Evolving catastrophic antiphospholipid syndrome with intracerebral hemorrhage: Treatment with plasma exchange and rituximab Free

Title

When Anticoagulation Falls Short: Immunomodulation in Severe Antiphospholipid Syndrome

Authors

Paul Wurtz, MD¹; David Pratico, MD²; Devin Moore, MD¹; Kristin Stoll, DO²

¹Internal Medicine, Brooke Army Medical Center, San Antonio, TX, USA

²Hematology and Oncology, Brooke Army Medical Center, San Antonio, TX, USA

Background

Antiphospholipid syndrome (APS) spans macro and microvascular thrombosis and can escalate to catastrophic APS (CAPS) with rapid multiorgan microthrombosis. When bleeding risk, laboratory interferences, or monitoring constraints limit anticoagulation—particularly when evolving CAPS is suspected—adjunctive immunomodulation may be warranted.

Case 1

A 44yearold woman with triplepositive APS and SLE developed recurrent ischemic infarcts after a subdural hematoma (SDH) that required anticoagulation reversal. With anticoagulation temporarily contraindicated, she received plasma exchange (five sessions) to rapidly reduce antibody burden and rituximab for Bcell depletion, along with highdose corticosteroids, and was transitioned to therapeutic heparin as bleeding risk abated. Antibody titers and inflammatory markers declined; she remained neurologically stable without new thrombosis. She was discharged on therapeutic enoxaparin, completed four weeks of rituximab, and later resumed full anticoagulation after SDH resolution, with mild residual weakness and independence in activities of daily living.

Case 2

A 72yearold man with ischemic cardiomyopathy presented with painful livedo racemosa and biopsyproven microthrombi in the setting of acute kidney injury (AKI). He had a persistent lupus anticoagulant with hightiter anticardiolipin IgM and antiβ2glycoprotein I IgM antibodies, fulfilling revised Sapporo/Sydney classification criteria for APS; a new smear showed 3–4 schistocytes per highpower field concerning for progression. Vitamin K deficiency and a lupusanticoagulant–related baseline aPTT prolongation complicated selection and monitoring of parenteral anticoagulants. New thrombocytopenia further limited unfractionated heparin use due to concern for heparininduced thrombocytopenia (HIT), with APS antibodies confounding confirmatory testing. Apixaban was discontinued; enoxaparin 1 mg/kg twice daily, aspirin, prednisone 1 mg/kg with taper, and rituximab 375 mg/m² weekly ×4 were initiated. Skin lesions and platelet count improved, kidney function recovered, and livedo nearly resolved. He was bridged from enoxaparin to warfarin (INR goal 2–3) for indefinite anticoagulation given APS and atrial fibrillation.

Outcomes and significance

Targeted immunomodulation controlled disease activity and enabled safe reescalation or bridging of anticoagulation in two very highrisk scenarios. In Case 1, five plasmaexchange sessions plus rituximab suppressed antibody/inflammatory activity, allowing transition from reversal after SDH to therapeutic heparin without recurrent thrombosis. In Case 2, rituximab with steroids and fulldose lowmolecularweight heparin led to rapid resolution of livedo, platelet recovery, and renal improvement without progression to CAPS, permitting a bridge to warfarin. These cases delineate practical impediments to standard agents—lupusanticoagulant–mediated aPTT prolongation where chromogenic antiIIa monitoring is unavailable, thrombocytopenia with concern for HIT limiting unfractionated heparin, and recent intracranial hemorrhage precluding fullintensity anticoagulation—and show that rituximab ± plasma exchange can provide disease control while a definitive anticoagulation plan is established.

Conclusions

In severe APS phenotypes—evolving CAPS with intracranial hemorrhage and microthrombotic livedo vasculopathy—rituximab, with or without plasma exchange, can stabilize disease when anticoagulation is limited or requires bridging. Given higher recurrent thrombosis with direct oral anticoagulants reported in highrisk APS, vitamin K antagonists remain preferred for longterm therapy when feasible; multidisciplinary coordination is essential to individualize immunomodulation, anticoagulant selection, and timing.

Disclaimer

The views expressed in this abstract are those of the author(s) and do not necessarily reflect the official policy or position of the Defense Health Agency, the Department of Defense, or the U.S. Government.