Deirdre Murphy

Extracorporeal Membrane Oxygenation—Hemostatic Complications

The use of extracorporeal membrane oxygenation (ECMO) support for cardiac and respiratory failure has increased in recent years. Improvements in ECMO oxygenator and pump technologies have aided this increase in utilization. Additionally, reports of successful outcomes in supporting patients with respiratory failure during the 2009 H1N1 pandemic and reports of ECMO during cardiopulmonary resuscitation have led to increased uptake of ECMO. Patients requiring ECMO are a heterogenous group of critically ill patients with cardiac and respiratory failure. Bleeding and thrombotic complications remain a leading cause of morbidity and mortality in patients on ECMO. In this review, we describe the mechanisms and management of hemostatic, thrombotic and hemolytic complications during ECMO support.

Determination of thickness, aspect ratio and size distributions for platey particles using sedimentation field-flow fractionation and electron microscopy

Abstract Sedimentation field-flow fractionation (SdFFF) can be used to prepare fractions of very narrow mass range for electron microscopic (EM) analysis. Assuming the particle density is the same for all particles within that fraction the equivalent spherical diameter for the particles can be calculated from SdFFF theory. Integration of the micrograph image of each particle yields an area measurement which, when used in conjunction with the equivalent spherical particle diameter (from SdFFF), provides information about the particle thickness and aspect ratio. Thus SdFFF-SEM can be used to provide detailed information about clay morphology across the particle size distribution of the sample. Three clay minerals have been studied using the methodologies outlined in this paper. The aspect ratio for the Purvis School Mine kaolinite ranged from 2.8–5.9, for RM30 illite from 11.3–24.3, and for Muloorina illite from 3.1–4.3.

Extracorporeal membrane oxygenation with plasma exchange in a patient with alveolar haemorrhage secondary to Wegener's granulomatosis

A 50-year-old woman with asthma presented with a 2-week history of worsening dyspnoea and cough with small volume haemoptysis. She gave a history of vague weakness, dry cough, sinus congestion and joint pains over the preceding 2-year period. Following 2 weeks of oral antibiotics without resolution of symptoms, a chest X-ray and computed tomography scan was performed, which showed right upper lobe consolidation. She was admitted to a rural hospital and commenced on intravenous ceftriaxone and doxycycline. Her condition rapidly deteriorated with increasing dyspnoea and small volume haemoptysis requiring oxygen therapy. A computed tomography pulmonary angiogram revealed progression of consolidation throughout the lobes (Fig. 1). No embolus was identified. She continued to deteriorate over a 48-h period with worsening hypoxia requiring endotracheal intubation and mechanical ventilation. Despite mechanical ventilation she remained too hypoxic to transfer safely on a portable ventilator to a tertiary setting. A medical retrieval team commenced venovenous extracorporeal membrane oxygenation (v-v ECMO) with peripheral cannulation. She was safely transferred to a tertiary hospital. On arrival to a tertiary hospital she was haemodynamically unstable requiring inotropic support and six-unit blood transfusion. A bronchoscopy revealed haemoptysis. She was deemed unsuitable for a lung (transbronchial or open) biopsy because of bleeding risk. Nasoendoscopy performed by the Ear Nose and Throat team was unremarkable. Examination of urinary red cell morphology revealed glomerular red cells despite normal serum creatinine (65 umol/L) and normal urine output. Her renal function subsequently deteriorated and she was supported on continuous veno-veno haemodiafilatration through the

The meaning of a high plasma free haemoglobin: retrospective review of the prevalence of haemolysis and circuit thrombosis in an adult ECMO centre over 5 years

Aims: In adults requiring extracorporeal membrane oxygenation (ECMO), we wanted to determine; i) the frequency of elevated plasma free haemoglobin (PFHb), ii) the reasons for circuit changes and iii) whether elevated PFHb was associated with higher in-hospital mortality. Materials and Methods: Patients requiring ECMO between January 2010 and August 2014 were identified from a prospectively collected ECMO database. Their scanned medical records and pathology results were reviewed. Relevant patient, biochemical and circuit data were collected on an Excel spreadsheet and analysed using Stata 13 (StataCorp, College Station, TX). The patients were analysed in three groups, depending on their peak PFHb during ECMO: ‘Normal PFHb’ (<0.1 g/L), ‘Low level PFHb’ (0.1 – 0.5 g/L), ‘High level PFHb’ (>0.5 g/L). Main Results: There were 184 ECMO runs (56 VV, 128 VA) – 61 ‘Normal PFHb’, 99 ‘Low level PFHb’, 24 ‘High level PFHb’. Circuit thrombosis (pump, oxygenator) or haemolysis requiring exchanges were significantly more common in VV ECMO compared to VA ECMO – 23.21% (13/56) vs. 0.78% (1/128), p<0.001. Elevated PFHb was associated with a longer duration of haemofiltration (p<0.001) and ECMO support (p<0.001). In-hospital mortality rates for the ‘Normal PFHb’, ‘Low level PFHb’ and ‘High level PFHb’ groups were 16.39% (10/61), 30.30% (30/99) and 37.50% (9/24), respectively, p=0.067. Conclusion: Elevated PFHb values during adult ECMO were common. Severe haemolysis or thrombosis requiring circuit changes were uncommon and occurred almost exclusively on VV ECMO. There was a non-statistically significant increase in in-hospital mortality with elevated PFHb and studies of larger registry data may clarify the prognostic value of PFHb in adult patients.

