Efficacy of Anagrelide Compared with Hydroxyurea in Patients with Essential Thrombocythemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4634-4634
Author(s):  
Rossella Rosari Cacciola ◽  
Ernesto Di Francesco ◽  
Francesca Pezzella ◽  
Daniele Tibullo ◽  
Rosario Giustolisi ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
Myocardial Infarct ◽  
Complete Response ◽  
Average Dose ◽  
Platelet Factor ◽  
Thrombotic Risk ◽  
The Mean ◽  
Lowering Drug ◽  
Ischemic Attack ◽  
Von Willebrand

Abstract The essential thrombocythemia (ET) is characterized by thrombohemorrhagic risk. ET patients receiving HU and anti-aggregants show normal platelets but present platelet coagulant and endothelial aggregation. Anagrelide (ANA) is a platelet-lowering drug that inhibits platelet aggregation. Therefore, we evaluated platelets, platelet factor 4 (PF4), prothrombin fragment 1+2 (F1+2), thrombin antithrombin complex (TAT) and d-dimer (DD) and von Willebrand factor (vWF) as markers of platelet coagulant and endothelial aggregation, respectively, in ET patients treated either with HU or ANA. All measurements were performed before treatment and when complete response, defined as platelet < 400 x109/L for more than 1 month, was achieved. Prolonged thrombocytosis causes thrombohemorrhagic risk. Hence, we investigated the cytoreduction time. The study comprised 36 patients (19 men, 17 women; mean age 65 years) who fulfilled PVSG and WHO. The mean duration of disease was 6 years. 17 patients received HU and 19 patients were on ANA. The average dose of HU was 0.5 g/d. ANA was initially administered at a dose of 0.5 mg/d. The dose was increased by 0.5 mg/d every week until the platelets had decreased to below 400 x 109/L. The average maintenance was 1.7 mg/d. All patients were on aspirin at dose of 100 mg/d and 50 mg/d in HU and ANA group, respectively. None of the patients had acquired or inherited thrombotic risk factors or had inherited coagulopathy. Eleven out of 17 HU patients (5 men, 6 women; mean age 68.6 years) developed thrombosis including six transient ischemic attack (TIA), three myocardial infarct (MI) and two deep venous thrombosis (DVT). The thrombosis occurred at a median time from diagnosis of 2 years. The ANA group did not experience thrombosis. Platelets were determined by automated analyser. PF4, F1+2, TAT and DD and vWF were assayed by ELISA and immunoturbidimetric assay, respectively. Before treatment, all patients had high platelets (1027±297 x 109/L) and elevated PF4, F1+2, TAT and DD (134±48 IU/mL vs 6±2 IU/mL, 3±2 nmol/L vs 0.6±0.2 nmol/L, 25±34 μg/L vs 2.7±1 μg/L, 224±172 μg/L vs 197±43 μg/L, respectively) (p< 0.0001, p<0.0001, p<0.0001 and p<0.0001, respectively) and low vWF (23±9% vs 102±30%) (p<0.0001). After treatment all patients had platelets <400 x 109/L (364 ±77 x 109/L), whereas PF4, F1+2, TAT and DD were higher (147±45 IU/mL, 3±2 nmol/L, 24±41 μg/L and 264±291 μg/L, respectively) and vWF was lower (34±9.9%) in HU group than controls (p<0.0001, p<0.0001, p<0.0001, p=0.001 and p<0.0001, respectively) and normal in ANA group (7±3 IU/mL, 1.1±0.8 nmol/L, 2.4±1.1 μg/L, 121±84 μg/L and 95±37%, respectively). The mean cytoreduction time was 3.2 and 1.8 months in HU and ANA group, respectively. A correlation there was between PF4 and F1+2 and TAT and DD and vWF (p=0.004, p=0.005, p=0.022 and p<0.0001, respectively). vWF did not correlate with F1+2, TAT and DD. Platelets did not correlate with thrombosis, whereas a correlation there was between PF4, F1+2, TAT and DD and thrombosis (p<0.0001, p=0.015, p=0.005 and p=0.034, respectively). A difference was observed in cytoreduction time between HU and ANA (p<0.0001). These results might support the superiority of ANA as antithrombotic drug besides its platelet-lowering effect.

