Plasma Free Hemoglobin Levels Research Articles

Improving hemolysis levels associated with cardiotomy suction.

The major source of hemolysis during cardiopulmonary bypass (CPB) remains the cardiotomy suction.1 Previous research has shown that the combination of negative pressures and the massive air-blood interface exponentially increases hemolysis in suctioned blood. This research aims to decrease hemolysis by eliminating the air-to-blood interface by implementing the Venturi effect to create powerful suction. This research effort hypothesizes that the Venturi suction will result in less hemolysis, indicated by lower plasma free hemoglobin levels (PFH) compared to current vacuum suction. The research hypothesizes that a paradigm approach to cardiotomy suction that utilizes the Venturi effect with shorter tubing lengths and weighted sucker tips will further reduce hemolysis. The vacuum-suctioned blood showed PFH levels significantly increased from baseline levels (p=0.0039). Neither the Venturi nor paradigm groups showed PFH levels significantly increased from baseline levels (p=0.0625 and p=0.125, respectively). There was a significant difference in PFH levels among the three conditions (p<0.0001). The vacuum condition showed significantly higher levels of PFH compared to both the Venturi and the paradigm conditions (p<0.001 for both). There was no significant difference in the PFH levels between the Venturi and the paradigm groups (p=1.00). This study concludes that vacuum suction causes excessive hemolysis. A Venturi-powered suction system does not cause hemolysis and can be employed to reduce the damaging effects of vacuum suction on blood.

New Technology Mimics Physiologic Pulsatile Flow During Cardiopulmonary Bypass.

The VentriFlo True Pulse Pump (Design Mentor, Inc., Pelham, NH, USA) is the first blood pump designed to mimic human arterial waveforms in a standard oxygenation circuit. Our aim was to demonstrate the feasibility and safety of this pump in preparation for future studies to determine possible clinical advantages. We studied four piglets (41.4-46.2 kg): three with an implanted VentriFlo pulsatile pump and one with the nonpulsatile ROTAFLOW pump (MAQUET Holding B.V. & Co. KG, Rastatt, Germany) as a control. Hemodynamics was monitored during 6-h cardiopulmonary bypass (CPB) support and for 2 h after weaning off CPB. The VentriFlo demonstrated physiologic arterial waveforms with arterial pulse pressure of 24.6 ± 5.7 mm Hg. Pump flows (2.0 ± 0.1 L/min in ROTAFLOW; 1.9 ± 0.1 L/min in VentriFlo) and plasma free hemoglobin levels (27.9 ± 12.5 mg/dL in ROTAFLOW; 28.5 ± 14.2 mg/dL in VentriFlo) were also comparable, but systemic O2 extraction (as measured by arterial minus venous O2 saturation) registered slightly higher with the VentriFlo (63.2 ± 6.9%) than the ROTAFLOW (55.4 ± 6.5%). Histological findings showed no evidence of ischemic changes or thromboembolism. This pilot study demonstrated that the VentriFlo system generated pulsatile flow and maintained adequate perfusion of all organs during prolonged CPB.

Prevalence of hemolysis and metabolic acidosis in patients with circulatory failure supported with extracorporeal life support: a marker for survival?

Elevated levels of plasma free hemoglobin (fHb) indicate red blood cell (RBC) damage. The aim of this study was to analyze the prevalence of hemolysis and metabolic acidosis in patients on extracorporeal life support (ECLS) and to investigate whether it is a marker for outcome. This retrospective analysis included 215 adult patients with cardiac failure treated with ECLS. The cohort was divided into three groups: ECLS (1) during ongoing cardiopulmonary resuscitation (CPR, n = 110); (2) after CPR with return of spontaneous circulation and sustained cardiogenic shock (n = 45); (3) in severe cardiogenic shock without previous CPR (n = 60). Lactate, arterial pH value and fHb were measured daily before (pre-fHb) and during ECLS. CPR caused a pronounced increase in pre-fHb (group1, 318 (138/586) mg/L; group2, 212 (107/439) mg/L; group3, 79 (53/232) mg/L; p < 0.001). Within 24 hours on ECLS, fHb declined significantly. Compared to group 3 without CPR, group1 and 2 had a lower pH value (group1, 7.10 (6.93/7.20); group2, 7.21 (7.16/7.27); group3, 7.28 (7.20/7.35); p < 0.001), and an increased lactate level (group1, 88 (55/129) mg/dL; group2, 76 (36/111) mg/dL; group3, 52 (25/83) mg/dL; p < 0.0001). Multivariante analysis showed that pre-fHb had no prognostic value for survival. Only a low pre-lactate was a surrogate marker for successful weaning (p < 0.0001) and discharge from hospital (p = 0.0028). CPR was associated with a strongly increased fHb irrespective of ECLS. Implantation of ECLS did not aggravate hemolysis but instead decreased it within 24 hours. In this study low pre-fHb had no predictive value for survival.

