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Review 1: "Association of D-dimer and fibrinogen magnitude with hypercoagulability by thromboelastography in severe COVID-19"

Fibrinogen & G-reactive protein levels correlate with macrothrombosis in critically ill COVID-19 patients, providing a more practical way of identifying at-risk patients. Reviewer consensus is that the paper is potentially informative but has serious methodological limitations.

Published onSep 10, 2020
Review 1: "Association of D-dimer and fibrinogen magnitude with hypercoagulability by thromboelastography in severe COVID-19"
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key-enterThis Pub is a Review of
Association of D-dimer and fibrinogen magnitude with hypercoagulability by thromboelastography in severe COVID-19

Thermoinhibition, or failure of seeds to germinate at warm temperatures, is common in lettuce (Lactuca sativa) cultivars. Using a recombinant inbred line population developed from a lettuce cultivar (Salinas) and thermotolerant Lactucaserriola accession UC96US23 (UC), we previously mapped a quantitative trait locus associated with thermoinhibition of germination to a genomic region containing a gene encoding a key regulated enzyme in abscisic acid (ABA) biosynthesis, 9-cis-EPOXYCAROTENOID DIOXYGENASE4 (NCED4). NCED4 from either Salinas or UC complements seeds of the Arabidopsis thaliana nced6-1 nced9-1 double mutant by restoring germination thermosensitivity, indicating that both NCED4 genes encode functional proteins. Transgenic expression of Salinas NCED4 in UC seeds resulted in thermoinhibition, whereas silencing of NCED4 in Salinas seeds led to loss of thermoinhibition. Mutations in NCED4 also alleviated thermoinhibition. NCED4 expression was elevated during late seed development but was not required for seed maturation. Heat but not water stress elevated NCED4 expression in leaves, while NCED2 and NCED3 exhibited the opposite responses. Silencing of NCED4 altered the expression of genes involved in ABA, gibberellin, and ethylene biosynthesis and signaling pathways. Together, these data demonstrate that NCED4 expression is required for thermoinhibition of lettuce seeds and that it may play additional roles in plant responses to elevated temperature.

RR:C19 Evidence Scale rating by reviewer:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.



I believe that this is a very comprehensive retrospective study for depicting higher values of fibrinogen and its correlation with macrothrombosis events through thromboelastography use in critically-ill COVID-19 patients.
My only comment, which should not reduce from the value of the study, is that:

There is already a significant inflammatory response caused by ECMO that occurs as a reaction to the exposure of blood to the extracorporeal circulation.
Fibrinogen, a consumption marker, also increases in inflammatory situations in patients on ECMO and is especially associated with COVID-19 patients.
A future multicenter prospective controlled study will be very useful and we should not associate these findings with only ECMO patients due to the above-mentioned facts.

The work in the study is clear and well-represented. Methods and data collection are quite impressive. I believe the main claims of the study should be considered conclusive.


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