Effect of aspirin,clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke

Although the mechanisms of action by which aspirin, clopidogrel and dipyridamole inhibit platelets are well characterised, their effects on soluble modulators of thrombosis, inflammation, and endothelial function have yet to assessed systematically. In this investigation aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in combination (A, C, D, AC, AD, CD, ACD) in random order for 2 weeks (without washout) to 11 healthy subjects and 11 patients with previous ischaemic stroke. At the end of each treatment period plasma cyclic guanosine monophosphate (cGMP), monocyte chemoattractant pertide-1 (MCP-1), nitric oxide metabolites (NO_x), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWf); and serum C-reactive protein (CRP) and platelet derived growth factor (PDGF); were measured blinded to treatment. Dipyridamole reduced plasma vWf levels (%) in both volunteers,??10.0 (4.95), and patients,??10.11 (4.34) (p?<?0.05). Dipyridamole also lowered CRP (mg/l) in patients,??0.96 (0.47), but not volunteers. Clopidogrel reduced PAI-1 (ng/ml) in volunteers,??5.30 (2.20) (p?<?0.05), and patients,??3.61 (2.75) (non-significant trend). Aspirin lowered PDGF (ng/ml) in volunteers,??3.46 (1.55), but not patients. Triple antiplatelet therapy was superior to dual and mono therapy in reducing vWf levels. In conclusion, antiplatelet agents have non-platelet-related effects on soluble modulators of thrombosis, inflammation, and endothelial function. In particular, dipyridamole reduces plasma vWf and clopidogrel lowers plasma PAI-1 levels. These effects may explain, in part, their roles in preventing atherothrombogenesis.     

Comparison between a new platelet count drop method PL-11, light transmission aggregometry,VerifyNow aspirin system and thromboelastography for monitoring short-term aspirin effects in healthy individuals

Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11.     

Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes

The antiplatelet efficacy of aspirin (ASA) is reduced in type 2 diabetes (T2D). As the best ex vivo method of measuring ASA efficacy remains uncertain, we compared nine platelet function tests to assess responsiveness to three ASA dosing regimens in 24 T2D patients randomized in a three-treatment crossover design to ASA 100 mg/day, 200 mg/day, or 100 mg twice daily for 2-week treatment periods. Platelet function tests compared were as follows: light transmission aggregometry (LTA)–0.5 mg/mL of arachidonic acid (AA) and 10 µM adenosine diphosphate (ADP); multiplate whole blood aggregometry (WBA)–0.5 mM AA and 6.5 µM ADP; platelet function analyzer (PFA)-100?–collagen and ADP (CADP) and collagen and epinephrine (CEPI); VerifyNow?–ASA; and urinary 11-dehydro-thromboxane B2 (TxB₂) and serum TxB₂. All cyclo-oxygenase (COX-1)-dependent tests and some COX-1-independent tests (PFA-CEPI, LTA-ADP) demonstrated significant reductions in platelet reactivity with all ASA doses. Two COX-1-independent tests (WBA-ADP and PFA-CADP) showed no overall reduction in platelet reactivity. Overall classifications for detecting all ASA doses, compared to baseline, were as follows: very good–LTA-AA (k = 0.95) and VerifyNow?-ASA (k = 0.85); good–serum TxB₂ (k = 0.79); moderate–LTA-ADP (k = 0.59), PFA-100?-CEPI (k = 0.56), urinary TxB₂ (k = 0.55), WBA-AA (k = 0.47); and poor–PFA-100?-CADP (k = –0.02) and WBA-ADP (k = –0.07). No significant kappa statistic differences were seen for each test for each ASA dose. Correlations for each test with serum TxB₂ measurements were as follows: very good–VerifyNow?-ASA (k = 0.81, R² = 0.56) and LTA-AA (k = 0.85, R² = 0.65); good–PFA-100^TM-CEPI (k = 0.62, R² = 0.30); moderate–urinary TxB₂ (k = 0.57, R² = 0.51) and LTA-ADP (k = 0.47, R² = 0.56); fair–WBA-AA (k = 0.31, R² = 0.31); and poor–PFA-100?-CADP (k = 0.04, R² = 0.003) and WBA-ADP (k = –0.04, R² = 0.0005). The platelet function tests we assessed were not equally effective in measuring the antiplatelet effect of ASA and correlated poorly amongst themselves, but COX-1-dependent tests performed better than non-COX-1-dependent tests.     