Traumatic Hemothorax Blood Contains Elevated Levels of Microparticles that are Prothrombotic but Inhibit Platelet Aggregation.

Autotransfusion of shed blood from traumatic hemothorax is an attractive option for resuscitation of trauma patients in austere environments. However, previous analyses revealed that shed hemothorax (HX) blood is defibrinated, thrombocytopenic, and contains elevated levels of D-dimer. Mixing studies with normal pooled plasma demonstrated hypercoagulability, evoking concern for potentiation of acute traumatic coagulopathy. We hypothesized that induction of coagulopathic changes by shed HX blood may be due to increases in cellular microparticles (MP) and that these may also affect recipient platelet function. Shed HX blood was obtained from 17 adult trauma patients under an Institutional Review Board approved prospective observational protocol. Blood samples were collected every hour up to 4 h after thoracostomy tube placement. The corresponding plasma was isolated and frozen for analysis. The effects of shed HX frozen plasma (HFP) and isolated HX microparticles (HMP) on coagulation and platelet function were assessed through mixing studies with platelet-rich plasma at various dilutions followed by analysis with thromboelastometry (ROTEM), platelet aggregometry (Multiplate), enzyme-linked immunosorbent assays, and flow cytometry. Furthermore, HFP was assessed for von Willebrand factor antigen levels and multimer content, and plasma-free hemoglobin. ROTEM analysis demonstrated that diluted HFP and isolated HMP samples decreased clotting time, clotting formation time, and increased α angle, irrespective of sample concentrations, when compared with diluted control plasma. Isolated HMP inhibited platelet aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. HFP contained elevated levels of fibrin-degradation products and tissue factor compared with control fresh frozen plasma samples. MP concentrations in HFP were significantly increased and enriched in events positive for phosphatidylserine, tissue factor, CD235, CD45, CD41a, and CD14. von Willebrand factor (vWF) multimer analysis revealed significant loss of high molecular weight multimers in HFP samples. Plasma-free hemoglobin levels were 8-fold higher in HFP compared with fresh frozen plasma. HFP induces plasma hypercoagulability that is likely related to increased tissue factor and phosphatidylserine expression originating from cell-derived MP. In contrast, platelet dysfunction is induced by HMP, potentially aggravated by depletion of high molecular weight multimers of vWF. Thus, autologous transfusion of shed traumatic hemothorax blood may induce a range of undesirable effects in patients with acute traumatic coagulopathy.

TCT-135 Increased circulating plasma-free hemoglobin levels, not lactate dehydrogenase, levels identify hemolysis among patients with cardiogenic shock treated with an Impella micro-axial flow catheter

Hemolysis is a complication of micro-axial impeller pumps (Impella). Markers of hemolysis among LVADs include lactate dehydrogenase (LDH) >2.5 times the upper limit of normal (ULN) and plasma-free hemoglobin (pf-Hb) >20mg/dL. We studied the predictive value of LDH or pf-Hb as hemolytic markers in

Plasma Free Hemoglobin Is a Predictor of Acute Renal Failure During Adult Venous-Arterial Extracorporeal Membrane Oxygenation Support.

