Abstract
Given the increasing use of transcatheter (para)valvular interventions and mechanical circulatory support, haemolysis is becoming a more frequently encountered complication. In this setting, patients should be actively monitored for signs of haemolysis, given the potential major adverse consequences. Although not commonly used, plasmapheresis is a very effective rescue method to remove plasma free haemoglobin from the circulation and preserve renal function while the underlying cause is being addressed, as illustrated in this case report

Introduction
Intravascular mechanical haemolysis or the destruction of red blood cells by mechanical (non-physiological) shear stress, despite their flexibility and deformation, is becoming a clinical challenge in the new era of transcatheter valvular interventions and mechanical circulatory support (MCS). In this case report on massive haemolysis after closure of a paravalvular leak (PVL), we provide an illustration of the potential benefit of plasmapheresis in reversing the renal dysfunction while the underlying cause of haemolysis is being addressed, and also emphasise the importance of proactive surveillance in this setting for signs of haemolysis.

Case
An 82-year-old female patient was admitted to our hospital for closure of a large paravalvular mitral leak. Four months earlier, the patient underwent mitral valve replacement with a bioprosthesis (Abbott Epic Mitral, 31 mm) due to symptomatic, severe degenerative mitral regurgitation. Three months after the procedure, she was readmitted with decompensated heart failure, and echocardiography revealed a severe prosthetic PVL, measuring 14x8 mm in diameter, with a regurgitant orifice area of 0.75 cm2 and regurgitant volume of 97 ml. This large lateral PVL was thought to originate in suture dehiscence in a zone of severe mitral annular calcification. There were no signs of infective endocarditis. Transapical closure of the PVL was performed via a small thoracotomy with a closure device normally used for ventricular septal defects (Occlutech 71 muscular VSD occluder, 14 mm) (figure 1A), with mild residual regurgitation between the device and the prosthesis and mainly through the device itself (figure 1B). Approximately 12 hours after the procedure, the patient’s urine appeared dark-red and she developed oliguric renal failure with a serum creatinine of up to 1.4 mg/dl (123.8 μmol/l) (reference 0.51-0.95 mg/dl or 45.1-84.0 μmol/l; baseline value 0.8 mg/dl or 70.7 μmol/l). Massive haemolysis was diagnosed, reflected by the strong elevation of plasma free haemoglobin (pfHb) (up to 190 mg/dl (29.5 μmol/l); reference <5 mg/dl or 0.775 μmol/l) and other haemolysis parameters (including lactate dehydrogenase and bilirubin), and fully suppressed haptoglobin. An initial attempt with hydration, forced diuresis and intravenous nitroprusside for left ventricular afterload reduction was unsuccessful. Approximately 24 hours after the procedure, membrane plasmapheresis was initiated. The plasma volume was calculated based on height (165 cm) and weight (58 kg) to be 2.94 litres. Plasma was substituted with 1500 ml of fresh frozen plasma and 1500 ml of albumin. Fresh frozen plasma was chosen in order to promote clotting of the paravalvular leakage. In the following hours, there was a rapid recovery of the diuresis with the urine colour returning to normal (figure 2A). Normalisation of pfHb levels was obtained about nine hours after the institution of plasmapheresis, and restauration of serum creatinine to baseline values 48 hours later. The effluent was notable for a ‘cola’ coloured liquid, indicating efficient removal of pfHb from the patient’s circulation (figure 2B). One two-hour session of plasmapheresis proved to be sufficient, given spontaneous clotting and obliteration of the remaining PVL after withholding anticoagulation. Transfusion of packed cells was not required.

Discussion
Intravascular mechanical haemolysis is becoming a clinical challenge in the new era of transcatheter valvular interventions and mechanical circulatory support (MCS). Subclinical haemolysis was present in 15% of 122 patients after balloon-expandable transcatheter aortic valve replacement.[1] In registries of HeartMate® II, haemolysis was noted in 13-18% of cases, while in HeartMate® III less than 1% of the cases were complicated with haemolysis.[2,3] Haemolysis is reported at meaningful frequencies of 8 to 63% in patients who receive short-term percutaneous MCS with the Impella® device.[4] Haemolysis is associated with increased mortality, along with an increased incidence of haemolytic anaemia (and increased blood product transfusions), acute kidney injury and, in cases of MCS, oxygenator failure and pump thrombosis.[5]