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IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia. Chest 2017 09;152(3):478-485

Date

04/22/2017

Pubmed ID

28427966

Pubmed Central ID

PMC5812774

DOI

10.1016/j.chest.2017.03.050

Scopus ID

2-s2.0-85028972116   40 Citations

Abstract

BACKGROUND: Heparin-induced thrombocytopenia (HIT) complicated by severe thrombocytopenia and thrombosis can pose significant treatment challenges. Use of alternative anticoagulants in this setting may increase bleeding risks, especially in patients who have a protracted disease course. Additional therapies are lacking in this severely affected patient population.

METHODS: We describe three patients with HIT who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but who achieved an immediate and sustained response to IVIg therapy. The mechanism of action of IVIg was evaluated in these patients and in five additional patients with severe HIT. The impact of a common polymorphism (H/R 131) in the platelet IgG receptor FcγRIIa on IVIg-mediated inhibition of platelet activation was also examined.

RESULTS: At levels attained in vivo, IVIg inhibits HIT antibody-mediated platelet activation. The constant domain of IgG (Fc) but not the antigen-binding portion (Fab) is required for this effect. Consistent with this finding, IVIg had no effect on HIT antibody binding in a solid-phase HIT immunoassay (platelet factor 4 enzyme-linked immunoassay). The H/R131 polymorphism in FcγRIIa influences the susceptibility of platelets to IVIg treatment, with the HH131 genotype being most susceptible to IVIg-mediated inhibition of antibody-induced activation. However, at high doses of IVIg, activation of platelets of all FcγRIIa genotypes was significantly inhibited. All three patients did well on long-term anticoagulation therapy with direct oral anticoagulants.

CONCLUSIONS: These studies suggest that IVIg treatment should be considered in patients with HIT who have severe disease that is refractory to standard therapies.

Author List

Padmanabhan A, Jones CG, Pechauer SM, Curtis BR, Bougie DW, Irani MS, Bryant BJ, Alperin JB, Deloughery TG, Mulvey KP, Dhakal B, Wen R, Wang D, Aster RH

Authors

Richard H. Aster MD Professor in the Medicine department at Medical College of Wisconsin
Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of Wisconsin
Binod Dhakal MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Mehraboon Irani MD Associate Professor in the Pathology department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aged
Anticoagulants
Female
Heparin
Humans
Immunoglobulins, Intravenous
Immunologic Factors
Male
Middle Aged
Receptors, IgG
Thrombocytopenia
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5