Anticoagulants of primary haemostasis

SummaryInhibition of platelet function plays an important role in the treatment and secondary prevention of cardiovascular or cerebrovascular ischemic diseases. Established antiplatelet agents use different pharmacological targets for this role. Acetylic salicylic acid achieves a reduction of thromboxane A2 formation by inhibition of COX-1. Ticlopidin or clopidogrel are ADP-P2Y12 receptor antagonists. Tirofiban, abciximab or eptifibatid are used for the inhibition of the glycoprotein IIb/IIIa receptor which is activated at the surface of platelets preceding the final step of their aggregation. The mechanism of dipyridamole is based on the inhibition of adenosine uptake and of phosphodiesterase-5.Efforts are made to improve antiplatetelet therapy with the aim to find agents with favorable clinical outcome and lower bleeding risk. Current clinical studies focus on a new generation of ADP receptor antagonists (prasugrel, cangrelor and ticagrelor) as successors of ticlopidin and clopidogrel after coronary arterial interventions. Developments using platelet targets different from established drugs are thrombin receptor antagonists (like SCH530348) or thromboxane receptor antagonists (like S18886/terutroban) in patients with cerebrovascular events. Results from recent experimental studies could lead to new strategies for antiplatetelet therapy (like inhibition of GP Ib receptor, GP VI receptor, platelet-leukocyte interaction, factor XII and others) in the future.

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Effect of thromboxane antagonists on ozone-induced airway responses in dogs

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.3.880 ◽

1990 ◽

Vol 69 (3) ◽

pp. 880-884 ◽

Cited By ~ 4

Author(s):

G. L. Jones ◽

C. G. Lane ◽

P. M. O'Byrne

Keyword(s):

Airway Hyperresponsiveness ◽

The Other ◽

Receptor Antagonists ◽

Thromboxane Receptor ◽

Before And After ◽

The Mean ◽

Airway Responses ◽

Control Infusion

Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness.

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Fibrinolyse- und Thrombophilieparameter unter systemischer Prostaglandin E1-Therapie bei peripherer arterieller Verschlusskrankheit

VASA ◽

10.1024/0301-1526.32.3.145 ◽

2003 ◽

Vol 32 (3) ◽

pp. 145-148 ◽

Cited By ~ 5

Author(s):

Kuss ◽

Heidrich ◽

Koettgen

Keyword(s):

Coagulation Factor ◽

Plasminogen Activator Inhibitor ◽

Bleeding Risk ◽

Arterial Disease ◽

Prostaglandin E ◽

Factor Xii ◽

Significant Difference ◽

Peripheral Arterial ◽

Fibrinolytic Capacity

Background: The study was designed to evaluate if there is any evidence of a hyperfibrinolytic bleeding-risk under systemic treatment with prostaglandin E1 (PGE1) of patients with peripheral arterial disease (PAD). Patients and methods: The in vivo effect of PGE1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with Alprostadil for 21 days using D-dimers (DD), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), antithrombin (AT), ProC-Global®, plasminogen, plasminogen activator inhibitor activity (PAI), alpha2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity (fib. cap.). Results: There was no significant difference in DD, fibrinogen, PT, PTT, AT, ProC-Global®, plasminogen, PAI, alpha2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity observed after the treatment. Conclusion: Summarizing this study there is no hyperfibrinolytic bleeding-risk after the systemic therapy with Alprostadil to be expected.

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Revival of PFA-100 – how far is it useful for the monitoring of ADP receptor antagonists?

Thrombosis and Haemostasis ◽

10.1160/th12-08-0548 ◽

2013 ◽

Vol 109 (03) ◽

pp. 564-565

Author(s):

Kamila Syska ◽

Cezary Watala ◽

Jacek Golanski

Keyword(s):

Receptor Antagonists ◽

Adp Receptor ◽

Adp Receptor Antagonists

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Optical Coherence Tomography Facilitating Early Withdrawal of Antiplatelet Agents in a High–Bleeding Risk Patient

JACC: Case Reports ◽

10.1016/j.jaccas.2020.04.049 ◽

2020 ◽

Vol 2 (8) ◽

pp. 1186-1191

Author(s):

Ioannis Gkirdis ◽

Dimitrios N. Nikas ◽

Theodora Bampali ◽

Theofilos M. Kolettis

Keyword(s):

Optical Coherence Tomography ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Risk Patient ◽

Optical Coherence ◽

Early Withdrawal ◽

High Bleeding Risk

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Clinical impact of the perioperative management of oral anticoagulants in bleeding after colonic endoscopic mucosal resection

BMC Gastroenterology ◽

10.1186/s12876-019-1124-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Shoko Ono ◽

Marin Ishikawa ◽

Kana Matsuda ◽

Momoko Tsuda ◽

Keiko Yamamoto ◽

...