Effect kinetics of desmopressin-induced platelet retention in healthy volunteers treated with aspirin or placebo

Desmopressin is often used for haemostatic treatment in platelet dysfunction, but the effect kinetics of platelet responses and the mechanism of action are poorly known. This study aimed to determine the kinetics of platelet function responses induced by desmopressin in healthy volunteers treated with aspirin or placebo. Another aim was to correlate platelet responses to changes of von Willebrand factor (vWF) in plasma. We measured platelet function with a glass bead retention test, Ivy bleeding time, vWF:Ag and multimeric structure in plasma. Median baseline platelet retention was 12% (normal reference range 16-27%) during aspirin treatment and 18% during placebo. Median peak platelet retention after desmopressin was 33% during aspirin treatment and 34% during placebo. After about 3 h platelet function had returned to baseline. A second desmopressin dose after 3 h stimulated platelet retention to a similar extent as the first dose. There was no correlation between platelet responses and quantitative or qualitative changes of vWF in plasma. Platelet count did not change significantly. Thus, desmopressin's effect on platelet function lasts for about 3 h, but may be prolonged by a second dose immediately thereafter. These findings may have important clinical implications for patients with aspirin-induced platelet dysfunction undergoing surgery.     

Antiplatelet effects of licking an aspirin tablet can be detected by thrombelastography

Aspirin is a cornerstone of treatment in cardiovascular disease. However, individual responses vary and hyporesponsiveness has been associated with poor outcomes following percutaneous intervention. Point of care assays for detecting the effects of aspirin in individual patients would therefore be useful. Thrombelastography has been shown to correlate with optical aggregation in the assessment of antiplatelet therapies and is suitable for use as a point of care assay. We demonstrate the ability of thrombelastography to detect the profound effects of even the tiny doses of aspirin obtained by licking an aspirin tablet.     

Decreased turnover aspirin resistance by bidaily aspirin intake and efficient cytoreduction in myeloproliferative neoplasms

Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN) with an increased risk of arterial and venous thrombosis. Aspirin is recommended to reduce this risk, but resistance to antiplatelet therapy seems to hamper its efficacy in some patients. We have previously shown that multiple electrode aggregometry (MEA) was a valuable tool to assess aspirin resistance in MPN. In this study, MEA was used to assess the reduction in aspirin resistance after bi-daily (BID) aspirin intake or cytoreduction.

Fifty one MPN patients (31 ET and 20 PV) receiving 75 mg aspirin once daily (OD) or BID, with or without cytoreductive treatment, were analyzed. Aspirin resistance was assessed using whole blood MEA (Multiplate®, Roche Diagnostics, Meylan, France).

In all patients, global aspirin resistance consisted mainly of turnover resistance (TOR). 94% of patients with OD aspirin intake and without cytoreduction displayed biological aspirin resistance. By switching to a BID aspirin regimen, the proportion of resistant patients reduced to 47%. Cytoreduction also contributed to reduce aspirin resistance in a similar way (50% of aspirin resistant patients). Combining cytoreduction and BID aspirin regimen was the most efficient way to reduce aspirin resistance yielding to 12% resistant patients. Moreover, a nonlinear correlation was observed between TOR and naive platelet counts regardless of aspirin regimen. Last, mutational status did not seem to affect TOR.

This study confirmed that BID aspirin is biologically more effective than OD aspirin in reduction of aspirin resistance. The latter was achieved through a reduction in TOR which was also decreased by cytoreductive therapy.     

