scholarly journals COVID-19 with essential thrombocythemia treated with apixaban for antithrombotic prophylaxis

2021 ◽  
Vol 14 (11) ◽  
pp. e246700
Author(s):  
Kazuki Takasaki ◽  
Takazumi Tsunenari ◽  
Kazuma Mori ◽  
Satsuki Aochi
Keyword(s):  
Essential Thrombocythemia ◽  
Clinical Benefit ◽  
Oxygen Therapy ◽  
Severe Illness ◽  
Thromboembolic Events ◽  
Good Recovery ◽  
Antithrombotic Prophylaxis ◽  
Standard Strategy

A 40-year-old man was admitted to our hospital for COVID-19. He had been treated for essential thrombocythemia (ET). He was diagnosed severe illness of COVID-19, oxygen therapy and dexamethasone were administered. There was a possibility of thromboembolic events in this case, apixaban for prophylaxis was added. With these treatments, the patient has made a good recovery, and he was discharged on hospital day 11. There is no standard strategy for prophylaxis of thrombosis in patients with ET, and apixaban could be a clinical benefit for these patients.

P1564Atrial fibrillation and thromboembolic prophylaxis: focus on the frail oldest patient. how net clinical benefit influences anticoagulant therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G I Greco ◽  
C Ninivaggi ◽  
A Graceffa ◽  
S Novello ◽  
F Bonfante ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Clinical Benefit ◽  
The Elderly ◽  
Thromboembolic Events ◽  
Intracranial Hemorrhages ◽  
Old Patients ◽  
The Difference ◽  
Net Clinical Benefit ◽  
Very Old Patients

Abstract Background Atrial fibrillation is highly prevalent among the elderly population, which is also frequently prone to thromboembolic complications. Anticoagulant prophylaxis is underused in the elderly due to fear of bleeding, which tends to be more frequent and severe within this group. Randomized controlled trials and several observational studies have shown the comparative effectiveness of direct oral anticoagulant (DOAC) against vitamin K antagonists (VKA), and their superior safety, at least in terms of intracranial bleeding. However, for patients aged 85 or older, there is still insufficient literature, leaving unanswered the question of which prophylaxis to use. Purpose The aim of the study is to compare the incidence of established outcomes and to investigate the net clinical benefit between DOAC and VKA in patients aged ≥85 years. Methods A cohort of 553 outpatients from the real world began treatment using DOACs at our clinic. The prospective follow-up on average lasted 1.97 years. Main endpoints were stroke and systemic thromboembolism, major hemorrhage, myocardial infarction and mortality for all causes. A sample of the 160 patients aged ≥85 years was compared with the remaining younger ones and with a second cohort of 298 outpatients aged ≥85 years. Retrospectively analyzed, with follow-ups at our center, who started VKAs; the average time was 2.03 years. The “net clinical benefit” of DOACs against VKAs was calculated as the difference between thromboembolic events with VKAs and with DOACs, minus the difference (weighted by 1.5) between spontaneous intracranial bleeding with DOACs and VKAs. Results In terms of thromboembolic events, DOACs and VKAs (2.43% p-y vs. 1.82% p-y, p=0.975) have shown comparable efficacy in a higher risk sample (CHA2DS2-VASc score: 5.2 vs. 4.5; p<0.001). There were no differences in spontaneous intracranial hemorrhages (0.81% p-y vs. 1.16% p-y; p=0.419). Major bleeding was more frequent in DOACs (10.11% p-y vs. 4.13% p-y, p<0.05), although they are comparable if we consider patients in VKAs achieving a time in therapeutic range (TTR) <60%. Mortality, in all cases similar (13.75% p-y vs. 9.92% p-y; p=0.778), but was reduced in patients with VKAs therapy, with a TTR ≥60%. The net clinical benefit of DOACs compared to VKAs is noticeable in patients with a previous stroke or with CHA2DS2-VASc score <6, while VKAs may be more beneficial to patients with vascular disease or with CHA2DS2-VASc score ≥6. Conclusions DOACs are as effective in very old patients with atrial fibrillation compared to very old patients receiving VKAs, but they are associated with increased major bleeding. The same is true when compared with younger DOACs users. TTR, representing quality achieved by the anticoagulation with a VKA, can influence the comparison with DOACs. Considering ischemic strokes and spontaneous intracranial hemorrhages, there is however a net benefit for DOACs use in specific categories of elderly patients.

