1. REPLY TO THE COMMENT
We appreciate the opportunity to respond to the comments by Dr. Marongiu et al. They presented only laboratory findings of disseminated intravascular coagulation (DIC), but no bleeding was mentioned, indicating that there was not overt DIC in our patients; instead, the abnormal laboratory findings could be an expression of local DIC (ie, a pulmonary vascular thrombosis). Thus, they suggested anticoagulant treatment in patients with coronavirus disease 2019 (COVID‐19).
First, bleeding is less common than thrombosis and presents late in DIC induced by infection, and the site of bleeding is sometimes hard to find (eg, brain, intra‐abdominal).1 We suggest the International Society of Thrombosis and Haemostasis diagnostic criteria2 rather than just relying on clinical manifestation for DIC diagnosis. In fact, because of neglect or lack of available coagulation tests, the diagnosis of DIC is often delayed until bleeding from multiple sites occurs.3
We agree with Dr. Marongiu et al that pulmonary vascular thrombosis may exist in some severe COVID‐19 cases, the pulmonary inflammatory reaction and hypoxemia resulting from SARS‐CoV‐2 infection can lead to hypercoagulability.4 However, because DIC is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin in the circulation,5 we disagree with the contradictory concept of “local DIC.” Once patients meet the diagnostic criteria of DIC, multiple organ dysfunction resulting from microthrombus should be considered, not only in the lung, although it may be the most affected organ.
Finally, anticoagulant treatment is a reasonable choice for preventing DIC and venous thromboembolism in COVID‐19. However, the activation of blood coagulation is essential in counteracting virus infections6; on the other hand, patients meeting the diagnostic criteria of overt DIC may have illness progression that no longer benefits from anticoagulant treat.7 Hence, it is important to identify patients who can benefit from anticoagulants using the criteria of sepsis‐induced coagulopathy suggested by International Society of Thrombosis and Haemostasis,8 markedly elevated D‐dimer on admission and so on can also be considered. We are retrospectively analyzing the association of anticoagulant treatment with outcome in severe COVID‐19 patients of our hospital, and hope the results will contribute to the management of COVID‐19 in the future.
CONFLICT OF INTEREST
None declared.
Footnotes
Manuscript handled by: David Lillicrap
Final decision: David Lillicrap and 19‐Mar‐2020
REFERENCES
- 1.Bernard G.R., Margolis B.D., Shanies H.M., et al. Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE US): a single‐arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest. 2004;125(6):2206–2216. doi: 10.1378/chest.125.6.2206. [DOI] [PubMed] [Google Scholar]
- 2.Taylor F.B., Toh C.H., Hoots W.K., et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86:1327–1330. [PubMed] [Google Scholar]
- 3.Thachil J. Platelets and infections in the resource‐limited countries with a focus on malaria and viral haemorrhagic fevers. Br J Haematol. 2017;177(6):960–970. doi: 10.1111/bjh.14582. [DOI] [PubMed] [Google Scholar]
- 4.Gupta N., Zhao Y.Y., Evans C.E. The stimulation of thrombosis by hypoxia. Thromb Res. 2019;181:77–83. doi: 10.1016/j.thromres.2019.07.013. [DOI] [PubMed] [Google Scholar]
- 5.Dalainas I. Pathogenesis, diagnosis, and management of disseminated intravascular coagulation: a literature review. Eur Rev Med Pharmacol Sci. 2008;12(1):19–31. [PubMed] [Google Scholar]
- 6.Antoniak S. The coagulation system in host defense. Res Pract Thromb Haemost. 2018;2:549–557. doi: 10.1002/rth2.12109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Gando S., Iba T., Eguchi Y., et al. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Crit Care Med. 2006;34:625–631. doi: 10.1097/01.ccm.0000202209.42491.38. [DOI] [PubMed] [Google Scholar]
- 8.Iba T., Levy J.H., Warkentin T.E., et al. Diagnosis and management of sepsis‐induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989–1994. doi: 10.1111/jth.14578. [DOI] [PubMed] [Google Scholar]