title: Complement, thrombotic microangiopathy and disseminated intravascular coagulation.
abstract: In the blurring boundaries between clinical practice and scientific observations, it is increasingly attractive to propose shared disease mechanisms that could explain clinical experience. With the advent of available therapeutic options for complement inhibition, there is a push for more widespread application in patients, despite a lack of clinically relevant research. Patients with disseminated intravascular coagulation (DIC) and thrombotic microangiopathies (TMA) frequently exhibit complement activation and share the clinical consequences of thrombocytopenia, microangiopathic hemolytic anemia, and microvascular thrombosis. However, they arise from very different molecular etiologies giving rise to cautious questions about inclusive treatment approaches because most clinical observations are associative and not cause-and-effect. Complement inhibition is successful in many cases of atypical hemolytic uremic syndrome, greatly reducing morbidity and mortality of patients by minimizing thrombocytopenia, microangiopathic hemolytic anemia, and microvascular thrombosis. But is this success due to targeting disease etiology or because complement is a sufficiently systemic target or both? These questions are important because complement activation and similar clinical features also are observed in many DIC patients, and there are mounting calls for systemic inhibition of complement mediators despite the enormous differences in the primary diseases complicated by DIC. We are in great need of thoughtful and standardized assessment with respect to both beneficial and potentially harmful consequences of complement activation in these patient populations. In this review, we discuss about what needs to be done in terms of establishing the strategy for complement inhibition in TMA and DIC, based on the current knowledge.
authors.affiliation: Boston University School of Medicine, 670 Albany Street, Boston, MA 02118 USA.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kurosawa
authors.affiliation: Boston University School of Medicine, 670 Albany Street, Boston, MA 02118 USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Stearns-Kurosawa
keywords: Acute kidney injury; Blood coagulation; Complement; Disseminated intravascular coagulation; Hemolytic uremic syndrome; Microangiopathic hemolytic anemia; Thrombocytopenia; Thrombotic microangiopathy