scholarly journals Effect of early oxygen therapy and antiviral treatment on disease progression in patients with COVID-19: A retrospective study of medical charts in China

2021 ◽  
Vol 15 (1) ◽  
pp. e0009051
Author(s):  
Lu Long ◽  
Liang Wu ◽  
Lang Chen ◽  
Daixing Zhou ◽  
Hongyu Wu ◽  
...  
Keyword(s):  
Disease Progression ◽  
Oxygen Therapy ◽  
Antiviral Treatment ◽  
Severe Disease ◽  
Great Influence ◽  
Lower Mortality ◽  
Severe Illness ◽  
Risk Of Death ◽  
Fatal Illness ◽  
Critical Patients

Background Until now, no antiviral treatment has been proven to be effective for the coronavirus disease 2019 (COVID-19). The timing of oxygen therapy was considered to have a great influence on the symptomatic relief of hypoxemia and seeking medical intervention, especially in situations with insufficient medical resources, but the evidence on the timing of oxygen therapy is limited. Methods and findings Medical charts review was carried out to collect the data of hospitalized patients with COVID-19 infection confirmed in Tongji hospital, Wuhan from 30th December 2019 to 8th March 2020. In this study, the appropriate timing of oxygen therapy and risk factors associated with severe and fatal illness were identified and the effectiveness of antivirus on disease progression was assessed. Among 1362 patients, the prevalence of hypoxia symptoms was significantly higher in those patients with severe and fatal illness than in those with less severe disease. The onset of hypoxia symptoms was most common in the second to third week after symptom onset, and patients with critical and fatal illness experienced these symptoms earlier than those with mild and severe illness. In multivariable analyses, the risk of death increased significantly when oxygen therapy was started more than 2 days after hypoxia symptoms onset among critical patients (OR, 1.92; 95%CI, 1.20 to 3.10). Compared to the critically ill patients without IFN-a, the patients who were treated with IFN-a had a lower mortality (OR, 0.60; 95%CI, 0.39 to 0.91). Conclusions Early initiation of oxygen therapy was associated with lower mortality among critical patients. This study highlighted the importance of early oxygen therapy after the onset of hypoxia symptoms. Our results also lend support to potentially beneficial effects of IFNα on critical illness.

Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial

2021 ◽  
Vol 31 (10) ◽  
pp. 1348-1355
Author(s):  
Raimondo Di Liello ◽  
Laura Arenare ◽  
Francesco Raspagliesi ◽  
Giovanni Scambia ◽  
Carmela Pisano ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Antithrombotic Therapy ◽  
Clinical Characteristics ◽  
Secondary Analysis ◽  
Thromboembolic Events ◽  
Antithrombotic Prophylaxis ◽  
Platinum Based Chemotherapy ◽  
Phase Iv

IntroductionThe use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial.MethodsIn this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated.ResultsFrom October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61).ConclusionsIn our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis.Trial registration numberNCT01706120

Thrombotic and Hemorrhagic Complications after Surgery in Patients with Essential Thrombocythemia and Polycythemia Vera.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2693-2693 ◽  
Author(s):  
Marco Ruggeri ◽  
Francesco Rodeghiero ◽  
Alberto Tosetto ◽  
Giancarlo Castaman ◽  
Francesca Scognamiglio ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Polycythemia Vera ◽  
Surgical Procedures ◽  
Essential Thrombocythemia ◽  
Arterial Thrombosis ◽  
Surgical Interventions ◽  
Antithrombotic Prophylaxis ◽  
Unfractioned Heparin ◽  
Hemorrhagic Complications

