The Role of Clopidogrel and Acetylsalicylic Acid in the Prevention of Early-Phase Graft Occlusion Due to Reactive Thrombocytosis after Coronary Artery Bypass Operation

Kayacioglu, Ilyas; Günay, Rafet; Şaşkın, Hüseyin; Idiz, Mustafa; Sensoz, Yavuz; Ateş, Mehmet; Tangürek, Burak; Alper, Ahmet Taha; Demirtaş, Mahmut Murat; Yekeler, İbrahim

doi:10.1532/hsf98.20071196

Cited by 26 publications

(12 citation statements)

References 17 publications

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“…platelet count over 1 million/lL). In the presence of aspirin-resistant symptoms, it is reasonable to use a twice-daily rather than once-daily regimen of low dose aspirin or alternative anti-platelet agents such as clopidogrel (75 mg/day) alone or in combination with aspirin [88], as long as patients are monitored closely for drug side effects. One might also consider platelet-lowering agents (e.g.…”

Section: Management Of Low-risk Pv or Et In The Absence Of Extreme Tmentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

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Disease overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms, respectively characterized by erythrocytosis and thrombocytosis. Other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: PV is defined by a JAK2 mutation, whose absence, combined with normal or increased serum erythropoietin level, makes the diagnosis unlikely. Differential diagnosis in ET includes reactive thrombocytosis, chronic myeloid leukemia, and prefibrotic myelofibrosis. Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) mutations occur in approximately 55%, 25%, and 3% of ET patients, respectively. The same molecular markers are also present in prefibrotic myelofibrosis, which needs to be morphologically distinguished from ET. Survival and leukemic/fibrotic transformation: Median survivals are ∼14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Life‐expectancy in ET is inferior to the control population. JAK2/CALR mutational status does not affect survival in ET. Risk factors for survival in ET and PV include advanced age, leukocytosis, and thrombosis. Leukemic transformation rates at 20 years are estimated at <10% for PV and 5% for ET; fibrotic transformation rates are slightly higher. Thrombosis risk stratification: Current risk stratification in PV and ET is designed to estimate the likelihood of recurrent thrombosis: high‐risk is defined by the presence of age >60 years or presence of thrombosis history; low‐risk is defined by the absence of both of these two risk factors. Recent data consider JAK2V617F and cardiovascular risk factors as additional risk factors. Presence of extreme thrombocytosis might be associated with acquired von Willebrand syndrome (AvWS) and, therefore, risk of bleeding. Risk‐adapted therapy: The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. In low risk patients, this is accomplished by the use of low‐dose aspirin and phlebotomy (hematocrit target <45%) in PV. In high risk (for thrombosis) patients, treatment with hydroxyurea is additionally recommended. Treatment with busulfan or interferon‐α is usually effective in hydroxyurea failures and the additional value of JAK inhibitor therapy in such cases is limited. Screening for AvWS is recommended before administrating aspirin, in the presence of extreme thrombocytosis. Am. J. Hematol. 90:163–173, 2015. © 2014 Wiley Periodicals, Inc.

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Section: Management Of Low-risk Pv or Et In The Absence Of Extreme Tmentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

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“…We recommend the use of low-dose aspirin ( (Figures 3 and 4). In the presence of aspirin-resistant symptoms, it is reasonable to utilize a twice-daily rather than once-daily regimen of low dose aspirin or alternative anti-platelet agents such as clopidogrel (75 mg/d) alone or in combination with aspirin, 50 as long as patients are monitored closely for drug side effects. One might also consider platelet-lowering agents (eg, hydroxyurea) in aspirinrefractory cases, but the target platelet count in this instance should be the level at which relief of symptoms is observed, and not necessarily 400 × 10 9 /L.…”

Section: Recommendations In the Management Of Low-risk Et Or Pv Witmentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk‐stratification and management

2018

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Disease Overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive JAK2, CALR, or myeloproliferative leukemia mutations. In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Survival: Median survivals are 14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life‐expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET. Risk of thrombosis is higher in JAK2‐mutated ET. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. Thrombosis Risk: In PV, 2 risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors); in ET, 4 risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wild‐type), low (same as very low but JAK2 mutation present), intermediate (age > 60 years, no thrombosis history, JAK2 wild‐type) and high (thrombosis history present or age > 60 years with JAK2 mutation). Risk‐Adapted Therapy: The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once‐ or twice‐daily aspirin (81 mg), in the absence of contraindications. Very low‐risk ET might not require therapy while aspirin therapy is advised for low‐risk disease. Cytoreductive therapy is recommended for high‐risk ET and PV but it is not mandatory for intermediate‐risk ET. First‐line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second‐line drugs of choice are interferon‐α and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs.