Right ventricular failure after implantation of continuous flow left ventricular assist device: analysis of predictors and outcomes

Postoperative right ventricular failure is a serious complication for up to 50% of patients following LVAD insertion. Predicting RV failure is an important factor for patients as planned BiVAD support has been shown to correlate with better outcomes compared to delayed BiVAD to LVAD conversion. This retrospective study examined prospectively collected data for 101 patients implanted with an LVAD between 2003 and 2013, aiming to establish preoperative predictive factors for RVF post‐LVAD insertion, analyze outcomes, and validate existing RVF scoring systems. In our cohort, 63 patients (62.4%) developed RV failure and consequently demonstrated consistently poorer survival throughout the follow‐up period (log‐rank p = 0.01). Multivariable logistic regression identified two significant variables: cardiac index <2.2 preoperatively despite inotropic support (OR 4.6 [95%CI 1.8–11.8]; p = 0.001) and preoperative tricuspid regurgitation (OR 8.1 [95%CI 1.9–34]; p = 0.004). Patients who developed RV failure had more complicated postoperative courses including longer ICU stay (p < 0.001), higher incidence of transfusions (p = 0.03) and re‐intubation (p = 0.001), longer ventilation duration (p < 0.001), and higher incidence of returning to theater (p = 0.0008). This study found that previous validation models had only moderate correlation with our population emphasizing the need for prospective validation of these scores in the current era of continuous flow devices.

Long-Term Right Ventricular Support with a Centrifugal Ventricular Assist Device Placed in the Right Atrium

This case series outlines the technique and results of right ventricular assist device (RVAD) support with the off‐label use of the centrifugal HeartWare HVAD (HeartWare Inc., Framingham, MA, USA) for long‐term support. Four patients in our institution have been implanted with BiVADs, using the Heartware device as the RVAD, and supported for between 117 days and 772 days. Three of the patients have been successfully supported for over 18 months. Three patients have successfully been transplanted and one patient remains on the device, now approaching two years of support. None of the patients have had RVAD device–related complications. doi: 10.1111/jocs.12440 (J Card Surg 2014;29:839–842)

Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI.

Essentials Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored. Patients with ventricular assist devices and on extracorporeal membrane oxygenation are investigated. Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients. Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk.

Autoregulation of von Willebrand factor function by a disulfide bond switch

We demonstrate mechanochemical regulation of platelet adhesion to von Willebrand factor in thrombosis and hemostasis. Force-dependent binding of platelet glycoprotein Ib (GPIb) receptors to plasma von Willebrand factor (VWF) plays a key role in hemostasis and thrombosis. Previous studies have suggested that VWF activation requires force-induced exposure of the GPIb binding site in the A1 domain that is autoinhibited by the neighboring A2 domain. However, the biochemical basis of this “mechanopresentation” remains elusive. From a combination of protein chemical, biophysical, and functional studies, we find that the autoinhibition is controlled by the redox state of an unusual disulfide bond near the carboxyl terminus of the A2 domain that links adjacent cysteine residues to form an eight-membered ring. Only when the bond is cleaved does the A2 domain bind to the A1 domain and block platelet GPIb binding. Molecular dynamics simulations indicate that cleavage of the disulfide bond modifies the structure and molecular stresses of the A2 domain in a long-range allosteric manner, which provides a structural explanation for redox control of the autoinhibition. Significantly, the A2 disulfide bond is cleaved in ~75% of VWF subunits in healthy human donor plasma but in just ~25% of plasma VWF subunits from heart failure patients who have received extracorporeal membrane oxygenation support. This suggests that the majority of plasma VWF binding sites for platelet GPIb are autoinhibited in healthy donors but are mostly available in heart failure patients. These findings demonstrate that a disulfide bond switch regulates mechanopresentation of VWF.

Impact of cardiac magnetic resonance imaging - cardiac contusion with intramural hemorrhage –

Received June 3, 2014; revised manuscript received August 20, 2014; accepted September 1, 2014; released online October 2, 2014 Time for primary review: 28 days Department of Cardiovascular Medicine (A.J.C.B., J.L.H., P.J.F., D.M.K., A.J.T.), Department of Trauma (M.F.), Intensive Care Unit (A.J.C.B., D.J.C., D.M.), Alfred Hospital, Melbourne, Victoria; Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria (A.J.C.B., D.J.C., D.M.); and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria (J.L.H., D.M.K., A.J.T.), Australia Mailing address: Aidan J.C. Burrell, MD, Department of Cardiovascular Medicine, Alfred Hospital, 55 Commercial Road, Melbourne, Vic. 3181, Australia. E-mail: aidan.burrell@monash.edu ISSN-1346-9843 doi: 10.1253/circj.CJ-14-0626 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp Impact of Cardiac Magnetic Resonance Imaging – Cardiac Contusion With Intramural Hemorrhage –

Complications of mechanical circulatory and respiratory support

Abstract Despite the benefits of mechanical circulatory and respiratory support (MCS), patients undergoing extracorporeal membrane oxygenation (ECMO) and the implantation of ventricular assist devices (VADs) continue to experience high rates of serious and life-threatening complications. These include bleeding, thrombosis, sepsis, multiorgan dysfunction, and death. These complications may be caused by the mechanical support or the underlying critical illness that necessitates its use. Reducing MCS complications remains an important goal for the future uptake of this technology.