Keyword(s):

Endoscopic Mucosal Resection ◽

Perioperative Management ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Multivariate Logistic Regression Analysis ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Clinical Impact ◽

Antithrombotic Agents ◽

Mucosal Resection

Abstract Background Heparin bridging therapy (HBT) is indeed related to a high frequency of bleeding after endoscopic mucosal resection (EMR). In this study, our aim was to investigate clinical impact of management of oral anticoagulants without HBT in bleeding after colonic EMR. Methods From data for patients who underwent consecutive colonic EMR, the relationships of patient factors and procedural factors with the risk of bleeding were analysed. Our management of antithrombotic agents was based on the shortest cessation as follows: the administration of warfarin was generally continued within the therapeutic range, and direct oral anticoagulants (DOACs) were not administered on the day of the procedure. We calculated bleeding risks after EMR in patients who used antithrombotic agents and evaluated whether perioperative management of anticoagulants without HBT was beneficial for bleeding. Results A total of 1734 polyps in 825 EMRs were analysed. Bleeding occurred in 4.0% of the patients and 1.9% of the polyps. The odds ratios for bleeding using multivariate logistic regression analysis were 3.67 in patients who used anticoagulants and 4.95 in patients who used both anticoagulants and antiplatelet agents. In patients with one-day skip of DOACs, bleeding occurred in 6.5% of the polyps, and there were no significant differences in bleeding risk between HBT and continuous warfarin or one-day skip DOACs. Conclusions The use of oral anticoagulants was related to bleeding after colonic EMR, and perioperative management of oral anticoagulants based on the shortest cessation without HBT would be clinically acceptable.

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Effect of oral antiplatelet agents on major bleeding in users of coumarins

Thrombosis and Haemostasis ◽

10.1160/th08-05-0290 ◽

2008 ◽

Vol 100 (12) ◽

pp. 1076-1083 ◽

Cited By ~ 19

Author(s):

Olaf H. Klungel ◽

Patrick C. Souverein ◽

Anthonius de Boer ◽

Tom Schalekamp

Keyword(s):

Major Bleeding ◽

Conditional Logistic Regression ◽

Vitamin K Antagonists ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Primary Diagnosis ◽

Antiplatelet Drugs ◽

Antiplatelet Drug ◽

Concurrent Use ◽

Increased Risk

SummaryTreatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. In order to elucidate the bleeding risk of users of antiplatelet drugs among users of coumarins, we assessed the odds ratio of major bleeding associated with use of antiplatelet drugs in users of the coumarins acenocoumarol and phenprocoumon. We used data froma Dutch record linkage system, including pharmacy and linked hospitalization records for approximately two million subjects, to conduct a nested case control study in a cohort of new users of coumarins. Cases were patients who were hospitalized with a primary diagnosis of major bleeding while taking coumarin and were matched with up to four control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CI).We identified 1848 case patients who were matched to 5818 controls. Users of clopidogrel or aspirin showed a significantly increased risk of hospitalization because of major bleeding (OR 2.9, 95% CI 1.2–6.9 and OR 1.6, 95% CI 1.3–1.9, respectively), whereas users of dipyridamole and combinations of antiplatelet drugs showed a strong trend (OR 1.5, 95% CI 1.0–2.3 and OR 1.8, 95 % CI 1.0–3.3, respectively). In all cases, the risks were greater for upper gastrointestinal bleedings than for other bleedings. In conclusion, the use of any antiplatelet drug increases the risk of hospitalization for major bleeding among users of coumarins. Concurrent use of clopidogrel or dipyridamole and coumarins is probably not safer than concurrent use of aspirin and coumarins.

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Recent Advances in the Development of P2Y12 Receptor Antagonists as Antiplatelet Agents

Annual Reports in Medicinal Chemistry ◽

10.1016/b978-0-12-800167-7.00007-9 ◽

2014 ◽

pp. 87-99 ◽

Cited By ~ 1

Author(s):

Allorie T. Caldwell ◽

E. Blake Watkins

Keyword(s):

Antiplatelet Agents ◽

P2y12 Receptor ◽

Receptor Antagonists ◽

Recent Advances

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Developments in Oral Antiplatelet Agents for the Treatment of Acute Coronary Syndromes

Journal of Pharmacy Practice ◽

10.1177/0897190014568383 ◽

2015 ◽

Vol 29 (3) ◽

pp. 239-249 ◽

Cited By ~ 6

Author(s):

David S. Roffman

Keyword(s):

Clinical Trials ◽

Major Bleeding ◽

Antiplatelet Agent ◽

Antiplatelet Agents ◽

Clinical History ◽

Bleeding Risk ◽

Phase Iii ◽

Coronary Syndrome ◽

Phase Iii Clinical Trials ◽

Increased Risk

A review of the literature was conducted for clinical trials evaluating the antiplatelet P2Y12 receptor antagonists, clopidogrel, prasugrel, and ticagrelor, as well as the guidelines for the management of acute coronary syndrome (ACS) or myocardial infarction. Clinical guidelines recommend that patients with ACS be treated with dual oral antiplatelet therapy of aspirin plus clopidogrel, prasugrel, or ticagrelor. The selection of an appropriate antiplatelet agent depends on the treatment approach and a patient’s bleeding risk and clinical history. With respect to antiplatelet activity, prasugrel and ticagrelor demonstrate greater potency and less interpatient variability than clopidogrel. In phase III clinical trials, prasugrel and ticagrelor reduced the incidence of ischemic events in patients with ACS compared with clopidogrel. Ticagrelor and clopidogrel were associated with a similar risk of major bleeding, whereas patients receiving prasugrel had an increased risk of major bleeding versus those receiving clopidogrel. Pharmacists can provide guidance on the appropriate use of antiplatelet agents as well as the use of concomitant medications, while being vigilant for any potential drug interactions.

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