Prophylactic fresh frozen plasma (FFP) infusions may be necessary to replenish ADAMTS13 activity and maintain a successful pregnancy in expectant mothers with congenital thrombotic thrombocytopenic purpura (cTTP), according to a study published in the Journal of Thrombosis and Haemostasis.
A germline mutation in the ADAMTS13 gene is the primary cause of cTTP. “In patients with cTTP, pregnancy without ADAMTS13 replenishment is not recommended,” corresponding study author Masanori Matsumoto, MD, PhD, of Nara Medical University in Japan, told ASH Clinical News. “Without prophylactic FFP infusion, about half of the pregnancies after 20 weeks of gestations would lead to stillbirth. Therefore, the diagnosis of cTTP during childhood [before a woman becomes pregnant] is extremely important.”
Since cTTP only occurs in about 1 patient per million in the population, however, little is known about the optimal management approach, Dr. Matsumoto explained. His research group has been compiling anecdotal experience about management of patients with cTTP during pregnancy for many years.
With this study, Dr. Matsumoto and colleagues compared fetal outcomes in 38 women: 12 who became pregnant after diagnosis of cTTP by ADAMTS13 gene analysis (Group 1) and 26 who became pregnant before cTTP diagnosis and were diagnosed during or after pregnancy (Group 2). Data from these women were retrospectively obtained from a cTTP registry at Nara Medical University.
In Group 1, ADAMTS13 activity was assessed and monitored through pregnancy and until delivery in most cases. Ten women in this group received prophylactic FFP infusions in an outpatient clinic. The investigators did not monitor ADAMTS13 activity in women in Group 2 who became pregnant prior to their cTTP diagnosis, and prophylactic FFP infusions were not administered.
Fetal survival rates were higher in patients who received FFP during pregnancy compared with those who did not receive FFP (p=0.016). Fetal survival rates of women who did not receive FFP dramatically decreased after 20 weeks’ gestation, the authors added. The live birth rate was significantly higher for Group 1 compared with Group 2 (92% vs. 50%; p=0.027).
The researchers noted that a woman in Group 1 became pregnant three times, but despite prophylactic use of FFP at varying dosages, none of the pregnancies were successful. “While prophylactic FFP infusion during pregnancy benefits both mother and baby, some patients with TTP episodes before pregnancy in spite of prophylactic FFP infusion had fetal deaths,” Dr. Matsumoto said. “We do not think that all [pregnancies can be] saved using even a considerable amount of FFP infusion.”
In contrast, one patient with cTTP had two successful pregnancies despite receiving FFP just before birth rather than throughout her pregnancy. The patient received 240 mL of FFP on the day prior to delivery and 480 mL on the day of delivery in one pregnancy, and 600 mL of FFP was administered 4 times just before delivery in another pregnancy. The pregnancies resulted in the delivery of healthy infants, with no evidence of microthrombotic complications in the mother or infant.
“The proper management of pregnancy is a critical issue in young female patients with cTTP, because pregnancy can evoke TTP episodes that have fatal outcomes in both mother and fetus,” the authors concluded. Given their study findings, they suggested that prophylactic FFP infusion should be started as soon as possible after conception, and an FFP infusion dosage of at least 5 mL/kg per week is optimal to successfully maintain pregnancy.
To maintain high trough ADAMTS13 activity levels, the investigators also recommend increasing FFP infusion dosages in the outpatient setting (up to 15 mL/kg per week), and daily FFP infusions until labor is complete.
Limitations of this study included its retrospective nature, as well as the relatively small sample size.
Study authors report no relevant conflicts of interest.
Sakai K, Fujimura Y, Nagata Y, et al. Success and limitations of plasma treatment in pregnant women with congenital thrombotic thrombocytopenic purpura. J Thromb Haemost. 15 August 2020. [Epub ahead of print]