Rescue Therapy in Chronic Prothrombotic Autoimmune Anti-PF4 Disorder

This NEJM correspondence details a case of a young woman with chronic autoimmune anti–platelet factor 4 (PF4) disorder who suffered recurrent thrombotic events despite anticoagulation, IVIG, and plasma exchange. She initially presented with DVT and pulmonary embolism, later developing arterial thromboses and persistent thrombocytopenia. Diagnostic assays (HIPA, PIPA, ELISA, AcuStar) confirmed platelet-activating anti-PF4 antibodies independent of heparin exposure. After a series of strokes following SARS-CoV-2 infection in 2022, she received high-dose IVIG and antiplatelet therapy, with partial response. Rescue therapy using ibrutinib (a Bruton tyrosine kinase inhibitor) led to temporary remission. After relapse, combining increased ibrutinib dosing (280 mg daily) with IVIG and six therapeutic plasma exchanges yielded sustained recovery: platelet counts normalized, D-dimer dropped, and neurological symptoms resolved  persistent pathogenic antibodies. This case suggests that ibrutinib may suppress platelet activation downstream of FcγRIIA, offering a promising adjunct in refractory autoimmune anti-PF4 syndromes such as autoimmune HIT and VITT.

This NEJM correspondence details a case of a young woman with chronic autoimmune anti–platelet factor 4 (PF4) disorder who suffered recurrent thrombotic events despite anticoagulation, IVIG, and plasma exchange. She initially presented with DVT and pulmonary embolism, later developing arterial thromboses and persistent thrombocytopenia. Diagnostic assays (HIPA, PIPA, ELISA, AcuStar) confirmed platelet-activating anti-PF4 antibodies independent of heparin exposure. After a series of strokes following SARS-CoV-2 infection in 2022, she received high-dose IVIG and antiplatelet therapy, with partial response. Rescue therapy using ibrutinib (a Bruton tyrosine kinase inhibitor) led to temporary remission. After relapse, combining increased ibrutinib dosing (280 mg daily) with IVIG and six therapeutic plasma exchanges yielded sustained recovery: platelet counts normalized, D-dimer dropped, and neurological symptoms resolved  persistent pathogenic antibodies. This case suggests that ibrutinib may suppress platelet activation downstream of FcγRIIA, offering a promising adjunct in refractory autoimmune anti-PF4 syndromes such as autoimmune HIT and VITT.