Markers of Endothelial and In Vivo Platelet Activation in Patients with Essential Thrombocythemia and Polycythemia Vera

2004 ◽  
Vol 79 (3) ◽  
pp. 253-259 ◽  
Author(s):  
Marina Karakantza ◽  
Nikolaos C. Giannakoulas ◽  
Panagiotis Zikos ◽  
George Sakellaropoulos ◽  
Alexandra Kouraklis ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Platelet Activation ◽  
Essential Thrombocythemia

Aspirin-Responsive, Migraine-Like Transient Cerebral and Ocular Ischemic Attacks and Erythromelalgia in JAK2V617F-Positive Essential Thrombocythemia and Polycythemia Vera

2014 ◽  
Vol 133 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Jan Jacques Michiels ◽  
Zwi Berneman ◽  
Alain Gadisseur ◽  
King H. Lam ◽  
Hendrik De Raeve ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Ex Vivo ◽  
Time Lapse ◽  
Blurred Vision ◽  
Activation Markers ◽  
Platelet Factor ◽  
Cox 1

Migraine-like cerebral transient ischemic attacks (MIAs) and ocular ischemic manifestations were the main presenting features in 10 JAK2V617F-positive patients studied, with essential thrombocythemia (ET) in 6 and polycythemia vera (PV) in 4. Symptoms varied and included cerebral ischemic attacks, mental concentration disturbances followed by throbbing headaches, nausea, vomiting, syncope or even seizures. MIAs were frequently preceded or followed by ocular ischemic events of blurred vision, scotomas, transient flashing of the eyes, and sudden transient partial blindness preceded or followed erythromelalgia in the toes or fingers. The time lapse between the first symptoms of aspirin-responsive MIAs and the diagnosis of ET in 5 patients ranged from 4 to 12 years. At the time of erythromelalgia and MIAs, shortened platelet survival, an increase in the levels of the platelet activation markers β-thromboglobulin and platelet factor 4 and also in urinary thromboxane B2 were clearly indicative of the spontaneous in vivo platelet activation of constitutively JAK2V617F-activated thrombocythemic platelets. Aspirin relieves the peripheral, cerebral and ocular ischemic disturbances by irreversible inhibition of platelet cyclo-oxygenase (COX-1) activity and aggregation ex vivo. Vitamin K antagonist, dipyridamole, ticlopidine, sulfinpyrazone and sodium salicylate have no effect on platelet COX-1 activity and are ineffective in the treatment of thrombocythemia-specific manifestations of erythromelalgia and atypical MIAs. If not treated with aspirin, ET and PV patients are at a high risk of major arterial thrombosis including stroke, myocardial infarction and digital gangrene.

Increased Thromboxane Biosynthesis in Essential Thrombocythemia

1995 ◽  
Vol 74 (05) ◽  
pp. 1225-1230 ◽  
Author(s):  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Raffaele Tartaglione ◽  
Sergio Cortelazzo ◽  
Tiziano Barbui ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Therapeutic Strategy ◽  
Low Dose ◽  
Thrombotic Risk ◽  
Dose Aspirin ◽  
Gender And Age ◽  
Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia

Blood ◽  
2011 ◽  
Vol 118 (12) ◽  
pp. 3359-3366 ◽  
Author(s):  
Norma Maugeri ◽  
Simona Malato ◽  
Eti A. Femia ◽  
Mariateresa Pugliano ◽  
Lara Campana ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Ad Hoc ◽  
Activated Platelets ◽  
Hydroxyurea Treatment ◽  
Independent Mechanism ◽  
Confocal And Electron Microscopy ◽  
Age And Sex

Abstract Essential thrombocythemia (ET) and polycythemia vera (PV) are characterized by persistent platelet activation. The mechanisms involved in their clearance are poorly characterized. In the present study, we report that leukocytes were actively involved in platelet disposal in 51 patients with ET and 30 with PV, but not in 70 age- and sex-matched controls. The fraction of circulating neutrophils and monocytes that had phagocytosed platelets, as assessed by flow cytometry, was significantly higher in patients with PV or ET, independently of hydroxyurea treatment, than in controls. Platelet phagocytosis by circulating leukocytes was confirmed by confocal and electron microscopy. The lack of effect of hydroxyurea, which disrupts the P-selectin/P-selectin glycoprotein ligand 1 (PSGL-1) interaction, suggests a P-selectin–independent mechanism. This hypothesis was confirmed in an ad hoc animal model based on the in vivo injection of activated platelets from P-selectin+/+ and P-selectin−/− mice. P-selectin expression was associated with an earlier and effective clearance of platelets by neutrophils. A second delayed, P-selectin–independent phase actively involved monocytes. Our results suggest that phagocytic clearance of platelets by leukocytes occurs in PV and ET, possibly involving P-selectin–dependent and -independent pathways, thus representing a novel mechanism to remove activated platelets from the circulation.

Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4261-4266 ◽  
Author(s):  
Anna Falanga ◽  
Marina Marchetti ◽  
Virgilio Evangelista ◽  
Alfonso Vignoli ◽  
Marina Licini ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Activation Parameters ◽  
Antigen Expression ◽  
Endothelial Damage ◽  
Coagulation System ◽  
Control Group ◽  
Leukocyte Activation ◽  
Increased Risk

Thrombohemorrhagic complications are a major cause of morbidity and mortality in patients with essential thrombocythemia (ET) and polycythemia vera (PV). The pathogenesis of these complications is not completely clarified. Several studies have described abnormalities of red blood cells and platelets in these patients. However, no studies are available on changes in the polymorphonuclear leukocytes (PMNs), which can play an important role in the activation of the hemostatic system. In patients with ET (n = 37) and PV (n = 34), a series of PMN activation parameters (PMN membrane CD11b and leukocyte alkaline phosphatase [LAP] antigen expression, cellular elastase content, plasma elastase, and myeloperoxidase levels) was evaluated simultaneously with the levels of plasma markers of endothelial damage (thrombomodulin and von Willebrand factor antigen) and hypercoagulation (thrombin-antithrombin complex, prothrombin fragment 1 + 2, and D-dimer). The results show the occurrence of PMN activation in both groups of patients compared with a control group of healthy subjects. An increase in CD11b and LAP expression by PMN membrane was observed, together with a significant increase in cellular elastase content, plasma elastase, and myeloperoxidase levels. In addition, patients had high plasma levels of endothelial and hypercoagulation markers compared with controls. For the first time, these data show that in ET and PV, 2 hematologic conditions that place patients at increased risk for thrombosis, an in vivo leukocyte activation occurs and is associated with laboratory signs of endothelium and coagulation system activation.

Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4261-4266 ◽  
Author(s):  
Anna Falanga ◽  
Marina Marchetti ◽  
Virgilio Evangelista ◽  
Alfonso Vignoli ◽  
Marina Licini ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Activation Parameters ◽  
Antigen Expression ◽  
Endothelial Damage ◽  
Coagulation System ◽  
Control Group ◽  
Leukocyte Activation ◽  
Increased Risk

Abstract Thrombohemorrhagic complications are a major cause of morbidity and mortality in patients with essential thrombocythemia (ET) and polycythemia vera (PV). The pathogenesis of these complications is not completely clarified. Several studies have described abnormalities of red blood cells and platelets in these patients. However, no studies are available on changes in the polymorphonuclear leukocytes (PMNs), which can play an important role in the activation of the hemostatic system. In patients with ET (n = 37) and PV (n = 34), a series of PMN activation parameters (PMN membrane CD11b and leukocyte alkaline phosphatase [LAP] antigen expression, cellular elastase content, plasma elastase, and myeloperoxidase levels) was evaluated simultaneously with the levels of plasma markers of endothelial damage (thrombomodulin and von Willebrand factor antigen) and hypercoagulation (thrombin-antithrombin complex, prothrombin fragment 1 + 2, and D-dimer). The results show the occurrence of PMN activation in both groups of patients compared with a control group of healthy subjects. An increase in CD11b and LAP expression by PMN membrane was observed, together with a significant increase in cellular elastase content, plasma elastase, and myeloperoxidase levels. In addition, patients had high plasma levels of endothelial and hypercoagulation markers compared with controls. For the first time, these data show that in ET and PV, 2 hematologic conditions that place patients at increased risk for thrombosis, an in vivo leukocyte activation occurs and is associated with laboratory signs of endothelium and coagulation system activation.

Platelet activation and inhibition in polycythemia vera and essential thrombocythemia

Blood ◽  
2013 ◽  
Vol 121 (10) ◽  
pp. 1701-1711 ◽  
Author(s):  
Carlo Patrono ◽  
Bianca Rocca ◽  
Valerio De Stefano
Keyword(s):  
Polycythemia Vera ◽  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Low Dose ◽  
Treatment Guidelines ◽  
Bleeding Complications ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
The Individual

Abstract Persistently enhanced platelet activation has been characterized in polycythemia vera (PV) and essential thrombocythemia (ET) and shown to contribute to a higher risk of both arterial and venous thrombotic complications. The incidence of major bleeding complications is also somewhat higher in PV and ET than in the general population. Although its efficacy and safety was assessed in just 1 relatively small trial in PV, low-dose aspirin is currently recommended in practically all PV and ET patients. Although for most patients with a thrombosis history the benefit/risk profile of antiplatelet therapy is likely to be favorable, in those with no such history this balance will depend critically on the level of thrombotic and hemorrhagic risks of the individual patient. Recent evidence for a chemopreventive effect of low-dose aspirin may tilt the balance of benefits and harm in favor of using aspirin more broadly, but the potential for additional benefits needs regulatory scrutiny and novel treatment guidelines. A clear pharmacodynamic rationale and analytical tools are available for a personalized approach to antiplatelet therapy in ET, and an improved regimen of low-dose aspirin therapy should be tested in a properly sized randomized trial.

In vivo lipid peroxidation and platelet activation in Helicobacter pylori infection

2001 ◽  
Vol 120 (5) ◽  
pp. A670-A670
Author(s):  
M NERI ◽  
G DAVI ◽  
D FESTI ◽  
F LATERZA ◽  
A FALCO ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Helicobacter Pylori ◽  
Platelet Activation ◽  
Helicobacter Pylori Infection
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