Thrombin generation in children with sickle cell Anemia is Higher in the presence of platelets^{⋆ and ⋆}

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.