Bleeding during disseminated intravascular coagulation

Abstract

I read with interest the recent letter to the editor by Jecko Thachil entitled “You can bleed, you are on blood thinners!”1.Thachil J. You can bleed, you are on blood thinners!.J Thromb Haemost. 2021; 19: 1379-1380Crossref PubMed Scopus (2) Google Scholar In this letter Dr. Thachil demonstrates that blood thinners neither “thin” the blood nor cause bleeding. Dr. Thachil asserts that in patients taking anticoagulants, bleeding is a result of injured blood vessels either directly from trauma/surgery or diseased vessels and widened endothelial gap junctions. Might not a similar concept apply to bleeding associated with disseminated intravascular coagulation (DIC)? A long‐held dogma of medicine is that bleeding from DIC is a result of consumption of coagulation factors.2.Lasch H. Heene D. Huth K. Sandritter W. Pathophysiology, clinical manifestation and therapy of consumption‐coagulopathy (“Verbrauchskoagulopathie”).Am J Cardiol. 1967; 20: 381-391Abstract Full Text PDF PubMed Scopus (91) Google Scholar However, during DIC endogenous anticoagulants are consumed as well.3.Thachil J. Disseminated intravascular coagulation ‐ new pathophysiological concepts and impact on management.Expert Rev Hematol. 2016; 9: 803-814Crossref PubMed Scopus (31) Google Scholar In other non‐DIC states, coagulation factor deficiencies do not lead to abnormal bleeding so long as they are balanced by anticoagulant deficiency. This occurs in liver disease and all healthy newborn humans.4.Lisman T. Porte R.J. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences.Blood. 2010; 116: 878-885Crossref PubMed Scopus (425) Google Scholar, 5.Andrew M. Paes B. Milner R. et al.Development of the human coagulation system in the full‐term infant.Blood. 1987; 70: 165-172Crossref PubMed Google Scholar Even in severe hemophilia, treatments targeted at reducing anticoagulant levels (antithrombin and tissue factor pathway inhibitor) ameliorate the bleeding tendency.6.Weyand A.C. Pipe S.W. New therapies for hemophilia.Blood. 2019; 133: 389-398Crossref PubMed Scopus (82) Google Scholar If coagulation factor deficiency does not lead to abnormal bleeding in people with liver disease and newborn infants, why should we continue to accept consumption of coagulation factors as an explanation for abnormal bleeding in people with DIC? During DIC endothelial cells can be perturbed, injured, and denuded.7.Semeraro N. Colucci M. Endothelial Cell Perturbation and Disseminated Intravascular Coagulation.Madame Curie Bioscience Database [Internet]. Landes Bioscience, 2000https://www.ncbi.nlm.nih.gov/books/NBK6509/Google Scholar In addition, patients with DIC are often subjected to invasive procedures. This loss of endothelial barrier function during DIC no doubt contributes to bleeding. Like patients taking blood thinners, consumption of coagulation factors alone does not seem to be a sufficient explanation for bleeding during DIC. The combination of a dysregulated coagulation system (platelets, fibrinolysis, procoagulants, and anticoagulants) along with endothelial dysfunction seems to be a better explanation. Although it may seem obvious that bleeding will not occur so long as blood vessels remain intact, this concept seems to have been lost regarding DIC. As a result, treatment of bleeding during DIC is often aimed at replacing consumed coagulation factors, frequently with fresh frozen plasma.3.Thachil J. Disseminated intravascular coagulation ‐ new pathophysiological concepts and impact on management.Expert Rev Hematol. 2016; 9: 803-814Crossref PubMed Scopus (31) Google Scholar, 8.Wada H. Matsumoto T. Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines.J Intensive Care. 2014; 2: 15Crossref PubMed Scopus (192) Google Scholar While this is widely recommended and prescribed, evidence demonstrating a benefit is lacking.8.Wada H. Matsumoto T. Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines.J Intensive Care. 2014; 2: 15Crossref PubMed Scopus (192) Google Scholar, 9.Stanworth S. Brunskill S. Hyde C. McClelland D. Murphy M. Is fresh frozen plasma clinically effective? A systemic review of randomized controlled trials.Br J Haematol. 2004; 126: 139-152Crossref PubMed Scopus (345) Google Scholar Inciteful treatments that target all aspects of the dysregulated coagulation system along with endothelial injury need to be devised to limit the morbidity and mortality associated with bleeding during DIC. None.