The HELLP syndrome, antiphospholipid antibodies, and syndromes

Abstract

A recent publication in this journal has drawn attention to the association of HELLP syndrome with antiphospholipid antibodies (aPL) accompanied by a 20210A mutation of the prothrombin gene, resulting in bilateral deep vein thromboses after termination of the pregnancy [1]. The association of hemolysis-elevated liver enzymes and thrombocytopenia, known as the HELLP syndrome, is a thrombotic microangiopathic state with thrombocytopenia complicating pregnancy [2]. It usually occurs before the 32nd week of gestation but may manifest in the postpartum period in 25% of cases [3]. Although usually resolving with delivery of the fetus without any complications, sequelae have been reported in 30% of patients [4]. The diagnosis of HELLP syndrome is based on the presence of hemolysis (anemia with characteristic blood smear), elevated levels of lactic dehydrogenase, total bilirubin of >1.2 mg/dl, and elevated alanine aminotransferase more than twofold. “Complete” HELLP syndrome is defined by the presence of all four criteria and partial or “incomplete” HELLP syndrome by the presence of two criteria [5]. The association of HELLP syndrome with aPL extends as far as back to 1994. Two cases of HELLP syndrome with demonstrable aPL were first reported by Ornstein and Rand in 1994 [6]. Their cases were refractory to delivery of the fetus, corticosteroids as well as anticoagulation, the first indication in the literature that this combination of events presaged a rather different clinical entity to the simple HELLP syndrome. Plasmapheresis resulted in resolution of the condition. The authors hypothesized whether an association between this “refractory” microangiopathic condition and the presence of the aPL existed. In 1995, Ibery et al. [7] then reported a single patient with positive lupus anticoagulant and HELLP complicated by hepatic, dermal, adrenal infarctions as well as placental abruption, the first true “overlap” of antiphospholipid syndrome (APS) and HELLP, although it seems that this case might have been an example of the catastrophic variant of the APS. Alsulyman et al. [8], Nagayama et al. [9], McMahon and Smith [10], and Amant et al. [11] all documented cases with demonstrable aPL; some of whom had developed hepatic infarctions, necrosis, or hemorrhage. Severe liver complications such as hemorrhage/rupture were only seen in 1% of HELLP patients in a large series of patients [12]. Roberts et al. [13] in 2003 documented a systemic lupus erythematosus patient with both HELLP and APS with acute renal failure who responded well to plasma exchanges. Hepatic infarcts occurring in two patients with HELLP syndrome were reported by Zissin et al. in 1999 [14]. No mention, however, is made of aPL in this article. Central retinal vein occlusion was reported in one patient [15], while thrombosis of the inferior vena cava was reported by Clin Rheumatol (2008) 27:1–4 DOI 10.1007/s10067-007-0742-7