The clinical impact of bleeding during oral anticoagulant therapy

Guerrouij, Minna; Uppal, Chitman S.; Alklabi, Ali; Douketis, James D.

doi:10.1007/s11239-010-0536-7

Cited by 60 publications

(22 citation statements)

References 23 publications

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“…In some cases, a substance with high anticoagulant activity, but a low antiplatelet effect, or the opposite, or even a molecule that does not inhibit all the signaling pathway of platelet aggregation or the coagulation cascade, would be interesting, because the hemorrhagic risk can be diminished. Hemorrhage is one of the most dangerous side effects of current antithrombotic drugs [35]. …”

Section: Resultsmentioning

confidence: 99%

Antiplatelet and Anticoagulant Effects of Diterpenes Isolated from the Marine Alga, Dictyota menstrualis

et al. 2014

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Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity and side effects. Marine organisms are prime candidates for such products, as they are sources of numerous and complex substances with ecological and pharmacological effects. In this work, we investigated, through in vitro experiments, the effects of three diterpenes (pachydictyol A, isopachydictyol A and dichotomanol) from the Brazilian marine alga, Dictyota menstrualis, on platelet aggregation and plasma coagulation. Results showed that dichotomanol inhibited ADP- or collagen-induced aggregation of platelet-rich plasma (PRP), but failed to inhibit washed platelets (WP). In contrast, pachydictyol A and isopachydictyol A failed to inhibit the aggregation of PRP, but inhibited WP aggregation induced by collagen or thrombin. These diterpenes also inhibited coagulation analyzed by the prothrombin time and activated partial thromboplastin time and on commercial fibrinogen. Moreover, diterpenes inhibited the catalytic activity of thrombin. Theoretical studies using the Osiris Property Explorer software showed that diterpenes have low theoretical toxicity profiles and a drug-score similar to commercial anticoagulant drugs. In conclusion, these diterpenes are promising candidates for use in anticoagulant therapy, and this study also highlights the biotechnological potential of oceans and the importance of bioprospecting to develop medicines.

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Section: Resultsmentioning

confidence: 99%

Antiplatelet and Anticoagulant Effects of Diterpenes Isolated from the Marine Alga, Dictyota menstrualis

et al. 2014

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“…Annually, 10% of patients taking anticoagulants require temporary discontinuation of therapy for surgical or other invasive elective procedures, in many cases represented by gastrointestinal (GI) endoscopy [3]. Furthermore, major GI bleeding represents a serious complication of anticoagulant therapy, with an occurrence ranging approximately from 1-4% per year and a case fatality rate up to 10% [4,5]. Among patients presenting with acute upper and lower GI bleeding, up to 15% and 32%, respectively take anticoagulants [6,7].…”

Section: Anticoagulant Therapymentioning

confidence: 99%

Gastrointestinal endoscopy in patients on anticoagulant therapy and antiplatelet agents

Zullo

Hassan

Radaelli

2016

aog

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Periprocedural management of antithrombotics for gastrointestinal endoscopy is a common clinical issue, given the widespread use of these drugs for primary and secondary cardiovascular prevention. For diagnostic procedures, with or without biopsy, no adjustments in antithrombotics are usually needed. For operative procedures, balancing the risk of periprocedural hemorrhage with the continuation of antithrombotics against the chance of recurrent thromboembolic events with their discontinuation may be challenging. Oral anticoagulants need to be temporarily withheld, and consideration must be given to whether a periendoscopic “bridge” therapy, typically a low-molecular-weight heparin, should be used in order to minimize the risk of thromboembolic events. Although some emerging evidence has shown that patients receiving heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to controls, bridging therapy is still recommended for patients on vitamin K antagonists who are at high thrombotic risk. Conversely, bridging therapy is usually not needed for patients taking new oral agents, which are characterized by shorter half-lives, and a rapid offset and onset of action. Management of antiplatelet therapy requires special care in patients on secondary prevention, especially those with coronary stents. This review is intended to summarize the recommendations of updated International Guidelines designed to help the decision-making process in such an intricate field.

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“…This surface-induced thrombosis may lead to a variety of device complications including obstruction of blood flow [4], thromboemboli [5,6], and infection [7,8], all of which result in diminished device efficacy or failure, ultimately jeopardizing patient health. Antithrombotic drugs can reduce such complications [9,10] but put the patient at risk for major bleeding events [11,12]. Therefore, silicone materials that are inherently resistant to protein adsorption and thrombosis, thereby reducing the need for antithrombotic drugs, would dramatically improve the efficacy and safety of blood-contacting medical devices.…”

Section: Introductionmentioning

confidence: 99%

Protein resistance efficacy of PEO-silane amphiphiles: Dependence on PEO-segment length and concentration

et al. 2016

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In contrast to modification with conventional PEO-silanes (i.e. no siloxane tether), silicones with dramatically enhanced protein resistance have been previously achieved via bulk-modification with poly (ethylene oxide) (PEO)-silane amphiphiles α-(EtO)3Si(CH2)2-oligodimethylsiloxane13-block-PEOn-OCH3 when n = 8 and 16 but not when n = 3. In this work, their efficacy was evaluated in terms of optimal PEO-segment length and minimum concentration required in silicone. For each PEO-silane amphiphile (n = 3, 8, and 16), five concentrations (5, 10, 25, 50, and 100 μmol per 1 g silicone) were evaluated. Efficacy was quantified in terms of the modified silicones’ abilities to undergo rapid, water-driven surface restructuring to form hydrophilic surfaces as well as resistance to fibrinogen adsorption. Only n = 8 and 16 were effective, with a lower minimum concentration in silicone required for n = 8 (10 μmol per 1 g silicone) versus n = 16 (25 μmol per 1 g silicone). Statement of Significance Silicone is commonly used for implantable medical devices, but its hydrophobic surface promotes protein adsorption which leads to thrombosis and infection. Typical methods to incorporate poly(ethylene oxide) (PEO) into silicones have not been effective due to the poor migration of PEO to the surface-biological interface. In this work, PEO-silane amphiphiles – comprised of a siloxane tether (m = 13) and variable PEO segment lengths (n = 3, 8, 16) – were blended into silicone to improve its protein resistance. The efficacy of the amphiphiles was determined to be dependent on PEO length. With the intermediate PEO length (n = 8), water-driven surface restructuring and resulting protein resistance was achieved with a concentration of only 1.7 wt%.

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The clinical impact of bleeding during oral anticoagulant therapy

Cited by 60 publications

References 23 publications

Antiplatelet and Anticoagulant Effects of Diterpenes Isolated from the Marine Alga, Dictyota menstrualis

Antiplatelet and Anticoagulant Effects of Diterpenes Isolated from the Marine Alga, Dictyota menstrualis

Gastrointestinal endoscopy in patients on anticoagulant therapy and antiplatelet agents

Protein resistance efficacy of PEO-silane amphiphiles: Dependence on PEO-segment length and concentration

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