Direct oral anticoagulants in cirrhosis: Rationale and current evidence.

Cirrhosis is a major health concern worldwide with a complex pathophysiology affecting various biological systems, including all aspects of haemostasis. Bleeding risk is mainly driven by portal hypertension, but in end-stage liver disease it is further increased by alterations in haemostatic components, including platelet function, coagulation, and fibrinolysis. Concurrently, patients with cirrhosis are prone to venous thromboembolic events (VTE) because of the altered haemostatic balance, in particular an increase in thrombin generation. In patients with cirrhosis, vitamin K antagonists (VKA) and low molecular weight heparins (LMWH) are currently the standard of care for VTE prevention, with VKA also being standard of care for stroke prevention in those with atrial fibrillation. However, direct oral anticoagulants (DOAC) could have specific advantages in this patient population. Clinical experience suggests that DOAC are a safe and possibly more effective alternative to traditional anticoagulants for the treatment of VTE in patients with compensated cirrhosis. In addition, emerging data suggest that primary prophylactic treatment with anticoagulants may improve clinical outcomes in patients with cirrhosis by reducing the risk of hepatic decompensation. The selection of the most appropriate DOAC remains to be clarified. This review focuses on the rationale for the use of DOAC in patients with cirrhosis, the specific effects of the different DOAC (as assessed by in vitro and in vivo pharmacokinetic and pharmacodynamic studies), as well as clinical outcomes in patients with cirrhosis on DOAC.

Intravenous ferric carboxymaltose is associated with lowering of plasma phosphate levels in patients with gastric bypass surgery: a retrospective case series.

AIMS: Bariatric surgery induces several micronutrient deficiencies that require supplementation. For iron, parenteral infusions are usually preferred over oral supplementation. Ferric carboxymaltose infusion has been associated with hypophosphataemia, mostly transient and asymptomatic. However, in some cases, ferric carboxymaltose-induced hypophosphataemia may persist for weeks to months and may induce muscle weakness, osteomalacia and bone fractures. The aim of this study was to identify possible predictors of a clinically relevant decrease in serum phosphate after ferric carboxymaltose infusion in patients with previous Roux-en-Y gastric bypass. METHODS: Patients with previous Roux-en-Y gastric bypass who received ferric carboxymaltose infusions between January 2018 and September 2019 and had recorded phosphataemia before and after ferric carboxymaltose infusion at the Lausanne University Hospital, Lausanne, Switzerland, were studied retrospectively. A multiple linear regression model was built with delta phosphataemia as the outcome to investigate the factors related to magnitude of serum phosphate lowering. RESULTS: Seventy-seven patients (70 females and 7 males) with previous Roux-en-Y gastric bypass were studied. Mean age (SD) was 43.2 (10.7) years and median BMI was 30.9 kg/m2 (IQR 27.9-36.4). Sixty-eight patients (88.3%) received an infusion of 500 mg ferric carboxymaltose and 9 patients (11.7%) received 250 mg ferric carboxymaltose. Forty-nine patients (63.6%) developed hypophosphataemia (<0.8 mmol/l) after ferric carboxymaltose infusion. Median plasma phosphate significantly decreased by 0.33 mmol/l (IQR 0.14-0.49) (p<0.0001). Multiple linear regression identified the ferric carboxymaltose dose as the only risk factor significantly associated with the magnitude of serum phosphate lowering, with an additional mean loss of 0.26 mmol/l with a 500 mg infusion compared to a 250 mg infusion (p = 0.020). CONCLUSION: Ferric carboxymaltose infusions substantially decreased plasma phosphate levels in patients with previous Roux-en-Y gastric bypass. Compared to a dose of 250 mg, infusion of a dose of 500 mg ferric carboxymaltose decreased the plasma phosphate further in this population.

Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation-A Conceptual Review Summarizing Current Knowledge.

Procoagulant platelets are a subtype of activated platelets that sustains thrombin generation in order to consolidate the clot and stop bleeding. This aspect of platelet activation is gaining more and more recognition and interest. In fact, next to aggregating platelets, procoagulant platelets are key regulators of thrombus formation. Imbalance of both subpopulations can lead to undesired thrombotic or bleeding events. COAT platelets derive from a common pro-aggregatory phenotype in cells capable of accumulating enough cytosolic calcium to trigger specific pathways that mediate the loss of their aggregating properties and the development of new adhesive and procoagulant characteristics. Complex cascades of signaling events are involved and this may explain why an inter-individual variability exists in procoagulant potential. Nowadays, we know the key agonists and mediators underlying the generation of a procoagulant platelet response. However, we still lack insight into the actual mechanisms controlling this dichotomous pattern (i.e., procoagulant versus aggregating phenotype). In this review, we describe the phenotypic characteristics of procoagulant COAT platelets, we detail the current knowledge on the mechanisms of the procoagulant response, and discuss possible drivers of this dichotomous diversification, in particular addressing the impact of the platelet environment during in vivo thrombus formation.