Inverse relationship of serum albumin to the risk of venous thromboembolism among acutely ill hospitalized patients: Analysis from the APEX trial

Abstract

Hypoalbuminemia is a common finding and independent predictor for unfavorable prognosis. The prognostic value of albumin measurement for short‐term VTE prediction in hospitalized patients remains unclear. In the APEX trial (http://ClinicalTrials.gov identifier: NCT01583218), medical inpatients were randomized to receive either extended‐duration betrixaban or shorter‐duration enoxaparin and followed for 77 days. Baseline albumin concentrations were obtained in 7266 subjects with evaluable VTE endpoints. The association of baseline albumin to VTE was assessed, with adjustment for patient characteristics, thromboprophylaxis, and biomarkers for fibrinolysis and inflammation (ie, D‐dimer and C‐reactive protein [CRP]). VTE risk refinement was evaluated by incorporation of albumin to well‐validated risk assessment models. A stepwise increase in the risk of VTE (P < .0001) was observed with lower levels of albumin. Patients at the bottom albumin quartile (<35 g/L) had a two‐fold greater odds for developing VTE compared with the top quartile (≥42 g/L) (OR = 2.119 [95% CI, 1.592‐2.820]; adjusted OR = 2.079 [1.485‐2.911]). The odds for VTE increased by 1.368 (95% CI, 1.240‐1.509) times per SD decrement of albumin (5.24 g/L). Compared with the propensity score‐matched pairs of patients with albumin ≥35 g/L, patients with albumin <35 g/L had a greater risk of VTE (OR = 1.623 [1.260‐2.090]; adjusted OR = 1.658 [1.209‐2.272]). Albumin measurement also refined VTE risk discrimination and reclassification after inclusion in the risk assessment models. In conclusion, acutely ill hospitalized patients with low serum albumin had an increased VTE risk through 77 days. VTE risk assessment models for medical inpatients should consider incorporation of baseline albumin measurement.

Association of Serum Albumin and Severity of Pulmonary Embolism

“…Moreover, the association between hypoalbuminemia and venous thromboembolism in renal conditions specifically nephrotic syndrome is mainly explained by the renal loss of antithrombotic proteins creating a state of hypercoagulability and hence this cannot be a plausible explanation for the association we find in the general population. Several retrospective studies confirmed the association between lower albumin and venous thromboembolism in the general population without nephrotic syndrome [31], in addition, one prospective study from an analysis of the ARIC and CHS [27] where albumin was measured before rather than after the thrombotic event also confirmed this association. This is the first study to link albumin level with severity of APE (massive versus non-massive cases) with big effect size between groups (2.8 gm/dL and 3.2 gm/dL in massive and non-massive APE, respectively) and hence it serves not only as a diagnostic but also a prognostic marker.…”

DVT incidence and risk factors in critically ill patients with COVID-19

“…Patients with DVT had a significantly longer disease duration (days from disease onset to CUS performed) compared with patients without DVT (34 vs 20 [15-32] days, P = 0.007). ICU length of stay in patients with DVT did not differ from patients without DVT (27 [19][20][21][22][23][24][25][26][27][28][29][30][31][32] days vs 21 [18][19][20][21][22][23][24][25][26][27][28][29] days, P = 0.257). Incidence of pulmonary arterial hypertension that occurred in patients with DVT was significantly higher than in patients without DVT (53% vs 32%, P = 0.044).…”

“…Hypoalbuminemia is associated with highly increased DVT risk (almost twofold higher risk), which builds on studies in acutely ill patients, and which we now identify as being a risk factor in critical COVID-19 as well. Several anticoagulative properties of albumin have been proposed to explain the relationship between low albumin and increased VTE risks, which include inhibiting fibrin polymerization and platelet aggregation, enhancing the effect of antithrombin III, and promoting hepatic synthesis of coagulation factors [23]. These findings highlight the importance of sustain normal albumin level in critical COVID-19.…”

Population attributable risk estimates of risk factors for contrast-induced acute kidney injury following coronary angiography: a cohort study

“…Patients with CKD were also divided into 3 stages (mild: eGFR: 45-60 mL/min/1.73 mm 2 ; moderate: eGFR: 30-45 mL/min/1.73 mm 2 ; severe: eGFR: < 30 mL/min/1.73 mm 2 ) [9]. Hypoalbuminemia was defined as serum albumin (ALB) < 35 g/L [10]. Anemia was defined as hematocrit < 36% for women and < 39% for men, and hypotension was defined as systolic blood pressure < 80 mmHg for at least 1 h requiring inotropic support with medications or intra-aortic balloon pump (IABP) within 24 h peri-procedurally [11]..…”