Advances in monitoring of aspirin therapy

The efficacy of aspirin to prevent thrombotic events in cardiovascular patients is well established, with >100 randomized trials having been conducted in high-risk patients and demonstrating a reduction in vascular death of approximately 15% and a further reduction in non-fatal vascular events of approximately 30%. While the benefit of aspirin is undisputed, it is also known that aspirin is associated with a dose-dependent increase in the risk of bleeding. It follows that most treatment guidelines advocate the use of the lowest aspirin dose effective in preventing thrombotic complications to minimize the risk of major bleeding. From this, a need for monitoring of aspirin therapy has emerged and prompted the development and investigation of numerous assays of platelet function. The intention behind monitoring of aspirin's antithrombotic effects is to maximize benefit and to personalize treatment based on individual patient characteristics. This article reviews the recent literature on the usefulness of platelet function testing in patients requiring aspirin; the variability of platelet reactivity in patients taking aspirin and its clinical impact; the potential mechanisms underlying suboptimal platelet inhibition by aspirin and future directions in terms of management of aspirin therapy.     

吲哚布芬在不稳定型心绞痛治疗中的应用

目的研究不稳定型心绞痛患者应用吲哚布芬的疗效与安全性,并与阿司匹林进行疗效比较。方法240例不稳定型心绞痛患者分为吲哚布芬组（200mg／d）和阿司匹林组（100mg／d）,1个月后,观察两组胸痛发作次数、持续时间和心电图改变。结果治疗组比对照组胸痛明显缓解,心电图改善（P＜0．05）,副反应无明显增加。结论不稳定型心绞痛患者应用吲哚布芬的临床疗效显著且安全。吲哚布芬效果优于阿司匹林。     

The effect of aspirin on mean platelet volume in patients with paroxysmal atrial fibrillation

Aspirin is one of the preferred therapies in the primary prevention of ischemic stroke in paroxysmal atrial fibrillation (PAF). Mean platelet volume (MPV) is a marker of platelet size and activation. Increased MPV reflects active and large platelets. The present observational study was designed to investigate whether aspirin treatment does affect MPV levels in patients with PAF. The study included 101 patients who were detected to have PAF by 24-hour Holter monitoring and divided into two groups based on aspirin treatment [ASA (+) and ASA (?)]. MPV was measured. Patients with aortic and mitral stenosis, hyperthyroidism, hypothyroidism, malignancy, infection, and pregnancy were excluded from the study. Of the 101 patients, 50 had no antiplatelet therapy and 51 had daily aspirin (100?mg) intake. Mean age of the patients was 66?±?10 years and 35 (68%) were male in ASA (+) group. There was no difference in median levels of MPV (9.9 vs. 10.2?fl, respectively; p?=?0.9) between groups. Both uni- and multivariate logistic regression analyses did not show an association between MPV and ASA use. Our results indicate that MPV as a predictive marker of platelet size and activity is not affected by aspirin use in patients with PAF.     

Low-dose aspirin in patients recovering from myocardial infarction. Evidence for a selective inhibition of thromboxane-related platelet function

The adequacy, selectivity and long-term persistence of inhibitionin cyclooxygenase-dependent platelet function by a daily low-dose(0.45 mg kg^–1 day^–1) aspirin treatment have beenevaluated in 15 patients after a recent (less than 17 days)acute myocardial infarction. Serum thromboxane (TX) B₂, an indexof platelet TXA₂ production, was decreased by 94–98% (P<0.001)by aspirin, while urinary excretion of 6-keto-prostaglandinF^la, as an index of extraplatelet cyclooxygenase activity, remainedunchanged. Compared to placebo, aspirin induced a persistentincrease in bleeding time (% difference 45.6±21.4, mean± SD) and a decrease in platelet aggregation by ADP,epinephrine, collagen and arachidonic acid. No tendency towardsan attenuation of the effects was apparent for the period ofaspirin administration (4 weeks). Aspirin 0.45 mg kg^–1 day^–1 is adequate and selectivein the long-term inhibition of TX-related platelet functionin patients after acute myocardial infarction. The clinicaleffectiveness of such a regimen remains to be proven in clinicaltrials.     