Abstract Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative diseases characterized by frequent episodes of deep venous thrombosis (DVT), arterial thromboembolism (AT) and by hemorrhagic complications. Surgical procedures could represent a risk factor for thrombosis and bleeding, but no data on the real frequency of these complications are available. To estimate the frequency of thrombosis and haemorrhages after surgical procedures and their outcomes, a multicenters retrospective analysis was performed. Data from 105 PV and 150 ET patients (128 males, 127 females, median age at diagnosis 60, were analyzed, for a total of 311 surgical interventions. At least one risk factor for arterial thrombosis (diabetes mellitus, hypercholesterolemia, arterial hypertension, previous AT, smoke) was present in 128/255 (50.1%), more frequently in PV than in ET patients (58.5 vs. 46.8%, p=0.02). An excess of male and older patients in PV than in ET explained this finding (multivariate analysis). Previous DVT was present in 9/255 patients (3.5%). After diagnosis, antiplatelet drugs were given to 211/255 patients (82.7%); cytoreductive treatments to 188/255 (74%), warfarin to 16/255 (6.2%); all PV patients were phlebotomized. In 25/311 surgeries (8.0%), an emergency procedure was performed; 195 surgeries were done under general anaesthesia; 21/91 abdominal interventions (23%) were performed under laparoscopy. Major surgeries were 160/311 (51.4%). Data about antithrombotic prophylaxis were available for 292/311 surgeries: in 126 (43.2%) low molecular heparin, in 38 (13%) unfractioned heparin, in 5 (1.7%) warfarin and in 123 no anticoagulant therapy was administered. In 45/123 (36.6%) patients without antithrombotic prophylaxis, antiplatelet therapy was administered before surgery. 189/255 (74%) were on cytoreductive therapy before surgery; for 9 surgical procedures, a short cycle of chemotherapy was administered before surgery. Clinical outcomes after surgery were recorded with a 3 months follow-up. No event was observed in 259/311 procedures (83.2%); there were 12 arterial and 12 venous thrombotic events, 23 major and 7 minor hemorrhages and 5 deaths. AT were more frequent in ET patients (5.3 vs. 1.5%, p=0.08) while venous events were more frequent in PV patients (7.7 vs. 1.1%, p=0.002). There was a strong risk gradient for AT associated with the presence of one or more arterial risk factors (OR for 4 or more risk factors: 40.9, p=0.003). Platelet count and hematocrit at surgery (median 477 x 109 /l and 42.6%, respectively) were not associated with either venous or arterial thrombosis. There was no correlation between bleeding episodes and type of diagnosis, use of antithrombotic prophylaxis and type of surgery. In conclusion, despite an active approach (cytoreduction and antithrombotic prophylaxis in the majority of the cases) a high proportion of PV and ET surgeries was complicated by DVT and AT (7.7%) but also by major hemorrhages (7.3%), requiring more investigation on the optimal prophylaxis in these patients.

scholarly journals Rivaroxaban or Placebo for Extended Antithrombotic Prophylaxis after Laparoscopic Surgery for Colorectal Cancer. the PRO-LAPS II Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1064-1064
Author(s):  
Cecilia Becattini ◽  
Ugo Pace ◽  
Felice Pirozzi ◽  
Giampiero Avruscio ◽  
Annibale Donini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Laparoscopic Surgery ◽  
Clinical Benefit ◽  
Cancer Surgery ◽  
Study Patient ◽  
Primary Study ◽  
Efficacy And Safety ◽  
Antithrombotic Prophylaxis ◽  
Study Results ◽  
Bayer Healthcare

