Thrombotic microangiopathy in a pregnancy with type 1 diabetes mellitus: A case report. [Australian and New Zealand Journal of Obstetrics and Gynaecology]

Abstract

Introduction: Thrombotic microangiopathies (TMAs) are a spectrum of disorders involving microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and organ injury. In pregnancy, differentiating between TMAs can be clinically challenging but is important due to the impact on fetal and maternal outcomes. Case Summary: We present the case of a 26-year-old primipara referred to our tertiary centre at 20 weeks gestation with a TMA of unclear cause in the setting of poorly-controlled type 1 diabetes mellitus. She reported fatigue and mild pedal oedema, and was normotensive. Investigations demonstrated a new-onset MAHA (haemoglobin [Hb] 70 g/L, moderate schistocytes, haptoglobin <0.06 g/L, LDH 747 U/L) and thrombocytopenia (platelets 98 x 10/L). Her renal function was preserved (serum creatinine [sCr] 50 ivmol/L, urea 6.6 mmol/L) but there was microscopic haematuria (370 x 10 cells/L) with glomerular morphology and heavy proteinuria (urine protein: creatinine ratio 0.5 g/mmol) on a background of baseline macroalbuminuria (pre-pregnancy urine albumin:creatinine ratio 132 mg/mmol). Fetal morphology and Doppler studies were normal. Thrombotic thrombocytopenic purpura was excluded. Regular blood transfusions were required to maintain Hb >80 g/L. Renal function worsened slightly over the following two weeks, and kidney biopsy demonstrated moderately advanced diabetic nephropathy and TMA without glomerular endotheliosis. Genetic testing for common atypical haemolytic uraemic syndrome (aHUS) genes returned a heterozygous mutation of unknown significance in exon 2 of the CFI gene (c.292A>G, p.Thr98Ala). Eculizumab was commenced for presumed aHUS, with minimal improvement in platelet count, renal function and blood transfusion frequency. Over the subsequent 5 weeks she developed hypertension, hyperreflexia, headache with visual disturbance, worsening oedema and increased proteinuria. Caesarean section was performed at 27 + 4 weeks gestation for pre-eclampsia, with a live infant delivered in good condition. Postpartum, her headache, visual disturbance and hyperreflexia rapidly resolved. Her thrombocytopenia also improved, although her haemolytic anaemia persists with longer transfusion intervals. Discussion(s): We discuss our approach to distinguishing the causes of TMA in pregnancy in this complex case.