TO THE EDITOR:

It is unclear whether women with immune thrombotic thrombocytopenic purpura (iTTP) are counseled regarding the risks during pregnancy or strategies to improve outcomes. This study aimed to understand how iTTP affects reproductive decisions and to describe outcomes of pregnancies after iTTP diagnosis. iTTP is characterized by recurrent episodes of thrombotic microangiopathy and ischemic organ failure due to a severe deficiency of ADAMTS13.1 Pregnancy is a known trigger for an initial episode or relapse of iTTP.2,3 Outcomes of pregnancy in women with iTTP are poor and include high rates of iTTP relapse, pregnancy loss, and preeclampsia.4-7 However, prophylactic immunosuppression and ADAMTS13 monitoring can improve maternal and fetal outcomes in pregnancy.6-8 Moreover, at least in the United States, iTTP is a condition that disproportionately affects Black women,9,10 who are already at higher risk of adverse pregnancy outcomes11,12 predominantly because of social determinants of health.11 

Participants with a self-reported diagnosis of iTTP were recruited to complete a web-based survey that was disseminated through email and social media posts from the United States Thrombotic Microangiopathy Alliance, a patient support and advocacy organization focused on TTP. Only participants who provided informed consent electronically were permitted to access and complete the survey. The survey remained open for 1 month (January 2023) and included sections on the following: (1) demographics, (2) experiences with iTTP and reproductive health care, and (3) outcomes of any pregnancies that occurred at the time of or after initial iTTP diagnosis with a focus on maternal and fetal outcomes. Results are primarily descriptive and are summarized as counts and proportions. We used the χ2 test to evaluate whether receiving counseling regarding the risks of pregnancy or regarding strategies to optimize pregnancy outcomes were associated with participants’ decisions to avoid pregnancy even if desired, or to avoid getting into relationships. STATA version 18 was used to perform all analyses. This study was approved by the Johns Hopkins Institutional Review Board and was conducted in accordance with the Declaration of Helsinki.

Seventy-five females with iTTP responded to the survey. The median age of the respondents was 44 years (range, 24-65 years). Sixty-five (74.7%) identified as White, 13 (14.9%) as Black, 6 (6.9%) as Asian, and 3 (3.4%) as other/prefer not to say. Nearly all (94.6%) were followed by a hematologist or hematologist-oncologist, and 82.9% reported being monitored regularly for iTTP, including regular testing of ADAMTS13 activity levels. Quality of life was affected, with 28.4% (21/74) responding that their iTTP diagnosis affected their ability to get into a relationship (Figure 1). Further analysis of only the 52 participants diagnosed in their childbearing years (ages, 15-45 years) revealed that counseling regarding safe and successful pregnancy was limited; 42.9% (21/49) reported that they were advised by their doctor to not get pregnant because of their iTTP. Only 36.5% (19/52) reported that their doctor had talked to them about measures that may help achieve a successful pregnancy. These measures included ADAMTS13 monitoring (n = 14), plasma exchange treatments (n = 10), rituximab (n = 9), and aspirin (n = 3) (options are not mutually exclusive, so total is >19). A significant proportion (48.1%) reported avoiding pregnancy even if desired out of fear of the consequences of iTTP. Women who had received counseling regarding the risks of pregnancy with iTTP were more likely to report avoiding pregnancy for iTTP-related reasons compared with those who did not receive this counseling (66.7% vs 24.5%; P = .032). Surprisingly, addressing strategies for managing pregnancy was also associated with avoidance of pregnancy (78.9% vs 21.1% avoidance in those who did not receive this information; P = .001).

Figure 1.

Reproductive health care experiences of women with iTTP.

Figure 1.

Reproductive health care experiences of women with iTTP.

Close modal

Fifty-three patients reported that they had had at least 1 pregnancy. Of these, 35 had pregnancies before iTTP diagnosis, 10 had pregnancies concurrent with the initial presentation of iTTP, and 8 women had a total of 11 pregnancies after diagnosis. Consistent with previous reports, a number of pregnancies that occurred in the setting of a first iTTP episode had poor outcomes, complicating pregnancy or pregnancies after an iTTP diagnosis (Table 1). iTTP relapse occurred in 27.3% (3/11) pregnancies in women with prior iTTP. Fetal loss occurred in 30% of pregnancies with first TTP diagnosis and 9% of pregnancies after iTTP. In both groups, ∼20% were small for gestational age. Preeclampsia or HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome occurred in 50% and 18.2% of pregnancies complicated by initial TTP diagnosis or after iTTP diagnosis, respectively. The treatments during these pregnancies included: 80% received steroids, 40% received plasma exchange, and 20% received IV immunoglobulin. However, 20% of the participants received no treatment during their pregnancy. Of the 8 pregnancies occurring first after iTTP diagnosis, 25.5% had preeclampsia, 25% had eclampsia, 37.5% had gestational hypertension, 25% had gestational diabetes, and 25% had a TTP relapse. None of the participants had HELLP syndrome or a stroke during this pregnancy. Fetal outcomes of the 8 first pregnancies after iTTP diagosis included preterm labor in 12.5%, miscarriage or fetal loss in 12.5%, and low birth weight in 12.5%. Only 3 respondents with acquired TTP had a second pregnancy after iTTP diagnosis, 33.3% of these were affected by iTTP relapse and 33.3% had low birth weight. Treatments received for both sets of pregnancies after diagnosis included steroids for 45.5%, cyclosporine for 18.1%, rituximab for 27.3%, and plasma exchange for 9.1%. Notably, 18.1% received no treatment during their subsequent pregnancy.