Abstract Background The clinical benefit of extending prophylaxis for venous thromboembolism (VTE) beyond hospital discharge after laparoscopic surgery for cancer is unclear. The efficacy and safety of thromboprophylaxis with direct oral anticoagulants in cancer surgery is unexplored. Methods PROLAPS II is an investigator-initiated, prospective, randomized, double-blind study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban compared with placebo after laparoscopic surgery for colorectal cancer (NCT03055026). All patients received antithrombotic prophylaxis with low molecular-weight heparin for 7±2 days and were then randomized to receive rivaroxaban (10 mg once daily) or placebo for the following 3 weeks (up to day 28±2 from surgery). The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT) or VTE-related death within 28±2 days from laparoscopic surgery. The primary safety outcome was ISTH-defined major bleeding. By assuming an 8% incidence of primary study outcome in patients randomized to placebo and a 60% reduction with rivaroxaban, 323 patients per group were necessary to show the superiority of rivaroxaban. Results. Patient recruitment in PROLAPS II study was preliminary closed in June 7 th, 2021 due to study drug expiry, after the inclusion of 577 patients. The main patients features are reported in the Table. Study results will be available after the last study patient will complete the 90-day follow-up (scheduled on September 7th, 2021) and will be ready to be presented at the ASH 2021 Congress. Conclusion PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery. The study has the potential to improve clinical practice by assessing the clinical benefit of extending prophylaxis after laparoscopic surgery for colorectal cancer. Figure 1 Figure 1. Disclosures Becattini: Bayer HealthCare: Honoraria; Daiichi Sankyo: Honoraria; Bristol Myers Squibb: Honoraria. Dentali: Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Daiichi Sankyo: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; Boehringer: Honoraria; Alfa Sigma: Honoraria. Agnelli: Bayer HealthCare: Honoraria; Daiichi Sankyo: Honoraria; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria.

Recurrent Thrombosis in Patients with Polycythemia Vera or Essential Thrombocythemia: Efficacy of Treatment in Preventing Rethrombosis in Different Clinical Settings.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 119-119 ◽  
Author(s):  
V. De Stefano ◽  
T. Za ◽  
E. Rossi ◽  
A.M. Vannucchi ◽  
M. Ruggeri ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protective Factors ◽  
Venous Thrombosis ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Antiplatelet Agents ◽  
Clinical Event ◽  
Antithrombotic Prophylaxis ◽  
Coronary Syndrome

Abstract Background: Thrombosis is a common cause of morbidity in polycythemia vera (PV) and essential thrombocythemia (ET). Prior thrombosis is a major risk factor for rethrombosis; yet optimal strategy for prevention of recurrence has been scarcely addressed. Objective: To assess in PV or ET patients with prior thrombosis the rate of recurrence, the risk factors for recurrence, and the efficacy of antithrombotic or cytoreductive strategies in preventing rethrombosis. Methods: We retrospectively investigated a cohort of 470 patients (M/F 227/243, PV/ET 235/235, median age at diagnosis 62 yrs, range 19–88) with a first arterial (n=328, 69.8%) or venous thrombosis (n=142, 30.2%). First thrombosis was cerebrovascular disease (CVD) in 184 cases, acute coronary syndrome (ACS) in 102, venous thromboembolism of limbs (VTE) in 102, and venous thrombosis of unusual sites (un-VTE) in 40. Microcirculatory events were not computed. Multivariate time-dependent models were developed having first recurrence as dependent variable and putative predictive or protective factors as covariates. Results: 158 patients (33.6%) had one or more recurrences during a total time from the first thrombosis of 2,821 pt-yrs (median 5.3 yrs); the overall incidence of events was 7.54% pt-yrs (4.60% arterial and 2.94% venous recurrences). Major bleeding occurred in 25 patients (84% receiving antithrombotic prophylaxis) with an incidence of 0.88% pt-yrs. The cumulative incidence of recurrence at 10 years after the first event was 64.7% (95%CI 49.1–80.3) in VTE patients, 51.9% (95%CI 37.8–66.0) in ACS, 46.6% (95%CI 35.1–58.1) in CVD, and 30.2% (95%CI 8.8–51.6) in un-VTE. In VTE patients analysis restricted to venous recurrences showed at 10 years a rate of 49.4% (95%CI 32.8–66.1). Sex, diagnosis (PV or ET), and presence of vascular risk factors did not affect the overall probability of recurrence. Age &gt;60 years predicted recurrence (multivariate hazard ratio 1.76, 95%CI 1.24–2.49); arterial or venous first thrombosis predicted either arterial (HR 4.43, 95%CI 1.22–16.07) or venous recurrence (HR 8.48, 95%CI 1.62–44.48), respectively. Cytoreductive treatment halved the probability of all types of recurrence in the overall cohort (HR 0.54, 95%CI 0.38–0.76). In the overall model long-term antiplatelet or anticoagulant treatment did not result as independent protective factors. However, analysis of patient groups showed that a significant efficacy in preventing rethrombosis was achieved in VTE only by long-term oral anticoagulation (HR 0.42, 95%CI 0.19–0.91), in ACS by cytoreduction (HR 0.37, 95%CI 0.17–0.78), and in CVD by antiplatelet agents (HR 0.34, 95% CI 0.16–0.69). Conclusions: In PV or ET the rate of recurrent VTE seems higher than the usually observed in patients with unprovoked first VTE. Moreover our findings suggest that strategies for preventing rethrombosis and based on cytoreduction or antithrombotic prophylaxis should be tailored according to the type of first clinical event. Further studies are needed to confirm such hypothesis.

