Childhood sarcoma increases risk of blood clots

Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, have determined that children and young adults with a form of cancer called sarcoma are at increased risk of having a thromboembolic event (TE) in their veins.

Thromboembolic events can be a blood clot in a vessel that can interfere with normal blood flow. Clots can sometimes break loose and travel through the blood stream to form new clots at locations in the body that are life-threatening. TEs are almost always treatable if detected early. Investigating the association between sarcoma and TE is important because the majority of children with sarcoma can be cured of their cancer, but the occurrence of TEs could adversely compromise this success.

The study investigators also found that pediatric patients whose cancer had spread beyond the original cancer site were more likely to develop a TE than those with localized cancer. These findings are from a study reported in the April 20, 2007 issue of the Journal of Clinical Oncology*. Researchers reviewed patient records for 122 children and young adults treated for sarcoma in the Pediatric Oncology Branch of the NCI between October 1980 and July 2002.

Cancer creates an environment that is conducive to thrombosis because of the propensity of tumor cells to promote coagulation as well the secretion of cytokines, or signaling compounds, that trigger inflammation. In addition, factors common to cancer patients, such as chemotherapy, surgery, immobilization, having a central venous access device (such as a central line), and having other diseases or conditions, all increase a person's risk for blood clots.

The study results showed that, over the 22-year study period, 16 percent of children and young adults with sarcoma developed a TE. However, the researchers noted that this figure probably underestimates the true frequency of TEs in this pediatric patient population. Since this was a retrospective study of archival patient records, most of the original physicians may not have specifically looked for TEs, so some blood clots would have gone unrecorded. Also, TEs often are asymptomatic and early screening was less accurate. As the study observed, the rate at which TEs were detected in sarcoma patients increased from 7 percent before 1993 to 23 percent since 1993 -- an increase they attributed to improved screening techniques.

Children whose cancer had spread to other parts of the body were 2.5 times more likely to develop a TE than those whose disease was localized. The most common locations of the blood clots were in the deep veins of the legs and arms, the lungs (pulmonary embolism), and the inferior vena cava, which is the large vein that carries blood from the lower half of the body into the heart. Of the patients who developed a TE, 40 percent had no symptoms related to their blood clot. Thromboses were often detected around the same time as the cancer diagnosis.

Previous research had shown a link between cancer and TEs in adults, but data regarding TEs in adults may not be applicable to children with cancer. Children differ from adults in the types of cancer that occur, as well as in the number and types of co-morbid conditions. The researchers only looked at sarcomas (cancers of the bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue) in children, so not all pediatric cancer types were represented. Sarcomas account for 15 to 20 percent of pediatric cancers and include rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma. Approximately two-thirds of these cases can be cured.

A total of 23 TEs occurred in 19 of the 122 patients during the 22-year period of record keeping. Twenty-three percent of patients with metastatic cancer developed a TE, compared to 10 percent of patients with localized cancer, suggesting an association between tumor burden and the risk of TE.

Senior researcher Alan S. Wayne, M.D., Clinical Director of NCI's Pediatric Oncology Branch at the Center for Cancer Research recommends, "Children and young adults with sarcoma should be closely monitored for thrombosis because these patients may not have any symptoms related to a TE and because thromboembolism is a potentially life-threatening complication that is almost always amenable to therapy."