OBJECTIVE: The primary pathologic reason for thrombotic thrombocytopenic purpura (TTP) lies in the systemic formation of platelet aggregations in association with endothelial cells damage. Endothelial damage is a result of an abnormal synthesis and metabolism of unusually large von Willebrand Factor (ULvWF) multimers. In normal conditions vWF cleaving metalloprotease, known as ADAMTS-13 (A Disintegrin And Metalloproteinase with Thrombospondin type-1 motif, member 13) prevents the ULvWF entrance in the circulation. It already has been proven that thrombotic thrombocytopenic purpura is strongly correlated with severe congenital or acquired deficiency of ADAMTS-13. Congenital ADAMTS-13 deficiency is known as Upshaw-Schulman Syndrome and it accounts for only 2-4% of all TTP cases. It is conditioned by genetic variants of the ADAMTS-13 gene causing reduced ADAMTS-13 synthesis and shows an autosomal recessive type of inheritance.
CASE PRESENTATION: We present an interesting case of a 20 year old patient, primigravida, nulliparous, in 28th gestational week of twin pregnancy with undiagnosed Upshaw-Schulman Syndrome. The patient was transferred from the district hospital to the Tertiary Perinatal Care Center because of thrombocytopenia and suspicion of hemolytic-uremic syndrome. Genetic analysis performed 5 years after patient's death (before 2008 that kind of genetic analysis had not been available in Poland) showed a homozygotic mutation in the ADMTS13 gene (4143insA) which confirmed the diagnosis of Upshaw-Schulman Syndrome.
CONCLUSIONS: 1. TTP, especially hereditary Upshaw-Schulman Syndrome, is extremely rare and complicates the course of pregnancy. It is usually very sudden and dramatic; 2. Differential diagnosis of this disease is difficult and treatment strategy very burdensome for the patient. For this reason, diagnosis of micro-angiopathic disorders need to be simultaneously based on both clinical symptoms and laboratory findings; 3. Genetic diagnosis that confirms exact recognition of Upshaw-Schulman Syndrome is not commonly available; 4. The described case was a huge diagnostic challenge, and actually the final diagnosis was published until five years after the patient's death. Before 2008, that type of genetic analysis had not been available in Poland; 5. Despite the enormous progress in medical knowledge and experience, the exact diagnosis of TTP, including Upshaw-Schulman Syndrome, of this condition remains very difficult.