Evaluation of thrombin generation in patients with sickle cell disease in stable disease and sickle cell crises

Objective Sickle cell disease (SCD) is complicated by repetitive pain crises and coagulation activation. In this study we looked for a possible way to monitor coagulation activation by using thrombin generation assay (Calibrated automated thrombogram CAT) as a global coagulation assay. After specifying preanalytical conditions we compared 11 patients suffering from SCD or sickle cell/beta thalassemia in stable disease and pain crises to 6 patients suffering from transfusion dependent thalassemia.

Material and Methods Blood probes were drawn using corn trypsin inhibitor (CTI) or citrate as anticoagulants and fresh probes were compared to frozen. The tests were performed on a CAT Thrombinoscope system using platelet poor plasma (PPP), phospholipids with high/low tissue factor (TF) concentrations.

Results Citrated blood showed higher peak heights with similar lag-times and endogenous thrombin potential (ETP) compared to CTI anticoagulant in 18 normal controls. There was no difference in fresh or frozen samples. In SCD patients and controls PPP with low TF resulted in a more prolonged lag-phase and lower peak while ETP differed only marginally to PPP high TF. SCD patients showed a higher peak and ETP values compared to controls, but ranges were overlapping. ETP was reduced during sickle cell crises. Patients suffering from crises showed higher ETP and peak heights even outside crises compared to patients with stable disease and lacking pain crises during observation period. TGA values were not related to D-dimers.

Conclusion Hypercoagulable states in SCD patients can be monitored by CAT. ETP is lowered during crises reflecting prolonged coagulation activation and factor consumption. ETP and peak heights ranges overlap between SCD patients and thalassemia patients. Including cellular components as platelet rich plasma or whole blood might reflect more physiological conditions.

Publication History

Article published online:
18 June 2021