Reduced antiplatelet effect of aspirin during 24 hours in patients with coronary artery disease and type 2 diabetes

Reduced antiplatelet effect of aspirin has been reported in patients with type 2 diabetes, and recent studies suggest that once-daily aspirin provides insufficient platelet inhibition. We investigated if the effect of aspirin declined during the 24-hour dosing interval in patients with coronary artery disease and type 2 diabetes, and whether this correlated with increased platelet turnover. Furthermore, the intra-individual variation in platelet aggregation was determined during a 28-day period. We included 47 patients with coronary artery disease and type 2 diabetes treated with aspirin 75?mg daily. Blood samples were obtained 1 and 24 hours after aspirin intake, and this was repeated three times with a 2-week interval between each visit. Platelet aggregation was evaluated by impedance aggregometry (Multiplate® Analyzer) using arachidonic acid (1.0?mM) and collagen (3.2?µg/ml) as agonists. Markers of platelet turnover were measured by flow cytometry. Compliance was confirmed by serum thromboxane B₂. Platelet aggregation levels measured 1 and 24 hours after aspirin intake were compared using the mean of 1- and 24-hour measurements at the three study visits. The difference in platelet aggregation was 70?±?97?AU?×?min (p?<?0.0001) when using arachidonic acid as agonist and 33?±?76?AU?×?min (p?=?0.01) when using collagen. Markers of platelet turnover correlated positively, though not significantly, with residual platelet aggregation 24 hours after aspirin intake (p values 0.06 and 0.07). Median intra-individual variation of platelet aggregation was 9–16%. Patients with coronary artery disease and type 2 diabetes had increased platelet aggregation at the end of the 24-hour aspirin dosing interval. Platelet turnover did not correlate significantly with residual platelet aggregation, although a trend was observed. The intra-individual variation of platelet aggregation after aspirin intake was low.     

Intravascular and total body platelet equilibrium in healthy volunteers and in thrombocytopenic patients transfused with single donor platelets

Instrument platelet counts used in corrected count increment (CCI) and percent platelet recovery (PPR) formulas presume the transfused platelets are in equilibrium during the first hour after platelet transfusion. The timing of the pre-transfusion count affects CCI results, and we postulate that timing of CCI post transfusion affects CCI results. Platelet equilibrium using indium-111 platelet transfusions has not been reported. Platelet redistribution was studied in 16 healthy volunteers and 12 thrombocytopenic patients by generally infusing less than 72-hr stored single-donor platelets along with an aliquot of indium-111-labeled platelets by intravenous push. Counts were measured at 10, 15, 20, 60, and 120 min, and 24, 48, 72 hr along with continuous body scanning for 2 hr in healthy volunteers, and static organ scanning in patients and volunteers. Results indicated transfused platelets do not reach intravascular equilibrium for 60 min post-infusion and that the 10-min count cannot detect platelet refractoriness. However, total body equilibrium varies considerably between normal volunteers and thrombocytopenic patients. It is recommended to continue with the 1-hr post transfusion count. Am. J. Hematol. 58:165–176, 1998. © 1998 Wiley-Liss, Inc.     

Comparison of methods to evaluate aspirin-mediated platelet inhibition after percutaneous intervention with stent implantation

