scholarly journals Association of platelet thromboxane inhibition by low‐dose aspirin with platelet count and cytoreductive therapy in essential thrombocythemia

2021 ◽  
Author(s):  
Alberto Tosetto ◽  
Bianca Rocca ◽  
Giovanna Petrucci ◽  
Silvia Betti ◽  
Denise Soldati ◽  
...  
Keyword(s):  
Platelet Count ◽  
Essential Thrombocythemia ◽  
Low Dose ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Platelet Thromboxane

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.

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.

scholarly journals Systemic Mastocytosis and Essential Thrombocythemia: Case Report and Literature Overview

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 528
Author(s):  
Mauro Cancian ◽  
Elisabetta Cosi ◽  
Marco Pizzi ◽  
Sandro Giannini ◽  
Irene Bertozzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Essential Thrombocythemia ◽  
Low Dose ◽  
Systemic Mastocytosis ◽  
Inflammatory Reactions ◽  
Zolendronic Acid ◽  
Literature Overview ◽  
Dose Aspirin ◽  
Low Dose Aspirin

Mastocytosis is a rare disease in which heightened amounts of mast cells accumulate in the skin, bone marrow, and other visceral organs. Upon activation, mast cells release a wide variety of preformed or newly synthesized mediators which can induce allergic symptoms and inflammatory reactions. Mastocytosis is diagnosed by biopsy and can be divided into cutaneous and systemic mastocytosis (SM). The first one affects the skin and is relatively benign, whilst SM, which involves bone marrow and other organs, may be aggressive and associate with both myelodisplastic and myeloproliferative diseases. Here we present a case of SM associated with essential thrombocythemia and complicated by severe osteoporosis, successfully treated with hydroxyurea, low-dose aspirin and zolendronic acid.

scholarly journals PB2196 ANTIPLATELET THERAPY IN ESSENTIAL THROMBOCYTHEMIA: LABORATORY STUDY OF LOW-DOSE ASPIRIN

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 984-985
Author(s):  
R. Cacciola ◽  
V. Vecchio ◽  
E. Gentilini Cacciola ◽  
E. Cacciola
Keyword(s):  
Antiplatelet Therapy ◽  
Laboratory Study ◽  
Essential Thrombocythemia ◽  
Low Dose ◽  
Dose Aspirin ◽  
Low Dose Aspirin

scholarly journals Trial of repeated low-dose aspirin in diabetic angiopathy

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 886-891 ◽  
Author(s):  
G DiMinno ◽  
MJ Silver ◽  
AM Cerbone ◽  
S Murphy
Keyword(s):  
Low Dose ◽  
Slow Release ◽  
Ex Vivo ◽  
Normal Subjects ◽  
High Rate ◽  
Diabetic Angiopathy ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Platelet Thromboxane

Abstract We compared the ability of aspirin to suppress platelet aggregation and thromboxane synthesis in ten normal subjects and ten patients with diabetic angiopathy and high rate of entry of new platelets into the circulation. When single doses of 100 to 1,000 mg aspirin were ingested daily for 1 month, there were time gaps between doses in which platelets from diabetics and normals aggregated and formed thromboxane ex vivo in response to the combination of arachidonic acid plus collagen. Similar gaps were also found for diabetics, but not for normals, following four daily doses (every six hours) of 25 or 100 mg. Our data show that dose schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation. We suggest that continual suppression of platelet thromboxane synthesis and aggregation by low-dose, “slow- release” preparations of aspirin would be an ideal long-term approach for the prevention of thrombosis in patients with a high rate of entry of new platelets into the circulation.

The Effect Of Low Dose Aspirin On Human Venous Prostacyclin Production And Platelet Thromboxane Synthesis

1981 ◽  
Author(s):  
S P Hanley ◽  
J Bevan ◽  
S Cockbill ◽  
S Heptinstall
Keyword(s):  
Vessel Wall ◽  
Low Dose ◽  
Varicose Veins ◽  
Normal Volunteers ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Radio Immunoassay ◽  
Prostacyclin Production ◽  
Specific Radio ◽  
Platelet Thromboxane

This study vas undertaken to determine if there was a dose of oral aspirin that would inhibit platelet cyclooxygenase but that had no effect on venous cyclo-oxygenase. Varicose veins were surgically removed from 68 patients of whom 21 had taken no medicines pre-operatively. Three groups of patients took aspirin 300 mg 14 hours (n=10), 24 hours (n=10) and 48 hours (n=9) pre-operatively. Two other groups took 40.5 mg (n=9) and 81 mg (n=9) 14 hours preoperatively. Two 6 mm discs of venous tissue were incubated with plasma that contained 1 mM sodium arachidonate (NaAA) and the anti-aggregatory activity of the plasma was compared with that of synthetic PGI2 in aspirinised citrated PRP challenged with ADP. PGI2 production in this procedure was confirmed by specific radio-immunoassay for 6-keto PGF1α. All doses of aspirin except 40.5 mg markedly inhibited PGI2 synthesis. Little recovery was seen with 300 mg at 48 hour post-drug.Five normal volunteers took aspirin 300 mg and 5 others 40.5 mg. Citrated PRP was prepared immediately before, 2, 24, 48, 96 and 192 hours after ingesting the drug. The amount of malondialdehyde (MDA, a marker for thromboxane synthesis) that was produced when 1 mM NaAA was added, was markedly reduced compared to the control at 2 and 24 hours by both 40.5 mg and 300 mg and thereafter it returned slowly to control values. This study indicates that 40.5 mg of aspirin inhibits platelet cyclo-oxygenase but not vessel wall cyclo-oxygenase.

