Thrombotic Thrombocytopenic Purpura and Atypical Hemolytic Uremic Syndrome Microangiopathy in Pregnancy

Abstract

Thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) are thrombotic microangiopathies (TMAs) that can present in pregnancy. The presentation can be with typical microangiopathic features and thrombocytopenia, but there is also a significant risk of in-utero fetal loss. TTP presents most commonly in the third trimester and aHUS in the postpartum period. On presumptive diagnosis, plasma exchange should be started and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity measured. An activity of < 10% is in keeping with TTP, which may be late-onset congenital TTP or acquired disease: the former will require regular plasma therapy and the latter immunosuppression. In aHUS, eculizumab is the therapy of choice. In future pregnancies, follow-up with a multidisciplinary team including fetomaternal and specialist obstetrics should be undertaken.

None of the above: thrombotic microangiopathy beyond TTP and HUS

“…21 HELLP is much more common in this scenario than TTP or aHUS (1/1000 for HELLP vs 1/200 000 pregnancies for TTP and aHUS). 22 Subtle differences may aid in making the correct diagnosis; severe headache, visual symptoms, and hyperreflexia are more common in severe preeclampsia and HELLP, whereas transient focal abnormalities and mental status changes are more characteristics of TTP. Declining renal function despite blood pressure control and delivery of the fetus should also raise the suspicion for aHUS.…”

Thrombocytopenia in pregnancy

“…Serologically documented acquired, antibody-induced TTP (aTTP) is estimated to occur in 1 in 200 000 pregnancies. 35,36 Approximately 10% of women with aTTP 24,37 and a quarter to half of those with congenital TTP (cTTP) 35,38,39 present for the first time during pregnancy, often the first pregnancy, 36 or postpartum. 35,40 This predisposition may reflect the fall in ADAMTS13 and rise in von Willebrand factor that occurs normally during gestation.…”

“…The diagnosis of TTP should become a prominent consideration when clinical signs and symptoms do not resolve and the platelet count does not increase above 100 3 10 9 /L by 48 to 72 hours postdelivery. 42 cTTP, which comprises up to 50% of all cases of gestational TTP in some series, 36 should be suspected when severe ADAMTS13 is detected in the absence of an IgG inhibitor even in the absence of a suggestive family history; gene sequencing is required for definitive diagnosis and to guide management of subsequent pregnancies. 44 Management.…”

“…35,39,43 Transplacental passage of anti-ADAMTS13 antibodies has been documented in the absence of clinical sequelae. There is little published guidance on the use of ritixumab, 45 azathioprine, 36 or other modalities in women with aTTP who do not respond to plasmapheresis. An intermediate purity factor VIII preparation containing ADAMTS13 has been used; data on use of recombinant ADAMTS13 are needed.…”

“…45 The frequency of exchange is based on platelet count and LDH 39 with generally excellent maternal outcomes. 36 Platelet counts should be followed monthly in women with a prior history of aTTP but normal levels of ADAMTS13 at the onset of pregnancy. 36 Women with pregnancy-associated TTP may also have an increased risk of PEC during subsequent pregnancies.…”