Chest 2005: Heparin antibodies, independent of HIT, common in patients undergoing cardiac surgery

The presence of antibodies to heparin is an independent risk factor for potentially serious complications following cardiac surgery, even in patients who do not develop heparin-induced thrombocytopenia (HIT), said David Kress, MD, at the 71st international scientific assembly of the American College of Chest Physicians in Montreal, Quebec, Canada.

The clinical risk associated with HPF4 antibodies in patients who don't have HIT is poorly understood in clinical practice, said Dr Kress, senior cardiothoracic surgeon at Aurora St Luke's Medical Center, Milwaukee, Wisc.

Using the Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database, postoperative outcomes were evaluated for 1,114 consecutive patients undergoing coronary artery bypass graft and/or valve surgery who were screened in an unselected manner for HPF4 antibody status over 2.5 years at a single surgical service.

Previous studies have found HPF4 antibodies in up to 22% of patients prior to cardiac surgery. "No other study used the STS database to evaluate postoperative outcomes and preoperative risk factors extensively," Dr Kress said. "It's really the gold standard in terms of looking at data collection for results in cardiac surgery."

In addition, St Luke's currently uses porcine heparin, whereas earlier studies exploring the incidence of HPF4 antibodies used bovine heparin, which is the more antigenic of the 2, he explained.

HPF4 antibodies typically indicate that a patient has had past exposure to heparin and is at greater risk for developing HIT, a life-threatening immune-mediated complication of heparin administration that contraindicates further heparin exposure.

"What's different about our study is that it looks at a syndrome of having positive antibodies that is not HIT," Dr Kress said. "We found that whether the patients developed thrombocytopenia postoperatively had no further effect on postoperative morbidity. It was the presence of the antibodies that appeared to be related to it. Most studies looking at complications of heparin only look at HIT. This syndrome that we're talking about is almost an entirely different disease than HIT. And it hasn't been discussed much in the literature up to this point."

HIT syndrome occurs in about 3% of the patients undergoing cardiac surgery and overt thrombosis occurs in 50% of HIT patients.

Positive HPF4 antibody status was an independent predictor for adverse outcomes by stepwise logistic regression analysis. "The patients that were heparin antibody-positive were more likely to have renal dialysis than diabetic patients, went on to develop acute limb ischemia than if they had peripheral vascular disease, and were more likely to have longer ventilation times than if they had low ejection fractions," Dr Kress said.

"In the future, there's a very good chance that heparin alternatives will come out which are safe and effective for bypass surgery, and ultimately we may want to use something other than heparin and just avoid the whole problem," Dr Kress said.

He continued: "Heparin is a very easy drug to use and it's inexpensive. What surgeons may do is check for the HPF4 antibody, and if it's present, then use a heparin alternative," he said. "That's probably the way most surgeons will go."

The development of HPF4 antibodies will be more frequent, he predicted, because many patients coming to surgery will have had previous percutaneous coronary interventions with heparin exposure.