IS IT TTP, HELLP OR BOTH?

Case Presentation: A healthy 27 year-old woman G1P0 presented at 29 weeks gestation with three days of headaches, intermittent confusion, blurry vision, vomiting, and shortness of breath. Physical exam was remarkable for hypertension to 160/93, a Petechial rash on extremities without neurologic signs. CBC was notable for hemoglobin of 5.9, Platelets 11000 with many schistocytes. Creatinine was 2.2 on admission but normalized the following day. LFTs were notable for AST 83, ALT 35, total bilirubin 2.7, LDH 1670, Haptoglobin undetectable. Direct Coombs test and coagulation panel were negative. Urinalysis showed 3+ proteins. At that time, diagnoses of Thrombotic Thrombocytopenic Purpura (TTP) and HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome were considered. Patient was immediately given FFP, corticosteroids, RBC transfusions, magnesium for seizure prophylaxis and daily plasma exchange (PLEX). On day four liver enzymes peaked in the 220s and emergent C-section was performed for worsening HELLP. She delivered a healthy baby. ADAMTS13 activity level resulted after delivery at less than 5% without inhibitor detected, and the diagnosis of TTP was made. She was transferred to the medicine floor and her postpartum course was notable for decreased transaminases and 2 relapses of TTP on day 10 and day 25 treated successfully with PLEX. The patient declined Rituximab due to concern for adverse effects. Low dose Aspirin was prescribed upon discharge.

Discussion: Thrombotic microangiopathies (TMA) include but are not limited to TTP (hereditary: 10% and acquired: 90%) and HELLP. Up to 5% of thrombocytopenia in pregnancy is related to TTP and the prevalence of HELLP syndrome is about 1% [1]. Both conditions are triggered by pregnancy and present with microangiopathic hemolytic anemia and thrombocytopenia. The diagnosis of HELLP requires elevated liver enzymes whereas the diagnosis of TTP requires ADAMTS13 activity less than 10%. The case we described fulfills the criteria for both conditions. Very high transaminases are very unusual in TTP [2]. The patient scored 7/7 on Plasmic score, which is a recently validated tool used to support diagnosis of TTP in TMAs and initiation of PLEX [3]. ADAMTS13 activity is usually delayed; therefore platelet transfusions should be thoughtfully discussed as transfusions can worsen disease course. Despite PLEX, the patient had continued elevation of liver enzymes, which improved after delivery. This finding further supports the co-occurrence of both conditions. Up to 66% of women who have their first episode of TTP during pregnancy are diagnosed with late onset hereditary TTP. Although genetic studies are missing the absence of an inhibitor and the initial presentation during pregnancy support the diagnosis of hereditary TTP [4]. In the event that TTP and HELLP are suspected, clinicians should have a low threshold to initiate PLEX for treatment of TTP as well as emergent C-section for HELLP based on clinical grounds [2,4].

Conclusions: Hospitalists are often confronted with the management of medical conditions in pregnant women. Although TTP and HELLP are rare conditions making an accurate and timely diagnosis is of utmost importance to ensure better feto-maternal outcomes and appropriate sub-specialty follow up.