Table 1.

Pregnancy outcomes with initial iTTP diagnosis and after iTTP diagnosis

ComplicationPregnancy with iTTP diagnosis (N = 10)Pregnancy after iTTP diagnosis (N = 11)
Preeclampsia 4/10 (40%) 2/11 (18.2%) 
Eclampsia 2/10 (20%) 2/11 (18.2%) 
Gestational hypertension 1/10 (10%) 3/11 (27.3%) 
Gestational diabetes mellitus 3/10 (30%) 2/11 (18.2%) 
TTP episode/relapse 1/10 (10%) 3/11 (27.3%) 
HELLP syndrome 1/10 (10%) 0/11 (0%) 
Stroke 0/10 (0%) 0/11 (0%) 
Fetal outcomes 
Preterm labor 3/10 (30%) 1/11 (9.1%) 
Premature rupture of membranes 1/10 (10%) 0/11 (0%) 
Miscarriage/fetal loss 3/10 (30%) 1/11 (9.1%) 
Low birth weight 2/10 (20%) 2/11 (18.2%) 
ComplicationPregnancy with iTTP diagnosis (N = 10)Pregnancy after iTTP diagnosis (N = 11)
Preeclampsia 4/10 (40%) 2/11 (18.2%) 
Eclampsia 2/10 (20%) 2/11 (18.2%) 
Gestational hypertension 1/10 (10%) 3/11 (27.3%) 
Gestational diabetes mellitus 3/10 (30%) 2/11 (18.2%) 
TTP episode/relapse 1/10 (10%) 3/11 (27.3%) 
HELLP syndrome 1/10 (10%) 0/11 (0%) 
Stroke 0/10 (0%) 0/11 (0%) 
Fetal outcomes 
Preterm labor 3/10 (30%) 1/11 (9.1%) 
Premature rupture of membranes 1/10 (10%) 0/11 (0%) 
Miscarriage/fetal loss 3/10 (30%) 1/11 (9.1%) 
Low birth weight 2/10 (20%) 2/11 (18.2%) 

Although outcomes of pregnancy after iTTP have historically been poor, it is now known that close monitoring before and during pregnancy and prophylactic interventions including immunosuppression and plasma-based therapy significantly improve maternal and fetal outcomes. Prepregnancy counseling is particularly important because assessment of disease activity and the use of rituximab to normalize ADAMTS13 activity before pregnancy minimize the risk of relapse and optimize maternal and fetal outcomes.13 However, our results highlight that in the United States counseling of women with iTTP regarding their reproductive options is suboptimal and, in the rare instances it is offered, focuses more on avoidance of pregnancy than a discussion of options should pregnancy be desired. With proper counseling and prophylactic treatment, there is not a strong indication that pregnancy outcomes would remain poor. This is a critical issue in disorders such as iTTP that predominantly affect women of childbearing age,14 in which concern regarding the inability to bear children can affect relationships and quality of life as reported in this survey. Outcomes of pregnancy after iTTP in this cohort were similar to those reported in the contemporary era with 90% resulting in live births even though nearly a third of pregnancies were affected by iTTP relapses and nearly 20% by preeclampsia highlighting the need for multidisciplinary care including maternal-fetal medicine and hematology during pregnancy.

Although our results are informative, there were limitations to this study including selection bias from the highly selected group that would be involved in a patient advocacy organization. It is likely that this study underestimates the gaps in pregnancy-related care and counseling in iTTP owing to responder bias; patients with greater access to information and resources (through patient support organizations, which is how the survey was disseminated) are more likely to respond to surveys. Responder bias also increases the risk of overestimation in this study, for example patients who are already having routine follow-up might be more likely to report unmet needs in health care because they are more engaged in their iTTP care. Due to the retrospective nature of this study, recall bias could also have affected the results. Moreover, the majority of survey respondents identified as White; iTTP predominantly affects Black women in the United States, who are disproportionately likely to be affected by structural barriers to receiving high quality maternal health care.15,16 Finally, we did not assess the desire of pregnancy in this cohort and how that plays a role in their ability to seek and receive reproductive health care.

In conclusion, a minority of women with iTTP are counseled regarding the risks of pregnancy, and even fewer receive counseling regarding their options to potentially improve pregnancy outcomes. This limits their reproductive choices and affects their relationships. Educating clinicians and providing information to patients though patient advocacy groups may help address these health care gaps. Furthermore, there is a need for international collaboration and multicenter studies focused on ameliorating the experiences of both iTTP and congenital TTP patients and providing comprehensive reproductive health care.

Acknowledgment: This work was supported by a grant from the National Institutes of Health, National Heart, Lung, and Blood Institute (grant K99HL150594) to S.C.

Contribution: J.B. collected data, and wrote, edited, and reviewed the manuscript; C.M. helped design study instruments and critically reviewed the manuscript; S.C. designed the study and wrote part of the first draft of the manuscript; M.M. edited and critically reviewed the manuscript; and all authors read and approved the final draft of the manuscript.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Shruti Chaturvedi, Division of Hematology, Department of Medicine, Johns Hopkins Hospital, 720 Rutland Ave, Ross Research Building 1025, Baltimore, MD 21212; email: schatur3@jhmi.edu.

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Author notes

Data are available on request from the corresponding author, Shruti Chaturvedi (schatur3@jhmi.edu).