The Interaction Between Coagulation and Complement Cascades in the Management of Thrombotic Microangiopathies Related to Postpartum Hemorrhage

We read with great interest the report by Kaufeld and colleagues who studied the impact of short-term complement inhibition in patients with thrombotic microangiopathy (TMA) associated with postpartum hemorrhage (PPH)1Kaufeld J.K. Kühne L. Schönermarck U. Bräsen J.H. Von Kaisenberg C. Beck B.B. et al.Features of Postpartum Hemorrhage-Associated Thrombotic Microangiopathy and Role of Short-Term Complement Inhibition.Kidney International Reports. Published online 2024; S2468024924000457https://doi.org/10.1016/j.ekir.2024.01.035Abstract Full Text Full Text PDF Scopus (0) Google Scholar. We agree with the authors regarding the need to propose a pragmatic management model by presenting a real-world cohort of patients affected by this infrequent complication. Nonetheless, we believe that some aspects deserve further discussion. Although critical-care diagnostic algorithm to investigate thrombocytopenia associated with TMA categorically separates atypical hemolytic uremic syndrome (aHUS) from disseminated intravascular coagulation2Manrique-Caballero C.L. Peerapornratana S. Formeck C. Del Rio-Pertuz G. Gomez Danies H. Kellum J.A. Typical and Atypical Hemolytic Uremic Syndrome in the Critically Ill.Critical Care Clinics. 2020; 36: 333-356https://doi.org/10.1016/j.ccc.2019.11.004Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, evidence shows that PPH-related TMA may lie at the intersection between these two clinical entities3Kurosawa S. Stearns-Kurosawa D.J. Complement, thrombotic microangiopathy and disseminated intravascular coagulation.j intensive care. 2014; 2: 61https://doi.org/10.1186/s40560-014-0061-4Crossref Scopus (48) Google Scholar,4Wada H. Matsumoto T. Suzuki K. Imai H. Katayama N. Iba T. et al.Differences and similarities between disseminated intravascular coagulation and thrombotic microangiopathy.Thrombosis J. 2018; 16: 14https://doi.org/10.1186/s12959-018-0168-2Crossref PubMed Scopus (74) Google Scholar. Considering several levels of reciprocal interaction between the coagulation and complement cascades, this statement appears to be justified from a pathophysiological point of view3Kurosawa S. Stearns-Kurosawa D.J. Complement, thrombotic microangiopathy and disseminated intravascular coagulation.j intensive care. 2014; 2: 61https://doi.org/10.1186/s40560-014-0061-4Crossref Scopus (48) Google Scholar. In fact, the tissue factor-activated coagulatory pathway is known to be triggered by the terminal complement complex. On the other hand, kallicrein, plasmin and thrombin are coagulation factors that act as activators of both complement factors C3 and C5, which are the convergence points of the classical and alternative complement cascades3Kurosawa S. Stearns-Kurosawa D.J. Complement, thrombotic microangiopathy and disseminated intravascular coagulation.j intensive care. 2014; 2: 61https://doi.org/10.1186/s40560-014-0061-4Crossref Scopus (48) Google Scholar. In this scenario, the degree of alteration of the coagulation system should be included in the clinical variables considered in the genesis of complications and response to treatment. Furthermore, blood transfusion therapy has demonstrated to impact as an immune system modulator which may influence critical patients' outcomes5Aguilar-Nascimento J.E. Zampieri-Filho J.P. Bordin J.O. Implications of perioperative allogeneic red blood cell transfusion on the immune-inflammatory response.Hematology, Transfusion and Cell Therapy. 2021; 43: 58-64https://doi.org/10.1016/j.htct.2020.03.003Crossref PubMed Scopus (16) Google Scholar, although this may be difficult to quantify in a real-life emergency setting. The level of several pro-inflammatory cytokines including IL1 along with markers of endothelium immuno-activation demonstrated to increase in the hours following red blood cell transfusion5Aguilar-Nascimento J.E. Zampieri-Filho J.P. Bordin J.O. Implications of perioperative allogeneic red blood cell transfusion on the immune-inflammatory response.Hematology, Transfusion and Cell Therapy. 2021; 43: 58-64https://doi.org/10.1016/j.htct.2020.03.003Crossref PubMed Scopus (16) Google Scholar. These alterations may also represent an additional element influencing complement function. In conclusion, we agree that short-term treatment with complement inhibition in patients with PPH-related TMA will deserve further investigation to confirm the benefits demonstrated by preliminary data, considering a relatively limited impact on healthcare costs. Studying the role played by coagulation activation and transfusion therapy in these patients could help clarify the pathogenesis and better predict the response to treatment. Response to "Features of Postpartum Hemorrhage-Associated Thrombotic Microangiopathy and Role of Short-Term Complement Inhibition": still a long way to goKidney International ReportsPreviewWe read with interest the work entitled "Features of Postpartum Hemorrhage-Associated Thrombotic Microangiopathy and Role of Short-Term Complement Inhibition" (1). The authors contend that patients in the post-partum presenting with thrombotic microangiopathy (TMA) may benefit from short-term C5 inhibition. Several lines of argumentation tend to mitigate this claim. First and foremost, no comparison is provided between patients who received C5 inhibition (72.5%) and those treated without these agents. Full-Text PDF Open AccessFeatures of Postpartum Hemorrhage-Associated Thrombotic Microangiopathy and Role of Short-Term Complement InhibitionKidney International ReportsVol. 9Issue 4PreviewIn pregnancy-related atypical hemolytic uremic syndrome (p-aHUS), transferring recommendations for treatment decisions from nonpregnant cohorts with thrombotic microangiopathy (TMA) is difficult. Although potential causes of p-aHUS may be unrelated to inherent complement defects, peripartal complications such as postpartum hemorrhage (PPH) or (pre)eclampsia or Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome may be unrecognized drivers of complement activation.