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.

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 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.

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.

Flow Cytometry For Platelet Function Assessment In Essential Thrombocythemia : Does Total Amount Of Platelets Makes Up For Individual Platelet Defect ?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4089-4089
Author(s):  
Nathalie Hezard ◽  
Bernard Pignon ◽  
Jean Claude Adjizian ◽  
Catherine Mace ◽  
Alain Delmer ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Count ◽  
Platelet Function ◽  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Bleeding Complications ◽  
Cytostatic Treatment ◽  
Thrombotic Risk ◽  
Clinical Events ◽  
Mode A

Abstract Background The assessment of platelet function is crucial during the course of essential thrombocythemia (ET), as this myeloproliferative disorder is associated with concomitant thrombotic and bleeding complications. In the context of high platelet count, the assessment of platelet function is challenging. Current recommendations suggest the adjustment of platelet count for functional assays. This adjustment does not take into account the entire pool of circulating platelets in patients. This may explain the lack of predictive value of such assessment towards bleeding/thrombotic risk. Our objective was: 1- to set up a new strategy to evaluate platelet function, taking into account the circulating pool of platelets; 2- to evaluate the effect of JAK-2 mutation and of cytostatic treatment on platelet function. Methods Fifty two patients presenting with essential thrombocythemia (ET) were enrolled. ET diagnosis was established according to WHO criteria. Seventeen males and 35 females were included (sex ratio = 0.48, mean age 52 ± 16 years old). Fifteen healthy subjects were enrolled according to the hospital policy. Platelets were analyzed in whole blood flow cytometry (Beckmann-Coulter). GPIIbIIIa, GPIb and P-selectin were quantified on resting and TRAP-activated platelets (Platelet GP Receptors, Diagnostica Stago). Calculation for quantification strictly followed the manufacturer’s instructions and results were expressed as a number of GPs/P-selectin per platelet (mode A). In order to take into account the total amount of platelets, we calculated the total number of GPs/ P-selectin x platelet count (mode B). As vWF binding to GPIb is critical in the prevention of bleeding, we measured the capacity of platelets to bind vWF in response to ristocetin using an original and sensitive assay in flow cytometry. JAK2 V617F mutation analysis, cytostatic treatment and clinical events (bleeding and thrombosis) were recorded. Data were expressed as median [interquartiles] and Mann-Whitney was used for statistical comparisons. p<0.05 was considered as statistically significant. Results 1) Comparison of two modes of quantification of GPs/P-selectin : mode A (per platelet quantification): GPs and P-selectin expressed per platelet were reduced in patients versus controls (figure 1) (p<0.05), mode B (per circulating pool of platelets) : total amount of GPs and P-selectin was much higher in patients (figure 2) (p<0.05). 2) vWF binding assay Results showed a statistically significant defect of ristocetin-induced vWF binding to platelets in ET patients versus controls (p<0.05). 3) Effect of JAK-2 mutation JAK-2 mutation was present in 23 patients. In this subgroup, platelet count was 748 G/L [555-912] (versus 560 G/L [500-750] in JAK-2 negative group, n = 27). In JAK2 + patients, the defect of GPIIbIIIa and of P-selectin per platelet (mode A) was more pronounced in comparison with patients without any JAK-2 mutation (p<0.05). On the contrary, when results were adjusted to the circulating platelet pool (mode B), total amount of GPs and P-selectin were not different according to the JAK-2 status. The expression of GPIb and the vWF binding were not affected by the JAK-2 mutation status. 4) Effect of cytostatic treatments : We compared platelet function in patients under treatment (n=8, 480 G/L [402-912]) versus patients who were not treated by any cytostatic drug (n = 48, 693 G/L [531-903]). Interestingly, ristocetin-induced vWF binding was improved in treated patients (p<0.05). As a consequence, vWF binding recovered normal range. 5) Clinical events: Three patients experienced bleeding whereas 8 patients developed thrombosis (one had both events). Platelet function profile was not statistically different un these subgroups. Discussion/conclusion Our results show a platelet defect of GPIb, GPIIb-IIIa, P-selectin and vWF binding. On the contrary, when quantification of platelet receptors was adjusted to the pool of circulating platelets, values suggested a prohemostatic phenotype. The JAK-2 status influences the defect severity per platelet of GPIIb-IIIa and P-selectin. Interestingly, we observed a defect in vWF binding in ET patients, which was normalized by treatment. Flow cytometry is adapted to assess platelet defect in ET. However, our results raise the question of the most relevant method of calculation (per platelet and per platelet pool) to predict clinical events. 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.

Treatment of hyperthyroidism with a small single daily dose of methimazole

1988 ◽  
Vol 119 (1) ◽  
pp. 139-144 ◽  
Author(s):  
Yasuo Mashio ◽  
Mutsuo Beniko ◽  
Akemi Ikota ◽  
Hiroaki Mizumoto ◽  
Haruhiko Kunita
Keyword(s):  
Divided Dose ◽  
Dose Regimen ◽  
Single Daily Dose ◽  
Once Daily ◽  
Daily Dose ◽  
The Mean ◽  
Time Required ◽  
Daily Dose Regimen ◽  
Mean Time ◽  
Immunoglobulin Levels

Abstract. A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 ± 2.8 and 6.0 ± 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).

