Patients who develop antibodies to the anti-clotting drug Heparin nearly double their risk of death or serious complication after heart surgery.

" Complications after heart surgery are typically attributed to the surgery alone," said Thomas Slaughter, co-principal investigator on the project and at Wake Forest University Baptist Medical Center. " Our study examined whether development of Heparin antibodies before surgery poses an independent risk."

The study, which involved 466 patients scheduled to undergo either coronary artery bypass or valve replacement surgery, is reported in the Journal of Thoracic and Cardiovascular Surgery.
Conducted by investigators at Wake Forest University Baptist and Duke University medical centers, it is the first study to convincingly demonstrate a relationship between Heparin antibodies and complications after cardiac surgery.

Heparin is administered intravenously during many procedures, including kidney dialysis, heart catheterization or angioplasty, as well as during heart and vascular surgeries. Estimates suggest that nearly half of patients treated with heparin develop the antibodies, which may last for months.

The researchers theorize that in patients with Heparin antibodies, subsequent treatment with Heparin activates blood components that cause clotting and inflammation, increasing the risk for heart attacks, heart rhythm problems, strokes and other complications.

" While it is too early to recommend universal testing for the antibodies, our study is the most definitive evidence to date that Heparin antibodies increase the risk for death and complications associated with cardiac surgery," said Slaughter.

The researchers tested Heparin antibody levels in all study patients before surgery.
They found that patients with the antibodies experienced a nearly twofold greater risk of death or hospitalization extending longer than 10 days. The researchers used an extended hospital stay as a surrogate marker for other complications after surgery such as heart attacks, strokes, infection and kidney problems.

To ensure that patients' baseline health status did not influence results, the researchers assessed each patient's predicted surgical risk using a standardized risk scoring system called the Parsonnet risk score. This system is based on 19 factors known to be associated with death or other complications after heart surgery. The researchers found that regardless of the Parsonnet score, patients with heparin antibodies before surgery fared worse than patients without the antibodies.

More than 350,000 adult cardiac surgeries are performed in the United States each year. In this study, as many as13 percent of surgical patients were found to have heparin antibodies before undergoing surgery.

Slaughter says there is no simple solution to the problem. Several anti-clotting medications may provide an alternative to Heparin, but they are not approved by the Food and Drug Administration for use during heart surgery. The safety of these alternative medications in the setting of complex heart surgery remains to be determined.

Another option may be for patients with the antibodies to delay surgery until the antibody levels subside. However, in some cases this might require months – and, in many cases, the severity of a patient's disease may not allow for safe delay of surgery.

" Researchers are at the cutting edge of learning about Heparin antibodies and how they affect surgical outcomes," said Slaughter. " We need to understand more about mechanisms underlying the adverse effects of Heparin antibodies and whether alternative anti-clotting medications will prove safer before informed recommendations can be made to patients and surgeons."

Source: Wake Forest University Baptist Medical Center, 2005


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