The Konkle laboratory conducts clinical and translational research studies in hemostasis and thrombosis.
Areas of Study
von Willebrand Factor (VWF) and von Willebrand Disease (VWD)
Dr. Konkle's recent research in this area relates to improved testing for VWD and changes of VWF and factor VIII (FVIII) in pregnancy in normal women and women with VWD. Her studies of VWF in pregnancy include collaborations with Dr. Jill Johnsen at Puget Sound Blood Center and Dr. Hilary Gammill at the University of Washington. With colleagues at the University of Pennsylvania and the Centers for Disease Control (CDC) in Atlanta, she described the population in the U.S. with severe VWD and has compared loss of joint range of motion (ROM) in patients with severe VWD compared to moderate hemophilia A with similar FVIII levels. They found that joint ROM is similar in the two groups supporting a primacy of FVIII deficiency in hemarthrosis. In collaboration with Drs. José López and William E. Hobbs, they are evaluating the role of VWF in pathologic thrombosis in patients with sickle cell disease and thrombotic thrombocytopenic purpura.
Heparin-Induced Thrombocytopenia (HIT)
Patients with HIT are at high risk of developing thrombosis, which can have devastating consequences including loss of limb or life. Her group was one of several to report the high incidence of heparin/PF4 antibodies following cardiopulmonary bypass. In ongoing work with collaborators at the University of Pennsylvania and Children's Hospital of Philadelphia, they are evaluating platelet biomarkers that may be predictive of HIT, as well as antibody evolution and specificity, and the relationship between heparin/PF4 antibody formation and atherosclerosis. Through this research, they hope to improve testing for HIT and better prediction of patients at higher risk of this complication so that treatment approaches can be modified.
Pregnancy-Associated Thrombosis
Venous thrombosis and vascular complications are the major causes of maternal death. Women are at particularly high risk of venous thrombosis (VTE) in the early postpartum period. Dr. Konkle, in collaboration with other investigators in Canada and the U.S., is evaluating whether broader application of prophylactic anticoagulation can decrease this risk. In addition, Dr. Konkle's laboratory is evaluating biomarkers predictive of postpartum VTE.
Cardiovascular Disease in Men with Hemophilia
With improved treatments, the life expectancy of men with hemophilia is approaching that of the general population. The downside of that great advance is the occurrence of heart attacks as these men age, despite their low clotting factor. With funding from the CDC, Dr. Konkle and colleagues across the U.S. are further evaluating cardiovascular disease in hemophilia.
Clinical Trials of Treatments for Hemophilia and Other Disorders
Dr. Konkle has a longstanding interest in the evaluation of new treatments for bleeding and clotting disorders and has participated in multiple trials. She was a lead investigator on the trial evaluating rFVIIa as secondary prophylaxis in patients with hemophilia and inhibitors and frequent bleeding. She was the Principal Investigator from the University of Pennsylvania for the NHLBI-sponsored clinical trial network (CTN) in Transfusion Medicine and Hemostasis and is a co-investigator from Puget Sound Blood Center's site. At Puget Sound Blood Center, in collaboration with Dr. Neil Josephson, they are evaluating new treatments for hemophilia and von Willebrand disease.