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Severe COVID-19 and coagulopathy: A systematic review and meta-analysis
Saikat Mitra1, Ryan Ruiyang Ling, Isabelle Xiaorui Yang
1Cardiothoracic Intensive Care Unit, National University Heart Centre, National University Hospital, Singapore.
Insights
COVID-19-induced coagulopathy (CIC) shows variable abnormalities. Severe cases exhibit lower platelet counts and higher D-dimer levels, predicting disease severity. Monitoring coagulation helps manage CIC.
Area of Science:
- Hematology
- Infectious Diseases
- Critical Care Medicine
Background:
- Coronavirus disease 2019 (COVID-19) is associated with coagulopathy (CIC), but the range of abnormalities is not well-defined.
- Understanding CIC is crucial for managing severe COVID-19 cases.
Purpose of the Study:
- To systematically review and assess COVID-19-induced coagulopathy (CIC) in relation to disease severity.
- To identify risk factors associated with CIC.
Main Methods:
- Systematic literature review of studies published until June 1, 2020.
- Meta-analyses and meta-regression of coagulation parameters (platelet count, D-dimer, prothrombin time, aPTT, fibrinogen) in non-severe versus severe COVID-19 patients.
- Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach used for certainty of evidence.
Main Results:
- Severe COVID-19 patients (n=5,243) showed significantly lower platelet counts and higher D-dimer, prothrombin time, and fibrinogen levels compared to non-severe patients.
- Platelet count and D-dimer levels were significant predictors of disease severity.
- Older men faced higher risks of severe coagulopathic disease.
Conclusions:
- Significant variability in CIC exists, with platelet count and D-dimer levels correlating with disease severity.
- Routine monitoring of coagulation parameters is recommended for assessing CIC and guiding management.
- Findings highlight the importance of coagulation assessment in COVID-19 patients.
Introduction:
Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has been highly variable.
Methods:
We conducted a systematic review of the literature (until 1 June 2020) to assess CIC and disease severity during the early COVID-19 pandemic. Primary outcomes were pooled mean differences in platelet count, D-dimer level, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen level between non-severe and severe patients, stratified by degree of hypoxaemia or those who died. The risk factors for CIC were analysed. Random-effects meta-analyses and meta-regression were performed using R version 3.6.1, and certainty of evidence was rated using the Grading of Recommendation, Assessment, Development, and Evaluation approach.
Results:
Of the included 5,243 adult COVID-19 patients, patients with severe COVID-19 had a significantly lower platelet count, and higher D-dimer level, prothrombin time and fibrinogen level than non-severe patients. Pooled mean differences in platelet count (-19.7×109/L, 95% confidence interval [CI] -31.7 to -7.6), D-dimer level (0.8μg/mL, 95% CI 0.5-1.1), prothrombin time (0.4 second, 95% CI 0.2-0.6) and fibrinogen level (0.6g/L, 95% CI 0.3-0.8) were significant between the groups. Platelet count and D-dimer level were significant predictors of disease severity on meta-regression analysis. Older men had higher risks of severe coagulopathic disease.
Conclusion:
Significant variability in CIC exists between non-severe and severe patients, with platelet count and D-dimer level correlating with disease severity. Routine monitoring of all coagulation parameters may help to assess CIC and decide on the appropriate management.
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