Enrico Bobbio-Pallavicini

Cancer Chemotherapy-Related Thrombotic Thrombocytopenic Purpura: Biological Evidence of Increased Nitric Oxide Production

The occurrence of thrombotic thrombocytopenic purpura (TTP) in cancer patients receiving chemotherapy has been well established; although this entity is rare, its clinical importance seems to be growing. We describe 3 cases of TTP developing in cancer patients receiving different chemotherapeutic regimens. Using a sensitive high-performance liquid chromatographic method, we evaluated the stable nitric oxide end products, nitrite and nitrate, in the plasma of these patients. Nitric oxide is one of the key components involved in maintaining the normal nonthrombogenicity of the vascular endothelium. In our 3 patients, we found increased nitrate titers that were substantially higher than those observed in patients with de novo TTP. The observed increased release of nitrate could be interpreted as the consequence of massive disruption of endothelial integrity, with consequent passive nitric oxide release in vivo, or an adaptive mechanism of the endothelium to compensate for diffuse microvascular occlusion. The 2 mechanisms may both be involved, but the normal titers of nitric oxide end products in de novo TTP suggest that the former mechanism is more important, at least in cancer chemotherapy-related TTP.

Nitrite and Nitrate Plasma Levels, as Markers for Nitric Oxide Synthesis, in Thrombotic Thrombocytopenic Purpura (TTP)

The enhanced platelet aggregation and thrombosis occurring in TTP is probably due to an unbalance between agents insulting endothelial integrity and natural antithrombotic factors, such as NO. Using a sensitive and specific HPLC assay, we tested the hypothesis of NO involvement in TTP, comparing NO production, as the stable end-products nitrites and nitrates, in the plasma of 29 TTP patients and of 29 healthy subjects matched for sex and age. Average nitrate titer was 25.868 μM/L in the TTP group vs 24.234 μM/L in the control group (p = n.s.), while nitrite were undetectable in both groups. Moreover, nitrate titers did not correlate with hemoglobin value, platelet count, LDH values, or with Rose and Eldors severity score. In conclusion, even though the enhanced platelet aggregation observed in TTP could be due to reduced natural antithrombotic substances, NO involvement in the pathogenesis of TTP appears unlikely.