The effect of radiation therapy on von Willebrand factor in patients with angiosarcoma

Radiation damages endothelial cells (EC) of malignant and normal tissues. Shortly after radiation injury platelet thrombi cause small vessel obstruction. Radiation doses of 20 Gy or higher release von Willebrand factor (VWF) from cultured human umbilical vein EC. Angiosarcoma (AS) is a vascular tumor with abnormal appearing EC which have detectable cytoplasmic VWF. We examined the effect of radiation therapy on VWF in three patients with AS. Each patient's malignant tissue was demonstrated to have cytoplasmic VWF present. Venous blood samples were drawn immediately before and at weekly intervals during treatment. Patient 1 received 80 Gy over 6 weeks and had no alterations in the VWF. Patient 2 received 64 Gy over 6 weeks and was noted to have loss of the high molecular weight multimers of VWF without loss of FVIII:C, VW: RIST, or von Willebrand antigen activity (VW:Ag). Patient 3 was treated with 64.4 Gy over 9 weeks and had a disproportionate increase of the VW: Ag and VW: RIST to FVIII: C. This returned to normal after completion of therapy. These changes were minimal and might be explained by either limited local release or no increased release of VWF from the irradiated tissue. The minimally abnormal multimeric pattern in patient 2 may be due to the release of an abnormal VWF in normal amounts or small amounts of proteolysis. The alteration in the VW: RIST and VW: Ag to FVIII: C ratio can be explained by activated coagulation secondary to radiation injury.