Pre-op sepsis increases risk of thrombosis

Arterial and venous thromboses are common serious postoperative complications. More than 4% of surgical procedures are followed by an arterial thrombosis and at least another 4% by venous thrombosis. Studies have identified risk factors such as existing coronary atherosclerosis, older age, male sex, previous venous thromboembolism (VTE), and malignancy, but limited data are available regarding infection as a risk factor.

A recent study evaluated the impact of preoperative sepsis on risk of postoperative arterial and venous thromboses. The study included 2.3 million patients who underwent surgical procedures over a seven-year period. The main outcome measures were arterial thrombosis (myocardial infarction or stroke) and venous thrombosis (deep venous thrombosis or pulmonary embolism) in the 30 days after surgery.

Patients with preoperative systemic inflammatory response syndrome or any sepsis had three times the odds of having an arterial or venous postoperative thrombosis compared with patients without any systemic inflammation. In patients with preoperative sepsis, both emergency and elective surgical procedures had increased the odds of thrombosis twofold.

The authors concluded that preoperative sepsis represents an important independent risk factor for both arterial and venous thrombosis and that suspicion of thrombosis should be higher in patients with sepsis who undergo surgery.

Source: Donze JD, Ridker PM, Finlayson SRG, et al. Preoperative sepsis is associated with risk for arterial and venous thrombosis. BMJ. 2014;349:g5334.

Predicting thrombosis in relatives of patients with VTE

Family history is an important consideration in determining risk of VTE for close relatives of patients with VTE. Researchers assessed the risk of VTE in 915 first-degree relatives of patients with provoked VTE and compared this to the risk in 1,752 first-degree relatives of patients with unprovoked VTE. The data was then combined to identify predictors of thrombosis.

The risk of VTE in first-degree relatives was higher if the index cases had an unprovoked VTE compared with a provoked VTE (odds ratio [OR] 2.38), if the index case was younger (OR 0.97 per year older), and if an additional family member had VTE (OR 2.71).

Among first-degree relatives of an index case with factor V Leiden or the prothrombin 20210A gene variant, the presence of these abnormalities also predicted thrombosis (OR 4.42). The authors concluded that unprovoked VTE at a young age predicts VTE in first-degree relatives, and that the influence of these two factors is additive.

Source: Couturaud F, Leroyer C, Tromeur C, et al. Factors that predict thrombosis in relatives of patients with venous thromboembolism. Blood. 2014 Sep 25;124(13):2124-30. Prepublished online July 21, 2014: doi:10.1182/blood-2014-03-559757.

Another novel anticoagulant nears FDA approval

A U.S. Food and Drug Administration (FDA) advisory panel voted overwhelmingly in favor of another novel anticoagulant for the treatment of patients with atrial fibrillation (AF). The Cardiovascular and Renal Drugs Advisory Committee voted 9 to 1 in favor of approving edoxaban (Savaysa; Daiichi Sankyo), a factor Xa inhibitor, for the prevention of stroke and non-central-nervous-system (CNS) systemic embolism in patients with nonvalvular AF.

The decision was based on the results of the ENGAGE AF-TIMI 48 trial, a large, event-driven study of 21,105 patients with nonvalvular AF. The trial compared once-daily therapy with edoxaban at either 30 mg or 60 mg with warfarin. Doses were reduced by 50% in patients with renal dysfunction, low body weight, or concomitant treatment with P-glycoprotein-inhibiting drugs such as verapamil or quinidine.

Overall, edoxaban was shown to be non-inferior and to be associated with significantly less major bleeding than the vitamin-K antagonist in the trial. The risk of hemorrhagic stroke went down 46% for high-dose edoxaban and 53% for low-dose edoxaban compared with warfarin (P<0.001 for both differences). But for ischemic stroke, high-dose edoxaban was comparable to warfarin (P=0.97), and the risk of this event went up 41% with low-dose edoxaban vs. warfarin (p<0.001).

Source: FDA Advisory Panel Votes 9 to 1 in Favor of Edoxaban for Stroke Prevention in AF Patients. Medscape. Oct 30, 2014. http://www.medscape.com/viewarticle/834164.