Plasma P-selectin is increased in thrombotic consumptive platelet disorders

Abstract

P-selectin is a 140-kD protein found in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells that on cell activation is expressed on the cell surface and also secreted into the plasma. The secreted form of P-selectin, like plasma P-selectin, differed from platelet membrane P-selectin in that its molecular mass was approximately 3 kD lower under reducing conditions. Both the secreted and plasma forms of P-selectin contained cytoplasmic sequence as determined by Western blot analysis with an affinity-purified rabbit anti-P-selectin cytoplasmic peptide antibody. We have measured plasma P- selectin and beta-thromboglobulin (beta TG) concurrently in (1) patients with consumptive thrombotic disorders, including disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), and thrombotic thrombocytopenic purpura (TTP)/haemolytic uremic syndrome (HUS); (2) patients with idiopathic thrombocytopenic purpura (ITP); and (3) healthy controls. Patients with DIC, HIT, and TTP/HUS, but not ITP, had significantly elevated plasma P-selectin and beta TG levels when compared with their age-matched healthy controls. The increased plasma P-selectin and beta TG in patients with thrombotic disorders were likely to be the result of in vivo platelet and endothelial cell damage or activation. We also found that avoidance of veno-occlusion and other tedious measures customarily taken during blood collection and sample preparation to prevent in vitro platelet activation did not affect plasma P-selectin assay results. In addition, plasma P-selectin levels were not influenced by the presence of renal failure or heparin administration. These results indicate that plasma P- selectin may be a useful new marker for thrombotic diseases.

Selectin‐P and interleukin‐8 plasma levels in coronary heart disease patients

“…Interleukin-8 is a potent angiogenic factor [22]. Elevated levels of selectin-sP and IL-8 can be detected in the plasma of patients with atherosclerosis, hypertension and trombotic disorders, but we need to fully investigate whether these markers may be risk factors for atherosclerosis [23,24]. Our data show a significantly increased level of selectin-sP in patients with unstable coronary heart disease in comparison with patients with stable coronary heart disease, and a nonsignificantly increased level in comparison with the control group.…”

Effects of desmopressin on circulating P‐selectin

“…What is the pathophysiological relevance of cP-selectin? Higher than normal plasma levels of cP-selectin have been found in various diseases, including peripheral vascular disease (Blann et al, 1995), unstable angina pectoris (Ikeda et al, 1995), myocardial infarction Wu et al, 1993), or thrombotic diseases (Katayama et al, 1993;Chong et al, 1994). These disease states are associated with damage of EC and thrombus formation, processes which could be mediated by P-selectin.…”

Thrombocytopenic conditions—autoimmunity and hypercoagulability: Commonalities and differences in ITP, TTP, HIT, and APS

“…In addition, impaired fibrinolysis and reduced production of prostacyclin have been implicated in the development of TTP [15]. Several authors have demonstrated that TTP plasma, as opposed to ITP plasma, causes activation and induces injury to endothelial cells [47,48], manifested by a significant increase in endothelial microparticles [47][48][49], e-selectin, p-selectin [50], thrombomodulin [51], and b-thromboglobulin [52], and all markers of endothelial cell and platelet activation, and induces increased expression of adhesion molecules such as ICAM-1 and VCAM-1 [48]. In addition, anti-endothelial cell antibodies (AECA) have been demonstrated in patients with TTP [53].…”