JAK2V617F Mutation Status and Thrombosis in Essential Thrombocythemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5262-5262
Author(s):  
Emma Cacciola ◽  
Ernesto Di Francesco ◽  
Francesca Pezzella ◽  
Daniele Tibullo ◽  
Rossella R Cacciola
Keyword(s):  
Essential Thrombocythemia ◽  
Jak2 V617f ◽  
Janus Kinase ◽  
Jak2 Mutation ◽  
Activation Markers ◽  
Platelet Factor ◽  
Vein Thrombosis ◽  
V617f Mutation ◽  
Ischemic Attack ◽  
Von Willebrand

Abstract Thrombosis frequently complicates the essential thrombocythemia (ET) and hypercytosis may play a role in the its occurrence as well as the platelet and coagulant activation. Therefore, we evaluated myeloproliferative and platelet and coagulant activation markers such as platelets (plts), white blood cell (WBC), haemoglobin (Hb) and hematocrit (Hct) and β-thromboglobulin (βTG) and platelet factor 4(PF4) and prothrombin fragment 1+2 (F1+2), thrombin-antothrombin (TAT), tissue factor (TF), von Willebrand factor (vWF) and d-dimer (DD), respectively in ET patients and thrombosis. As has been reported that the Janus Kinase 2 (IAK2) V617F mutation gives ET a proliferative advantage, we also evaluated the JAK2 mutation. The study group consisted of fifty ET patients (24 males and 26 females, mean age 58 years) who fulfilled PVSG and WHO. Their mean duration of disease was 7 years. Of 50 patients, 18 were on hydroxyurea whereas 32 were not receiving any cytoreduction. All patients were on antiplatelets. Plts, WBC, HB and HCT were measured by automated analyser. βTG, PF4, F1+2, TAT, TF and DD and vWF were assayed by ELISA and immunoturbimetric assay, respectively. Jak2 mutation was analysed by melt curve analysis. Of 50 patients, 24 were JAK2 V617F-positive and 26 were wild-type (WT). Among JAK2-positive ET, 11 experienced thrombosis including 5 episodes of myocardial infarction (MI), 3 of deep vein thrombosis (DVT), 2 of transient ischemic attack (TIA) and 1 of erytromelalgia (E), whereas of WT ET, 5 developed thrombosis such as 1 DVT, 2 TIA and 2 E. All patients had thrombocytosis (684±299×109/l) and normal WBC (7.8±2.2×109/l) and HB(13±1.8 g/dl) whereas HCT and βTG were higher in JAK2-positive ET than WT (41±5.2 % vs 37±5.2 %) ( p=0.034) (266±83 IU/ml vs 193±18 IU/ml) (p&lt;.0001). PF4 (113±39 IU/ml vs 6.9±2.2 IU/ml), F1+2 (3.4±3.6 nmol/l vs 0.7±0,2 nmol/l), TAT (16.9±28 μg/l vs 2.6±0.9 μg/l) and TF (93±132 pg/ml vs 6.4±2.8 pg/ml) (p&lt;.0001 and p&lt;.0001 and p=0.001 and p&lt;.0001, respectively) were increased in all patients whereas vWF and DD were normal (56±42 % and 185±208 ng/l). There was no correlation between JAK2 mutation and plts and WBC and HB and any activation marker. A positive correlation there was between JAK2 mutation and HCT (p=0.034) and thrombosis (p=0.059). These data suggest that JAK2 V617F mutation is responsible for a hematopoietic expansion which might play a role in the pathogenesis of thrombosis in ET.

scholarly journals Aspirin-Platelet Sensitivity in Patients with Essential Thrombocythemia: Role βfibrinogen G-455-a Gene Polymorphism

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5197-5197
Author(s):  
Rossella Rosari Cacciola ◽  
Elio Cacciola Gentilini ◽  
Emma Cacciola
Keyword(s):  
Platelet Count ◽  
Gene Polymorphism ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Platelet Factor ◽  
Thrombotic Risk ◽  
Myeloid Neoplasm ◽  
The Mean ◽  
Platelet Hyperaggregation

