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Systemic complications following vascular reconstruction
Published in Sachinder Singh Hans, Mark F. Conrad, Vascular and Endovascular Complications, 2021
Srihari K. Lella, Mark F. Conrad
Heparin-induced thrombocytopenia (HIT) is a rare condition that may be encountered in vascular surgery due to the common exposure to heparin in these patients. It involves the formation of immunoglobulin antibodies against heparin-platelet factor 4 complex. These complexes coat platelets, activate them, and cause them to be removed by macrophages. This results in thrombocytopenia. There is generally a 30–50% decline in platelet count 5–10 days after the initiation of heparin, but this isolated thrombocytopenia is not usually associated with significant bleeding complications. Indeed, with HIT, thrombosis is the more severe complication that leads to increased morbidity and mortality. Venous thrombotic complications are most common, but HIT may affect any vascular bed. Interestingly, not all patients with seropositivity progress to the severe form with thrombosis. Management of HIT-positive patients begins with immediate discontinuation of all heparin products (i.e., unfractionated and low molecular weight heparin) on suspicion. If there is a need for anticoagulation, direct thrombin inhibitors are generally the preferred agents. Vitamin K antagonists are avoided with the acute phase of thrombocytopenia due to the increased risk of warfarin-induced skin necrosis and venous limb gangrene in the absence of a heparin bridge.97 Anticoagulation is recommended for 1 month for nonthrombotic HIT while it may be continued for 3–6 months for those patients with thrombotic HIT.98
Anti-coagulation in acute coronary syndrome
Published in K Sarat Chandra, AJ Swamy, Acute Coronary Syndromes, 2020
Nitin Parashar, Deepti Siddharthan, Sivasubramanian Ramakrishnan
Direct thrombin inhibitors (e.g. bivalirudin) potentially have an advantage over UFH or LMWH as they inhibit clot bound thrombin. Additionally, direct thrombin inhibitors don't interact with plasma proteins, provide a stable anti-coagulation effect and do not cause thrombocytopenia. Bivalirudin is a synthetic analogue of hirudin which directly binds and inhibits thrombin (factor IIa) without activation of antithrombin. Its action can be monitored by ACT and aPTT when used in high doses and low doses, respectively. It causes less bleeding than heparin and can be safely used in patients with heparin-induced thrombocytopenia who require PCI.
Anticoagulation in Pregnancy
Published in Afshan B. Hameed, Diana S. Wolfe, Cardio-Obstetrics, 2020
Rachel A. Newman, Ather Mehboob, Judith H. Chung
There are a multitude of new oral anticoagulants. These include direct thrombin inhibitors, such as dabigatran and argatroban, as well as direct factor Xa inhibitors, such as rivaroxaban and apixaban. In general, they should not be used in pregnancy as little is known about efficacy and fetal safety [21]. If a woman is on one of these medications and becomes pregnant, she should switch to LMWH immediately.
Outpatient treatment of emergency department patients diagnosed with venous thromboembolism
Published in Postgraduate Medicine, 2021
William B. Stubblefield, Jeffrey A. Kline
In the US, four DOAC medications have received clearance to market from the Food and Drug Administration (FDA) for the treatment of VTE: apixaban (Eliquis®), dabigatran (Pradaxa®), edoxaban (Savaysa®), and rivaroxaban (Xarelto®) (Table 2). Three of these medications are factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban) and one is a direct thrombin inhibitor (dabigatran). Approval of each of these medications was the result of several phase III trials that were conducted with each medication being compared to warfarin (Coumadin). The primary endpoints of these studies were VTE recurrence or VTE-related death. In all trials, the DOAC showed similar efficacy and each was noninferior to warfarin in incidence of VTE and VTE-related deaths. DOACs also had lower rates of major bleeding [46], clinically relevant non-major bleeding, and serious adverse events when compared to warfarin [47–52].
Pharmacokinetic-Pharmacodynamic Analysis’ Role in Design of Phase ⅠClinical Trials of Anticoagulant Agents: A Systematic Review
Published in Expert Review of Clinical Pharmacology, 2020
Nan Zhao, Qian Xiang, Zhiyan Liu, Xia Zhao, Yimin Cui
Our review shows that sustained interests are paid in exploring newer and better FⅩa inhibitors. However, several FⅩa inhibitors have been discontinued or temporarily halted with no additional benefit over established treatments [77–79]. It seems that few new direct thrombin inhibitors is in the pipeline of the drug development from the literature we searched [2,26]. Various agents targeting intrinsic coagulation factors (FⅫ, FⅪ, FⅧ, and FⅨ) have been under study, some displaying promising anticoagulant effect [2,74,76,80]. Among them, FⅪ factor inhibitors were promising at the present stage [81]. Current FⅪ inhibitors under development include factor Ⅺ directed antisense oligonucleotides(ASOs) inhibiting hepatic synthesis of FⅪ, monoclonal antibodies targeting catalytic activity of FⅪ/FⅪa, and aptamers or small molecules that block the active site of FⅪ or FⅪa [82]. We expect more exciting progress in the field of anticoagulant.
Thrombin-induced platelet aggregation −effect of dabigatran using automated platelet aggregometry−
Published in Platelets, 2020
Mie Shimizu, Tatsunori Natori, Keisuke Tsuda, Makiko Yoshida, Asami Kamada, Kiyotaka Oi, Yoko Ishigaku, Kazumasa Oura, Shinsuke Narumi, Masahiro Yamamoto, Yasuo Terayama
Unfractionated heparin, low-molecular-weight heparin, and direct thrombin inhibitors such as lepirudin, argatroban, bivalirudin, and dabigatran, unlike PAR1 antagonists, are anticoagulants rather than specific antiplatelet drugs. However, the inhibition of thrombin results in less platelet activation via PAR-1 on human platelets [19,20]. Dabigatran is a direct thrombin inhibitor that is used to decrease the risk of ischemic stroke in patients with atrial fibrillation [21]. In an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial, reductions in ischemic stroke and bleeding outcomes correlated with dabigatran plasma concentrations [22]. Although dabigatran is administered twice a day, the timing of peak and trough plasma concentrations of dabigatran is not fully understood. Factors such as renal function, age, and sex may contribute to differences in plasma concentrations of dabigatran between individuals [22,23]. Renal function is a major determinant of trough dabigatran concentrations, which correlate with the risk of thromboembolic and hemorrhagic outcomes [24,25]. A report by Terayama [26] indicated that effects on cerebrovascular events may differ between direct thrombin inhibitors and Factor Xa inhibitors. Direct thrombin inhibitors may play important roles in preventing atherothrombosis and reducing intracerebral hemorrhage and atherothrombotic events, but suitable tests to investigate the effects of dabigatran have yet to be developed.