Splenic infarction and bevacizumab

A 49-year-old man with metastatic sigmoid adenocarcinoma who had received six cycles of chemotherapy with fl uorouracil, folinic acid, irinotecan, and bevacizumab was seen in the emergency department with a 36 h history of abdominal pain in the left-upper quadrant. The patient was afebrile and had no recent history of trauma. Physical examination showed tenderness in the left-upper quadrant. Blood pressure and pulse were normal. Laboratory studies, including complete blood-cell count, were unrevealing. CT scan (fi gure A) showed liver metastases (green arrows) and several wedge-shaped defects in the spleen with the apex directed toward the hilum, consistent with splenic infarcts (blue arrow). Physical examination, electrocardiogram, laboratory tests, and blood cultures ruled out common causes of splenic infarction (eg, thromboembolic disease stemming from atrial fi brillation or myocardial infarction, haematological malignant disease, or sepsis). No underlying thrombophilia or coagulation disorder was seen. PET ruled out splenic metastases from colon carcinoma. Bevacizumab was immediately withdrawn. The patient was treated conservatively, and abdominal pain resolved spontaneously within 72 h. 2 months later, after four further chemotherapy cycles (without bevacizumab), a follow-up CT scan showed partial regression of the splenic infarcts (fi gure B, white arrow). Liver metastases were still present (red arrow). The patient died 6 weeks later from metastatic progression. No post mortem was done. Decreased concentrations of protein C, protein S, and antithrombin; activation of factor X; heightened fi brinogen and platelet catabolism; and direct generation of thrombin have been implicated in the hypercoagulability in patients with cancer. Whether, and to what extent, chemotherapy drugs, and even the drug administration method (eg, bolus vs infusional fl uorouracil) contribute to this complex remains unknown. In contrast to fl uorouracil and folinic acid regimens a retrospective analysis of two early randomised trials has shown that combinations of irinotecan, fl uorouracil, and folinic acid cause a signifi cantly higher incidence of acute myocardial infarction, pulmonary embolism, and cerebral events immediately after the start of treatment (the so-called vascular syndrome). However, this association was not confi rmed in subsequent randomised trials. Moreover, to our knowledge, none of these drugs, whether given alone or in combination, have been reported to cause splenic infarcts. Bevacizumab, however, a recombinant, humanised, monoclonal antibody that binds and inhibits vascular endothelial growth factor, has been clearly associated with arterial thrombotic events. This case draws attention to the importance of considering new angiogenesis inhibitors as a potential cause of splenic infarction in patients with cancer.