Soluble P-selectin and Correlation with Prothrombin Fragment 1+2 in Myeloid Malignancies in Cipto Mangunkusumo General Hospital (original) (raw)
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Identification of P-selectin glycoprotein ligand-1 as a useful marker in acute myeloid leukaemias
British Journal of Haematology, 2001
Immunophenotyping is considered to be less valuable in the diagnosis of acute myeloid leukaemias (AML) compared with acute lymphoid leukaemias. Here, we present data on the use of quantitative flow cytometry (QFC) of P-selectin glycoprotein ligand 1 (PSGL-1, CD162) and three-colour immunophenotyping including CD162 staining in the identification of myeloid precursors in AML. Analysis of normal peripheral blood (n 20) and normal bone marrow (n 5) samples and on 20 samples from de novo M1, M2, M4 and M5 AML patients demonstrated that PSGL-1 is differentially expressed on various mature and immature leucocyte subsets. It was found by QFC that neutrophils expressed 26500^4500 and monocytes 47200^9900 copies of PSGL-1 on their surface, whereas AML blasts from M1 and M2 AML patients expressed significantly less PSGL-1 (12 000^5300) than mature neutrophils (P , 0´001). In M4 and M5 leukaemias, however, the amount of PSGL-1 on monocytic precursors is displayed in a fairly broad range that is not significantly different from that of mature monocytes (P 0´084). Using three-colour immunophenotyping PSGL-1-dim staining was co-expressed with CD7 and C34 positivity and PSGL-1 staining intensity on immature myeloid cells paralleled with CD45 expression. This would imply a differential expression of PSGL-1 during myeloid haematopoietic development and suggests that quantification of surface PSGL-1 may aid in differentiating myeloblasts from monoblasts by immunophenotyping in different AML subsets.
Thrombosis Research, 2008
Background: Plasma levels of soluble P-selectin (sP-selectin) are often used to demonstrate platelet activation. Methods: We determined sP-selectin in a variety of disorders characterized by high or low platelet counts and compared their levels with those in healthy subjects. Furthermore, we determined the Thr715Pro polymorphism in all subjects. Results: Total concentrations of sP-selectin were clearly associated with levels of platelet counts. Thus, calculation of sP-selectin per platelet showed that these levels in patients with thrombocytopenia due to marrow failure and in patients with increased platelet counts were similar to those in controls. Only patients with an increased platelet turnover had elevated sP-selectin per platelet. While carriers of the Pro715 polymorphism had lower sP-selectin levels than non-carriers, this genetic disposition was overruled in patients with increased platelet turnover. Conclusion: For the demonstration of platelet activation it is preferable to define sPselectin based on platelet counts under the consideration of the Pro715Thr polymorphism.
Clinical Chemistry, 2007
Methods: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age-and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event. Results: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) g/L vs 36.8 (11.0) g/L, P <0.001. The unadjusted odds ratio (OR) for sP-selectin >55.1 g/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%). sP-selectin concentrations were lower in this subgroup than in noncarriers: 31.3 (7.9) g/L vs 44.1 (14.1) g/L; P <0.001). Conclusions: Increased sP-selectin concentrations are associated with VTE and genotype status. sP-selectin concentrations are lower in individuals carrying the P-selectin Pro715 variant than in those without this variant.
P-selectin and leukocyte microparticles are associated with venous thrombogenesis
Journal of Vascular Surgery, 2003
Objectives: P-selectin inhibition has been found to limit venous thrombosis. We hypothesize that elevated levels of P-selectin will amplify thrombosis, mediated by procoagulant microparticles (MPs). Methods: Male mice (Mus musculus, n659), 20 to 25 grams, underwent IVC ligation to induce thrombosis. Groups consisted of wild type (WT) C57BL/6 controls, mice with high circulating levels of soluble P-selectin (^CT), P-selectin gene-interrupted knockout mice (PKO), and E-and P-selectin gene-interrupted mice (EPKO). Additional groups were used to evaluate the ability of a P-sel antagonist (rPSGL-Ig) and an antibody directed against PSGL-1 to downregulate the effects of P-sel in^CT mice and WT mice administered soluble P-sel at time of thrombosis. Animals were sacrificed on days 2 and 6 after IVC ligation. Thrombus mass (TM), vein wall morphometrics, and serum leukocyte/platelet microparticles (MPs) were evaluated by means of double-stained fluorescence-activated cell scanning analysis, and soluble P-and E-sel protein determination by ELISA. Results: At days 2 and 6 in phase I of the experiment, significant differences (P < .01) in TM were noted between groups, with^CT animals having the largest thrombi (50% and 57% increase in TM compared to WT at days 2 and 6) while EPKO mice had the smallest thrombi. Statistically, greater levels of neutrophils and total inflammatory cells were noted in the vein walls of^CT animals at day 2 compared with WT and PKO animals. A significant difference was noted between^CT and EPKO for neutrophils, monocytes, and total inflammatory cells, also at day 2. At day 6, the only statistically significant difference was found for monocytes, with a higher number in the^CT animals than in WT animals. The evaluation of MPs revealed that the^CT mice had a mixed leukocyte (MAC-1) and platelet (CD41) MP population that was also present in WT and PKO mice on day 2 and day 6. EPKO mice revealed a primarily platelet-derived MP population. Of interest, the^CT mice with the highest TM showed a high amount of mean channel fluorescence for MAC-1 (phycoerythrin) antibody, indicative of leukocyte MPs.^CT mice revealed statistically higher levels of soluble P-selectin at days 2 and 6. In phase 2, an antibody directed against PSGL-1 was more effective than rPSGL-Ig in decreasing TM and limiting leukocyte-derived MP fluorescence. Conclusions: This study demonstrates that high circulating levels of P-selectin are associated with increased thrombosis, whereas a lack of P-selectin and E-selectin is associated with a lessening of thrombosis. Additionally, leukocyte MPs are associated with venous thrombus formation. These data suggest the importance of selectins to venous thrombogenesis and show that P-selectin and leukocyte-derived MPs should be good targets to limit venous thrombus formation. (J Vasc Surg 2003;38:1075-89.)