Hemolysis is a common and severe complication during extracorporeal membrane oxygenation (ECMO). Increased plasma free hemoglobin (PFHb) is related to renal injury. The aim of this study was to investigate whether increased PFHb during adult venous-arterial ECMO was associated with acute renal failure (ARF). A retrospective, observational, single-center study. Fuwai Hospital in Beijing, China. The study comprised 84 venous-arterial ECMO patients. None. A total of 84 consecutive adult patients (≥18 years) with cardiac diseases requiring venous-arterial ECMO support were studied retrospectively. Demographics of patients, clinical and ECMO characteristics, and PFHb level were collected within the first 3 days after ECMO. ARF was defined as a≥300% rise in serum creatinine from baseline or application of dialysis. Repeated measurement analysis of variance revealed that the main effect for the non-ARF group and ARF group in PFHb (p = 0.002) was significant. A significant main effect for time points (p<0.001) and time×group interaction (p = 0.014) in PFHb was obtained. In a multiple logistic regression model, peak PFHb during ECMO (odds ratio 1.052, 95% confidence interval 1.016-1.089, p = 0.005) was a risk factor for ARF during ECMO and patients who underwent heart transplantation (odds ratio 0.240, 95% confidence interval 0.060-0.964, p = 0.044) experienced less ARF. There was a linear correlation between peak serum creatinine and peak PFHb (Spearman's r = 0.223, p = 0.042). Increased PFHb is a predictor of ARF among adult patients on venous-arterial ECMO support.

Plasma Free Hemoglobin Is an Independent Predictor of Mortality among Patients on Extracorporeal Membrane Oxygenation Support.

BackgroundHemolysis is common in all extracorporeal circuits as evident by the elevated plasma free hemoglobin (PFHb) level. We investigated whether increased hemolysis during extracorporeal membrane oxygenation (ECMO) is an independent mortality predictor.MethodsWe performed a retrospective observational study of consecutive subjects who received ECMO at a tertiary care facility from 2007-2013 to investigate independent predictors of in-hospital mortality. We examined variables related to patient demographics, comorbidities, markers of hemolysis, ECMO characteristics, transfusion requirements, and complications. 24-hour PFHb> 50 mg/dL was used as a marker of severe hemolysis.Results154 patients received ECMO for cardiac (n= 115) or pulmonary (n=39) indications. Patients’ mean age was 51 years and 75.3% were males. Compared to nonsurvivors, survivors had lower pre-ECMO lactic acid (p=0.026), lower 24-hour lactic acid (p=0.023), shorter ECMO duration (P=0.01), fewer RBC transfusions on ECMO (p=0.008) and lower level of PFHb 24-hours post ECMO implantation (p=0.029). 24-hour PFHb> 50 mg/dL occurred in 3.9 % versus 15.5% of survivors and nonsurvivors, respectively, p=0.002. A Cox proportional hazard analysis identified PFHb> 50 mg/dL 24-hours post ECMO as an independent predictor of mortality (OR= 3.4, 95% confidence interval: 1.3 – 8.8, p= 0.011).ConclusionPFHb> 50 mg/dL checked 24-hour post ECMO implantation is a useful tool to predict mortality. We propose the routine checking of PFHb 24-hours after ECMO initiation for early identification and treatment of the cause of hemolysis.

Hemolysis of irradiated leukoreduced red blood cells during rapid warming: An in vitro experimental study.

BackgroundAlthough water chambers are often used as surrogate blood-warming devices to facilitate rapid warming of red blood cells (RBCs), these cells may be damaged if overheated. Moreover, filtered and irradiated RBCs may be damaged during the warming process, resulting in excessive hemolysis and extracellular potassium release.MethodsUsing hand-held syringes, each unit of irradiated and leukocyte-filtered RBCs was rapidly passed through a water chamber set to different temperatures (baseline before blood warming, 50℃, 60℃, and 70℃). The resulting plasma potassium and free hemoglobin levels were then measured.ResultsWarming RBCs to 60℃ and 70℃ induced significant increases in free hemoglobin (median [interquartile ranges] = 60.5 mg/dl [34.9–101.4] and 570.2 mg/dl [115.6–2289.7], respectively). Potassium levels after warming to 70℃ (31.4 ± 7.6 mEq/L) were significantly higher compared with baseline (29.7 ± 7.1 mEq/L; P = 0.029). Potassium levels were significantly correlated with storage duration after warming to 50℃ and 60℃ (r = 0.450 and P = 0.001; r = 0.351 and P = 0.015, respectively).ConclusionsRapid warming of irradiated leukoreduced RBCs to 50℃ may not further increase the extracellular release of hemoglobin or potassium. However, irradiated leukoreduced RBCs that have been in storage for long periods of time and contain higher levels of potassium should be infused with caution.

