Multiple healthcare organizations, such as the National Quality Forum (NQF), Joint Commission on Accreditation of Healthcare Organizations (JCAHO), and Agency for Healthcare Research and Quality (AHRQ) have identified VTE as a preventable condition in hospitalized patients. Formal risk assessment must be conducted as a first step, followed by the initiation of timely prophylaxis to improve patient safety.
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Review of the Data
Mechanical forms of prophylaxis, such as graduated compression stockings, have been evaluated in patients with stroke and myocardial infarction. Intermittent pneumatic compression stockings and venous foot pumps have not been studied in randomized controlled trials (RCTs) in general medical patients.
Although there is data supporting the efficacy of these devices in surgical patients, the American College of Chest Physicians’ (ACCP) guidelines recommend against the use of mechanical forms of prophylaxis in medical patients unless there is a contraindication to pharmacologic prophylaxis.7
The ideal prophylactic agent is cost-effective and has no side effects. Available pharmacologic options for prevention of VTE in medical patients include unfractionated heparin (UFH), low molecular weight heparins (LMWHs), and the synthetic pentasaccharide, fondaparinux. Oral anticoagulants, (e.g., vitamin K antagonists [VKA]), have not been adequately studied in medical inpatients. Since VKA take several days to achieve therapeutic anticoagulation, we do not recommend using them de novo as VTE prophylaxis.
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However, patients taking an oral VKA in the outpatient setting who have a therapeutic international normalized ratio (INR) during hospitalization probably are adequately protected from VTE and do not need additional pharmacologic prophylaxis. Newer anticoagulants in phase III testing for prevention of VTE in medically ill patients include oral direct thrombin inhibitors and anti-Xa inhibitors. ACCP guidelines recommend either low-dose UFH or LMWH as first-line agents for VTE prevention in medical inpatients.
Unfractionated heparin: UFH is a heterogeneous mixture of repeating polysaccharide chains of varying sizes, averaging about 15,000 Daltons. It binds anti-thrombin III (AT-III) and facilitates AT-III-mediated inactivation of factors IIa, IXa, Xa, and XIIa; of these, IIa and Xa are most responsive to inhibition.
Due to its large size, UFH only is partially absorbed from subcutaneous (SC) tissue, and it has a variable anticoagulant response due to interactions with plasma proteins, macrophages, and endothelial cells.8 However, in prophylactic SC doses (5,000 units two or three times daily), monitoring of the activated partial thromboplastin time (aPTT) is not required. In some cases, (e.g., frail or elderly patients), prophylactic SC doses may slightly prolong the aPTT.
UFH also binds to platelets and platelet factor 4 (PF4), and may precipitate heparin-induced thrombocytopenia (HIT). At least three clinical trials have compared the efficacy of SC UFH with a placebo and found prophylactic doses of UFH decrease the relative risk of DVT as detected by fibrinogen uptake test by about 70% without increasing the risk of bleeding.9-11
Low molecular weight heparins: LMWHs are derived from UFH through a chemical depolymerization, or fractionation, process. They are about one-third the size of UFH, with a molecular weight of approximately 5,000 Daltons.
These smaller molecules are readily absorbed from the SC tissue, eliciting a more predictable anticoagulant response than UFH. Unlike UFH, LMWHs have only minimal nonspecific binding to plasma proteins, endothelial cells, and monocytes, resulting in a predictable dose response. This obviates the need for lab monitoring, even when used in full, therapeutic dosing.
Compared with UFH, these agents have a longer plasma half-life, allowing them to be dosed SC once or twice daily. Also, they don’t bind platelets as readily as UFH resulting in a lower risk of HIT. Because they’re smaller, LMWHs tend to preferentially inhibit factor Xa, whereas UFH tends to inhibit factors Xa and IIa equally.