Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients

Abstract

Coronavirus disease 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019 and spread rapidly around the world. Several patients with severe COVID-19 infection can develop a coagulopathy according to the ISTH criteria for disseminated intravascular coagulopathy (DIC) with fulminant activation of coagulation, resulting in widespread microvascular thrombosis and consumption of coagulation factors. We conducted a meta-analysis in order to explore differences in coagulopathy indices in patients with severe and non-severe COVID-19. An electronic search was performed within PubMed, Google Scholar and Scopus electronic databases between December 2019 (first confirmed Covid-19 case) up to April 6th, 2020. The primary endpoint was the difference of D-dimer values between Non-Severe vs Severe disease and Survivors vs Non-Survivors. Furthermore, results on additional coagulation parameters (platelet count, prothrombin time, activated partial thromboplastin time) were also analyzed. The primary analysis showed that mean d-dimer was significantly lower in COVID-19 patients with non-severe disease than in those with severe (SMD − 2.15 [− 2.73 to − 1.56], I2 98%, P < 0.0001). Similarly, we found a lower mean d-dimer in Survivors compared to Non-Survivors (SMD − 2.91 [− 3.87 to − 1.96], I2 98%, P < 0.0001). Additional analysis of platelet count showed higher levels of mean PLT in Non-Severe patients than those observed in the Severe group (SMD 0.77 [0.32 to 1.22], I2 96%, P < 0.001). Of note, a similar result was observed even when Survivors were compared to Non-Survivors (SMD 1.84 [1.16 to 2.53], I2 97%, P < 0.0001). Interestingly, shorter mean PT was found in both Non-Severe (SMD − 1.34 [− 2.06 to − 0.62], I2 98%, P < 0.0002) and Survivors groups (SMD − 1.61 [− 2.69 to − 0.54], I2 98%, P < 0.003) compared to Severe and Non-Survivor patients. In conclusion, the results of the present meta-analysis demonstrate that Severe COVID-19 infection is associated with higher D-dimer values, lower platelet count and prolonged PT. This data suggests a possible role of disseminated intravascular coagulation in the pathogenesis of COVID-19 disease complications.

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

“…Coagulopathies [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102], and especially the formation of extensive microclots in vivo, are a hallmark of both COVID [85,[103][104][105][106][107][108][109][110][111][112][113][114][115] and long COVID [116,117], and we have demonstrated that these microclots too are amyloid in character [108,109,116]. Importantly, the addition of purified, recombinant SARS-CoV-2 S1 spike protein to coagulation-competent normal plasma is sufficient to induce the formation of anomalous clots [118] that adopt amyloid states that are also resistant to fibrinolysis [108].…”

Coagulopathies in Intensive Care Medicine: Balancing Act between Thrombosis and Bleeding

“…Results of a meta-analysis of 35 studies and 6427 patients demonstrate that a severe COVID-19 infection is associated with higher D-dimer values, lower platelet count, and prolonged PT. This data suggest a possible role of disseminated intravascular coagulation in the pathogenesis of severe COVID-19 infection [103]. A favorable outcome has been reported with the use of heparin in COVID-19 patients, especially in those with markedly high D-dimer levels or with sepsis-induced coagulopathy [104].…”

Biomarkers during COVID-19: Mechanisms of Change and Implications for Patient Outcomes

“…This immune response-triggered thrombosis causes widespread vascular damage, complement-induced thrombosis, systemic microangiopathy, and thromboembolism, that may ultimately lead to multi-organ failure [ 84 , 85 , 86 ]. Additionally, disseminated intravascular coagulopathy (DIC) with fulminant activation of coagulation, also reported in COVID-19 patients, has been shown to induce massive microvascular thrombosis and coagulation factor consumption [ 87 ]. Prolonged activated partial thromboplastin time, elevated D-dimer, and thrombocytopenia are all associated with the development of severe SARS-CoV-2 infection [ 88 ].…”

“…D-dimer is a soluble fibrin degradation product used as a marker for evaluating ongoing thrombotic and thrombolytic events such as pulmonary embolism [ 89 ]. D-dimer has been found in increased quantities among COVID-19 patients following the activation of coagulation and fibrinolysis [ 87 ]. As raised D-dimer has been associated with higher in-hospital mortality and increasing COVID-19 severity, it may be a reliable prognostic factor [ 90 ].…”