Subcutaneous Heparin Not Adequately Absorbed After Abdominal Surgery

Subcutaneously administered heparin might not provide optimal protection against venous thromboembolism (VTE) for patients who have undergone major abdominal surgery because absorption appears to be decreased in these patients, researchers said here at the Society of Critical Care Medicine 40th Critical Care Congress.

“Subcutaneous heparin is the current standard of care for VTE prophylaxis,” Sara Cheng, MD, from the University of Colorado at Denver School of Medicine in Aurora, told Medscape Medical News. “However, I began to hear anecdotal reports that a surgical oncologist was using low-dose heparin infusion in the [intensive care unit with] no untoward effects. In fact, his patients tended to do better overall.”

Intrigued by this report, Dr. Cheng did a retrospective chart analysis, “which almost killed me,” looking at hundreds of the surgeon’s patients. She found no difference in bleeding between those who got subcutaneous heparin and those who got intravenous (IV) heparin.

To explore the use of IV heparin further, she and her team randomized 50 intensive care unit (ICU) patients immediately after major abdominal surgery to receive subcutaneous heparin (5000 U) 3 times daily — the standard of care — or an IV heparin infusion titrated to a target activated partial thromboplastin time range of 40 to 45 s.

The majority of patients in the study had cancer. “This is important because cancer patients are known to have molecular hypercoagulability at baseline. In addition, when they get sent to the ICU, they are more likely to have hypercoagulable risk factors,” Dr. Cheng said.

Daily blood heparin activity levels, daily whole blood coagulation parameters, and screening of the lower extremities with ultrasound for 10 days after surgery were also performed.

The patients were well matched demographically. Most were slightly overweight, with a body mass index of 27 kg/m²; their average Acute Physiology and Chronic Health Evaluation (APACHE) score was 13.

The researchers found that patients receiving subcutaneous heparin had no detectable levels of anti-Xa activity 5 days after surgery. “Their peak levels of anti-Xa activity were 0. Undetectable,” Dr. Cheng emphasized.

In contrast, patients receiving IV heparin showed statistically significant increases in anti-Xa activity on day 3 (0.04 vs 0.00 U/mL; P = .01) and day 4 (0.05 vs 0.00 U/mL; P = .03).

“These are still low levels. The generally accepted range for [deep vein thrombosis] prophylaxis is an anti-Xa range of 0.1 to 0.3, so we are barely getting there, even with these IV heparin patients, but it’s better than nothing,” Dr. Cheng noted.

Using a whole blood coagulation device called the Sonoclot, the researchers found that the patients who received subcutaneous heparin had a hypercoagulable profile for up to 5 days after surgery, but that patients who received IV heparin had a normal profile. “These patients do not seem to be anticoagulated per se, but they are normalized. This is important in a postsurgical population at high risk of bleeding,” she said.

No lower-extremity deep vein thrombosis was found on screening ultrasounds in either group, nor were there any episodes of major bleeding or heparin-induced thrombocytopenia.

“There were no differences in ICU length of stay or 28-day mortality, and we are confident that we are not overtly hurting people. This allows us to push forward and study the efficacy of IV heparin for the prevention of postoperative VTE in surgical intensive care patients. A larger phase 3 study is definitely warranted,” Dr. Cheng concluded.

Commenting on this study, Rahul Nanchal, MD, from the Medical College of Wisconsin, Madison, who was one of the moderators of the session, told Medscape Medical News that he found it extremely intriguing and agreed with Dr. Cheng that more studies should be done to explore this further.

“It’s a great study. It shows that if you are actually targeting something, then the subcutaneous route is not the best way to do it,” he noted. “A larger study is needed. I don’t know whether it is clinically significant right now, but of course it is worth reporting. It is very interesting.”

Dr. Cheng and Dr. Nanchal have disclosed no relevant financial relationships.

Society of Critical Care Medicine (SCCM) 40th Critical Care Congress: Abstract 756. Presented January 18, 2011.

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