In Vitro Apixaban Removal By CytoSorb Whole Blood Adsorber: An Experimental Study.

OBJECTIVES: The use of unopposed oral anticoagulants while undergoing cardiothoracic surgery is associated with severe bleeding and increased morbidity. The aim of this experimental study was to examine if the apixaban concentration in reconstituted blood could be reduced in an in vitro setup by the use of CytoSorb whole blood adsorber, and to study how this affected global coagulation assays. DESIGN AND SETTING: An experimental study performed in a laboratory. PARTICIPANTS: An in vitro setup with reconstituted whole blood. INTERVENTIONS: Reconstituted whole blood spiked with apixaban circulated in an in vitro circuit with the CytoSorb 300 mL device connected. MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn at 0, 5, 15, 30, 60, and 120 minutes of adsorption. The apixaban concentration was measured at each time point. In addition, the global coagulation assays, thromboelastometry clotting time and thrombin generation, were performed, and the results were compared with baseline values obtained before spiking blood with apixaban. After 30 minutes of adsorption, the mean apixaban concentration was reduced from 414.3 (±69.1) ng/mL to 33 (±11.4) ng/mL. Thrombin generation showed maximum effect after 60 minutes, and the thromboelastometry clotting time was close to baseline values after 120 minutes. CONCLUSIONS: In this in vitro study, apixaban concentrations were effectively reduced, and the clotting time and thrombin generation assays were normalized by the use of CytoSorb whole blood adsorber.

Operative survival in patients with acute aortic disease in the era of newer oral anticoagulants.

AIMS: The aim of this study was the analysis of the risk associated with direct oral anticoagulants (DOACs) in patients undergoing non-elective operations on the proximal aorta due to aortic disease. METHODS AND RESULTS: Data from the department's register of cardiac surgery was analysed retrospectively with emphasis on operative mortality. 135 non-elective operations for proximal aortic disease (October 2016 to 2018) were identified, of which 19 died during the first 90 days. DOAC use was the top-ranked risk factor in the univariate analysis with a HR of 9.6 (3.1 to 29), p=0.00007. Using a Cox proportional hazards model including the most relevant risk factors, the risk associated with DOAC use remained significant with a HR of 6.1 (1.4 to 26.3), p=0.015. We did not find increased risk associated with warfarin use. CONCLUSION: In patients undergoing non-elective operations on the proximal aorta due to aortic disease, the use of DOAC is associated with increased operative mortality.

[A man in his fifties with syncope and hypotension]. / En mann i 50-årene med synkope og hypotensjon.

A man in his fifties was admitted to our hospital because of syncope and hypotension. In the emergency room he reported abdominal pain, but focused assessment with sonography for trauma (FAST) was negative. His systolic blood pressure varied between 60 and 90 mmHg and an arterial blood gas revealed lactic acidosis with normal haemoglobin, which still might indicate acute bleeding. An ECG did not indicate myocardial infarction. In the absence of an obvious bleeding focus, the patient was urgently transported to a CT lab nearby, to identify possible bleeding and rule out other causes of circulatory shock, such as cardiac tamponade. Before radiologic scanning was initiated, the patient lost consciousness and displayed pulseless electrical activity. Resuscitation was initiated and pericardiocentesis was resultless. On vital indication and clinical suspicion of cardiac tamponade, an emergency median sternotomy was performed and a haematoma was evacuated from the pericardial space. The patient was stabilised and immediately taken to the operation theatre where a ruptured ascending aortic aneurysm was identified. The operation was successful, but following serious hypoperfusion, the patient suffered acute kidney failure requiring dialysis for several months, gram-negative septicaemia caused by a central venous catheter, cerebral infarction leading to hemiparesis and impaired vision, ventilator-associated pneumonia/acute lung injury and acalculous cholecystitis. This case report describes the findings on admission, the diagnostic process including surgical resuscitation and a complicated course of multi-organ failure. After almost 5 months, the patient was discharged from our hospital to another institution for further rehabilitation. He now has minimal sequelae and lives at home. Our take-home message is that seriously ill patients require fast, resolute and broad examination; they may need immediate surgical treatment including emergency intervention; and a good clinical outcome may be achieved in spite of serious complications.

Collagen isoform shift during the early phase of reverse left ventricular remodelling after relief of pressure overload.

AIMS: Aortic stenosis induces pressure overload and myocardial remodelling with concentric hypertrophy and alterations in extracellular matrix (ECM). Aortic valve replacement leads to reverse remodelling, a process of which knowledge is scarce. The aims of the present study were to examine alterations in myocardial gene expression and subsequently identify molecular alterations important for the early phase of reverse remodelling. METHODS AND RESULTS: After 4 weeks of ascending aortic banding, mice were subjected to a debanding operation (DB) and followed for 3, 7, or 14 days. Cardiac function was assessed by echocardiography/tissue Doppler ultrasonography. Myocardial gene expression was examined using Affymetrix microarray and the topGO software and verified by real-time polymerase chain reaction. Quantitative measurements of collagen subtypes were performed. Aortic banding increased left ventricular mass by 60%, with normalization to sham level 14 days after DB. Extracellular matrix genes were the most regulated after DB. Three days after DB, collagen I was transiently increased, whereas collagens III and VIII increased later at 7 days. CONCLUSION: The ECM genes were the most altered during reverse remodelling. There was a change in isoform constitution as collagen type I increased transiently at 3 days followed by a later increase in types III and VIII at 7 days after DB. This might be important for the biomechanical properties of the heart and recovery of cardiac function.