Featured Publications
Thrombin generation in children with sickle cell Anemia is Higher in the presence of platelets
Cellular and plasma interactions underlie hypercoagulability in sickle cell anemia (SCA). In healthy adults, thrombin generation (TG), a biomarker of hypercoagulability, is similar in plasma with and without platelets. Studies investigating TG in SCA using platelet-poor plasma (PPP) show conflicting results. There are no studies in SCA simultaneously comparing TG using platelet rich plasma (PRP) and PPP. This prospective study compares TG in children with SCA, at steady state, in PPP versus PRP and investigates the association of predefined clinical variables with the difference between PRP and PPP. Our secondary aim was to investigate derangements in the protein C and S pathway measuring TG with and without thrombomodulin (TM). In forty-three paired samples from SCA patients, aged 2-15 years, TG in the presence of platelets was 5.9 % higher [1239 nmol/(min*L) (SD: 224.1) vs. 1151 nmol/(min*L) (SD 223.3); p = 0.026]. The difference was highest in the 6-10 year age group (9.5 %; SD 14.1) followed by the 2-5 year age group (5.4 %; SD 21.4). In a multiple linear regression model, age, gender, current use of hydroxyurea, degree of hemolysis and severity of pain crises were not predictive of the difference between PRP and PPP. In PPP, TG reduction after TM addition was 7.4 % (SD 16.8), signifying activated protein C resistance. In conclusion, TG in children with SCA aged 2-10 years is higher in the presence of platelets. TG using PRP along with TM addition may be a useful biomarker of hypercoagulability in this population.
Thrombin Generation in a patient with Triple Positive Antiphospholipid Syndrome Treated with Three Different Anticoagulants
Venous and arterial thrombosis is one of the hallmarks of Antiphospholipid Antibody Syndrome (APS). The traditional treatment for individuals with APS and venous thrombosis has been vitamin K antagonists. However, with the widespread use of direct oral anticoagulants (DOACs) there has been conflicting evidence regarding their safety and failure rate as alternatives to warfarin. Reasons for this failure remain elusive. We utilized the thrombin generation assay (TGA) to investigate the anticoagulation efficacy of three different agents in a patient with triple-positive APS to acquire a better understanding of the pathophysiology of APS.
Blood samples were obtained from a single patient with APS at five distinct time points while on three different anticoagulants: rivaroxaban, warfarin, and enoxaparin. The effects of these anticoagulants on TG potential were evaluated using the TGA.
In the presence of thrombomodulin, rivaroxaban had the highest endogenous thrombin potential, thrombin peak, velocity index, and thrombin inactivation velocity (821.9 nMmin, 121.5 nM, 36.44 nM/min, 7.19 nM/min) when compared to warfarin (121-367 nMmin, 13.85-121.5 nM, 3.02-3.85 nM/min, 0.64-4.55 nM/min) and enoxaparin (242-378.8 nM min, 21.33-23.78 nM, 2.87-3.85 nM/min, 0.747-0.784 nM/min). This trend was also observed in the absence of thrombomodulin.
These results suggest that patients with APS treated with rivaroxaban may be at greater risk for thrombosis compared to warfarin or enoxaparin. The findings may provide insight into the recent studies in patients with triple positive APS randomized to different anticoagulants demonstrating high rates of thrombosis with rivaroxaban. Further studies are necessary to elucidate the clinical significance.
Congenital disorders of glycosylation as an unusual cause of antithrombin deficiency and elevated thrombin generation
This case was previously presented as a poster at the 2019 meeting of American Society of Pediatric Hematology Oncology (New Orleans, LA) on May 2, 2019. Congenital glycosylation disorders as a usual cause of thrombophilia (http://doi.org.ezproxy.library.wisc.edu/10.1002/pbc.27713).