Table 2.

Consensus recommendations on platelet markers in COVID-19

Measure	LoE supporting usefulness in COVID-19-related thrombosis			Summary of evidence supporting usefulness	Consensus recommendation	LoEa
	Prognosis	Diagnosis	Management
Platelet count	✓⨯ LoE 1; multiple, mainly retrospective studies, large sample sizes, including several meta-analyses showing that low platelet count is associated with adverse prognosis. LoE 1; DIC (rare) with thrombocytopenia is associated with adverse prognosis. No data that low platelet count predicts thrombosis	⨯	✓ LoE 1; only in the setting of severe thrombocytopenia and DIC	Already a component of standard care; the presence of thrombocytopenia might indicate more severe COVID-19, although prospective study and validation is needed for this particular purpose	Routine use to guide both prognosis and clinical management	1
Immature platelet fraction or count	✓ LoE 2; multiple cohort studies of reasonable size	⨯	⨯	Potentially of use in assessing risk of events such as ICU admission	Potential is evident, but prospective study and validation are needed	2
Blood film (presence of platelet aggregates and free dense granules)	✓ LoE 4; evidence from small case–control studies	⨯	⨯	Potentially of use in detecting severe COVID-19 (requiring treatment in the ICU) versus non-severe disease	Potential is evident, but prospective study and validation are needed	4
Platelet P-selectin expression	✓ LoE 3; evidence from a small case–control study	⨯	⨯	Potentially of use in detecting severe COVID-19 (requiring treatment in the ICU) versus non-severe disease	Potential is evident, but prospective study and validation are needed	4
Soluble P-selectin	✓ LoE 3; evidence from multiple small case–control studies	⨯	⨯	Potentially of use in detecting severe COVID-19 (requiring treatment in the ICU) versus non-severe disease and in predicting death	Potential is evident, but prospective study and validation are needed	3
Soluble CD40L	⨯ Associated with adverse prognosis and treatment in the ICU, but not specifically with thrombosis	⨯	⨯	Evidence of raised levels in COVID-19 versus healthy controls, but no convincing data on usefulness as a marker of thrombosis, although possibly useful as a marker of adverse prognosis	Measurement is not recommended on the basis of current evidence	3
Platelet cytosolic calcium level	✓ LoE 4; evidence from a small case–control study	⨯	⨯	Potentially of use in detecting severe COVID-19 (requiring treatment in the ICU) versus non-severe disease	Potential is evident, but prospective study and validation are needed	4
Platelet phosphatidylserine externalization	✓ LoE 4; evidence from small case–control studies	⨯	⨯	Potentially of use in detecting severe COVID-19 (requiring treatment in the ICU) versus non-severe disease	Potential is evident, but prospective study and validation are needed	4
Platelet glycoprotein Ib or glycoprotein IX	⨯	⨯	⨯	Evidence of raised levels in COVID-19 versus healthy controls, but no evidence as a marker of severity	Measurement is not recommended on the basis of current evidence	4
Platelet–leukocyte aggregates	✓ LoE 3; evidence from multiple small case–control studies	⨯	⨯	Potentially of use in detecting severe COVID-19 (requiring mechanical ventilation) versus non-severe disease	Potential is evident, but prospective study and validation are needed	3
Urinary 11-dehydro-thromboxane B2	✓ LoE 3; evidence from multiple case–control studies	⨯	⨯ Observational study assessed inadequate response to aspirin	Potentially of use in predicting adverse events (including death)	Potential is evident, but prospective study and validation are needed	3
Serum thromboxane B2	⨯ Limited data suggest that levels are elevated in patients with severe disease	⨯	⨯	Conflicting reports of whether or not significant differences are present	Measurement is not recommended on the basis of current evidence	3
Light transmission aggregometry: ADP-induced platelet aggregation	⨯	⨯	⨯	Some evidence of significant differences between those requiring or not requiring treatment in the ICU, but not conclusive and might be affected by confounders	Measurement is not recommended on the basis of current evidence	4–5
Light transmission aggregometry: other agonists	⨯	⨯	⨯	No evidence of significant differences between COVID-19 severities (only between patients with COVID-19 and healthy controls)	Measurement is not recommended on the basis of current evidence	4–5
Multiple electrode aggregometry	⨯	⨯	⨯	No evidence of significant differences between COVID-19 severities (only between patients with COVID-19 and healthy controls)	Measurement is not recommended on the basis of current evidence	4–5
TEG platelet mapping	✓ LoE 3; a small number of studies show an association with thrombotic events	⨯	⨯✓ LoE 4–5; one non-randomized study showed improved outcome with TEG platelet mapping algorithm	Potentially of use to identify patients at risk of thrombosis, especially for those in the ICU; no convincing data that use can improve prognosis or predict thrombotic events	Potential is evident, but prospective study and validation are needed	3
Platelet Function Analyser (PFA-100)	⨯	⨯	⨯	No evidence of significant differences between patients with COVID-19 and healthy controls or between COVID-19 severities	Measurement is not recommended on the basis of current evidence	4–5
Proteomic, transcriptomic or metabolomic studies	⨯	⨯	⨯	No evidence of significant differences between COVID-19 severities (only between patients with COVID-19 and healthy controls)	Measurement is not recommended on the basis of current evidence	4–5

CD40L, CD40 ligand; COVID-19, coronavirus disease 2019; DIC, disseminated intravascular coagulation; ICU, intensive care unit; LoE, level of evidence; TEG, thromboelastography. ^aThe level of evidence to support measurement as a biomarker of thrombosis is based on the scoring system of the Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (ref.²⁵).