PADGEM/GMP‐140 expression on platelet membranes from homozygous beta thalassaemic patients

Abstract

Thromboembolic events, which are associated with significant morbidity and mortality, occur in beta-thalassaemia. We studied the expression of the platelet selectin PADGEM/GMP-140 on intact cells from thalassaemic patients, as a marker of in vivo platelet activation. The mean of positive cells (%) was 38.143 +/- 20.65 in the patients versus 5.048 +/- 1.8 in the controls, n = 21, P < 0.001. No correlation was found between GMP-140 expression and splenectomy, platelet counts, plasma ferritin and natural coagulation inhibitors. Instead an indirect correlation was found between GMP-140 expression and HDL-cholesterol. Moreover platelet activation was directly correlated with pre-beta lipoproteins. Our data indicate that thalassaemic patients present an in vivo platelet activation, which possibly depends on the dyslipidaemia, which is now regarded as a frequent feature of this disease.

In‐vivo platelet activation correlates with red cell anionic phospholipid exposure in patients with β‐thalassaemia major

“…Thus, sickle RBC were shown to display a procoagulant effect in in-vitro assays and were thought to be operative in the induction of a hypercoagulable state (Middelkoop et al, 1988;Hermann & Devaux, 1990). Although occlusive vascular complications are frequent in sickle cell disease, the existence of a hypercoagulable state in thalassaemia major and intermedia was recognized only recently (Eldor et al, 1987(Eldor et al, , 1991Musumeci et al, 1987;Del Principe et al, 1993;Cappellini et al, 1995Cappellini et al, , 1996. Despite the fact that none of our TM or TI patients had an overt thrombotic event, a chronic hypercoagulable state was evident by the increased fraction of circulating platelets expressing activation dependent neoantigens, p-selectin (CD62p) and the lysosomal glycoprotein CD63.…”

“…Despite the fact that none of our TM or TI patients had an overt thrombotic event, a chronic hypercoagulable state was evident by the increased fraction of circulating platelets expressing activation dependent neoantigens, p-selectin (CD62p) and the lysosomal glycoprotein CD63. Overt thromboembolic events occur only rarely in thalassaemic patients; however, laboratory tests have provided evidence for a chronic hypercoagulable state which already exists in early childhood (Eldor et al, 1991(Eldor et al, , 1992Musumeci et al, 1987;Del Principe et al, 1993;Cappellini et al, 1995Cappellini et al, , 1996. Low lung capacity, hypoxaemia and right ventricular heart failure are observed in many young and adult TM patients (Cooper et al, 1980;Grant et al, 1986).…”

“…Several platelet and coagulation anomalies, frequently observed in TM or thalassaemia intermedia (TI) patients, suggested the existence of a hypercoagulable state. These include changes in platelet aggregation (Eldor, 1978), shortened (by about 50%) mean platelet life-span (Eldor et al, 1989), increased urinary excretion of thromboxane (TX) A 2 metabolites (2,3-dinor-TXB 2 and 11-dehydro-TXB 2 ) (Eldor et al, 1991), enhanced expression of p-selectin (PADGEM/GMP 140) on intact thalassaemic platelets (Del Principe et al, 1993), elevated plasma levels of thrombin-antithrombin III (TAT) complexes and low plasma levels of the natural anticoagulants, protein C and protein S (Musumeci et al, 1987;Eldor et al, 1992;Cappellini et al, 1995).…”

The hypercoagulable state in thalassemia

“…37,38 In addition, morphologic changes in thalassemic platelets, elevated plasma platelet factor 3 (PF3), and increased spontaneous whole blood platelet aggregation were reported. [39][40][41] The results from these studies show that, in addition to their increased number in splenectomized patients, chronic platelet activation is present in ␤-TM and ␤-TI.…”

Correction of hypercoagulability and amelioration of pulmonary arterial hypertension by chronic blood transfusion in an asplenic hemoglobin E/β-thalassemia patient

“…A role of phosphatidylserine (PS)-exposing red blood cells (RBCs) in hypercoagulability, 7,8 platelet activation, [9][10][11][12] and adhesion to the vascular endothelium 13 leading to thrombotic pulmonary arteriopathy was recently suggested in splenectomized ␤-Thal. 4 To test the hypothesis, we used chronic transfusion of RBCs to reduce the proportion of these pathologic RBCs in such a patient and evaluated plasma thrombin-antithrombin III complex (TAT) levels, PA pressure, and the above hemodynamic parameters by serial assessment.…”