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 replacement of ADAMTS13 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. Age at diagnosis was reported for 202 patients; 117 were female and 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 injury, or cardiac injury that occurred at a median age of 21 years. Sixty-two patients had stroke; 13 strokes occurred in children age 10 years or younger. Of the 54 patients who survived their initial major morbidity and were subsequently observed, 37 (69%) had sustained or subsequent major morbidities. Of the 39 patients who were observed after age 40 years, 20 (51%) had experienced a major morbidity. Compared with an age- and sex-matched US 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 started at a younger age are required to improve health outcomes.

Graphical abstract

Figure 1.

Age at diagnosis and death in patients with hTTP. Age at diagnosis was reported for 202 (89%) of the 226 patients (85 male, 117 female). Deaths were reported for 32 patients (18 male, 14 female). Patients whose age at diagnosis or death occurred at a decade marker are counted in the following decade. Newborn infants (NBs) are distinguished from children age 0 to 9 years because they were recognized by their severe hyperbilirubinemia. Twelve infants were diagnosed at birth; 9 died. The diagnosis of newborn infants occurred within several days of birth. Among the other children age 0 to 9 years, the youngest child diagnosed with hTTP was a 1-month-old girl; the youngest death was in a 2-year-old boy.

Figure 2.

Age at occurrence and follow-up of major morbidities in patients with hTTP. Each of the 73 patients is shown at the age of their initial major morbidity by a blue circle (living) or red circle (died). If patients survived their initial major morbidity and were subsequently observed, the duration of survival or follow-up is indicated by the horizontal line. These data are also presented in Table 3.

Figure 3.

Survival of patients with hTTP. The survival data are from 221 patients, excluding 5 patients for whom the duration of follow-up was not reported. (A) The probability of survival of the patients with hTTP (green line) was compared with the age- and sex-matched US population (red line) values using Kaplan-Meier methods. The difference between the patients with hTTP and the expected deaths in the US population was determined by using 95% CIs for the patients’ deaths (blue lines). Beginning at birth, the 95% CIs did not overlap with the survival line for the US population. (B) The probabilities of survival of male and female patients with hTTP were calculated separately by using Kaplan-Meier methods and a log-rank test to determine differences. The 95% CIs are illustrated by blue for female and red for male.