Oxygen: risks as well as benefits

2017 ◽  
Author(s):  
Rory McDermott ◽  
Craig Davidson
Keyword(s):  
Emergency Medicine ◽  
United Kingdom ◽  
Clinical Benefit ◽  
Annual Cost ◽  
Oxygen Therapy ◽  
Symptom Relief ◽  
Acute Setting ◽  
Oxygen Administration ◽  
The United Kingdom

Oxygen administration is the most commonly used therapy in emergency medicine. It is given to 18,000 patients in the United Kingdom every day, and 14% of patients in hospital receive it at some time during their stay. Whilst some of this activity is helpful, or indeed lifesaving, in some patients, oxygen can lead to harm, or even death. The domiciliary use of oxygen is also an area in which there is the potential for both waste and harm. When appropriately used, it prolongs life and provides valuable symptom relief; yet, in up to 43% of the cases, such therapy was either not used by patients as directed or provided no clinical benefit. At an annual cost in excess of £110 million, this is a lot of waste. This chapter examines the use of oxygen in both the acute setting and the assessment for home oxygen, with a focus on the pathophysiology behind oxygen therapy and the potential dangers.

P4750Uninterrupted and minimally-interrupted direct oral anticoagulant therapy in patients undergoing catheter ablation for atrial fibrillation. An updated meta-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Ottoffy ◽  
P Hegyi ◽  
T Habon
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Major Bleeding ◽  
Clinical Benefit ◽  
Oral Anticoagulant Therapy ◽  
Meta Analysis ◽  
Thromboembolic Events ◽  
Significant Difference ◽  
Life Threatening ◽  
Net Clinical Benefit

Abstract Background Adequate anticoagulation in catheter ablation of atrial fibrillation (AF) is crucial in preventing both thromboembolic events and life-threatening bleeding. As clinicians gain more experience and reassurance with data from clinical trials, the usage of Direct Oral Anticoagulants (DOAC) in patients undergoing catheter ablation of AF has rapidly increased over the last years. The purpose of this updated meta-analysis was to assess the latest evidence and compare the safety and efficacy of uninterrupted and minimally interrupted periprocedural DOAC anticoagulation protocols with uninterrupted Vitamin K Antagonists (VKA) in this setting. Methods Randomized or prospective controlled observational studies comparing DOACs to VKAs were identified with multiple databases (Embase, PubMed, Cochrane, and Scopus). Uninterrupted and minimally interrupted DOAC (single dose of dabigatran or apixaban withheld) were distinguished, VKA therapy was always uninterrupted. The primary outcomes were stroke or transient ischemic attack (TIA), major bleeding, and net clinical benefit. Results 32 studies were included in the final analysis, encompassing a total of 19.437 patients. The incidence of thromboembolic events was rare (less than 0.2%), with no significant difference between groups. Occurrence of major bleeding and net clinical benefit were significantly improved in patients assigned to uninterrupted DOAC treatment compared to VKAs (1.5% vs 2.2%, POR: 0.74, CI: 0.56–0.98, I2=0,0% and 1.7% vs 2.4%, POR: 0.76; CI: 0.59–0.99, I2=0,0%, respectively). Net clinical benefit Conclusion This updated meta-analysis, based on a large database, showed that DOAC therapy is equally effective as VKA in preventing stroke and TIA. Minimally-interrupted DOAC therapy is a non-inferior peri-procedural anticoagulation strategy, however, uninterrupted DOAC therapy showed superiority when compared to VKA regarding major, life-threatening bleeding. Our findings showed that uninterrupted periprocedural DOAC therapy is a safe and preferable alternative to VKAs in patients undergoing catheter ablation for atrial fibrillation. Acknowledgement/Funding This study was supported by an Economic Development and Innovation Operative Programme Grant (GINOP 2.3.2-15-2016-00048).