Abstract Essential thrombocythemia (ET) is a myeloid neoplasm characterized by platelet activation and thrombotic risk. Aspirin (ASA) is the standard therapy to normal platelet hyperaggregation and to prevent the thrombosis. It is reported that thrombocythaemic patients are ASA insensitive. It is debated if inherited thrombophilia increases the thrombocythemic platelet activation and, hence, the ASA platelet insensitivity. Therefore, we evaluated βFibrinogen G-455-A gene polymorphism, as thrombophilic molecular mutation associated with increased platelet aggregation, platelet count, β-thromboglobulin (β-TG) and platelet factor 4(PF4) as markers of platelet activation, fibrinogen (Fg), platelet functional activity (PFA), as indicator of ASA platelet sensitivity, clot formation time (CFT) and the maximum clot firmness (MCF), as indicators of aspirinated platelet contribution to clot firmness. We studied 40 patients (24 men, 16 women; mean age 56 years, range 37-77) with ET according to WHO criteria. The mean duration of disease was 11 years. All patients were on ASA 100 mg once daily. The βFibrinogen G455-A genotype was determined using a commercialized polymerase chain reaction kit with sequence-specific primers. Platelets were measured by automated analyzer. β-TG and PF4 were determined by ELISA. PFA, CFT and MCF were measured by Platelet Function Analyzer (PFA-100) and by ROTEM delta, respectively. All patients had heterozygous βFibrinogen G455-A. The mean platelet count was 441±72x109/L. All patients had normal Fg (244±47 mg/dl) high β-TG and PF4 (244±15 IU/ml vs 20±11 IU/ml and 162±56 IU/ml vs 6±2 IU/ml, respectively) (p<.0001 and p<.0001, respectively), prolonged C/EPI closure time (CT, unit: s, n.v. 84-160 s) (252±48 s), normal CFT (CFT, unit: s, n.v. 30-110 s) (50±7s) and MCF (MCF, unit: mm, n.v. 50-72 mm) (71±2 mm). These findings suggest that βFibrinogen G-455-A gene polymorphism does not affect the clonal platelet hyperaggregation in ET. Disclosures No relevant conflicts of interest to declare.

scholarly journals Morning Vs Bedtime Aspirin Intake in Patients with Essential Thrombocythemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4295-4295
Author(s):  
Emma Cacciola ◽  
Elio Gentini Cacciola ◽  
Veronica Vecchio ◽  
Rossella Rosari Cacciola
Keyword(s):  
Platelet Count ◽  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Clot Formation ◽  
Optimal Timing ◽  
Platelet Factor ◽  
Thrombotic Risk ◽  
Once Daily ◽  
Daily Dose ◽  
The Mean

