (2015) What’s new about heparin-induced thrombocytopenia type II. Intensive Care Med 41:1824–1827
  10. Glick D, Dzierba AL, Abrams D, Muir J, Eisenberger A, Diuguid D, Abel E, Agerstrand C, Bacchetta M, Brodie D (2015) Clinically suspected heparin-induced thrombocytopenia during extracorporeal membrane oxygenation. J Crit Care 30:1190–1194
    • View reference on publisher's website
    • View reference on PubMed
  11. Sokolovic M, Pratt AK, Vukicevic V, Sarumi M, Johnson LS, Shah NS (2016) Platelet count trends and prevalence of heparin-induced thrombocytopenia in a cohort of extracorporeal membrane oxygenator patients. Crit Care Med 44:e1031–e1037
    • View reference on publisher's website
    • View reference on PubMed
  12. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A (2006) Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 4:759–765
    • View reference on publisher's website
    • View reference on PubMed
  13. Cuker A (2014) Clinical and laboratory diagnosis of heparin-induced thrombocytopenia: an integrated approach. Semin Thromb Hemost 40:106–114
    • View reference on PubMed
  14. Lin J, Gallagher M, Bellomo R, Duan M, Trongtrakul K, Wang AY (2018) SOFA coagulation score and changes in platelet counts in severe acute kidney injury: analysis from the randomised evaluation of normal versus augmented level (RENAL) study. Nephrology (Carlton) (Epub ahead of print)
  15. Selleng S, Selleng K (2016) Heparin-induced thrombocytopenia in cardiac surgery and critically ill patients. Thromb Haemost 116:843–851
    • View reference on publisher's website
    • View reference on PubMed
  16. Bakchoul T, Zollner H, Greinacher A (2014) Current insights into the laboratory diagnosis of HIT. Int J Lab Hematol 36:296–305
    • View reference on publisher's website
    • View reference on PubMed
  17. Marler J, Unzaga J, Stelts S, Oliphant CS (2015) Consequences of treating false positive heparin-induced thrombocytopenia. J Thromb Thrombolysis 40:512–514
    • View reference on publisher's website
    • View reference on PubMed
  18. Sanfilippo F, Asmussen S, Maybauer DM, Santonocito C, Fraser JF, Erdoes G, Maybauer MO (2017) Bivalirudin for alternative anticoagulation in extracorporeal membrane oxygenation: a systematic review. J Intensive Care Med 32:312–319
    • View reference on publisher's website
    • View reference on PubMed
  19. Schmidt M, Burrell A, Roberts L, Bailey M, Sheldrake J, Rycus PT, Hodgson C, Scheinkestel C, Cooper DJ, Thiagarajan RR, Brodie D, Pellegrino V, Pilcher D (2015) Predicting survival after ECMO for refractory cardiogenic shock: the survival after veno-arterial-ECMO (SAVE)-score. Eur Heart J 36:2246–2256
    • View reference on publisher's website
    • View reference on PubMed
  20. Smith M, Vukomanovic A, Brodie D, Thiagarajan R, Rycus P, Buscher H (2017) Duration of veno-arterial extracorporeal life support (VA ECMO) and outcome: an analysis of the Extracorporeal Life Support Organization (ELSO) registry. Crit Care (London, England) 21:45
    • View reference on publisher's website
  21. Watson H, Davidson S, Keeling D (2012) Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol 159:528–540
    • View reference on PubMed

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement