Z. Z. Young1, D. Mix1, S. Toth1, R. Schmidt1, J. Ellis1, R. Glocker1, A. Doyle1, K. Raman1, M. Stoner1, S. Cameron1 1University Of Rochester Medical Center – Strong Memorial Hospital,Division Of Vascular Surgery,Rochester, NY, USA
Introduction:
Chronic venous insufficiency (CVI) is a major public health concern accounting for thousands of hospital and primary care encounters annually in the U.S. CVI causes leg pain, swelling, wounds, and has been linked to deep vein thrombosis (DVT). The etiology of CVI is incompletely understood but may involve alterations in endothelial cell and platelet function at regions of venous reflux where valves become incompetent. Our hypothesis is that platelet reactivity in CVI is altered locally in incompetent veins and globally in response to reflux which may be a risk factor for myocardial infarction (MI) and cerebrovascular accidents (CVA).
Methods:
Purified platelets (platelet rich plasma) were obtained from venous blood from control antecubital (AC) veins, CVI patient AC veins, CVI patient saphenous veins (SV) and platelet function assessed through the three platelet receptors for which prescription anti-platelet medications exist: Protease Activated Receptor (PAR1) (vorapaxar), Thromboxane (aspirin – indirectly), and P2Y12 (Plavix). The three receptor agonists used were: TRAP (PAR1), U46619 (Thromboxane), and ADP (P2Y12). Platelet activation was assessed by Fluorescence-activated cell sorting (FACS, P-selectin expression, Mean Fluorescence Intensity (MFI) SEM, performed in quadruplicate in each group).
Results:
Isolated, washed platelets from healthy volunteer subject antecubital veins (n=6), CVI patient antecubital veins (n=4) or incompetent saphenous veins (n=4) were included in analysis. Platelet reactivity in CVI patients is generally suppressed in the circulation, but enhanced locally in the incompetent vein (Figure 1). All three activation pathways were significantly different when comparing the CVI AC vein with CVI incompetent SV and Control AC veins (p<0.01).
Conclusion:
Mechanical reflux of platelets locally may lead to enhanced activation and portend a risk for superficial vein thrombosis and further vein remodeling and potential progression to DVT. However, suppressed platelet function in the general circulation suggests a paradoxical and unrecognized compensatory mechanism, perhaps conferring a reduced risk of MI or stroke in select CVI patients.
