212 G . Budhu et al .: J Extra Corpor Technol 2024 , 56 , 211 – 215
the selective removal of plasma volume ( usually 1 ), replaced with either albumin or fresh frozen plasma ( FFP ), depending on the specific indication for TPE [ 2 ]. It is being used in tandem with ECMO for a variety of disorders , such as rejection of transplanted organs , sepsis with multiple organ failure , thrombocytopenia-associated multiple organ failure , alveolar hemorrhage in polyangiitis with granulomatosis , acute lung injury from H1N1 infection , acute respiratory failure due to COVID-19 infection , or as a strategy to reduce the cytokine burden [ 7 ]. In both pediatric and adult patients , the tandem use of ECMO and TPE was associated with electrolyte abnormalities ( most notably hypocalcemia ) and coagulopathies , along with hemodynamic instability [ 7 ]. However , only case reports mention TPE as a form of therapy for ECMO-induced hemolysis [ 8 ]. The purpose of this case series is to present the use of TPE in severe ECMO-induced hemolysis .
Description Case 1
A 7-day-old male neonate born at term by emergency C-section for fetal distress due to congenital diaphragmatic hernia and secondary respiratory decompensation , weighing 3.2 kg ( birth weight 3.27 kg ), was placed on ECMO , Rotaflow system with Quadrox-ID oxygenator ( Maquet , Germany ). He was cannulated peripherally ( neck ): V-10Fr , A-8Fr . The hemolysis became apparent , as evidenced by a steady rise in PFH ( tested with HemoCue [ 9 ]), within a day of ECMO initiation . Revolutions per minute ( RPM ) was kept below 3,000 ( average 2,000 – 2,600 ), and venous pressure average �9 ( range�6 to �24 ). Other causes of hemolysis , not related to ECMO , were excluded ( i . e ., enzyme deficiencies , hemoglobinopathies , autoimmune hemolytic anemia , microangiopathies , etc ). The oxygenator was changed , he underwent echocardiographic repositioning of cannulae , and because fibrinous deposits were noted , the ECMO circuit was exchanged ( equivalent to an exchange transfusion ), though it yielded no improvement in PFH , which peaked at 1,050 mg / dL . TPE using the Spectra Optia system ( Terumo Medical Corporation , Tokyo , Japan ) was performed in tandem with ECMO ( see diagram of connection Figure 1 ).
Packed red blood cells ( pRBCs ) were used to prime the TPE circuit . Even though he received systemic heparin , the interface could not be achieved after 45 min . Therefore , we used an anticoagulation protocol previously described [ 10 ]. Citrate was added in a blood-to-citrate ratio of 15:1 . After the interface was quickly established , citrate was replaced with a 0.9 % NaCl decoy solution to complete the therapy about 2 h later , with a total of 4 mL of citrate . Plasma volume ( 1 ) was replaced with FFP . Post-procedure ionized calcium was 1.26 mmol / L , normal range in our laboratory 1.16 – 1.45 mmol / L .
After TPE , PFH levels fell immediately to 680 mg / dL and further down to 120 mg / dL during the ensuing hours . However , this improvement was short-lived as levels slowly increased close to 500 mg / dL ( Figure 2 ) 2 days later . A second round of TPE was performed . Due to a higher hematocrit , treatment had a slightly longer duration . No hypotension or hypocalcemia were noted . After that second round , PFH dropped to 220 mg / dL .
Levels were monitored closely and remained between 210 and 350 mg / dL . The patient was liberated from ECMO and de-cannulated two days after his second TPE , without sacrificing the carotid artery . He experienced respiratory decompensation , culminating in cardiac arrest before continuous renal replacement therapy ( CRRT ) could be started for new onset oligoanuria . At the time of arrest , he did not meet the requirements for re-cannulation and did not survive . Case 2
A term male neonate , small for gestational age , with a birth weight of 2.52 kg , was diagnosed with hypoplastic left heart syndrome , mitral stenosis , and aortic stenosis . On DOL # 3 underwent a modified Norwood procedure and coarctation resection . On DOL # 4 developed pulmonary over-circulation and worsening lactic acidosis . Cardiac catheterization revealed an obstructive process at the level of the aorta . During cardiac catheterization , the patient experienced cardiac arrest , requiring prolonged resuscitation , followed by central cannulation ( V-16Fr , A-8Fr ) for V-A ECMO ( Rotaflow system with Quadrox-ID oxygenator , Maquet , Germany ). While receiving ECMO , PFH peaked at 620 mg / dL . The RPM was kept below 3,000 ( range 2,190 – 2,255 ) and the venous pressures were between �25 and + 10 . TPE was initiated in tandem with ECMO ( Figure 1 ). The previously mentioned causes of hemolysis were excluded in this case as well .
As in case # 1 , since the patient was already on heparin therapy , citrate was added as previously described . The patient received less than 5 mL of citrate during the treatment , which was completed in less than 2 hours . Plasma volume ( 1 ) was replaced by FFP . No hypotension was noted and ionized calcium remained normal ( 1.33 mmol / L ) during the procedure .
Before TPE , PFH was 620 mg / dL . Immediately after , levels improved to 360 mg / dL and , in the ensuing days , to below 130 mg / dL ( Figure 3 ). Unsuccessful attempts were made to liberate the neonate from ECMO due to hypotension and systemic hypoxemia on the background of severe tricuspid regurgitation . Ultimately , care was withdrawn at the parental request .
Comment
Hemolysis is a life-threatening complication associated with extracorporeal life support ( ECLS ) [ 3 ]. The morbidity is mainly secondary to the byproducts of hemolysis , namely PFH . During ECMO , PFH levels can increase well above normal levels [ 11 ]. At such elevated levels of PFH , tissue hypoxia and cell death can occur [ 12 ]. High PFH levels are linked to multi-organ failure , including direct kidney injury [ 1 , 3 ]. Moreover , PFH depletes vascular nitric oxide , resulting in peripheral vasoconstriction , inappropriate platelet activation , worsening ischemic injury , and increasing risk of thrombus formation [ 1 , 2 ]. Some consequences of ECMO-induced hemolysis include increased requirement for blood products , need for CRRT , prolonged ECMO , implicit extended ICU stays , and increased mortality [ 1 , 13 , 14 ]. Despite several improvements aimed at mitigating hemolysis during ECMO [ 6 ], it remains a significant source of morbidity .