Atypical hemolytic-uremic syndrome (aHUS) is one of the most severe forms of thrombotic microangiopathy (TMA) that might develop during pregnancy and after childbirth. It is conditioned by a severe, progressive course of disease, unfavourable prognosis and difficult differential diagnosis between this and other forms of TMA – first of all, with classical obstetric complications: preeclampsia (PE) and HELLP syndrome. It is considered that pregnancy-associated aHUS (P-aHUS) is triggered by pregnancy itself. But an analysis of publications dealing with pregnancy-associated aHUS and our own experience accumulated by the present time indicate that the overwhelming majority of P-aHUS cases develop not during pregnancy, but after delivery, and almost always an acute TMA episode is preceded by various complications of pregnancy (PE, bleeding, placental abruption, antenatal intrauterine fetal death), infections, operative interventions, etc. As is known, they all might be regarded as a complement-activating conditions (CACs). The objective. To study the effects of obstetric complications, mainly preeclampsia, on the development, course and prognosis of pregnancy-associated aHUS. Patients and methods. From 2011 to 2019, 69 patients aged 16–44 years were examined, in whom aHUS developed during pregnancy or directly after childbirth. Most women (47 of 69, 68%) were secondiparas without any bad obstetric history. In 62 (90%) of 69 patients disease developed during the postpartum period at terms from several hours to 8 days after childbirth. Results. All patients had a full symptom complex of TMA: microangiopathic hemolytic anaemia (lower haemoglobin levels 62.3 ± 15.0 g/l, higher lactate dehydrogenase levels 2683.7 ± 2143.1 U/l, schisocytosis, a decrease in haptoglobin), thrombocytopenia (50.0 ± 32.8 thous. per μl), involvement of the kidneys (higher creatinine levels 509.0 ± 349.8 μmol/l, oligoanuria) and other organs (liver, heart, central nervous system, lungs). Severe multiple organ failure was observed in 91.3% of patients. In all cases, the development of aHUS was preceded by additional CACs, the most common of which were caesarean section (73.5%), bleeding (69.5%) and PE (69.5%), although the number of CACs did not have a significant effect on the severity and outcome of aHUS. Neither were found significant differences in the clinical and laboratory manifestations in patients with the presence/absence of caesarean section, PE or bleeding (each taken separately). 40 (58%) of 69 patients received a complement-blocking therapy with Eculizumab. In patients receiving Eculizumab, compared to the patients who received only fresh frozen plasma therapy (29 women), complete recovery of renal function was noted in 26 (65%) vs 10 (34.5%) women, 5 (12.5%) vs 5 (17.5%) remained dialysis-dependent, 5 (12.5%) vs 11 (38%) died. Nineteen (47.5%) of 40 patients received only a full course of induction therapy or only 1–2 infusions of Eculizumab, in three more patients the drug was discontinued after 4–24 months. None of the women had a recurrence of TMA after discontinuation of Eculizumab. Conclusion. In all women with P-aHUS pregnancy was combined with additional CACs, as a rule, their number was >3. In 69.5% of cases, the disease was preceded by PE, which, in its turn, is considered as a specific obstetric variant of TMA. Considering interrelationships between PE and P-aHUS, we can suppose that glomerular capillary endotheliosis, characteristic for PE and conditioned by an imbalance between PlGF- and sFlt1-factors of angiogenesis/antiangiogenesis, promotes additional activation of the complement, creating preconditions for fast generalisation of endothelial lesions in patients with genetic defects in the complement system, which gives every reason to discuss the possibility of transformation of PE into aHUS. In this connection, all patients with PE, especially with severe one, should be referred to a group of risk for possible postpartum generalisation of the microangiopathic syndrome. It would be appropriate to regard P-aHUS as a heterogeneous group that includes both «classical» aHUS, and «secondary» HUS, not associated with constitutional ysregulation of the complement system. Early beginning of Eculizumab therapy permits not only to save the life of a patient with aHUS, but also to fully recover their health. In case of development of «secondary» aHUS, a course of Eculizumab might be reduced to 1–2 infusions. Key words: pregnancy-associated atypical haemolytic-uraemic syndrome, pregnancy, thrombotic microangiopathy, Eculizumab
Síndrome urémico hemolítico atípico. Reporte de caso y revisión de la bibliografía