Anticoagulating obese patients in the modern era

Abstract

The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.

The use of anticoagulants in morbidly obese patients

“…Studies on clinical use of anticoagulants provide no basis for any adjustment of doses in obese patients as compared to patients with normal body weight [10,16]. In our opinion, however, further studies are required in this specific population.…”

“…Novel anticoagulants belong to two different classes of the inhibitors of factor X (apixaban, rivaroxaban, edoxaban) and the inhibitors of factor II, or thrombin (dabigatran) [16].…”

Venous thromboembolism: a role for weight-stratified thromboprophylaxis?

“…An inverse correlation between anti-Xa levels in the first 10 hours and body weight with fixed prophylactic doses of 40 mg enoxaparin has been demonstrated, which suggests that current fixed-dose thromboprophylaxis is likely inadequate in heavier patients. 3,4 A review of observational studies suggests that with fixed dose thromboprophylaxis, VTE rates in the obese are twice that of the non-obese, with a subgroup analysis of the PREVENT trial demonstrating no benefit of standard-dose dalteparin over placebo in the morbidly obese population. 3 Randomised control trials involving bariatric surgery groups have demonstrated lower rates of VTE with higher doses of LMWH, with no associated increase in bleeding events.…”

“…3,5 Furthermore, studies have shown that obese patients have increased renal clearance compared to the non-obese, and LMWHs are renally excreted. 3,4 Royal Bournemouth Hospital and Poole Hospital had two serious untoward incidents in which patients died due to pulmonary emboli. The patients had both been on standard VTE prophylaxis as per the trust guidelines.…”

“…Upper GI cancer miss rates are reported to be approximately 5-13%. 1,4 It is accepted that a cancer detected within three years following an endoscopy is considered to be a 'potential miss' and if detected within one year after an endoscopy is likely to be a 'definite miss'. 4,5 In view of public health campaigns to detect cancer at an earlier stage we sought to review missed cancers in our trust over a four-year period.…”