Abstract The essential thrombocythemia (ET) is a myeloid neoplasm characterized by platelet hyperreactivity and thrombotic risk. The treatment with aspirin (ASA) is recommended in ET patients at risk of first-time or recurrent thrombotic events. An unexplored topic is the optimal timing of once daily ASA intake. On the basis of the presumptions that 1) platelet aggregation is higher in the morning and that 2) the platelet inhibitory effect of ASA is not sustained during the usual 24-hour (h) dosing interval and that 3) a higher gastric mucosal resistance in the evening, we evaluated platelet count, β-thromboglobulin (β-TG) and platelet factor 4 (PF4), as markers of platelet activation, the clotting time (CT), clot formation time (CFT) and maximum clot formation/firmness (MCF), as indicators of aspirinated platelet contribution to clot formation/firmness. We studied 60 patients (20 men, 40 women; mean age 51 years, range 32-70) with ET according to WHO criteria. The mean duration of disease was 11 years. All patients were on ASA 100 mg once daily. Of these, 30 took ASA on awakening and 30 took ASA at bedtime. Of the 60 patients, 45 were on anagrelide hydrochloride (daily dose 1.5 mg) (10 men, 35 women), 15 were on hydroxyurea (daily dose 2 mg) (10 men 5 women). None had inherited or acquired thrombotic risk factors. Sixty subjects served as controls. Platelets were measured by automated analyzer. β-TG and PF4 were determined by ELISA. CT, CFT and MCF were measured by ROTEM delta. The mean platelet count was 455±200x109/L. The awakening ASA patients had normal β-TG and PF4 (12±5 IU/ml and 4±1 IU/ml), normal CT (CT, unit: s. n.v. 100-240 s) ( 110±20 s), normal CFT (CFT, unit: s, n.v. 30-110 s) (45±5 s) and normal MCF (MCF, unit: mm, n.v. 50-72 mm) (61±2 mm), whereas the bedtime ASA patients had high β-TG and PF4 (200±15 IU/ml vs 20±11 IU/ml and 170±50 IU/ml vs 6±2 IU/ml, respectively) (p<.0001 and p<.0001, respectively), shortened CT (CT, unit: s. n.v. 100-240 s) ( 80±10 s), CFT (CFT, unit: s, n.v. 30-110 s) (15±5 s) and MCF (MCF, unit: mm, n.v. 50-72 mm) (40±2 mm). These findings suggest that in ET patients the optimal timing of once daily ASA intake is in the morning. Disclosures No relevant conflicts of interest to declare.

Inherited Thrombophilias in Essential Thrombocythemia and Polycythemia Vera Are Not an Additional Risk Factor for Thrombosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4934-4934
Author(s):  
Emma Cacciola ◽  
Antonio Cipolla ◽  
Ernesto Di Francesco ◽  
Rosario Giustolisi ◽  
Rossella R. Cacciola
Keyword(s):  
Risk Factor ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Thrombotic Complication ◽  
Additional Risk Factor ◽  
Clotting Factors ◽  
Platelet Factor ◽  
Thrombotic Risk ◽  
Additional Risk ◽  
Mthfr Mutation

Abstract Patients with essential thrombocythemia (ET) and polycythemia vera (PV) have a high risk of thrombosis. Inherited thrombophilias are established risk factors for thrombosis. To determine if inherited thrombophilic abnormalities might contribute to the thrombotic risk in ET and PV, we investigated antitrombin III (ATIII), protein C (PC) and protein S (PS), polymorphisms of clotting factors V (FVQ506) and II (G20210A) and methylenetetrahydrofolate reductase (MTHFR) mutation in patients with ET and PV and we tried to correlate these results with prothrombotic markers such as bthromboglobulin (bTG), platelet factor 4 (PF4), prothrombin fragment 1+2 (F1+2) and d-dimer (DD). In addition, we analysed a possible association between inherited coagulopathy and thrombosis. ATIII, PC and PS antigen levels were assayed by ELISA as well as bTG, PF4 and F1+2. PCR-based assays were used for FVQ506, prothrombin and MTHFR. DD was measured by immunoturbimetric latex agglutination. The study involved 101 patients diagnosed with ET (71 patients, 30 men, 41 women, mean age 62.3 years) or PV (30 patients, 21 men, 9 women, mean age 65.4 years) according to conventional criteria. The duration of disease ranged between 1 to 12 years. Of 101 patients, 53 (52,47%) were non-carriers of mutations and among these 24 (45.28%) experienced thrombosis, 48 (47.52%) were carriers and 27 (56.25%) had thrombosis. With reference to carriers, 9/48 (14.58%) had combined mutations such as PC and PS (2/9), PS and G20210A (1/9), PC and MTHFR (4/9), G20210A and MTHFR (2/9). The prevalence of studied defects was 31.25% (15/48) and 18.75% (9/48) for deficiency of PC and PS, respectively, 8.33% (4/48) and 14.58% (7/48) for heterozygosity of FVQ502 and G20210A, respectively, and 45.83% (22/48) for MTHFR mutation. Deficiency of ATIII was not present. All patients had higher bTG, PF4 and F1+2 (365±654 IU/ml, 133±64 IU/ml and 2.6±2.5 nmol/L, respectively) than to controls (23.8±9.1 IU/ml, 5.5±2.8 IU/ml and 0.60.2 nmol/L, respectively) (p&lt;0.0001) and normal DD (144±92 ng/L). No correlation between studied polymorphisms genetic and bTG, PF4, F1+2 and DD was found as well as with thrombotic complication. The frequency of thrombosis was not statistically different between non-carriers and carriers. Based on these data, it appears that inherited thrombophilias are not an additional risk factor for thrombosis in ET and PV and that the thrombotic phenomena are due to the abnormal platelet function that is part of the myeloproliferative disorders.