Urinary 11-dehydro thromboxane B2 (d-TXB2) concentrations in the highest quartile have been associated with an increased risk of adverse outcomes in patients at high risk for atherothrombotic events. However, the determination of d-TXB2 is time consuming and not suitable for daily clinical routine. We therefore sought to determine the test correlating best with d-TXB2 to estimate aspirin-mediated platelet inhibition in 225 patients on dual antiplatelet therapy after percutaneous intervention with stent implantation. We selected light transmission aggregometry, the VerifyNow aspirin assay, the Platelet Function Analyzer-100, multiple electrode platelet aggregometry (MEA) and Impact-R for comparisons with d-TXB2. Cut-off values for high on-treatment residual arachidonic acid-inducible platelet reactivity (HRPR) were defined according to quartiles of each assay. Sensitivities and specificities of the different platelet function tests were based on d-TXB2 results. The results from all assays correlated poorly with d-TXB2. Only MEA showed a weak, but significant correlation with d-TXB2 (r?=?0.14, p?=?0.042). Further, the five platelet function tests showed a poor agreement with d-TXB2 regarding the determination of HRPR. Sensitivities and specificities for HRPR ranged from 17.5 to 44.6%, and from 70.8 to 77.9%, respectively. In conclusion, the evaluated assays did not mirror d-TXB2 results, suggesting that thromboxane inhibition can be circumvented in assays that determine platelet function. Therefore, large trials with clinical outcome data are needed to determine the diagnostic value of the various test systems and to define the gold standard method for assessing residual AA-inducible platelet reactivity.     

Effect of combined administration of clopidogrel and lysine acetylsalicylate versus clopidogrel and aspirin on platelet aggregation and activated GPIIb/IIIa expression in healthy volunteers

Platelet activation contributes to thrombotic events in cardiovascular disease. Acetylsalicylic acid (ASA) is used in combination with clopidogrel to reduce cardiovascular events. Lysine acetylsalicylate (L-ASA), also inhibits platelet activation with fewer gastrointestinal side effects than ASA. Dual therapy with L-ASA and clopidogrel may result in an antiplatelet effect with fewer side effects. We compared the antiplatelet effect of combined ASA/clopidogrel versus L-ASA/clopidogrel in healthy subjects. Fourteen volunteers (seven men and seven women, aged 25–45 years) received antiplatelet therapy during 14-day periods in the following sequence: 75?mg ASA; 160?mg L-ASA; 75?mg clopidogrel; 160?mg L-ASA plus 75?mg clopidogrel, and 75?mg ASA plus 75?mg clopidogrel. We evaluated platelet aggregation and glycoprotein IIb/IIIa activation. Our results show that administration of L-ASA/clopidogrel is as effective as ASA/clopidogrel combination.     

Evening intake of aspirin is associated with a more stable 24-h platelet inhibition compared to morning intake: a study in chronic aspirin users

Daily generation of novel platelets may compromise aspirin’s platelet inhibitory action, especially near the end of the regular 24-h dosing interval. A contributor to this attenuation could be the endogenous circadian rhythm.

The primary objective of this study was to assess platelet activity 12 and 24 h after different times of aspirin intake (c.q. 8.00 AM and 8.00 PM). A randomized open-label crossover study was conducted, comprising outpatients with stable cardiovascular disease taking aspirin once daily. We measured platelet aggregation with the platelet function analyzer (PFA)-200^® and light transmission aggregometry (LTA). The attenuation of aspirin’s inhibitory action was most apparent in the 8.00 AM regimen. The platelet function analyzer—closure time was 78 s faster at 24 h than at 12 h after intake in the 8.00 AM regimen (IQR: 166.8–301 vs. 132.8–301; p = 0.006) and 0 s faster at 24 h than at 12 h after intake in the 8.00 PM regimen (IQR: 198.8–837.0 vs. 169.8–301; p = 0.653). The adenosine diphosphate 1.0 µmol/L maximum amplitude was 5.40% higher at 24 h than at 12 h after intake in the 8.00 AM regimen (95% confidence interval (CI): ?0.03–?10.8; p = 0.040) and was 0.75% higher 24 h than at 12 h after intake in the 8.00 PM regimen (95% CI: ?4.83–3.33; p = 0.705). The platelet inhibitory effect of aspirin decreases after 24 h, particularly after intake in the morning. These results suggest that patients might benefit from evening intake or twice daily intake regimens.     

