TTP and pregnancy

TTP is a rare, life-threatening disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia often associated with renal failure and neurologic manifestations.²  Previously, survival rates for patients with TTP were ∼10%. With the intervention of plasma exchange, however, it has now increased to >80%.³  At the center of the deficiency is severe depletion of a von Willebrand factor cleaving protease termed ADAMTS13 protease. There are both congenital and acquired forms of this disorder both of which are classified based on diminished levels of ADAMTS13. The Oklahoma TTP-HUS Registry represents a database of patients in which data have been collected dating back to 1995. In this registry, >70% of the cases of TTP occur in women, 45% of whom are of childbearing age.⁴ 

Although it is well established that pregnancy may predispose to TTP, little is understood regarding pregnancy outcomes in women with a history of acquired TTP who subsequently become pregnant.⁵  Hematologists caring for these women are often asked to estimate the risk of recurrence of TTP during pregnancy and also the negative impact on the pregnancy itself. Because this is a rare disorder, and because few studies have been conducted on pregnant women with a past history of TTP, physicians have limited anecdotal studies to consult when advising these patients. Because congenital TTP behaves differently in pregnancy, experience with those patients cannot be extrapolated to women with the acquired form of the disorder.⁶  In women with hereditary ADAMTS13 deficiency, it is known that TTP can occur during pregnancy and is associated with fetal loss.⁷  Prophylaxis with plasma exchange can be initiated in those pregnancies, especially in women with documented low levels of ADAMTS13 in the peripartum period. Whether acquired forms of TTP are also associated with poor pregnancy outcomes is not well understood. In addition, there are no data regarding ADAMST13 levels and pregnancy outcome in women with a history of TTP.

Jiang and colleagues specifically address the risk of TTP recurrence and pregnancy outcomes in pregnant women.¹  The authors build on their original report regarding recurrent TTP in pregnancy published in 2004.⁴  The previous report focused on the frequency of recurrent TTP with subsequent pregnancy in 19 women in the Oklahoma TTP-HUS Registry. In this new manuscript, the authors specifically use the Oklahoma TTP-HUS Registry, focusing primarily on women who had TTP associated with acquired, severe ADAMTS13 deficiency (level <10%). No data regarding the level of ADAMTS13 in the population were discussed in the previous manuscript.

The primary outcomes of the new study were not only risk of recurrence of TTP but also development of pregnancy complications. The results presented in the manuscript are based on 10 women who recovered from TTP and went on to have a total of 16 pregnancies. Nine of the 10 women in the study had TTP associated with inhibitors that were measureable at the time of their first TTP episode. Of the 10 women, 3 had TTP associated with pregnancy or postpartum, 2 women had systemic lupus erythematosus and the other 5 women were “idiopathic.” As shown in Table 1, 2 patients had recurrent episodes of TTP associated with pregnancy. Interestingly, these cases did not occur in the women who initially had pregnancy-associated TTP. In addition to the recurrence of TTP, 2 patients had preeclampsia. There were also 2 cases of pregnancy loss. The majority of the rest of the pregnancies (10) were not associated with any poor pregnancy outcomes.

Because there were such small patient numbers in their study, the authors also performed a literature search and pooled information from other studies to identify all reported cases of pregnancies in women following recovery from TTP associated with acquired, severe ADAMTS13 deficiency. In their literature search that included 10 additional pregnancies, 6 pregnancies were associated with recurrent episodes of TTP. Although the episodes of recurrent TTP were minimal, the frequency of poor pregnancy outcomes was increased. This included risk of preeclampsia and severe preeclampsia. These data, however, are less transparent than that from the Oklahoma registry, as 3 of the patients had a preexisting history of preeclampsia, which may have accounted for the increased frequency of preeclampsia in this study population.

The authors acknowledge that an obvious limitation of their data is the small number of women and pregnancies as is expected based on the low frequency of this disorder. This manuscript, however, represents data on more women and pregnancies than all the previously published reports and therefore represents the most comprehensive body of data to date. Also, because these patients were followed closely through the Oklahoma TTP-HUS Registry, it provides a comprehensive evaluation of these women for up to 18 years. For these reasons, this manuscript provides a compendium of data to guide decisions regarding pregnancy in women with a past history of TTP.

Still, there are many questions left unanswered. More information is needed to fully understand the risk of recurrent TTP in this population as well as the risk of poor pregnancy outcomes. The utility of ADAMTS13 measurement is not discussed in this manuscript, although it may represent a means of surveillance for women at risk of TTP recurrence in pregnancy. Perhaps serial measurement of ADAMTS13 levels in pregnancy could represent a monitoring mechanism for risk of recurrence. In patients at risk, therapeutic plasma exchange could be initiated as a preventative measure. Further studies using these levels during pregnancy are needed.

The findings of this study, therefore, albeit based on small patient numbers, demonstrate good pregnancy outcomes for over 80% of women with a history of TTP. It should provide reassurance to physicians caring for these women that healthy pregnancies can occur with diligent observation and careful monitoring.