The impact of shear stress on device-induced platelet hemostatic dysfunction relevant to thrombosis and bleeding in mechanically assisted circulation

The aim of this study was to examine the impact of the nonphysiological shear stress (NPSS) on platelet hemostatic function relevant to thrombosis and bleeding in mechanically assisted circulation. Fresh human blood was circulated for four hours in in vitro circulatory flow loops with a CentriMag blood pump operated under a flow rate of 4.5 L/min against three pressure heads (70 mm Hg, 150 mm Hg, and 350 mm Hg) at 2100, 2800, and 4000 rpm, respectively. Hourly blood samples from the CentriMag pump-assisted circulation loops were collected and analyzed for glycoprotein (GP) IIb/IIIa activation and receptor shedding of GPVI and GPIbα on the platelet surface with flow cytometry. Adhesion of platelets to fibrinogen, collagen, and von Willebrand factor (VWF) of the collected blood samples was quantified with fluorescent microscopy. In parallel, mechanical shear stress fields within the CentriMag pump operated under the three conditions were assessed by computational fluid dynamics (CFD) analysis. The experimental results showed that levels of platelet GPIIb/IIIa activation and platelet receptor shedding (GPVI and GPIbα) in the blood increased with increasing the circulation time. The levels of platelet activation and loss of platelet receptors GPVI and GPIbα were consistently higher with higher pressure heads at each increasing hour in the CentriMag pump-assisted circulation. The platelet adhesion on fibrinogen increased with increasing the circulation time for all three CentriMag operating conditions and was correlated well with the level of platelet activation. In contrast, the platelet adhesion on collagen and VWF decreased with increasing the circulation time under all the three conditions and was correlated well with the loss of the receptors GPVI and GPIbα on the platelet surface, respectively. The CFD results showed that levels of shear stresses inside the CentriMag pump under all three operating conditions exceeded the maximum level of shear stress in the normal physiological circulation and were strongly dependent on the pump operating condition. The level of platelet activation and loss of key platelet adhesion receptors (GPVI and GPIbα) were correlated with the level of NPSS generated by the CentriMag pump, respectively. In summary, the level of NPSS associated with pump operating condition is a critical determinant of platelet dysfunction in mechanically assisted circulation.     

Percutaneous venoarterial extracorporeal membrane oxygenation as a bridge to double valve implantation in acute biventricular heart failure with profound cardiogenic shock

A 71‐year‐old woman was admitted with acute hypoxic and hypercapnic respiratory failure and cardiogenic shock, secondary to acute on chronic biventricular systolic and diastolic congestive heart failure and severe aortic and mitral valve stenosis. She further presented with pulmonary hypertension and moderate‐to‐severe tricuspid regurgitation requiring high and increasing doses of vasopressors. The patient was percutaneously cannulated for venoarterial extracorporeal membrane oxygenation (VA‐ECMO) and stabilized on ECMO, with a urine output of 17.3 L within the following 8 days. Balloon valvuloplasty and/or transcatheter aortic valve replacement were discussed but ruled out by the multidisciplinary team considering the mitral valve could not be fully addressed. Though lung function was not fully optimized, a window of opportunity was identified and used for double valve replacement on day 8 of VA‐ECMO support. After a 24‐hour vasoplegic period, the patient was extubated to continuous positive airway pressure and further transitioned to nasal cannula, following which she recovered well.     

A description of a prototype miniature extracorporeal membrane oxygenation circuit using current technologies in a sheep model

In the United States, standardization of neonatal extracorporeal membrane oxygenation (ECMO) circuit was achieved during the 1980s. Since that time, the consoles and components of the ECMO circuit have remained fundamentally unchanged (bladder, rollerpump, silicone membrane oxygenator). Extracorporeal technology, however, has witnessed many significant advancements in components during the past two decades. These new technologies have characteristics that may improve outcomes when applied in the ECMO arena. Understanding how these technologies perform in long-term applications is necessary. Therefore, the purpose of this project is to evaluate the performance of a miniature ECMO circuit consisting of current generation technologies in an animal model. An ECMO circuit (prime volume 145 mL) was designed that included a hollow fiber oxygenator and a remote mounted centrifugal pump. All circuit tubing and components were surface coated. Three sheep (approx 13 kg) were placed on ECMO using standard neck cannulation techniques and maintained according to clinical protocols. Technical implementation, oxygenator function, and hematological parameters were accessed. Duration of ECMO was 20, 48, and 58 hours. There was no evidence of oxygenator failure, as measured by pressure drop and oxygen transfer, in any of the procedures. No plasma leak was observed in any oxygenators. Platelet count trended downward after 24 hours. Visual inspection after ECMO showed very little evidence of gross thrombosis. This ECMO circuit design departs dramatically from the typical North American systems. The use of this console and components facilitated a 70% reduction in priming volume over a traditional ECMO circuit. Further investigations should be conducted to determine if circuit miniaturization can reduce the morbidity associated with blood product consumption and the bloods contact with the artificial surfaces of the ECMO circuitry.     

