We present a case of extremely severe postpartum HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, associated with activation of coagulation, massive recurrent intra-abdominal bleeding requiring two laparotomies, renal failure, and central nervous system symptoms. This case underlines the complexity of pregnancy-related thrombotic microangiopathies regarding their differential diagnosis, multiple organ dysfunction, as well as management. Systemic endothelial cell injury plays a central role in the pathogenesis of thrombotic microangiopathies. Treatment of HELLP syndrome usually consists of administration of antihypertensive therapy and magnesium sulfate. No consensus exists regarding the use of plasma exchange or corticosteroids. Plasma exchange was a major part of the treatment regime in our patient. Early plasma exchange may be considered as an adjuvant therapy in severe and progressive postpartum HELLP syndrome.