scholarly journals Effects of Antiplatelet Treatment with Aspirin (ASA) on Platelet Reactivity in Patients with Essential Thrombocythemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4253-4253
Author(s):  
Marina Marchetti ◽  
Sara Gamba ◽  
Cinzia Giaccherini ◽  
Cristina Verzeroli ◽  
Laura Russo ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Platelet Reactivity ◽  
Venous Blood ◽  
Myeloproliferative Neoplasm ◽  
Platelet Surface ◽  
Antithrombotic Prophylaxis ◽  
Mutational Status ◽  
Induced Aggregation

Abstract INTRODUCTION: Essential Thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increased rate of thrombotic complications. Antithrombotic prophylaxis with aspirin (ASA), alone or in combination with cytoreduction with hydroxyurea (HU), is widely utilized in ET patients. However, thrombosis occurrence/recurrence in spite of antithrombotic prophylaxis remains a relevant issue. Growing data support the possible contribution to this failure of the inter-individual variability of pharmacological ASA response. AIM: Aim of this study was to characterize, in a group of ET patients receiving 100 mg/d ASA, the platelet reactivity in terms of platelet aggregation and activation properties. MATERIALS AND METHODS: Venous blood samples were obtained from 77 ET patients (26M/51F), and two control groups, i.e., one including 72 non-ET patients receiving chronic ASA prophylaxis, and the other including 111 healthy control subjects (57M/54F). The mutational status of ET was: 35 patients were JAK2V617F⁺, 22 CALR⁺, 3 MPL⁺, and 17 triple negative. Thirty-three ET patients were on ASA+HU, 23 on ASA alone, 5 on HU alone, and 16 were not receiving any of these drugs. Platelet aggregation was assessed in whole blood by the Multiplate® analyzer (Roche). The platelet response to the thrombin receptor activating peptide (TRAP) trigger was the measure of the overall platelet aggregation capacity, while the response to the arachidonic acid (AA) trigger was the measure of ASA effect on platelet aggregation. A normalized AA-induced aggregation (r-AA-agg), defined as AA/TRAP ratio, was calculated for each sample to reflect the individual variation of platelet inhibition by ASA. The platelet activation status was evaluated before and after aggregation by measuring the surface expression of CD62P (P-selectin) by flow cytometry (Accuri™ C6, BD Bioscience). RESULTS: The analysis of subgroups according to treatments shows that AA-induced platelet aggregation in ASA- and ASA+HU-treated ET patients was significantly lower compared to non-ASA ET subjects (p<0.001), and was significantly greater compared to ASA-treated non-ET patients (145±85 AU; p<0.001). The same results were observed with TRAP-induced platelet aggregation. Accordingly, the r-AA-agg. was greater in ET subjects on ASA (=53%) or ASA+HU (=50%) as compared to non-ET ASA-treated individuals (=19%). Furthermore, among ET patients on ASA±HU, those with platelet >450x109/L showed AA-induced aggregation significantly greater than subjects with platelet <450x109/L. The increment of platelet surface CD62P expression after AA stimulation (as a marker of platelet activation) was not influenced by anti-platelet therapy, but was significantly associated with JAK2V617F mutation. CONCLUSIONS: Our data show that in more than 70% of ET patients, in spite of ASA intake, the platelet reactivity remains higher than in non-ET patients receiving the same drug regimen. This phenomenon, together with the so-called "turnover" resistance, i.e. increased platelet turnover associated to short aspirin half-life, may contribute to aspirin failure in ET. Studies are necessary to evaluate the efficacy and safety of a different dose or timing of ASA administration in these patients. Project funded by "AIRC-IG2013" grant Nr. 14505 from the "Italian Association for Cancer Research" (A.I.R.C.). Disclosures Falanga: Pfizer: Speakers Bureau; Aspen: Speakers Bureau; Janssen: Speakers Bureau.

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