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Anand Padmanabhan, MD

Dr. Pawlinski presents his talk “Hemostasis: Coagulation and Inflammation.”

As a thrombosis researcher, I am particularly excited for the Special Symposium on the Basic Science of Hemostasis and Thrombosis (live Q&A Monday, December 7, at 1:30 p.m. Pacific time). Three exciting talks will discuss the inter-relationships between inflammatory processes and the hemostatic system.

In this session, Dr. Rafal Pawlinski discusses the interplay between coagulation and inflammation in sickle cell disease (SCD) — an area of intense recent research. SCD causes high levels of morbidity and mortality globally, and the contribution of vascular inflammation and hypercoagulable state to the pathology of SCD has been recently recognized. Chronic activation of coagulation can lead to increased incidence of prothrombotic complications, and emerging data suggest that inhibiting the activation of the intrinsic coagulation pathway and contact pathways could provide benefits associated with reduced thrombosis, vascular inflammation, and end-organ damage in SCD without increasing risk of bleeding complications. Dr. Pawlinski specifically covers targeting factor XIIa in this setting. As an apheresis practitioner, I see firsthand the debilitating effect of thrombosis and stroke in patients with SCD, and look forward to learning about innovative ways to understand and treat this debilitating disease.

The second speaker, Dr. Mark Ginsberg, discusses vascular signaling in the pathology of cerebral cavernous malformations (CCMs). CCMs are common brain vascular malformations prone to acute and chronic hemorrhage, which can have significant clinical consequences. Recent research in mouse models suggests that deletion of CCM susceptibility genes results in the increased expression of elevated anticoagulant endothelial receptors. Dr. Ginsberg presents the implications of this on the generation of activated protein C and the resultant risk of CCM hemorrhage. Are there ways to predict CCM hemorrhage? There may be, and the speaker delves into the role of soluble thrombomodulin measurement as a biomarker, and as possible targets for decreasing hemorrhage in CCMs.

The third speaker, Dr. Gowthami Arepally, covers the role of complement activation in the pathogenesis of heparin-induced thrombocytopenia (HIT), which is associated with substantial morbidity and mortality. HIT is initiated by ultra-large immune complexes (ULICs) containing IgG antibodies to a multivalent antigen composed of platelet factor 4 (PF4). The mechanisms underlying thrombosis in HIT are only partially understood. HIT ULICs and HIT antibodies recognizing PF4 bound to platelet and monocyte/neutrophil surfaces can activate the cellular IgG receptor, FcGRIIA, to initiate diverse cellular effector functions that engender a prothrombotic environment. However, recent research suggests that ULICs also exert other important biologic effects. HIT patient samples robustly activate complement leading to its deposition on endothelial cells and circulating platelets. However, it is not clear to what extent these disparate activities of HIT ULICs contribute to the hypercoagulable state in HIT. Dr. Arepally reviews recent data that demonstrate the complex interplay between HIT antibodies, complement activation, and cellular activation mediated by FcGR receptors. These points will be highlighted with the use of both in vitro techniques and in vivo models. As a HIT researcher myself, I would love to see these innovative approaches result in newer and better nonanticoagulant interventions in HIT, especially in light of recent data showing that not only is current alternative anticoagulant therapy ineffective in many patients, but also that it may cause severe bleeding in some. This interesting new data may also provide insights into the contribution of the complement system to other immune complex–mediated thrombotic disorders.

I expect this special symposium to be of interest to a broad range of audiences from junior to senior, basic to translational, and clinical researchers with interests in hemostasis and thrombosis. I think you will be struck by the innovativeness of the research conducted. This is a session you should not miss!

Dr. Padmanabhan indicated no relevant conflicts of interest.

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