Familiar Chronic Myeloproliferative Syndromes in First-Degree Relatives and Monozygotic Twins.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4908-4908
Author(s):  
Stefano Pulini ◽  
Serena Rupoli ◽  
Gaia Goteri ◽  
Angela Tassetti ◽  
Anna Rita Scortechini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Low Dose ◽  
Factor V Leiden ◽  
Trephine Biopsy ◽  
Bone Marrow Trephine ◽  
First Degree Relatives ◽  
Bone Marrow Trephine Biopsy ◽  
Dose Aspirin ◽  
Low Dose Aspirin

Abstract Chronic myeloproliferative syndromes (MPS) are clonal stem cell disorders resulting in excessive proliferation of one or more cell lineages. Rare families exist with first-degree relatives affected by MPS. Familial or hereditary essential thrombocythemia (HT) is described among children with primary thrombocytosis and it is inherited in an autosomal-dominant manner. In HT germ-line activating mutations of thrombopoietin (TPO) gene or its receptor, c-MPL can be recovered. A 31-year-old woman was first referred to our Clinic for an isolated high platelet count. On routine blood testing performed when she was 14 years old the platelet count was 1020 × 103/μl; at that time she refused other laboratory examinations, instrumental and histological diagnostic procedures and subsequent therapy and she remained asymptomatic. During the first pregnancy the platelet count went down to 500 × 103/μl but after the second it raised over one million per microliter. Bone marrow trephine biopsy showed clusters of megakaryocytes with hyperlobulated forms and platelet clumps; the caryotype was normal and bcr-abl rearrangements were negative. Leukocytic alkaline phosphatase was high, there was reduced platelet aggregation, the thrombophilic study didn’t demonstrate either factor V Leiden G1691A or prothrombin Gene G20210A mutations. During the follow up the platelet count remained under 1000 × 103/μl so that a watch-and-wait strategy seemed appropriate in this asymptomatic case and low-dose aspirin has been started. What is remarkable in this case is that it is a not-frequent example of HT since the patient’s father, sister and niece are all affected by essential thrombocytemia (ET); moreover the patient’s own little daughter is affected by neonatal thrombocytosis. The relatives are being treated only with low-dose aspirin, they are completely asymptomatic without thrombohemorrhagic events. Some authors report that HT appears to be a different disease from sporadic ET and with a more benign course. The somatic activating point mutation (V617F) in the JAK2 gene was not demonstrated in our patient; as for TPO and c-MPL mutations we are now completing the genetic study. Among other familiar chronic MPS we describe the occurrence of ET/PV and idiopathic myelofibrosis (IMF) in two monozygotic twin sisters. They both were diagnosed with MPS at the median age of 65 years old. The first had splenomegaly, thrombocytosis and erythrocytosis and was treated with aspirin, hydroxyurea and phlebotomy. The other, affected by IMF, had important epato-splenomegaly and the bone marrow trephine biopsy showed myelofibrosis with &gt;90% collagen fibres. She received low dose hydroxyurea together with nandrolone decanoate; the organomegaly reduced and the hematic crasis improved. The JAK2 gene mutation was demonstrated only in the IMF patient. This second familial case strengthens the concept of a common pathogenesis of chronic MPS and suggests a genetic and hereditary etiology; moreover the occurrence of multiple disease phenotypes in a family is consistent with the theory of MPS as arising from clonal expansion of a pluripotential haematopoietic precursor cell that retains its pluripotentiality and produces an array of inter-related syndromes.

High Prevalence Of Aspirin-Resistance In Myeloproliferative Neoplasms

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5250-5250
Author(s):  
Jean-Loup Demory ◽  
Judith Bruge ◽  
Nathalie Cambier ◽  
Christian Rose ◽  
Agnès Charpentier
Keyword(s):  
Arachidonic Acid ◽  
Platelet Count ◽  
Whole Blood ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Aspirin Resistance ◽  
Dose Aspirin ◽  
Low Dose Aspirin

Abstract Aspirin is recommended and widely prescribed to MPN patients without any evaluation of its efficacy. We report on 46 patients followed in our institution for a Myeloproliferative Neoplasm and treated by low-dose aspirin (75 to 160 mg p. day) alone or aside a cytoreductive therapy, mainly hydroxy-urea ; on the occasion of a routine visit we measured the response of their platelets to arachidonic acid in order to assess their sensibility to aspirin. Most patients (25) had ET, 15 had PV, 4 had CML and 2 Myelofibrosis. Response to arachidonic acid was measured on a citrated whole blood sample using an impedance-based semi-automatic aggregometer (Multiplate®) ; TRAP (Thrombin Receptor Activating Peptide) aggregation was performed systematically as a positive control. In 20 patients out of 46 (43,5%) there was persistence of a significant aggregability to arachidonic acid defining the resistance to aspirin according to our reference values : 10/25 ET (38%), 9/15 PV (62%)and 1/4 LMC. These proportions are much higher than those we note in heart or vascular diseases as well as those reported in published series. The observance of aspirin treatment could be considered doubtful only in a minority of patients (5/46) ; as the resistance appeared more frequent in PV we could assume a biais linked to the utilization of whole blood, but most PV patients were well controlled and did not have an elevated hematocrit. In untreated or refractory ET patients, the persistence of an increased platelet count suggests that aspirin dosage was not adequate although there was no statistical significance between daily dose and resistance. We observed an ischemic complication (transient stroke) in a single patient whose platelet count was not controlled despite hydroxy-urea but remained sensible to aspirin. We conclude that aspirin resistance is frequent in MPN treated with low-dose aspirin and that a monitoring is worth to increase the dose or change for another inhibitor. Disclosures: No relevant conflicts of interest to declare.

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