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Fifty-five dogs with spontaneous tumors of varied histology were evaluated by platelet counts and 51Cr labeled autologous platelet survivals to determine if platelet hemostasis was altered. None of the dogs received cancer-directed therapy during the course of these studies. In 12 dogs with local tumors, platelet counts were 303,000/ul - 28,000 (normal 391,000/ul - 34,000, P &gt; O.05), and platelet survival was 4.9 days - 0.2 (normal 5.6 days - 0.2, p &lt; 0.05). In contrast, 23 dogs with metastatic tumor had platelet counts of 268,000/ul ± 26,000 (p &lt; 0.005) and platelet survivals of 3.4 days ± 0.3 (p &lt; 0.001). When the platelet survival was less than 4 days, the platelet count was also depressed with a correlation coefficient of 0.60.  After baseline studies, 17 additional dogs with metastatic disease were treated with drugs (RA233 and sulfinpyrazone) that interfere with two different enzyme systems. Although there was some improvement in platelet survived in 6 of 9 dogs treated with RA233 or sulfinpyrazone alone (2.4 days ± 0.3 baseline vs. 3.5 days ± 0.4 treated, p &lt; 0.05), platelet counts were not elevated (241,000/ul ± 54,000 baseline vs. 201,000/ul ± 46,000 treated). However, when the two drugs were given in combination to 8 other dogs, all had increased platelet survivals (2.7 days ± 0.4 baseline vs. 4.4 days ± 0.6 treated, p &lt; 0.02), and this was associated with improved platelet counts in 6 of 8 (259,000/ul ± 46,000 baseline vs. 367,000/ul ± 47,000 treated, p &lt; 0.05). Five had completely normal platelet survivals  This study indicates that metastatic tumors, regardless of histology, are associated with significant platelet consumption resulting in depressed platelet counts. This consumption can be modified and platelet counts increased by treatment with a combination of two platelet active drugs that may act synergistically. We plan to determine whether similar treatment programs would maintain platelet counts and/or improve the survival of transfused platelets in human subjects with malignant disorders.

Interruption Of Malignancy-Associated Platelet Consumption With A Combination Of RA233 And Sulfinpyrazone