Chronic venous insufficiency is associated with increased platelet and monocyte activation and aggregation
Department of Pediatrics; Department of Surgery
Adult; Case-Control Studies; Female; Humans; Macrophage-1 Antigen; Male; Middle Aged; *Monocytes; *Neutrophil Activation; *Platelet Activation; *Platelet Aggregation; Varicose Ulcer; Venous Insufficiency
Hematology | Oncology | Pediatrics
PURPOSE: This study assessed whether the increased numbers of platelet-monocyte aggregates observed in patients with venous stasis ulceration (VSU) represent a response to dermal ulceration or if it is a condition associated with underlying chronic venous insufficiency (CVI). We also analyzed the expression of CD11b in patients with CVI to determine whether leukocyte activation, known to occur in VSU, is a precursor of or a response to ulceration.
METHODS: Patients with varying classes of CVI (n = 24) and healthy control subjects (n = 15), whose status was documented by means of duplex scanning, stood upright and stationary for 10 minutes. Two aliquots of blood, drawn from a distal leg vein and an antecubital fossa vein, were incubated with either buffer or one of three platelet agonists. After fixation, these samples were further incubated with fluorescent-labeled monoclonal antibodies (f-MoAb) specific for CD14 (monocytes) and CD61 (platelets). The activated leukocyte assay was performed by incubating another aliquot of the blood samples with f-MoAb specific for CD11b and CD14. All samples were evaluated by means of flow cytometry.
RESULTS: We observed significantly more platelet-monocyte aggregates throughout the circulation in patients with CVI than in control subjects (29% vs. 8%; P andlt;.0002). Furthermore, patients with CVI formed significantly more of these aggregates in response to all platelet agonists than did control subjects. There were no significant differences between baseline numbers of aggregates or response to agonists in patients who had CVI with (n = 10) or without (n = 14) ulceration. Patients with CVI had more circulating platelet-neutrophil aggregates than control subjects (7.2% vs. 3.6%; P =.05). The addition of platelet agonists to the blood of patients with CVI resulted in more platelet-neutrophil aggregates than in control subjects. Monocyte CD11b expression was higher in patients with CVI than in control subjects (7.5 vs. 3.7; P andlt;.01), with no differences noted in CD11b expression between patients with or without ulceration. Neutrophil CD11b expression was low and similar in control subjects and patients with CVI.
CONCLUSION: All classes of CVI are associated with significantly increased percentages of platelet-monocyte aggregates and increased percentages of platelet-neutrophil aggregates throughout the circulation. The presence of more of these aggregates and the increased propensity to form aggregates in the presence of platelet agonists in all classes of CVI suggests an underlying state of platelet activation and increased reactivity that is independent of the presence of ulceration. The increased expression of monocyte CD11b throughout the circulation in all classes of CVI suggests that although systemic monocyte activation occurs in CVI, its presence is independent of VSU as well.
DOI of Published Version
J Vasc Surg. 1999 Nov;30(5):844-51. doi 10.1016/S0741-5214(99)70009-1
Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Powell, Craig C.; Rohrer, Michael J.; Barnard, Marc R.; Peyton, Brian D.; Furman, Mark I.; and Michelson, Alan D., "Chronic venous insufficiency is associated with increased platelet and monocyte activation and aggregation" (1999). Hematology/Oncology. 17.