Morbidities and mortality in patients with hereditary thrombotic thrombocytopenic purpura

Abstract

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.

No aggravation of congenital thrombotic thrombocytopenic purpura by mRNA-based vaccines against COVID-19: a Japanese registry survey

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Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare disorder caused by severe ADAMTS13 deficiency [1]. Between 2001 and 2020, only 226 patients with cTTP were reported worldwide [2]. As of 2021, we identified 67 patients with cTTP in Japan alone [3,4].

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Thrombotic Thrombocytopenic Purpura: From 1972 to 2022 and Beyond

“…The difference was caused by the occurrence of severe complications during pregnancy. 48,49 Also, there were fewer deaths among women after the age of 40 years. This may be due to undiagnosed deaths during pregnancy.…”

Aspirin prophylaxis for hereditary and acquired thrombotic thrombocytopenic purpura?

“…Stroke is a common, critical complication and the major cause of morbidity for patients with hereditary thrombotic thrombocytopenic purpura (hTTP). 1,2 Patients with acquired autoimmune TTP (iTTP) also have a high risk for stroke and other thrombotic events during remission, especially when plasma ADAMTS13 activity is less than normal. 3,4 Current management of hTTP and of iTTP during remission is not sufficient for prevention of stroke and other thrombotic events.…”

“…3,4 Current management of hTTP and of iTTP during remission is not sufficient for prevention of stroke and other thrombotic events. [1][2][3][4] The result is premature deaths among patients with hTTP 1 or iTTP. 4 Although low-dose aspirin is effective for secondary prevention of stroke and other thrombotic events, it has been assumed that aspirin may not be effective for preventing stroke and thrombotic events in patients with TTP.…”

“…Fourteen patients developed end-stage kidney disease. 1 In telephone interviews with 27 United States patients enrolled in the International Hereditary TTP Registry, 17 (63%) had a history of stroke (median age, 26 years). 2 Eleven of these 17 patients had residual symptoms; 7 received disability support.…”