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“…We recommend the use of low‐dose aspirin (81 mg/day; range 40 mg/day‐100 mg/day) in all patients with low‐risk PV or ET, provided there are no major contraindications; the latter include clinically significant (ristocetin cofactor activity of <20%‐30%) AvWS that might be associated with extreme thrombocytosis (ie, platelet count over 1 million/μL). In the presence of aspirin‐resistant symptoms, it is reasonable to utilize a twice‐daily rather than once‐daily regimen of low dose aspirin or alternative anti‐platelet agents such as clopidogrel (75 mg/day) alone or in combination with aspirin, as long as patients are monitored closely for drug side effects. One might also consider platelet‐lowering agents (eg, hydroxyurea) in aspirin‐refractory cases, but the target platelet count in this instance should be the level at which relief of symptoms is observed, and not necessarily 400 × 10 9 /L.…”

Section: Risk‐adapted Therapymentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk‐stratification, and management

2016

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Disease overview Polycythemia Vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis PV is defined by a JAK2 mutation, whose absence, combined with normal or increased serum erythropoietin level, makes the diagnosis unlikely. JAK2, CALR, and MPL mutations are the mutually exclusive “driver” mutations in ET with respective incidences of 55%, 25%, and 3%; approximately 17% are triple‐negative. However, the same molecular markers might also be present in prefibrotic myelofibrosis, whose morphological distinction from ET is prognostically relevant. Survival and leukemic/fibrotic transformation Median survivals are approximately 14 years for PV and 20 years for ET; the corresponding values for younger patients (age <60 years) are 24 and 33 years. Life‐expectancy in ET is inferior to the control population. Driver mutational status has not been shown to affect survival in ET whereas the presence of JAK2/MPL mutations has been associated with higher risk of arterial thrombosis and that of MPL with higher risk of fibrotic progression. Risk factors for overall survival in both ET and PV include advanced age, leukocytosis and thrombosis. Leukemic transformation rates at 20 years are estimated at <10% for PV and 5% for ET; fibrotic transformation rates are slightly higher. Most recently, ASXL1, SRSF2, and IDH2 mutations have been associated with inferior overall, leukemia‐free or fibrosis‐free survival in PV; similarly adverse mutations in ET included SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2. Thrombosis risk stratification Current risk stratification in PV and ET is designed to estimate the likelihood of recurrent thrombosis. Accordingly, PV includes two risk categories: high‐risk (age >60 years or thrombosis history) and low‐risk (absence of both risk factors). In ET, risk stratification includes four categories: very low risk (age ≤60 years, no thrombosis history, JAK2/MPL un‐mutated), low risk (age ≤60 years, no thrombosis history, JAK2/MPL mutated), intermediate risk (age >60 years, no thrombosis history, JAK2/MPL un‐mutated), and high risk (thrombosis history or age >60 years with JAK2/MPL mutation). In addition, presence of extreme thrombocytosis (platelets >1000 × 10(9)/L) might be associated with acquired von Willebrand syndrome (AvWS) and, therefore, risk of bleeding. Risk‐adapted therapy The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once‐daily aspirin (81 mg). In addition, high‐risk patients with PV require cytoreductive therapy. Very low risk ET patients might not require any form of therapy while low‐risk patients require at least once‐daily aspirin therapy. Cytoreductive therapy is also recommended for high‐risk ET patients but it...

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The Role of Clopidogrel and Acetylsalicylic Acid in the Prevention of Early-Phase Graft Occlusion Due to Reactive Thrombocytosis after Coronary Artery Bypass Operation

Abstract: Combination antiplatelet therapy with ASA and clopidogrel seems to be more effective than ASA alone for maintaining graft patency in patients with reactive thrombocytosis.

Cited by 26 publications

References 17 publications

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk‐stratification, and management

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