Mehraboon Irani1,2, Eric Siegal3, Abhay Jella3, Richard Aster4,5, Anand Padmanabhan1,2,4. 1. Medical Sciences Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin. 2. Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin. 3. Department of Medicine, Advocate Aurora Health, Milwaukee, Wisconsin. 4. Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin. 5. Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Abstract
BACKGROUND: Spontaneous heparin-induced thrombocytopenia (HIT) is a rare but serious prothrombotic syndrome characterized by thrombosis, thrombocytopenia, and strong platelet-activating HIT antibodies in the absence of heparin exposure, and is frequently characterized by a suboptimal response to standard therapies. Here, we present the first report of intravenous immunoglobulin G (IVIG) use in a patient with spontaneous HIT. STUDY DESIGN AND METHODS: Patient information, including demographic, clinical, and laboratory results, were obtained from the electronic medical record. Laboratory testing was performed in the serotonin release assay, platelet factor 4 (PF4)-dependent P-selectin expression assay, and PF4/polyvinylsulfonate enzyme-linked immunosorbent assay to study the impact of IVIG on HIT antibody-mediated platelet activation. The patient was also genotyped for a polymorphism in the IgG receptor on platelets, FcγRIIa, at amino acid position 131. RESULTS: A 30-year-old man had a thrombotic stroke and thrombocytopenia and strong HIT serologies in the absence of proximate heparin use. Direct thrombin inhibitor therapy was not associated with a prompt response. Due to severity and extent of thrombosis and persistent thrombocytopenia, he was treated with high-dose IVIG. This treatment was associated with rapid and sustained normalization of platelet counts and a gradual improvement in thrombotic complications. Platelet activation induced by HIT antibodies in the PF4-dependent P-selectin expression assay (low PF4) was significantly lower after IVIG treatment, correlating well with platelet rise. Consistent with the severity of thrombosis, the patient was found to possess the 131HR polymorphism in FcγRIIa. CONCLUSION: These results suggest that IVIG may be a useful adjunctive therapy in spontaneous HIT.
BACKGROUND: Spontaneous heparin-induced thrombocytopenia (HIT) is a rare but serious prothrombotic syndrome characterized by thrombosis, thrombocytopenia, and strong platelet-activating HIT antibodies in the absence of heparin exposure, and is frequently characterized by a suboptimal response to standard therapies. Here, we present the first report of intravenous immunoglobulin G (IVIG) use in a patient with spontaneous HIT. STUDY DESIGN AND METHODS: Patient information, including demographic, clinical, and laboratory results, were obtained from the electronic medical record. Laboratory testing was performed in the serotonin release assay, platelet factor 4 (PF4)-dependent P-selectin expression assay, and PF4/polyvinylsulfonate enzyme-linked immunosorbent assay to study the impact of IVIG on HIT antibody-mediated platelet activation. The patient was also genotyped for a polymorphism in the IgG receptor on platelets, FcγRIIa, at amino acid position 131. RESULTS: A 30-year-old man had a thrombotic stroke and thrombocytopenia and strong HIT serologies in the absence of proximate heparin use. Direct thrombin inhibitor therapy was not associated with a prompt response. Due to severity and extent of thrombosis and persistent thrombocytopenia, he was treated with high-dose IVIG. This treatment was associated with rapid and sustained normalization of platelet counts and a gradual improvement in thrombotic complications. Platelet activation induced by HIT antibodies in the PF4-dependent P-selectin expression assay (low PF4) was significantly lower after IVIG treatment, correlating well with platelet rise. Consistent with the severity of thrombosis, the patient was found to possess the 131HR polymorphism in FcγRIIa. CONCLUSION: These results suggest that IVIG may be a useful adjunctive therapy in spontaneous HIT.
Authors: Anand Padmanabhan; Curtis G Jones; Brian R Curtis; Daniel W Bougie; Mia J Sullivan; Namrata Peswani; Janice G McFarland; Daniel Eastwood; Demin Wang; Richard H Aster Journal: Chest Date: 2016-02-19 Impact factor: 9.410
Authors: B Singh; A Kanack; A Bayas; G George; M Y Abou-Ismail; M Kohlhagen; M Christ; M Naumann; K Moser; K Smock; A Grazioli; D Murray; A Padmanabhan Journal: medRxiv Date: 2021-09-24
Authors: Adam J Kanack; Bandana Singh; Gemlyn George; Krishna Gundabolu; Scott A Koepsell; Mouhamed Yazan Abou-Ismail; Karen A Moser; Kristi J Smock; David Green; Ajay Major; Clarence W Chan; Geoffrey D Wool; Mark Reding; Aneel A Ashrani; Antonios Bayas; Diane E Grill; Anand Padmanabhan Journal: Am J Hematol Date: 2022-02-21 Impact factor: 13.265