Abstract
Several serious disorders may present during pregnancy or postpartum with thrombotic microangiopathy (p-TMA). Signs of microangiopathic hemolytic anemia and thrombocytopenia may arise due to pregnancy complications such as severe preeclampsia (sPE) and HELLP-syndrome (hemolysis, elevated liver enzymes, and low platelets) or severe independent diseases: atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP). Recent evidence and clinical similarities suggest a link sPE/HELLP to aHUS, a disease of excessive activation of the alternative complement pathway. Pregnancy-associated aHUS is a severe disorder with a high risk of maternal and fetal morbidity and mortality, defined by the occurrence of comlement-mediated TMA without ADAMTS13 deficiency. Triggered by pregnancy and another complement-amplifying conditions women develop the syndrome, leading to a disastrous hemolytic disease characterized by diffuse endothelial damage and platelet consumption. Delivery is the treatment of choice of sPE and HELLP, but can lead to progression in case of aHUS: even now it is associated with unfavorable outcomes.
We observe 116 women with p-TMA: 43 aHUS, 36 HELLP, 35 sPE, 2 TTP. PE diagnosed in accordance with the WHO criteria of 2008. HELLP- in accordance with Tenessee criteria (laboratory parameters normalized beyond 48-72 hours after delivery). TTP was associated with ADAMTS 13 deficiency <10%. We compare results with those of 28 healthy pregnant women. All patients with aHUS and TTP received plasma therapy (30-40ml/kg), in 20 cases of aHUS eculizumab was administered.
The overall outcomes differed depending on the TMA type. Condition of PE/HELLP patients improved only with supportive treatment in 28-72 hours after delivery. Women with TTP received successful prolonged plasma exchange. Survival was the worst in aHUS patients 32(74.4%), among other patients with TMA no one died. Neonates survived in 33(76,7%) mothers with aHUS, 70(98,6%) with PE and HELLP. Sepsis diagnosed only in aHUS-15(34,9%). Acute kidney injury registered in 100% aHUS 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 damaged 2-5 organs without any proved infections, but treated with combination of antibiotics. 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 (recovery of TMA laboratory signs - 87,2%, but a full course was not held anyone). Survival of aHUS patients on eculizumab treatment was 81,4%, without it - 66,5%.
All p-TMA are life-threatening disorders with different therapeutic approaches. Start therapy before specification of the diagnosis can be carried out with the use of plasma exchange for 24-48 hours. Patients with aHUS have a worst prognosis and require the rapid differential diagnosis. The revealed regularities allow us to assume the presence of the following triggers for the development of aHUS: surgical interventions and gestational complications. Early specific therapy complement inhibitor in complex with escalation treatment of multiple organ failure can contribute to the improvement of aHUS outcomes.
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Disclosures
No relevant conflicts of interest to declare.
Thrombotic Microangiopathies Associated with Pregnancy: Diagnostic and Therapeutic Challenges
