Thrombotic thrombocytopenia purpura is characterised by microangiopathic haemolytic anaemia and red cell fragmentation on the peripheral smear, neurological involvement and thrombocytopenia. Diagnosis in the context of sickle cell disease can be challenging due to the inherent haemolytic state and the multitude of other associated complications of the latter. Specifically, fat embolism syndrome characterised by respiratory failure, neurological impairment and thrombocytopenia can be misdiagnosed this way. Confirmation of a diagnosis of thrombotic thrombocytopenic purpura requires demonstration of very low levels (<10%) of the metalloproteinase ADAMTS13 which in fat embolism syndrome is normal. Existing scoring systems used to estimate the pre-test probability for thrombotic thrombocytopenic purpura cannot be applied in patients with sickle cell disease due to the chronic underlying haemolysis. Here, we analyse the diagnostic approach in published cases of thrombotic thrombocytopenic purpura affecting patients with sickle-cell disease. The vast majority of cases were characterised by severe respiratory failure before any other manifestation, a feature of fat embolism syndrome but not of thrombotic thrombocytopenic purpura, and all received red cell transfusion prior to receiving therapeutic plasma exchange. Despite the potential overestimation of the pre-test probability using the existing scoring systems, a large number of cases still scored low. There were no cases with documented low ADAMTS13. In the majority this was not tested, while in the 3 cases that ADAMTS13 was tested, levels were normal. Our review suggests that due to many overlapping clinical and laboratory features thrombotic thrombocytopenic purpura may be erroneously diagnosed in sickle cell disease instead of other complications such as fat embolism syndrome and confirmation with ADAMTS13 testing is essential.
Keywords: fat embolism syndrome; sickle cell disease; therapeutic plasma exchange; thrombotic thrombocytopenic purpura.