Treatment of Essential Thrombocythemia with Anagrelide: A Novel Antiangiogenic Agent?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4742-4742
Author(s):  
E. Cacciola ◽  
A. Cipolla ◽  
E. Di Francesco ◽  
R. Giustolisi ◽  
R. R. Cacciola
Keyword(s):  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Complete Response ◽  
Latex Agglutination ◽  
Myeloproliferative Disorder ◽  
Vascular Endothelial ◽  
Platelet Factor ◽  
Duration Of Disease ◽  
Endothelial Growth Factor ◽  
D Dimer

Abstract Essential thrombocythemia is a myeloproliferative disorder complicated by thrombotic phenomena as a result of the platelet-clotting hyperactivation linked to increased angiogenesis. It is reported that vascular endothelial growth factor (VEGF) generates thrombin and promotes platelet activation and that activated megakaryocytes and platelets release VEGF. Anagrelide (ANA) is a newer cytoreductive agent which decreases megakaryocyte mass and inhibits the platelet activation. Therefore, we studied platelet factor 4 (PF4), as indicator of platelet activation, VEGF and prothrombin fragment 1+2 (F1+2) and d-dimer (DD), as indicators of thrombin generation, in 22 patients (12 males and 10 females, mean age 50 years) affected by ET diagnosed according to PVSG criteria. Their mean duration of disease was 4.8 years. All patients were on either HU (6 patients) or IFN-α (4 patients) and ANA (12 patients). HU was used at doses ranging between 1 and 1.5g/day. The dosage of IFN-α was 3 MIU, 3 days/week. ANA was initially administered in dose of 0.5 mg/day, with increases of 0.5 mg/day every 7 days until the platelets decreased below 500×109/L and with a average maintenance dosage of 2.2 mg/day. All patients recieved antiplatelets either aspirin (ASA) (15 patients) or indobufen (IND) (6 patients) and dipirydamole (DYP) (1 patient). Platelets, PF4, VEGF, F1+2 and DD were measured before cytoreduction and to complete response defined as platelets≤ 500×109/L. Platelets were determined by automated analyser. PF4, VEGF and F1+2 were assayed by ELISA and DD by immunoturbimetric latex agglutination. Before treatment all patients had marked platelets (1060±356×109/L) and high PF4 and VEGFPLT (157±83 IU/ml vs 1.6±0.9 IU/ml and 1.2±1 pg/ml vs 0.3±0.2 pg/ml, respectively) (p<0.0001 and p= 0.002, respectively). F1+2 and DD were elevated 3.6±3.7nml/L and 205±83 μg/L, respectively) than controls (0.6±0.3nmol/L and 75±21 μg/L, respectively) (p<0.0001 and p<0.0001, respectively). After a median time of 4.5 months from cytoreduction all patients had platelets ≤ 500 × 109/L (430±70 × 109/L). PF4 and VEGFPLT remained high (121±72 IU/ml and 3.5±4.6 pg/ml, respectively) such as F1+2 and DD (3.5±3.8 nmol/L and 197±55 μg/L, respectively) in the HU- and IFN-α-treated patients. PF4 and VEGFPLT normalised (7.4±3 IU/ml and 0.9±0.5 pg/ml, respectively) in the ANA-treated patients such as F1+2 and DD (1.1±0.4 nmol/L and 98±62 μg/L, respectively). These measurements were repeated in another sample collected after 1 o 2 months and showed concordance for PF4, VEGFPLT, F1+2 and DD concentrations. A positive correlation we found between PF4 and F1+2 and DD (p=0.023 and p=0.019, respectively) and between VEGF and F1+2 (p=0.020, respectively). Interestingly, these data might suggest that ANA has antiangiogenic property and hence antiplatelet and anticoagulant effects.

