Delayed-onset heparin-induced thrombocytopenia and thrombosis.
BACKGROUND
Heparin-induced thrombocytopenia is a prothrombotic drug reaction caused by platelet-activating antibodies that recognize complexes of platelet factor 4 and heparin.


OBJECTIVE
To describe a syndrome termed delayed-onset heparin-induced thrombocytopenia, in which thrombocytopenia and thrombotic events begin 5 or more days after withdrawal of heparin.


METHODS
Case series.


METHODS
Secondary and tertiary care hospitals.


METHODS
12 patients who presented with serologically confirmed, delayed-onset heparin-induced thrombocytopenia, including 6 outpatients presenting after hospital discharge.


METHODS
The platelet serotonin-release assay was used to measure IgG-induced heparin-dependent and heparin-independent platelet activation; an enzyme immunoassay that detects IgG against platelet factor 4-heparin complexes was also used.


RESULTS
Patients with delayed-onset heparin-induced thrombocytopenia presented with thrombocytopenia and associated thrombosis a mean of 9.2 days (range, 5 to 19 days) after stopping heparin therapy. Nine patients received additional heparin, with further decrease in platelet counts. Compared with controls, patients with delayed-onset heparin-induced thrombocytopenia had higher titers of IgG antibodies to platelet factor 4-heparin and greater IgG-induced heparin-dependent and heparin-independent platelet activation.


CONCLUSIONS
Delayed-onset heparin-induced thrombocytopenia should be suspected when patients present with thrombocytopenia and thrombosis up to 3 weeks after exposure to heparin. This syndrome could be caused by high titers of platelet-activating IgG induced by heparin.
Warkentin
T E
TE
Hamilton Regional Laboratory Medicine Program, Hamilton General Hospital, Hamilton Health Sciences, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Kelton
J G
JG
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000276:immunology; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D015539:Platelet Activation; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000276:immunology; D012701:Serotonin / Q000097:blood; D013577:Syndrome; D013921:Thrombocytopenia / Q000139:chemically induced*; D013927:Thrombosis / Q000139:chemically induced*; D013997:Time Factors
D000925:Anticoagulants; D007074:Immunoglobulin G; D012701:Serotonin; D010978:Platelet Factor 4; D006493:Heparin