Recent studies have demonstrated a strong association between type II (immunologically mediated)
heparin-induced
thrombocytopenia/
thrombosis (HITP) and
antibodies reactive with complexes consisting of
heparin and
platelet factor 4 (PF4), a
heparin-binding protein normally found in platelet-alpha granules. However, the frequency with which such
antibodies develop in patients given treatment with
heparin has not yet been defined. We studied the development of
heparin:PF4-specific
antibodies in 51 patients who received a single dose of
unfractionated heparin (UFH) during cardiac catheterization and were then given UFH or
low-molecular-weight heparin (
LMWH) again during and after open heart surgery. Eleven of the 51 patients (22%) had
antibodies reactive with
heparin:PF4 when they were admitted for cardiac surgery; these
antibodies were mainly of the
immunoglobulin M (
IgM) class and were apparently stimulated by exposure to UFH at cardiac catheterization. Seventeen of 34 patients (50%) without preexisting antibody who were given UFH during and for 1 to 3 days after surgery formed
immunoglobulin G antibodies or
IgM antibodies (or both) by the sixth postoperative day. Overall, 27 of 44 patients (61%) who were given UFH at surgery had
antibodies by the time of hospital discharge. None of 6 patients without preexisting antibody who were given
LMWH at surgery formed
antibodies (p < 0.03). However,
LMWH was given as a single injection only on the day of surgery. The titer of the
antibodies formed by patients receiving UFH ranged from 1:10 to 1:200, significantly lower than those in patients with a clinical diagnosis of HITP. Moderate
thrombocytopenia was common after open heart surgery, but platelet levels in patients who had preexisting
antibodies or formed new
antibodies did not differ significantly from those in patients without antibody. Clinically significant
thrombosis did not develop in any patient and HITP was not diagnosed in any patient.
Antibodies reactive with
heparin:PF4 formed in only 3 of 66 patients (4.5%) undergoing other types of surgery. One of these patients had been given UFH 3 months previously; the other 2 may have been exposed to
heparin used to flush intravenous lines postoperatively. No
antibodies reactive with
heparin:PF4 were found in any of 108 normal subjects. We conclude that UFH is more immunogenic than has been thought and that patients exposed to this
anticoagulant during open heart surgery are at high risk to form low titer (</= 1:200)
antibodies reactive with
heparin:PF4. Further studies are needed to determine whether such
antibodies are clinically significant--that is, whether sensitized patients are at risk to develop HITP if
heparin treatment is continued for more than 1 to 3 days or is reinstituted at a later date.