Inflammation and Thrombosis In Essential Thrombocythemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5175-5175
Author(s):  
Rossella Cacciola ◽  
Ernesto Di Francesco ◽  
Carmen Ferlito ◽  
Francesca Pezzella ◽  
Elisa Seria ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Thrombotic Risk ◽  
Vein Thrombosis ◽  
Myeloid Neoplasm ◽  
Duration Of Disease ◽  
Interleukin 15 ◽  
Ischemic Attack ◽  
Endothelial Growth Factor ◽  
Deep Vein

Abstract Abstract 5175 The essential thrombocythemia (ET) is a myeloid neoplasm characterized by an inflammatory component responsible for coagulant activation and angiogenesis. Therefore, we evaluated platelets, interleukin-8 (IL-8) and interleukin-15 (IL-15), as inflammatory indicators, tissue factor (TF), as marker of coagulative activation, and vascular endothelial growth factor (VEGF), as indicator of angiogenesis, in patients with ET and thrombosis. We recruited 25 thrombocythemic patients (10 males and 15 females, mean age 58 years) who fulfilled WHO.criteria. Their mean duration of disease was 8 years (range, 5–21 years). All patients were on aspirin. None of the patients had thrombotic risk factors. Of 25 patients, 10 developed thrombosis including 5 episodes of microvascular thrombosis of extremities (erythromelalgia), 2 of transient ischemic attack (TIA), 2 of myocardial infarction (IMA) and 1 of deep vein thrombosis (DVT)) whereas 15 did not. Platelets were measured by automated analyser. IL-8, IL-15, and VEGF and DD were measured by ELISA and immunoturbidimetric assay, respectively. All patients had thrombocytosis (961±235×109/L). IL-8, IL-15, TF and VEGFPLT were higher in patients with thrombosis than patients without thrombosis (27±14 pg/ml and 14±4 pg/ml and 214±266 pg/ml and 2±1 pg/106l vs 14±7 pg/ml and 26±6 pg/ml and 108±64 μg/l and 1±0.9 pg/ml, respectively) (p=0.009 and p<.0001 and p=0.005 and p=0.059, respectively). A positive correlation there was between IL-8 and IL-15 (p<.0001) and between IL-15 and TF (p=0.046). A tendency towards correlation was found between IL-15 and VEGF (p=0.082). These findings suggest a inflammatory IL-8-IL-15 interplay responsible for coagulation and angiogenesis activation that might mean increased thrombophilia in ET. Disclosures: No relevant conflicts of interest to declare.

Effect Of Heterozygous JAK2 V617F On Thrombotic Risk In Patients With Polycythemia Vera: Measuring The Uncertain

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5251-5251
Author(s):  
Emma Cacciola ◽  
Antonino Cipolla ◽  
Ernesto Di Francesco ◽  
Elisa Seria ◽  
Maria Torre ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Transient Ischemic Attack ◽  
Conflicts Of Interest ◽  
Myocardial Infarct ◽  
Janus Kinase ◽  
Thrombotic Risk ◽  
Allele Burden ◽  
Vein Thrombosis ◽  
Ischemic Attack ◽  
Deep Vein

