Catastrophic Antiphospholipid Syndrome: A Medical Complex Case of Multi-Organ Dysfunction following a Severe PET and HELLP Syndrome diagnosis at 21 weeks gestation
Antiphospholipid Syndrome (APS) is an acquired autoimmune disorder characterised by thrombosis (venous/arterial/small vessel) in the context of persistent antiphospholipid autoantibodies (aPL); namely anti-cardiolipin (α-CL), lupus anti-coagulant (LA) and anti-β2 glycoprotein-1 (anti-β2 GP-1). Among the many clinical manifestations of this condition are those presenting in the context of pregnancy. These include; recurrent fetal loss (first trimester and late), pre-eclampsia, HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome, eclampsia, and intra-uterine growth restriction1,2. APS can be classed as primary or secondary, with the latter presenting alongside other autoimmune conditions such as systemic lupus erythematosus (SLE). ‘Catastrophic’ Antiphospholipid Syndrome (CAPS) is a rare accelerated form of APS in which multi-organ failure ensues over a period of days-to-weeks secondary to small vessel occlusion at multiple sites. It carries a mortality rate of approximately 50%3. Triggers include infection and surgery. Diagnosis can be challenging, but essentially requires a known history of APS or aPL, the involvement of 3 or more organs, and the histologic confirmation of microthrombosis4. High rates of HELLP syndrome and placental infarctions have been reported in cases of CAPS during pregnancy and the pueperium. Additional features include renal (renal thrombotic microangiopathy (TMA)), respiratory (e.g. acute respiratory distress syndrome (ARDS), respiratory failure, pulmonary embolism), and central nervous system (infarcts, haemorrhage, encephalopathy) pathology5. Management of CAPS includes anticoagulation, steroid administration, plasma exchange, intravenous immunoglobulins and immunosuppression.
39 year-old G5P0 with known APS diagnosis following 4 early miscarriages (<8 weeks gestation) and positive anti-β2 GP-1 and LA. Aspirin dose was increased from 75mg to 150mg after uterine artery dopplers showed bilateral increased resistance and notching on the left side. Prophylactic Fondaparinux 2.5mg commenced at 6/40 (systemic reactions to enoxaparin and dalteparin).
Presented in May 2018 at 21+4/40 unable to tolerate oral intake, vomiting, diarrhoea and epigastric pain.
Following day (21+5/40) feeling short of breath & transferred to delivery suite HDU:
This case presented multiple challenges and highlighted the importance of multidisciplinary team working. It also demonstrates the difficulties faced in diagnosing CAPS in the context of pregnancy; from initial presentation with symptoms that could fit with viral gastroenteritis, to a rapidly evolving early-onset pre-eclampsia and subsequent HELLP syndrome, followed by failure of the CNS with evidence of PRES and renal failure. The co-existence of PE and SAH also presented a dilemma regarding management with anti-coagulation. Placental examination revealed scattered small infarcts, as is often seen in CAPS. Although the patient developed C.Difficile infection late in the course of her illness, we cannot attribute her preceding and persistent pyrexias to this source; fevers have been reported as part of a post-partum syndrome in the context of APS2 and we wonder whether her temperatures could have been secondary to a systemic inflammatory-type response rather than an infection.
As with many medical conditions in pregnancy, pre-pregnancy counselling and initiation of prompt and appropriate risk-reducing treatments is key. CAPS only affects <1% of patients with APS, and so the importance of learning from each case as a medical community is paramount to further our understanding of this devastating condition.