PATIENTS WITH VENOUS STASIS ULCERATION HAVE INCREASED MONOCYTE-PLATELET AGGREGATION

Purpose: Leukocyte activation has been implicated in the pathogenesis of venous stasis ulceration, but the involvement of activated platelet s and leukocyte-platelet aggregates has not been previously investigat ed. The purpose of this study was to determine whether patients with v enous stasis ulceration have increased platelet activation and a prope nsity toward formation of leukocyte-platelet aggregates. Methods: Bloo d was drawn from the superficial veins of the leg just proximal to a v enous stasis ulcer and from an antecubital vein in 14 patients with ve nous stasis ulceration. Blood was also drawn from the antecubital vein of 14 volunteers without evidence of venous disease. Whole-blood flow cytometry was used to analyze the samples before and after activation with a panel of agonists for evidence of platelet activation and the formation of leukocyte-platelet aggregates. Results: Patients with ven ous stasis ulceration had a greater number of monocyte-platelet aggreg ates in both the arm and leg samples than did the control subjects (p < 0.01). Furthermore, antecubital blood samples from patients with ven ous stasis ulceration stimulated with either thrombin-receptor agonist peptide, adenosine diphosphate, or phorbol myristate acetate formed m ore monocyte-platelet aggregates than did control samples (p < 0.05). No differences in platelet activation or neutrophil-platelet aggregate formation were noted among the three sample groups. Conclusions: Pati ents with venous stasis ulceration have an increase in the number of m onocyte-platelet aggregates in systemic venous blood as well as in ven ous blood adjacent to a venous stasis ulcer, implicating the monocyte as the leukocyte involved in the pathogenesis of venous stasis ulcerat ion. No association was identified between the presence of a venous st asis ulcer and either neutrophil-platelet aggregation or the activatio n of individual platelets. Because platelet activation is necessary fo r the formation of monocyte-platelet aggregates, these data also sugge st that monocyte-platelet aggregation is a more sensitive marker for i n vivo platelet activation than is the identification of individual ac tivated platelets.