Journal of thee Medical Sciences (Berkala Ilmu Kedokteran), 2017
Thrombocyte concentrate (TC) transfusion is an important supportive therapy in patients with thrombocytopenia. The risks in platelet transfusions may be related to the content of TC including the contaminant leukocytes. The aim of this study was to assess the risk of increased level of P-Selectin (CD62P) expression of non-leukodepleted TC transfusions. This was a quasi-experimental study. Subjects were children patients aged 1-18 years who received a non-leukodepleted or a leukodepleted TC transfusions. Comparison of the proportion of increased expression of CD62P in both groups expressed as relative risk. The subjects consisted of 51 patients who received non-leukodepleted and 52 patients who received leukodepleted TC transfusions. The risk of increased expression of CD62P in patients receiving non-leukodepleted TC transfusions were 2.38 (95%CI:1.60-3.53) times higher than those who received leukodepleted TC. Non-leukodepleted have significant higher risks of increased CD62P expression than leukodepleted TC transfusions.
The emerging value of P-selectin as a disease marker
Clinical Chemistry and Laboratory Medicine (CCLM), 2004
Activated platelets are key components in many arterial disorders. P-selectin is an activation-dependent platelet receptor, which is also identified in endothelial cells. Together with E-and L-selectin it constitutes the selectin family. These transmembrane proteins have continued to attract great interest as they support rapid and reversible cell adhesion in flow systems and thus play an essential role in multicellular interactions during thrombosis and inflammation. Similarly to other lectins, selectins bind to different glycoconjugates with varying affinities. Protein ligands, equipped with the appropriate carbohydrate and sulfate moieties for P-selectin binding, have been identified in normal peripheral blood leukocytes and several non-hematopoietic organs, as well as on cancer cells. For diagnostic purposes, P-selectin can readily be detected on the platelet surface by flow cytometry and by ELISA as a soluble ligand in the plasma. Along with other markers, these data can be use...
Plasma P-selectin is increased in thrombotic platelet disorders
Blood
P-selectin is a 140-kD protein found in the a-granules of platelets and the Weibel-Palade bodies o f 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 "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 j3thromboglobulin (BTG) 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) pa-From the Centre for Thrombosis and Vascular Research, the
2020
Background There is a high number of deep vein thrombosis (DVT) incidence among cancer patients undergoing chemotherapy. Chemotherapy-induced vascular endothelial cell activation (VECA) is marked with increasing plasma levels of von Willebrand Factor (VWF) and soluble P-selectin (sP-selectin) leading to activation of endothelial cells and coagulation cascade. The biological role of a disintegrin-like and metalloproteinase with thrombospondin type 1, motif 13 (ADAMTS13) is to control the activity of VWF. The objectives of this study is to investigate the role of sP-selectin, VWF, and ADAMTS13 as risk factors for the incidence of DVT in cancer patients undergoing chemotherapy. Methods This prospective cohort study was conducted in Dr. Kariadi hospital, Semarang Indonesia, on 40 cancer patients. Soluble P-selectin, VWF, and ADAMS13 plasma levels were determined with enzyme-linked immunosorbent assay (ELISA) method, examined before and after chemotherapy. These patients were observed fo...
Stroke, 2002
Background and Purpose-The increased risk of stroke and thromboembolism in atrial fibrillation (AF) may be related to a prothrombotic or hypercoagulable state, with abnormalities of hemostasis and platelet activation. To investigate the role of platelets in AF and the influence of antithrombotic therapy, we developed and then applied a new assay to detect the absolute amount of P-selectin per platelet (pP-selectin) based on cell lysis. Thus, pP-selectin in AF patients was compared with that of healthy controls and also with plasma soluble P-selectin (sP-selectin) and -thromboglobulin as established indices of platelet activation. Methods-We studied 122 patients (mean [SD] age, 71 [9] years; 65 men) with chronic AF of Ͼ6 weeks' duration: 34 were not on antithrombotic therapy, 30 were taking aspirin (75 to 300 mg/d), and 58 were fully anticoagulated with warfarin. pP-selectin was compared with sP-selectin and plasma -thromboglobulin levels (enzyme-linked immunosorbent assay). Results were compared with those of 23 healthy controls (mean [SD] age, 74 [9] years; 7 men) in sinus rhythm. Results-pP-selectin was significantly lower in AF patients on no antithrombotic therapy (Pϭ0.03) than in healthy controls, but sP-selectin and -thromboglobulin levels were not significantly different and did not differ in patients taking aspirin or warfarin. However, pP-selectin was lower in patients with AF on aspirin than in those on warfarin (PϽ0.05). pP-selectin/sP-selectin correlated significantly in healthy controls (rϭ0.47, Pϭ0.03) but inversely (rϭϪ0.43, Pϭ0.03) in AF patients on no antithrombotic therapy. Conclusions-Lower levels of pP-selectin may represent a depletion of pP-selectin after platelet activation in AF. Aspirin further decreases pP-selectin levels compared with warfarin. On the basis of the principle of platelet lysis, we demonstrate that it is possible to determine the amount of P-selectin per platelet, which may be regulated in the megakaryocyte through a cyclooxygenase-dependent pathway. (Stroke. 2002;33:1237-1242.)