Effect Of Prednisone On Platelet Function In Patients With Bleeding Disorders

1981 ◽  
Author(s):  
R McKenna ◽  
F Bachmann ◽  
O Pichairut ◽  
B Whittaker
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Bleeding Time ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Before And After ◽  
History Of ◽  
The Mean ◽  
One Year

There is considerable controversy regarding the effect of Prednisone on the hemostatic mechanism of normal people versus patients with bleeding diatheses. We administered Prednisone 15 mg TID to patients with a positive history of a bleeding disorder, and evaluated the bleeding time and other in-vitrc tests of platelet function prior to and between the 5th and 7th day after Prednisone.Eleven patients were admitted into this study over a one year period. All patients had a history of excessive bruising, epistaxis, bleeding after dental extractions, and gastrointestinal or other bleeding in various combinations. Two out of the eleven had template bleeding times of greater than 15 minutes both before and after the Prednisone. These two patients were subsequently proven to have von Willebrand’s disease by the washed platelet ristocetin assay. In the remaining 9 patients, the pre-Prednisone bleeding time was 9.3 ±3.7 minutes (x ± 1 S.D.) whereas the post-Prednisone bleeding time was 5.8 ±3.6 minutes (x ±1 S.D.). These results were significant(td=3.83;df:7;p=0.007).Platelet aggregation in response to exogenous ADP (1 μM, 3 μM) Sigma bovine tendon collagen (1.8 mg/ml F) and epinephrine (5.5 × 104M), platelet retention in a glass bead column or platelet factor 3 availability did not improve or worsen after Prednisone therapy. The mean platelet count of 328,000±94,000 (x ±1 S.D.) was significantly (p=0.05) higher than the mean pre-Prednisone platelet count of 268,000±77,000 (x ±1 S.D.).In conclusion, we have shown that large doses of Prednisone appear to shorten the bleeding time in patients with significant defects in the primary hemostatic mechanism. However the bleeding time improvement is not evident in patients with von Willebrand’s disease.

Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3595-3603 ◽  
Author(s):  
Silvia Pascale ◽  
Giovanna Petrucci ◽  
Alfredo Dragani ◽  
Aida Habib ◽  
Francesco Zaccardi ◽  
...  
Keyword(s):  
Platelet Count ◽  
Essential Thrombocythemia ◽  
Low Dose ◽  
Once Daily ◽  
Dosing Interval ◽  
Aspirin Dose ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Enteric Coated Aspirin ◽  
Enteric Coated

Abstract Essential thrombocythemia (ET) is characterized by enhanced platelet generation and thrombotic complications. Once-daily low-dose aspirin incompletely inhibits platelet thromboxane A2 (TXA2) in the majority of ET patients. In the present study, we investigated the determinants of aspirin-insensitive platelet TXA2 biosynthesis and whether it could be further suppressed by changing the aspirin dose, formulation, or dosing interval. In 41 aspirin-treated ET patients, the immature platelet count predicted serum TXB2 independently of platelet count, age, JAK-2 V617F mutation, or cytoreduction (β = 3.53, P = .001). Twenty-one aspirin-treated patients with serum TXB2 ≥ 4 ng/mL at 24 hours after dosing were randomized to the following 7-day regimens in a crossover design: enteric-coated aspirin 100 mg twice daily, enteric-coated aspirin 200 mg once daily, or plain aspirin 100 mg once daily. A twice-daily regimen caused a further 88% median (IQR, 78%-92%, P < .001) TXB2 reduction and normalized the functional platelet response to aspirin, as assessed by urinary 11-dehydro-TXB2 excretion and the VerifyNow Aspirin assay. Doubling the aspirin dose reduced serum TXB2 only partially by 39% median (IQR, 29%-54%, P < .05). We conclude that the abnormal megakaryopoiesis characterizing ET accounts for a shorter-lasting antiplatelet effect of low-dose aspirin through faster renewal of platelet cyclooxygenase-1, and impaired platelet inhibition can be rescued by modulating the aspirin dosing interval rather than the dose.

Carteolol Treatment of Essential Hypertension: A Long-Term Study of Safety and Efficacy

1986 ◽  
Vol 14 (4) ◽  
pp. 175-184 ◽  
Author(s):  
Robert R Luther ◽  
Clemeth J Maurath ◽  
Michael J Klepper ◽  
Robert O Peckinpaugh ◽  
Gary L Ringham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Multicenter Trial ◽  
Open Label ◽  
Once Daily ◽  
Long Term Study ◽  
Daily Dose ◽  
Baseline Values ◽  
The Mean ◽  
Oral Doses

The long-term safety and antihypertensive efficacy of carteolol were evaluated in an open-label, multicenter trial of 245 hypertensive patients. For those patients maintained on carteolol monotherapy, three months of treatment with once-daily oral doses of carteolol ranging from 2.5 to 60 mg reduced the mean recumbent blood pressure by 12/14 mm Hg from baseline values of 151/100. Blood pressure reductions observed at three months were maintained throughout the study. The final daily dose of carteolol for most patients was 10 mg or less. Carteolol was shown to be safe and well tolerated by most patients.

Long-Term Efficacy of Trilostane Administered Twice Daily in Dogs With Pituitary-Dependent Hyperadrenocorticism

2006 ◽  
Vol 42 (4) ◽  
pp. 269-276 ◽  
Author(s):  
Dolores Perez Alenza ◽  
Carolina Arenas ◽  
Mari Luz Lopez ◽  
Carlos Melian
Keyword(s):  
Total Daily Dose ◽  
Final Dose ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Once Daily ◽  
Safe Medication ◽  
Mean Survival Time ◽  
Daily Dose ◽  
The Mean

Trilostane is considered an efficacious and safe medication for canine pituitary-dependent hyperadrenocorticism (PDH). Its recommended frequency of administration is once daily. In this prospective study, the efficacy, toxicity, and long-term outcome of trilostane administered twice daily per os were evaluated in 44 dogs with PDH. Mean initial dose was 3.1 mg/kg q 12 hours, and mean final dose was 3.2 mg/kg q 12 hours. The final total daily dose was lower than previously reported for once-daily administration. The mean survival time for affected dogs was 930 days.

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