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Key Clinical Updates in Antithrombotic Therapy

For patients with morbid obesity, standard doses of apixaban or rivaroxaban should be chosen rather than dabigatran or edoxaban.

DOACs are not recommended for VTE treatment in the acute setting following bariatric surgery but can be considered for ongoing treatment after the initial 4 weeks of therapy.

Heparins may be preferable as initial therapy in hospitalized patients with clinical instability and fluctuating renal or hepatic function, when bleeding risk is high, or when there is concern that thrombolysis may be required.

Stevens SM et al. Chest. [PMID: 34352278]

The currently available anticoagulants include unfractionated heparin, LMWHs, fondaparinux, vitamin K antagonists (ie, warfarin), and DOACs (ie, dabigatran, rivaroxaban, apixaban, edoxaban). (For a discussion of injectable DTIs, see section Heparin-Induced Thrombocytopenia above.)


A. Unfractionated Heparin and LMWHs

Unfractionated heparin is a biologic product most commonly derived from porcine intestinal tissue rich in heparin-bearing mast cells. It is heterogeneous with respect to sulfation and polymer length; individual molecules may range from 3000 to 30,000. About one-third of the molecules in a given preparation of unfractionated heparin contain the crucial pentasaccharide sequence necessary for binding of antithrombin and exerting its anticoagulant effect upon thrombin. Heparin is highly negatively charged, and upon intravenous infusion, it binds to a large array of blood components, such as endothelial cells, platelets, mast cells, and plasma proteins. The degree of anticoagulation with unfractionated heparin is typically monitored by aPTT or anti-Xa level in patients who are receiving the drug in therapeutic doses, although the pharmacokinetics of unfractionated heparin are poorly predictable. Only a fraction of an infused dose of heparin is metabolized by the kidneys, making it safe to use in most patients with significant kidney disease.

The LMWHs are produced from chemical depolymerization of unfractionated heparin, resulting in products of lower molecular weight (mean molecular weight, 4500–6500d, depending on the LMWH). Due to less protein and cellular binding, pharmacokinetics of the LMWHs are much more predictable than those of unfractionated heparin, allowing for fixed weight-based dosing. All LMWHs are principally renally cleared and must be avoided or used with extreme caution in individuals with creatinine clearance less than 30 mL/minute. Compared to unfractionated heparin, LMWHs have a longer half-life, which allows once- or twice-daily subcutaneous dosing and thus greater convenience and outpatient therapy in selected cases. Most patients do not require monitoring, although monitoring using the anti-Xa activity level is appropriate for patients with moderate kidney disease, those with elevated BMI or low weight, and selected pregnant patients. LMWHs are associated with a lower frequency of HIT and thrombosis (approximately 0.6%) than unfractionated heparin (3%).

B. Fondaparinux

Fondaparinux is a synthetic molecule consisting of the highly active pentasaccharide sequence found in LMWHs. As such, it exerts almost no thrombin inhibition and works to indirectly inhibit factor Xa ...

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