Rare disorder, small-scale impact? Guess again! Sunday’s Plenary abstract “C1 Inhibitor Deficiency Results in Increased Activation of Coagulation and Enhanced Venous Thrombosis” presented by Dr. Steven P. Grover, illustrated how careful observation of clinical trends in patients with hereditary angioedema (HAE) led to the identification of C1 esterase inhibitor (C1INH) as an endogenous anticoagulant. Dr. Grover’s observations deepen our understanding of the regulatory mechanism of hemostasis, risks of venous thromboembolism (VTE) and potential targets for future anticoagulant drugs.
This work challenges the notion that patients with C1INH deficiency are not at increased risk for thrombosis, even though C1INH inhibits activated coagulation factors XII, XI, and kallikrein in the contact system. This study exemplifies true translational science., starting with the observation that patients with hereditary angioedema from a large Swedish cohort indeed had higher rates of VTE compared to controls, followed by the identification of increased markers of coagulation activation in clinical samples, and subsequently the development of a mouse model.,
The study also showcases how crucial and powerful national and international collaborations can be, especially for rare disorders such as HAE, which affects only one in 50,000 people in the general population. Dr. Grover shared that “our epidemiological insights into the association between hereditary angioedema (HAE) and venous thromboembolism (VTE) would not have been possible without the vital work of collaborators Drs. Sundler Björkman and Arne Egesten in assembling a comprehensive registry of Swedish Hereditary Angioedema patients.” He added, “likewise, our findings of enhanced contact pathway mediated thrombin generation in hereditary angioedema (patient) plasmas would not have been possible without access to samples collected by Dr. Henriette Farkas.”
Mentorship remains a crucial element for the success of scientists at all career stages. Dr. Grover is a postdoctoral fellow and T32 trainee at the Mackman Laboratory of the University of North Carolina, Chapel Hill. When asked about his mentor, Dr. Grover stated that Dr. Nigel Mackman's mentorship and advice have been essential to his growth as a scientist. “Dr. Mackman has been incredibly supportive of my efforts to develop an independent research program on the biology of C1 inhibitor,” He said.
What comes next? Continuing to explore the intersection between complement and coagulation, improve VTE risk stratification and prevention for patients with HAE, and application of these findings in the development of safer anticoagulation strategies that do not increase bleeding risk. Ultimately, this will allow us to reach many by studying a rare few.
Dr. Perez Botero indicated no relevant conflicts of interest.
