The Effects of Aspirin on Megakaryocyte Prostaglandin Production

Demers, Laurence M.; Budin, Robert E.; Shaikh, Bahu S.

doi:10.3181/00379727-163-40716

Cited by 30 publications

(10 citation statements)

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“…Such direct interactions have been proposed previously. Demers et al (24) have suggested that aspirin inactivates cyclooxygenase of megakaryocytes as well as platelets. However, the changes in platelet size and increases in 3sS incorporation seen at the later time periods are consistent with changes observed in response to a thrombopoietin-mediated event.…”

Section: Discussionmentioning

confidence: 99%

Acetylsalicylic Acid Stimulates Murine Megakaryocyte Precursor Cells

Sullivan

McDonald

1990

Experimental Biology and Medicine

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Depression of platelet function with a single intraperitoneal injection of acetylsalicylic acid was found to produce significant increases in several thrombocytopoietic indicators despite no observed change in platelet counts. There was an increase in the number of megakaryocytic precursor cells (small acetylcholinesterase positive or "SAChE+" cells), platelet size, and 35S incorporation into platelets. The results are qualitatively comparable to data from previous experiments showing that treatment of mice with a thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) and rabbit anti-mouse platelet serum will elevate thrombocytopoiesis. The results presented herein indicate that interruption of platelet function by aspirin results in the production of new platelets, presumably by the action of a feedback system controlling thrombocytopoiesis.

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Section: Discussionmentioning

confidence: 99%

Acetylsalicylic Acid Stimulates Murine Megakaryocyte Precursor Cells

Sullivan

McDonald

1990

Experimental Biology and Medicine

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“…but these data did not offer evidence of the presence of thrombopoietin. Since ASA has been shown by Demers et al (14) to inactivate cyclooxygenase in the megakaryocytes, Sullivan and McDonald (6) proposed that the early change in SAChE+ cells at 24 hr might be due to either an autoregulation response by the megakaryocyte to the direct effects of ASA, or the release and action of thrombopoietin. An increase in platelet sizes at 32 hr and elevated %35S incorporation into platelets at 48 hr after ASA injection are consistent with endogenous release and action of thrombopoietin.…”

Section: Discussionmentioning

confidence: 99%

Thrombopoietin Production in Mice Treated with Acetylsalicylic Acid

Clift

Cottrell

McDonald

1991

Experimental Biology and Medicine

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Recent work revealed that mice in which platelet function was inhibited by acetylsalicylic acid (ASA) treatment showed evidence of increased platelet production. It was proposed that poorly functioning platelets gave rise to elevated thrombocytopoiesis by causing the release and action of thrombopoietin. However, direct evidence is lacking. Therefore, in the work reported here, plasma from mice treated with ASA was injected into normal recipient mice in an attempt to document the existence of the humoral factor. Compared with control mice given normal plasma, the injection of mice with plasma from ASA-treated mice resulted in increased thrombocytopoiesis, as evidenced by significant increases in the percentage of 35S incorporation into platelets, larger platelet size, and elevated megakaryocyte precursor cells (the small acetylcholinesterase-positive cell). For a positive control, additional mice were treated with plasma from animals made thrombocytopenic by an injection of antiplatelet serum. These mice also showed significant increases in thrombocytopoiesis. The results support the hypothesis that platelet production in ASA-treated mice is elevated by release and action of thrombopoietin.

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“…There are several factors that contribute to the platelet inhibitory effect of low-dose aspirin. These include the relative selectivity of the drug at low-doses for platelet COX-1 [28], a likely inhibitory effect on COX-1 in mature megakaryocytes [29], and, most importantly, a short plasma half-life time of about 15-20 minutes. The latter and the irreversibility of the acetylation at the serine residues lead to complete inhibition of cyclooxygenase in anucleate, cell-like structures like platelets, but an ineffective inhibition of cyclooxygenases in cells that are able to resynthesize the enzyme.…”

Section: Low-dose Aspirinmentioning

confidence: 99%

Cyclooxygenase Inhibition and Atherothrombosis

Sohn¹,

Krötz

2006

CDT

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Cyclooxygenases represent a major target of pharmaceutical therapy. Cyclooxygenase inhibitors are applied in order to reduce inflammation, to relieve from pain, or to prevent atherothrombotic complications in cardiovascular disease. Inhibition of platelet aggregation by aspirin, which is due to inhibition of platelet cyclooxygenase-dependent formation of thromboxane A2, is a cheap, safe and effective strategy to prevent myocardial infarction or stroke and is thus the most established strategy of secondary prevention of atherothrombotic disease. However, the existence of several isoforms of the cyclooxygenase enzyme, their tissue-specific expression patterns, their spatial and functional association with enzymes that further degrade the major cyclooxygenase products and the specific pharmacological properties of substances that have the potential of inhibiting cyclooxygenase make the ultimate physiological effects of a specific cyclooxygenase inhibitor a highly sophisticated pharmacological question. Specific inhibitors of the cyclooxygenase-2 isoform (COX-2) have at first promised to represent a major improvement of pharmaceutical therapy, but later have been suggested to enhance the risk of atherothrombotic events in vivo. This has led to the withdrawal of some of these substances from global markets and also initiated a discussion as to whether some non-selective cyclooxygenase inhibitors (non-steroidal anti-inflammatory drugs, NSAID), such as naproxen would also have an antithrombotic effect in vivo. This review summarizes current pathophysiological and clinical knowledge about the effects on atherothrombosis of drugs that target cyclooxygenases either as specific inhibitors of a cyclooxygenase isoform, or as non-specific cyclooxygenase inhibitors. It specifically discusses the question, whether all selective COX-2 inhibitors may have an intrinsic risk of enhancing the risk of atherothrombosis.

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The Effects of Aspirin on Megakaryocyte Prostaglandin Production

Cited by 30 publications

References 0 publications

Acetylsalicylic Acid Stimulates Murine Megakaryocyte Precursor Cells

Acetylsalicylic Acid Stimulates Murine Megakaryocyte Precursor Cells

Thrombopoietin Production in Mice Treated with Acetylsalicylic Acid

Cyclooxygenase Inhibition and Atherothrombosis

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