Morbidities and Mortality in Patients with Hereditary Thrombotic Thrombocytopenic Purpura

Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare disorder caused by severe ADAMTS13 deficiency. Major morbidities and death at a young age are common. Although ADAMTS13 replacement can prevent morbidities and death, current regimens of plasma prophylaxis are insufficient. We identified 226 patients with hTTP in 96 reports published from 2001 through 2020. In 202 patients the age at diagnosis was reported; 117 were female, 85 were male. The difference was caused by diagnosis of 34 women during pregnancy, suggesting that many men and nulliparous women are not diagnosed. Eighty-three patients had severe jaundice at birth; hTTP was suspected and effectively treated in only 3 infants. Of the 217 patients who survived infancy, 73 (34%) had major morbidities, defined as stroke, kidney or cardiac injury, that occurred at a median age of 21 years. Sixty-two patients had stroke; 13 strokes occurred in children ≤10 years old. Of the 54 patients who survived their initial major morbidity and were subsequently followed, 37 (69%) had sustained or subsequent major morbidities. Of the 39 patients who were followed past age 40, 20 (51%) had experienced a major morbidity. Compared to age and gender-matched United States population, probability of survival was lower at all ages, beginning at birth. Prophylaxis was initiated in 45 patients with a major morbidity; in 11 (28%) a major morbidity recurred after prophylaxis had begun. Increased recognition of hTTP and more effective prophylaxis begun at a younger age are required to improve health outcomes.