Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy

Abstract

Primary membranous nephropathy is associated with increased risk of venous thromboembolic events, which are inversely correlated with serum albumin levels. To evaluate the potential benefit of prophylactic anticoagulation (venous thromboembolic events prevented) relative to the risk (major bleeds), we constructed a Markov decision model. The venous thromboembolic event risk according to serum albumin was obtained from an inception cohort of 898 patients with primary membranous nephropathy. Risk estimates of hemorrhage were obtained from a systematic literature review. Benefit-to-risk ratios were predicted according to bleeding risk and serum albumin. This ratio increased with worsening hypoalbuminemia from 4.5:1 for an albumin under 3 g/dl to 13.1:1 for an albumin under 2 g/dl in patients at low bleeding risk. Patients at intermediate bleeding risk with an albumin under 2 g/dl have a moderately favorable benefit-to-risk ratio (under 5:1). Patients at high bleeding risk are unlikely to benefit from prophylactic anticoagulation regardless of albuminemia. Probabilistic sensitivity analysis, to account for uncertainty in risk estimates, confirmed these trends. From these data, we constructed a tool to estimate the likelihood of benefit based on an individual’s bleeding risk profile, serum albumin level, and acceptable benefit-to-risk ratio (http://www.gntools.com). This tool provides an approach to the decision of prophylactic anticoagulation personalized to the individual’s needs and adaptable to dynamic changes in health status and risk profile.

Management of Membranous Nephropathy in Western Countries

“…Low serum albumin (<28 g/l) in multivariate analysis was the dominant factor associated with a higher incidence of VTE. Recently, a risk-benefit tool has been developed to help clinicians in their decision-making based on the data surrounding the question of prophylactic anticoagulation, which takes into account not only the risks of thromboembolism but also the risks of bleeding (www.gntools.com) [48]. Interestingly, episodes of VTE were not shown to affect renal survival.…”

Pharmacological treatment of primary membranous nephropathy in 2016

“…The KDIGO guideline suggests that in patients with marked reductions in serum albumin (<25 g/L) and additional risks for thrombosis, prophylactic anticoagulant therapy might be considered [10]. Lee et al developed a useful tool to provide a more personalized decision about the initiation of prophylactic anticoagulation [18]. Recently, it became clear that the risk of arterial thrombosis is also high [19].…”

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

“…Although thrombosis could potentially be prevented with prophylactic anticoagulation, this approach remains controversial because of the treatment-associated risk of bleeding complications. [10][11][12] Recent epidemiologic studies have revealed that both proteinuria and serum albumin may be associated with the likelihood of thrombosis, with higher proteinuria and lower serum albumin correlating with increased thrombotic risk, suggesting that disease severity may be directly correlated with the severity of coagulation system derangement. [13][14][15][16][17][18] Thus, determining the relationship between hypercoagulopathy and these markers of disease severity may lead to the identification of clinically meaningful urine protein and/or serum albumin levels beyond which prophylaxis with anticoagulants may be warranted.…”