Use of thromboelastograph and factor VII for the treatment of postoperative bleeding in a pediatric patient on ECMO after cardiac surgery

This report describes a case of possibly fatal bleeding treated successfully with an "overdose" of recombinant factor VII (rFVII; Novo7). A 3.5-year-old boy had surgery for aortic stenosis and aortic arch repair and was placed on extracorporeal membrane oxygenation (ECMO) after a prolonged cardiopulmonary bypass time (CPB); there was subsequent failure to wean from CPB because of right ventricular failure. Subsequently, a severe coagulopathy developed, and despite large volume transfusions with blood and blood products, this was unresolved. Thromboelastograph (TEG) measurements were obtained, and on the advice of the Hematology Department, Novo7 (recommended dose: 15-30 microg/kg) was administered at a dose of 200 microg/kg because of the severity of the bleeding. TEG was repeated, and a further dose of Novo7 was administered at 500 microg/kg; a further TEG after 15 minutes showed normalization, and the remaining bleeding was treated surgically. The patient was weaned from ECMO 48 hours later and was subsequently discharged home with no further problems. Novo7 in an "overdose" can apparently correct major coagulopathy even in patients on ECMO support with no dire effects on the ECMO circuit or the patient in a life-threatening scenario.     

Impact of oxygenator selection on hemodynamic energy indicators under pulsatile and nonpulsatile flow in a neonatal extracorporeal life support model

This study compared the quality of perfusion delivered by two oxygenators--the hollow-fiber membrane Capiox Baby RX05 and silicone membrane Medtronic 0800--using hemodynamic energy indicators. The oxygenators were tested across varying flow rates and perfusion modes in a neonatal extracorporeal life support (ECLS) model. The experimental ECLS circuit included a Jostra HL-20 heart/lung machine with Jostra Roller pump, oxygenators with associated tubing and components, and a neonatal pseudo-patient. We used a 40/60 glycerin/water solution in the circuit as a blood analog. Testing occurred at flow rates of 250, 500, and 750 mL/min at 37°C under both pulsatile and nonpulsatile flow conditions. Hemodynamic data points consisted of recording 20-s intervals of data, and a total of 96 experimental repetitions were conducted. The pressure drop across the Capiox Baby RX05 oxygenator was significantly lower than the pressure drop across the Medtronic 0800 at all flow rates and perfusion modes. Furthermore, the Medtronic 0800 oxygenator showed significantly lower post-oxygenator energy equivalent pressures, total hemodynamic energy values, and surplus hemodynamic energy retention values compared to those of the Capiox Baby RX05. These results indicate the Medtronic 0800 oxygenator significantly dampens the hemodynamic energy compared to the Capiox Baby RX05. Consequently, clinical use of the Medtronic 0800 in a pulsatile ECLS setting is likely to mitigate the benefits provided by pulsatile flow. In contrast, the Capiox Baby RX05 better transmits hemodynamic energy to the patient with much lower pressure drop.     

Device‐induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding

Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulatory support (MCS) beyond the current use. While providing the needed hemodynamic support, those devices can induce damage to blood, particularly to platelets. In this study, we investigated device‐induced alteration of three major platelet surface receptors, von Willebrand factor (VWF) and associated hemostatic functions relevant to thrombosis and bleeding. Fresh human whole blood was circulated in an extracorporeal circuit with a clinical rotary blood pump (CentriMag, Abbott, Chicago, IL, USA) under the clinically relevant operating condition for 4 hours. Blood samples were examined every hour for glycoprotein (GP) IIb/IIIa activation and receptor loss of GPVI and GPIbα on the platelet surface with flow cytometry. Soluble P‐selectin in hourly collected blood samples was measured by enzyme linked immunosorbent assay to characterize platelet activation. Adhesion of device‐injured platelets to fibrinogen, collagen, and VWF was quantified with fluorescent microscopy. Device‐induced damage to VWF was characterized with western blotting. The CentriMag blood pump induced progressive platelet activation with blood circulating time. Particularly, GPIIb/IIIa activation increased from 1.1% (Base) to 11% (4 hours) and soluble P‐selectin concentration increased from 14.1 ng/mL (Base) to 26.5 ng/mL (4 hours). Those device‐activated platelets exhibited increased adhesion capacity to fibrinogen. Concurrently, the CentriMag blood pump caused progressive platelet receptor loss (GPVI and GPIbα) with blood circulating time. Specifically, MFI of the GPVI and GPIbα receptors decreased by 17.2% and 16.1% for the 4‐hours sample compared to the baseline samples, respectively. The device‐injured platelets exhibited reduced adhesion capacities to collagen and VWF. The high molecular weight multimers (HMWM) of VWF in the blood disappeared within the first hour of the circulation. Thereafter the multimeric patterns of VWF were stable. The change in the VWF multimeric pattern was different from the progressive structural and functional changes of platelets with the circulation time. This study suggested that the CentriMag blood pump could induce two opposite effects on platelets and associated hemostatic functions under a clinically relevant operating condition. The device‐altered hemostatic function may contribute to thrombosis and bleeding simultaneously as occurring in patients supported by a rotary blood pump. Device‐induced damage of platelets may be an important cause for bleeding in patients supported with rotary blood pump MCS systems relative to device‐induced loss of HMWM‐VWF.