Pregnancy in Patients with Immune Thrombotic Thrombocytopenic Purpura (iTTP): Single Centre Experience and Review of Literature

Abstract

Background: Pregnancy is a known trigger for acute episodes of immune thrombotic thrombocytopenic purpura (iTTP). Pregnancy outcomes of TTP patients in a Canadian population are not well described, especially for patients in remission at time of conception. Here, we describe the experience with iTTP in pregnancy at a large Canadian tertiary apheresis centre and conduct a narrative review of the literature. Methods: Consecutive patients with iTTP treated at St. Michael's Hospital, Toronto, Canada between January 1, 2002 and August 31, 2021 were screened for pregnancy using registry data. Patients who presented with acute iTTP during pregnancy, post-partum or who became pregnant while in TTP remission were included in the study. Data were collected using a local TTP registry, electronic medical records, and were analyzed using simple descriptive statistics (proportions, median, IQR). A narrative literature review was conducted based on a systematic search of Ovid MEDLINE, EMBASE, and CINAHL; studies presenting original data (N>3) on iTTP patients with pregnancy in remission were included. Institutional research ethics board approval was obtained. Results: A total of 13 pregnancies in 9 patients with iTTP were included in the retrospective review. Of these, 9 occurred during iTTP remission, 1 was associated with initial acute iTTP episode, and 3 were cases of post-partum iTTP. In pregnancies occurring during iTTP remission, median time between last iTTP episode and delivery was 7 years (IQR 3-9). Median maternal age at delivery was 33.5 years (IQR 32-34.5), and median gestational age at birth was 38 weeks. Delivery was vaginal in 5 cases and via planned cesarian section in 4 cases; 7 female and 2 male newborns were delivered with a median birthweight of 2897g (IQR 2715-3080) and birth length of 49 cm (IQR 47-51). Relapse of iTTP after delivery occurred in one pregnancy (7.7%) in a patient with persistent ADAMTS13 deficiency (activity <1%); all other patients had normal ADAMTS13 activity before delivery, without relapse (median 0.70 IU/L, IQR 0.68-0.75). In the pregnancy associated with an initial acute iTTP episode, maternal age at delivery was 41 years, and gestational age at birth was 36 weeks for a female newborn (birthweight 2415g). In all cases, there was no maternal or fetal/newborn mortality. Literature Review: Literature search resulted in 1021 abstracts, of which 11 studies met our inclusion criteria after abstract and full-text review. Of these studies, we excluded 3 that presented older data from existing registries, and 4 that did not specify whether TTP was immune. The 4 remaining studies reported on 49 TTP patients. Out of 67 pregnancies, 56 (84%) delivered live babies and 10 (15%) were associated with TTP relapse. ADAMTS13 deficiency (activity <10%) was noted in 6 pregnancies, all 6 of which resulted in TTP relapse in the peripartum period. The remaining 4 relapses occurred in pregnancies with normal or unreported ADAMTS13 activities. Conclusion: We describe pregnancy outcomes in iTTP at a large Canadian apheresis centre. One pregnancy (7.7%) was complicated with new acute iTTP in a mother of advanced age and delivery occurred prematurely. Proportion of peripartum iTTP relapse was low (7.7%) and occurred in a patient with documented ADAMTS13 deficiency in pregnancy, in keeping with the existing literature. Our findings and narrative literature review suggest that pregnancy may be safe in iTTP remission as long as ADAMTS13 activity is normal.