Rapid determination of anti-heparin/platelet factor 4 antibody titers in the diagnosis of heparin-induced thrombocytopenia.
OBJECTIVE
Heparin-induced thrombocytopenia is mediated by antibodies directed against the heparin-platelet factor 4 (heparin/PF4) complex. Our aim was to investigate whether rapid measurement of anti-heparin/PF4 antibodies could improve the diagnostic workup of patients with suspected heparin-induced thrombocytopenia.


METHODS
We examined 148 consecutive patients in our laboratory between January 1995 and June 2001 for suspected heparin-induced thrombocytopenia. Clinical data allowed retrospective assessment of the likelihood of heparin-induced thrombocytopenia. Antibodies against the heparin/PF4 complex were detected by a rapid particle gel immunoassay.


RESULTS
Anti-heparin/PF4 antibodies were detected in 69 (47%) of the 148 patients, at dilution titers from 1 to 256. Clinically "likely" or "very likely" heparin-induced thrombocytopenia was significantly more common in patients with titers >or=4 (95% [39/41]) than in those with undetectable antibodies (13% [9/70]; P <0.0001), a titer of 1 (18% [4/22]; P <0.0001), or a titer of 2 (33% [2/6]; P = 0.001). All 19 samples with a positive platelet aggregation test had anti-heparin/PF4 antibody titers of at least 4, including 15 samples with titers >or=32. Thromboembolic complications in heparin-treated patients were significantly more prevalent in patients with titers >or=4 (63% [26/41]) than in those with undetectable antibodies (8% [6/79]; P <0.0001) or a titer of 1 (9% [2/22]; P <0.0001). Of the 11 patients with a titer of 1 who were maintained on heparin, none developed worse thrombocytopenia or thromboembolic complications.


CONCLUSIONS
Anti-heparin/PF4 antibody titers, which can be measured rapidly and reproducibly using a particle gel immunoassay, can be used as a confirmatory test to complement a clinical likelihood score among patients with suspected heparin-induced thrombocytopenia.
Alberio
Lorenzo
L
Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland. lorenzo.alberio@insel.ch
Kimmerle
Sabine
S
Baumann
Annalies
A
Taleghani
Behrouz Mansouri
BM
Biasiutti
Franziska Demarmels
FD
Lämmle
Bernhard
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood* / Q000276:immunology*; D000925:Anticoagulants / Q000009:adverse effects* / Q000097:blood* / Q000276:immunology; D003029:Coagulants / Q000097:blood* / Q000276:immunology*; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000097:blood* / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000032:analysis* / Q000276:immunology*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000097:blood* / Q000139:chemically induced* / Q000276:immunology; D013997:Time Factors
D000906:Antibodies; D000925:Anticoagulants; D003029:Coagulants; D010978:Platelet Factor 4; D006493:Heparin