More than 25 percent of patients undergoing chemotherapy before and after surgery for ovarian cancer develop blood clots, according to a new retrospective cohort study from researchers at the University of Michigan Rogel Cancer Center.

The findings were published in Obstetrics & Gynecology.

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It has long been understood that patients with ovarian cancer are at a much higher risk of blood clots than the general population, but no previous studies had looked at patients who receive chemotherapy before surgery. The results were surprising — and indicate opportunities for intervention in such patients to prevent clots.

"If you asked me for a guess before we examined the data, we would have thought the number was 10 percent," says senior author Shitanshu Uppal, M.D. "It was quite a surprise to see that what we were talking about was more than 25 percent."

The study suggests providers should consider using prophylactic blood thinners before and after surgery to decrease the incidence of blood clots and improve outcomes.

"Historically, patients have been given blood thinners during postoperative chemotherapy, but what we're seeing is that nearly half of those diagnosed with clots in this study were diagnosed before surgery," says Uppal.

If a patient develops a blood clot prior to surgery, she must be on a much higher dose of blood thinner and for a much longer time, he says.

"The other problem is if you have had a clot and are on that very high dose of blood thinner, the risk of bleeding increases," says Uppal. "As surgeons, we might then be hesitant to do very aggressive surgery in these cases because we might be worried about the bleeding."

The bottom line, Uppal says, is that blood clots affect a surgeon's ability to treat these patients.

"Readmission rates are higher, and they have a lower rate of survival," says Uppal. "Outcomes will improve if we can prevent these blood clots."

Driving risk

Multiple factors contribute to an increased chance of blood clots during cancer, Uppal says. One is the nature of malignant tumors: They secrete chemicals that promote clotting of the blood, so developing clots is more likely. Another contributing factor is decreased mobility.

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"Imagine a person whose abdomen is full of cancer, and now they are receiving chemotherapy; they can't move around as much," says Uppal. Recovery time after surgery also accounts for a loss of mobility.

"Put all this together, and we have a scenario where an exceptionally high number of patients develop blood clots," Uppal says.

The standard of care for ovarian cancer patients is surgery to remove the cancer, followed by six courses of chemotherapy. But for some patients with inoperable tumors or those with other medical problems that prevent immediate surgery, the treatment begins with chemotherapy.

"We all knew that the risk was high for women with ovarian cancer, but none of the existing literature has focused on patients who had chemotherapy prior to surgery, or neoadjuvant chemotherapy," says Uppal.

The study

Uppal and his co-investigators looked at the records of 112 patients with ovarian cancer who received chemotherapy prior to and after surgery at U-M. Of this group, 26.9 percent experienced a blood clot.

• 11.6 percent developed a blood clot during the preoperative chemotherapy.

• 5.4 percent developed a postoperative blood clot.

• 9.9 percent developed a blood clot during adjuvant chemotherapy.

"We initiated the study based purely on clinical observation," says Uppal. "We saw a lot of blood clots in our daily clinical practice.

"What we found not only validated those observations, but also gives us the basis to recommend anticipatory prophylactic blood thinners for this patient group — a group that is rapidly increasing in the United States. American Society of Clinical Oncology guidelines do allow for case-by-case use of low-molecular heparin in patients with a very high risk of clots. The risk is so high, we decided we need to act now."

Uppal says a randomized control trial is needed to definitively demonstrate outcomes, and he is seeking funding to start that work.