Time to Use our Thinking CAPS: A Case of Catastrophic Antiphospholipid Syndrome (CAPS) and a Review of Current Guidelines

Summary: Background CAPS is a complex clinical syndrome characterized by rapid onset of multifocal thrombosis associated with multiorgan failure in patients meeting serological criteria for Antiphospholipid Syndrome. CAPS currently lacks strong evidence-based guidelines. CAPS generally occurs related to a precipitating factor. A trigger was found in 68% of episodes of which most frequently were infections (29%), followed by surgeries (9%), malignancies (9%), estrogen use (4%), pregnancy (3%), drugs (3%), and SLE flare (2%). CAPS clinically manifests by affecting the kidneys (74%), lungs (55%), brain (56%), heart (53%), skin (45%), peripheral vessels (37%), liver (34%), and GI tract (12%). Lab findings typically present with thrombocytopenia (60%), Lupus Anticoagulant positive (present in 83% of episodes), IgG and IgM isotype anticardiolipin antibodies (81% and 51% respectively), Anti-b2-glycoprotein-I and IgM isotype antibodies (75% and 44% respectively), and less commonly with features of microangiopathic hemolytic anemia (15%). Case This is a 45-year-old Male with chronic history of protein malabsorption disorder, chronic diarrhea reported as possible “autoimmune enteropathy”, and left superficial femoral artery thrombosis s/p femoral-popliteal bypass in 2016 on Lovenox who presented as a hospital transfer for further workup of C. Difficile colitis with hemoptysis. Prior workup included EGD/Colonoscopy showing nonspecific inflammation with biopsies negative for Celiac disease, IBD, amyloidosis, and microscopic colitis. ANA, C3, C4, Pr3 antibody, and inflammatory markers were all negative. CTA chest significant for bilateral pulmonary infiltrates concerning for aspiration vs vasculitis. Labs significant for Hgb of 8.6, with both inflammatory markers and ANA panel unremarkable. US arterial and venous were significant for acute, non-obstructing DVT in bilateral subclavian veins; acute and obstructing DVT in right soleus vein. HRCT showed bilateral interstitial thickening, bronchiectasis, areas of ground glass opacities (GGO) in upper lobes and perihilar regions, and moderate bilateral pleural effusions. Two days after admission, rapid response called for PEA arrest with ROSC achieved after one round of CPR and epinephrine. There was a STAT CBC ordered that showed an acute drop in Hgb from 8 to 3, and patient was then transferred to MICU after stabilization. CTA chest/abdomen/pelvis after PEA arrest showed large retroperitoneal hematoma and active arterial bleed in multiple areas of left retroperitoneum, large pericardial effusion, narrowing of external iliac arteries bilaterally, weblike filling defect in proximal celiac artery, and diffuse bowel wall thickening of the small bowel with cobblestone appearance. TTE negative for tamponade, with a reduced EF 35%, moderate global hypokinesis of left ventricle, and moderate sized pericardial effusion. Patient transfused aggressively, underwent IR embolization x2, and thoracentesis significant for 1,588,000 RBCs and 571 WBCs. Additional labs significant for plt of 48, LDH 1407 and haptoglobin <10 with a peripheral smear showing 2+ anisocytosis and poikilocytosis in addition to fragment cells, schistocytes, and occasional tear drop cells and giant platelets. APS labs positive for anticardiolipin IgM > 150. The patient was treated for CAPS with high dose steroids, followed by solumedrol 60mg daily, and IVIG 1g/kg/day for 2 days. Labs after treatment with IVIG improved, Plt 76 increased from 56, and LDH 1250 increased from 1407. Discussion The preliminary criteria for classification of CAPS: involvement of three or more organs that develop in less than one week, biopsy confirmed small vessel occlusion in at least one tissue, and presence of antiphospholipid antibodies. This patient was diagnosed with Probable CAPS as he had 3 organs involved within a week and was positive for anticardiolipin IgM. Following current available data, the patient was treated with high dose steroids, IVIG, and ultimately recovered. Therapeutic dose anticoagulation may be given but was held due to risk/benefit assessment by multidisciplinary team. This is considered the first-line treatment of patients with CAPS; Rituximab or other combination therapies is not recommended currently (conditional recommendation, with very low certainty of evidence currently). Conclusion CAPS can be deadly, requiring a high index of suspicion, and further research to assist in clinical decision making; it is also imperative to test the hypothesis that guidelines can develop for rare diseases.