Abstract The Janus Kinase (JAK)2 V617F mutation and its homozygous allele burden influences the thrombotic risk in Ph-negativemyeloid chronic disorders. Recent studies report that the vera polycythemia (PV) is a heterozygous JAK2V617F disease. The heterozygous PV is characterized by high hemoglobin (Hb), hematocrit (HCT) and red blood cell (RBC) and low thrombocytosis. Therefore, we evaluated allele burden, Hb, HCT, RBC and platelets and the occurrence of thrombotic events in patients with heterozygous PV disease. The study group included 50 patients (30 male, 20 female, mean age 68 years) affected by PV according WHO criteria. Their mean duration of disease was 11 years (range, 1-26 years). All patients were on aspirin. The percentage of granulocyte mutant alleles was evaluated using a quantitative real-time polymerase chain reaction-based allelic discrimination assay. Hb, HCT, RBC, platelets were measured by automated analyser. Of 50 patients, 28 had allele burden > 10% (34±5) and 22 had allele burden < 10% (6±1)). 10/28 had thrombosis (35%) including 6 transient ischemic attack (TIA), 2 myocardial infarction (MI) and 2 deep vein thrombosis (DVT), 18/22 (81%) had thrombosis including 8 transient ischemic attack (TIA), 4 myocardial infarct (MI) and 6 deep vein thrombosis (DVT). HB, HCT and RBC were elevated in all patients (19±1.8 g/dl, 56±4 %, 7±0.6 x106/L) and the platelets were higher in patients with allele burden > 10% than the patients with allele burden < 10% (500±127x109/L vs 381±128x109/L) (p = 0.030) whereas the thrombosis were more in patients with allele burden < 10% than the patients with allele burden > 10% (81% vs 35%). These data suggest that the heterozygous allele burden is a uncertain thrombotic risk factor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Increased Thromboxane in Patients with Polycythemia Vera and Thrombosis: Evidence for Aspirin-Unsuppressible Platelet Activation In Vivo

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5372-5372
Author(s):  
Rossella Rosari Cacciola ◽  
Elio Gentilini Cacciola ◽  
Veronica Vecchio ◽  
Emma Cacciola
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Platelet Function ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasm ◽  
Vascular Events ◽  
Platelet Factor ◽  
Thrombotic Risk ◽  
Closure Time ◽  
The Mean

Polycyhemia vera (PV) is a myeloproliferative neoplasm characterized by increased thromboxane (TX) production and thrombotic risk. It is reported that serum TXB2 concentrations in PV patients are twofold higher than healthy controls and that low-dose aspirin (ASA) therapy reduces the risk of major vascular events by 50 to 60%. To evaluate this unusual size of the effect of ASA we have studied platelet count, hematocrit (HCT), β-thromboglobulin (β-TG) and platelet factor 4 (PF4), as markers of platelet activation, TXB2, as primary indicator of platelet activation, the platelet function activity (PFA), as indicator of ASA platelet sensitivity, and the clotting time (CT), as parameter of thrombin formation. We studied 60 patients (38 men, 22 women; mean age 51 years, range 32-70) with PV according to WHO criteria. The mean duration of disease was 12 years. All patients were on ASA 100 mg once daily. All patients were on phlebotomy. None had inherited or acquired thrombotic risk factors. Of 60 patients, 30 had thrombosis (20 men, 10 women) and 30 had no thrombosis. Of 30 with thrombosis, 15 developed nonfatal myocardial infarction (10 men, 5 women) defined by chest pain of typical intensity and duration and ST-segment elevation in any limb lead on electrocardiography, 10 had nonfatal stroke (8 men, 2 women) confirmed with the use of magnetic resonance imaging, and 5 (2 men , 3 women) had deep venous thrombosis confirmed by ultrasonography. Platelet count and HCT were measured by automated analyzer. β-TG and PF4 were determined by ELISA. TXB2 was measured by radioimmunoassay technique. ASA platelet sensitivity was measured by Platelet Function Analyzer (PFA-100). CT was measured by thromboelastometry. The mean platelet count was 430±170x109/L. The mean HCT value was 42±3%. The patients with thrombosis had high β-TG, PF4 and TXB2 (110±45 IU/ml, 45±21 IU/ml, and 1.700±1.990 nmol/L, respectively), shortened C/EPI closure time (T, unit: s, n.v. 84-160 s) (55±10 s) and shortened CT (CT, unit: s. n.v. 100-240 s) (45±20 s) whereas the patients without thrombosis had normal β-TG, PF4 and TXB2 (20±11 IU/ml, 6±2 IU/ml, and 800±280 nmpl/L, respectively), prolonged C/EPI closure time (249±40 s) and normal CT (110±20 s). These findings might suggest that in PV patients and thrombotic complications might need a platelet-selective dosage of ASA. Disclosures No relevant conflicts of interest to declare.

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.

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