Investigation of thrombin generation assay to predict vaso-occlusive crisis in adulthood with sickle cell disease

Abstract

IntroductionSickle cell disease (SCD) is an inherited hemoglobinopathy disorder. The main consequence is synthesis of hemoglobin S leading to chronic hemolysis associated with morbidity. The aim of this study was to investigate Thrombin Generation Assay (TGA) to assess hypercoagulability in SCD and TGA parameters as biomarkers of vaso-occlusive crisis (VOC) risk and hospitalization within 1 year.Materials and methodsWe performed TGA in platelet poor plasma (PPP) with 1 pM of tissue factor and 4 μM of phospholipid-standardized concentration, in duplicate for patients and controls. We measured thrombomodulin (TM), soluble endothelial Protein C Receptor and Tissue Factor Pathway Inhibitor (TFPI).ResultsA total of 113 adult patients with SCD, 83 at steady state and 30 during VOC, and 25 healthy controls matched on age and gender were included. Among the 83 patients at steady state, (36 S/S-1 S/β0, 20 S/Sα3.7, and 19 S/C-7 S/β+) 28 developed a VOC within 1 year (median: 4 months [2.25–6]). We observed an increase of peak and velocity associated with a shortening of lagtime and time to peak (TTP) and no difference of endogenous thrombin potential (ETP) in patients compared to controls. TFPI (p < 0.001) and TM (p = 0.006) were significantly decreased. TGA confirmed hypercoagulability in all SCD genotypes and clinical status. The association of ETP > 1,207 nM.min and peak >228.5 nM presented a sensitivity of 73.5% and a specificity of 93.9% to predict VOC development within 1 year.ConclusionWe have demonstrated a hypercoagulable state in SCD associated with chronic hemolysis. These preliminary findings suggest that TGA parameters, as ETP and peak, could be used to predict VOC development within 1 year.

Lactate dehydrogenase and hemolysis index to predict vaso-occlusive crisis in sickle cell disease

“…Based on our results, LDH > 260 U/L and HI > 12 UA/L presented a sensitivity of 90.0%, a specificity of 72.9%, a PPV of 40.9% and a NPV of 97.2% to predict VOC development within 1 year. Previously, we demonstrated that thrombin generation assay and reticulocyte parameters allowed VOC prediction 7 , 8 . However, LDH and HI association reported higher sensitivity.…”

“…Several comparisons between manufacturers have also been carried out 6 . Recent studies have demonstrated the use of coagulation or erythrocytic parameters to predict VOC 7 , 8 .…”

Extracellular Vesicle Size Reveals Cargo Specific to Coagulation and Inflammation in Pediatric and Adult Sickle Cell Disease

“… 21 Moreover, the current literature does not establish a definitive coagulation signature in the pediatric or adult SCD patient populations. Several studies do suggest that TG, TATs (Thrombin-antithrombin complexes) , and d -dimers may be a marker of general coagulation risk, 7 cerebral vascular disease, 22 , 23 and risk of vaso-occlusive episodes 24 in adults and children. Cell-derived EVs within the plasma compartment of SCD patients are easily isolated and potentially contain important pathophysiological markers that identify similarities and differences between pediatrics and adults.…”