Thrombotic Microangiopathy Associated with Pregnancy: Various Outcomes in Different Disorders

Thrombotic microangiopathy (TMA) associated with pregnancy can be fulminant and fatal disorder. Pregnancy outcomes and survival of patients depend on the precise diagnose and appropriate treatment approaches. When a pregnant or postpartum woman presents with sudden and severe microangiopathic hemolytic anemia and thrombocytopenia, conditions that require urgent care must be considered: preeclampsia with severe features (PE/HELLP syndrome), thrombotic thrombocytopenic purpura (TTP), catastrophic antiphospholipid syndrome (CAPS), complement-mediated thrombotic microangiopathy (atypical hemolytic-uremic syndrome, aHUS). The distinction among these syndromes is often unclear because they share multiple clinical features. Overlap between PE/HELLP and TTP, CAPS and aHUS is also apparent from the fact that pregnancy can be a trigger for TMA before and after delivery. These disorders, especially PE imitators, are very important as the causes of maternal and fetal death.

Since 2010 we observed 104 patients with pregnancy-associated TMA. Women's age at the time of pregnancy was 32,04±0,83 years old, delivery performed at 34,89±0,74 gestation weeks. The reasons of TMA defined as PE/HELLP in 71 (68,3%) women (main signs: blood pressure more than 160 mm systolic or 110 mm diastolic, platelet count <100 x 10⁹/l and/or abnormal liver function, renal insufficiency, pulmonary edema, cerebral symptoms, eclampsia - generalized seizures, peripartum cardiomyopathy), aHUS- 32 (30,8%), TTP-1 (0,9%) (ADAMTS13 level less than 10%). All of them required preterm operative delivery. Therapeutic plasma exchange (1-9 procedures) performed in 88 (84,6%). ADAMTS13 level assessed before plasma therapy (45-84%, excluding the TTP case), as well as lupus anticoagulant (LA) and antiphospholipid antibodies (APLA) (negative in all patients). In cases of aHUS we use eculizumab in 14/32 (43,75%), but a full course with subsequent successful discontinuation of the drug was received only by one patient. 13/14 patients received 1 to 6 injections of eculizumab.

Overall mortality rate was 10 (9,6%), It is noteworthy that only patients with aHUS died- 10/32 (31,25%). Antenatal fetal death occured in 16 (15,4%), among them 12/32 (37,5%) were diagnosed with aHUS. The condition of patients with PE/HELLP improved on 1-3 days after delivery in all cases. In aHUS patients, life-threatening complications persisted and even progressed after delivery: massive uterine bleeding required hysterectomy occurred in 23,2%, acute kidney injury registered in 100% patients, neurological symptoms had 61%, respiratory distress syndrome- 55%, dilated cardiomyopathy- 16,7%. 61,3% required hemodialysis, 51,8%- respiratory care. All of patients who died had 2 "waves" of TMA: first wave has damaged 2-5 organs without any proved infections, but treated with antibacterial combination. Second TMA wave was fatal due to superimposed septic disorders, resistant to antibiotic therapy. Patients on eculizumab treatment had more severe disease at debut with shorter history of aHUS and responded well to eculizumab. Survival of aHUS patients on eculizumab treatment was 71,4%, without it - 64,7%.

Therapeutic approaches in TMA associated with pregnancy are different and survival of patients depends on a timely diagnosis. Clinical vigilance requires for early detection of TMA. After that is necessary as soon as possible investigate the ADAMTS13 level to avoid TTP, and LA and APLA to avoid CAPS. Plasma exchange may be first urgent step of treatment in all cases of TMA, but after clarifying the diagnosis therapy should be adjusted. Timely diagnosis and effective approaches including early prescribed targeted therapy in aHUS patients can improve the survival rate and pregnancy outcomes.