抵克力得、阿司匹林对糖尿病患者高纤维蛋白原血症影响的比较

目的观察抵克力得（T组）、阿司匹林（A组）对糖尿病（DM）高纤维蛋白原（FG）血症的治疗作用和副作用。方法选择无明显异常心电图和感染及脑梗死病史的DM高FG血症患者473例,随机分为两组,分别予抵克力得、阿司匹林治疗,以脑或心肌或皮肤梗死、出血倾向、白细胞减少事件为观察终点,治疗时间8～47个月,观察两组FG等炎性因子和临床终点事件的发生情况。结果T组的FG、WBC、hsC-RP明显降低,而A组则无明显变化;T组病人的心、脑、皮肤梗死和消化道、牙龈、皮肤出血倾向较A组病人明显减少;T组有6例发生白细胞减少症（A组0例）,但均未发生粒细胞缺乏和感染,且停药或（和）集落细胞刺激因子等升白细胞治疗后缓解。结论与阿司匹林相比,抵克力得治疗DM高FG血症更有效,并明显减少患者的梗死和出血倾向,但白细胞减少事件明显多于使用阿司匹林。在不宜使用阿司匹林（如过敏等）的病例可小心试用抵克力得。     

不同阿司匹林肠溶片对老年人上消化道黏膜影响的比较

目的 观察不同阿司匹林肠溶片对老年人上消化道黏膜的影响. 方法将我院近3年服用阿司匹林肠溶片(100 mg,1次/d)≥3个月、年龄>65岁的老年患者404例,按服用药物不同分为拜阿司匹灵组232例和普通阿司匹林肠溶片组172例,对两组患者的临床资料和胃镜检查结果进行比较,通过χ2检验,比较两种不同阿司匹林肠溶片对老年人上消化道影响的差异. 结果拜阿司匹灵组上消化道出血47例(20.3%),普通阿司匹林肠溶片组55例(32.0%),差异有统计学意义(χ2=7.19,P<0.01);拜阿司匹灵组胃镜检查显示胃、十二指肠炎症16例(6.9%),消化性溃疡8例(3.5%);普通阿司匹林肠溶片组分别为12例(7.0%)和36例(20.9%),检出消化性溃疡差异有统计学意义(χ2=31.10,P<0.01);胃肠道不良应发生率拜阿司匹灵组20例(8.6%),普通阿司匹林肠溶片组40例(23.3%),差异有统计学意义(χ2=16.73,P<0.01). 结论拜阿司匹灵对老年人上消化道的影响明显小于普通阿司匹林肠溶片,在临床上使用拜阿司匹灵比普通阿司匹林肠溶片更安全.     

华法令和肠溶阿司匹林防治高龄不稳定型心绞痛的疗效对比

目的探讨华法令和肠溶阿司匹林用于预防不稳定型心绞痛患者发生急性心肌梗死和心脏性死亡的疗效。方法应用统一人群分组对照群组研究的方法,在本院住院和门诊的高龄患者中随机挑选服用阿司匹林(ASA300mg/d)者73例,服用华法令(WFR2～5mg/d)者82例,并随访12个月。结果用药14d后,WFR组患者心绞痛改善率明显高于ASA组(86.6%vs67.1%),P<0.01。随访12个月期间,复合终点事件(非致死性急性心肌梗死和心脏性死亡)WFR组明显低于ASA组(9.8%vs26.0%),P<0.01。结论华法令防治不稳定型心绞痛的近期和远期疗效显著,优于阿司匹林组,小剂量应用副作用小,值得推广。     

Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis

Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid (ASPItest 0.5 mM) as agonist and (2) serum thromboxane B₂ levels determined using an enzyme-linked immunosorbent assay. The difference in platelet aggregation from 1h to the end of the dosing interval (24h/12h) was used to compare the two regimens. We demonstrated a significantly smaller difference in platelet aggregation in the twice-daily regimen compared to the once-daily: mean of difference = 228 AU*min (95% confidence interval (CI): 92–363, p < 0.01). In addition, a significantly smaller difference in thromboxane B₂ was demonstrated in the twice-daily regimen compared to the once-daily regimen: mean of difference = 16.3 ng/mL (95% CI: 9.9–22.7, p < 0.01). In conclusion, twice-daily dosing with low-dose aspirin provides a more consistent platelet inhibition compared with standard once-daily dosing in patients with essential thrombocytosis.