November 2, 2020

An article review from the ESICM Journal Review Club

A comprehensive evaluation of thrombocytopenia and platelet function in adult ECMO patients.

Haemorrhagic and thromboembolic complications are common during ECMO treatment and result in increased morbidity and mortality. Considering that alterations of platelet activity may play a pivotal role, Jiritano et al. conducted a systematic review and meta-analysis in order to identify the prevalence of thrombocytopenia, platelet dysfunction and major complications in different ECMO modes.

21 randomised controlled trials (RCT), prospective and retrospective observational cohort studies were included in the systematic review, with a total of 7,190 patients. The primary outcome was the occurrence of thrombocytopenia and the platelet dysfunction. The secondary outcomes were the occurrence of confirmed heparin-induced thrombocytopenia (HIT), the rate of platelet transfusion, the occurrence of bleeding and re-exploration for bleeding, and in-hospital mortality.

The authors found a considerable prevalence (up to 21%) of thrombocytopenia in ECMO patients, regardless of the type of ECMO (pooled prevalence: V-A ECMO 23.2% vs V-V ECMO 25.4%). Its origin is likely to be multifactorial (contact with foreign surfaces, platelet activation, inflammatory and coagulative cascade activation), with some contributing factors, such as sepsis, medication, surgery, bleeding, intravascular devices and blood transfusions.

The platelet count usually decreases during the first 2-3 days, for up to 7 days after implantation. The authors found no significant relationship between ECMO duration and the occurrence of thrombocytopenia.

Platelet dysfunction was correlated to different mechanisms, such as impaired platelet aggregation, receptor shedding (i.e. reduced expression of adhesion receptors GP1ba and GPVI), reduced biomarkers of platelet activation and reduced expression of biomarkers of granule secretions (CD62 and CD63).

HIT is an immune-mediated reaction to heparin characterised by thrombocytopenia and paradoxical pro-thrombotic state. Its pooled prevalence during ECMO treatment was 3.7%.

The need for platelet transfusion was reported in two studies and it varied between none and 21.8% of patients.

The studies included showed a high rate of bleeding (16.6% – 50.7%) among ECMO patients. Alternative anticoagulants instead of heparin, such as bivalirudin1, led to a reduced rate of haemorrhagic complications. Re-exploration for bleeding (34%) was reported, especially for post-cardiotomy ECMO.

Finally, the authors found a high in-hospital mortality prevalence (6-88%), which is unlikely to be due to thrombocytopenia or platelet dysfunction only.

STUDY STRENGTHS & LIMITATIONS

Strengths

A comprehensive evaluation of thrombocytopenia and platelet function in adult ECMO patients.

Limitations
  • Low quality of evidence available, with high heterogeneity among populations.
  • Only 9 had low risk of bias, and among these there was just one RCT enrolling about 100 patients.
  • In the included papers, there was no sufficient information to perform other subgroups analysis besides ECMO mode.
  • Not enough data was reported about the technology used, the priming solution, and the anti-platelet medication.
  • The studies included are designed specifically to find out the incidence or suspicions of HIT, which may over-estimate the occurrence of the disease.
TAKE HOME MESSAGE

Thrombocytopenia and platelet dysfunction occur frequently during EMCO treatment and contribute to the high risk of haemorrhagic and thromboembolic complications, with no significant difference between ECMO mode.

This article review was prepared and submitted by Drs. Claudia Stella & Temistocle Taccheri, Fondazione Policlinico A. Gemelli IRCCS, Rome (Italy), on behalf of the ESICM Journal Review Club.


REFERENCES
  1. Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis: Intensive Care Medicine 2020 Jun;46(6):1154-1169. doi: 10.1007/s00134-020-06031-4. Epub 2020 Apr 23.
  2. Bivalirudin versus heparin as an anticoagulant during extracorporeal membrane oxygenation: a case-control study: Cardiothorac VAsc Anesth2013 Feb;27(1):30-4. doi: 10.1053/j.jvca.2012.07.019. Epub 2012 Oct 1.

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