Premium
Platelet activation in the presence of neutral protamine Hagedorn insulin: a new feature of antibodies against protamine/heparin complexes
Author(s) -
Zöllner H.,
Jouni R.,
Panzer S.,
Khadour A.,
Janzen L.,
Wesche J.,
Berg M.,
Schellong S.,
Heinken A.,
Greinacher A.,
Bakchoul T.
Publication year - 2017
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13547
Subject(s) - protamine , heparin , insulin , medicine , nph insulin , endocrinology , platelet , diabetes mellitus , antibody , chemistry , immunology , insulin glargine , hypoglycemia
Essentials Protamine (PRT) is used to stabilize insulin in neutral protamine Hagedorn (NPH) insulin. The interaction between NPH‐insulin, anti‐PRT/heparin antibodies and platelets was investigated. Anti‐PRT/heparin antibodies activate platelets in presence of NPH‐insulin dependent on heparin. Cross‐reactivity seems to have no major effect on the clinical outcome of medical patients.Summary Background Protamine ( PRT ) is used to stabilize insulin in neutral protamine Hagedorn ( NPH ) insulin, a commonly used therapeutic agent for diabetes mellitus. Immunization against PRT /heparin complexes is common in diabetic patients. Objectives To investigate the impact of NPH ‐insulin on the interaction between anti‐ PRT /heparin antibodies and platelets. Methods The interaction between NPH ‐insulin and anti‐ PRT /heparin antibodies was tested using in‐house enzyme immunoassays. The ability of anti‐ PRT /heparin antibodies to activate platelets in the presence of NPH ‐insulin (and heparin) was investigated using flow cytometry. Results Twenty‐one out of 80 sera containing anti‐ PRT /heparin IgG showed binding to NPH ‐insulin. Anti‐ PRT /heparin IgG from immunized patients bound to platelets in the presence of NPH ‐insulin, but not in the presence of native insulin. Anti‐ PRT /heparin antibodies induced P‐selectin expression in the presence of NPH ‐insulin in a heparin‐dependent way (median mean fluorescence intensity in the presence of NPH ‐insulin: 55, 95% confidence interval [ CI ] 18.7–100.5 vs. NPH ‐insulin and heparin: 204, 95% CI 106.5–372.8). The clinical relevance of platelet‐activating anti‐ PRT /heparin antibodies was assessed by investigating a multicenter study cohort of 332 acutely ill medical patients who received heparin. None of the 21 patients with anti‐ PRT /heparin IgG developed thrombocytopenia or thromboembolic complications. Conclusions Anti‐ PRT /heparin antibodies activate platelets in the presence of NPH ‐insulin in a heparin‐dependent way. However, results from our preliminary study indicate no major impact of these antibodies on the clinical outcome in medical patients receiving heparin, particularly on thromboembolic complications.