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Distinguishing between anti–platelet factor 4/heparin antibodies that can and cannot cause heparin‐induced thrombocytopenia
Author(s) -
Nazi I.,
Arnold D. M.,
Warkentin T. E.,
Smith J. W.,
Staibano P.,
Kelton J. G.
Publication year - 2015
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.13066
Subject(s) - platelet factor 4 , heparin , heparin induced thrombocytopenia , antibody , platelet , platelet activation , medicine , immunology
Summary Background Many patients exposed to heparin develop antibodies against platelet factor 4 ( PF 4) and heparin, yet only those antibodies that activate platelets cause heparin‐induced thrombocytopenia ( HIT ). Patients who produce anti‐ PF 4/heparin antibodies without developing HIT either have antibodies that do not cause platelet activation or produce pathogenic antibodies at levels that are insufficient to cause HIT . Understanding the differences between anti‐ PF 4/heparin antibodies with and without HIT will improve test methods and reduce overdiagnosis. Aims To investigate the presence of low levels of platelet‐activating antibodies in patients investigated for HIT who had anti‐ PF 4/heparin antibodies but failed to cause platelet activation in the 14 C‐serotonin release assay ( SRA ). Materials/methods We developed a platelet activation assay similar to the SRA using exogenous PF 4 without added heparin ( PF 4‐ SRA ). This assay was able to detect low levels of platelet‐activating antibodies. We used this PF 4‐ SRA to test for platelet‐activating antibodies in patients investigated for HIT . Results The PF 4‐ SRA detected platelet‐activating antibodies in seven (100%) of seven SRA ‐positive sera even after the samples were diluted until they were no longer positive in the standard SRA . Platelet‐activating antibodies were detected in 14 (36%) of 39 patients who had anti‐ PF 4/heparin antibodies but tested negative in the SRA and did not have clinical HIT . The clinical diagnosis of HIT was confirmed by chart review and concordant with the SRA results. Conclusions A subset of heparin‐treated patients produce subthreshold levels of platelet‐activating anti‐ PF 4/heparin antibodies that do not cause HIT . An increase in the titer of these pathogenic antibodies, along with permissive clinical conditions, could lead to HIT .