Modified TandemHeart Ventricular Assist Device for Infant and Pediatric Circulatory Support

The development of pediatric ventricular assist device (VAD) circuits with lower flow ranges for infants and small children is ongoing. We present our results with modifying a readily available adult VAD to support the pediatric population. The TandemHeart VAD (CardiacAssist, Pittsburgh, PA) circuit was modified to include a variable restrictive recirculation shunt to permit lower flow ranges in small pediatric patients. Initial benchtop flow rates and pressures were studied. Hemolysis trials were performed using whole bovine blood to compare plasma-free hemoglobin levels between modified and unmodified VAD circuits. The modified VAD was surgically implanted in 7 piglets (6 to 14 kg) and which supported them for 4 hours. Levels of hemolysis did not increase and full hemodynamic support was achieved. The modified TandemHeart VAD with a recirculation shunt was subsequently implanted in 2 pediatric patients who were bridged to transplant successfully. Because of its simplicity, availability, low prime volume, greater patient flow range, and lower cost, the modified TandemHeart VAD with a recirculation shunt should be considered as an alternative to extracorporeal membrane oxygenation and other pulsatile VADs in children.

Plasma Catalytic Iron, AKI, and Death among Critically Ill Patients

Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans. A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria. ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 µmol/l [interquartile range, 0.31-3.65] versus 0.29 µmol/l [0.22-0.46]; P<0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (rs=0.29; P<0.001) and plasma free hemoglobin levels on ICU day 1 (rs=0.32; P<0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality. Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.

In Vivo Testing of a Novel Blood Pump for Short-Term Extracorporeal Life Support

Centrifugal pumps are used increasingly for temporary mechanical support for the treatment of cardiogenic shock. However, centrifugal pumps can generate excessive negative pressure and are afterload sensitive. A previously developed modified roller pump mitigates these limitations both in vitro and in preliminary animal experiments. We report the results of intermediate-term testing of our evolving pump technology, known as the BioVAD. The BioVAD was implanted in 6 adult male sheep (62.5±3.9 kg), with drainage from the left atrium and reinfusion into the descending aorta. The sheep were monitored for 5 days. Heparin was given during the initial implantation, but no additional anticoagulants were given. Data collected included hemodynamic status, pump flow and pressures, laboratory values to monitor end-organ function and hemolysis, pathologic specimens to evaluate for thromboembolic events and organ ischemia, and explanted pump evaluation results. All animals survived the planned experimental duration and there were no pump malfunctions. Mean BioVAD flow was 3.57±0.30 L/min (57.1 mL/kg/min) and mean inlet pressure was -30.51±4.25 mm Hg. Laboratory values, including plasma free hemoglobin, creatinine, lactate, and bilirubin levels, remained normal. Three animals had small renal cortical infarcts, but there were no additional thromboembolic events or other abnormalities seen on pathologic examination. No thrombus was identified in the BioVAD blood flow path. The BioVAD performed well for 5 days in this animal model of temporary left ventricular assistance. Its potential advantages over centrifugal pumps may make it applicable for short-term mechanical circulatory support.

Hyperbilirubinemia Complicating Plasma-Free Hemoglobin and Antifactor Xa Level Monitoring on Venovenous Extracorporeal Membrane Oxygenation

Optical spectrophotometric methods are used to detect both plasma-free hemoglobin and antifactor Xa level, so hyperbilirubinemia can interfere with the measurement of both the monitoring laboratory tests for extracorporeal membrane oxygenation (ECMO) due to similar absorbance wavelengths. We present a seven-year-old child with acute respiratory failure on venovenous ECMO who developed an acute increase in plasma-free hemoglobin and undetectable antifactor Xa level due to acute hyperbilirubinemia from hepatic dysfunction related to antifungal therapy.

Mannitol‐adenine‐phosphate: a novel solution for intraoperative blood salvage

Intraoperative blood salvage (IBS) procedures include washing with normal saline (NS), which may deplete red blood cell (RBC) nutrients. The mannitol-adenine-phosphate (MAP) solution, commonly used for RBC preservation, provides glycolytic substrates; therefore, MAP should be a better solution than NS in IBS. In this study, we determined whether using MAP could reduce washing-associated RBC damage and destruction. Adenine nucleotide contents, RBC morphology, and plasma free hemoglobin (PF-Hb) level of RBCs treated with NS or MAP solution were compared under three conditions: (1) 4-hour preservation of fresh blood from healthy volunteers, (2) collection from the shed blood of patients, and 3) incubation of the collected shed blood with plasma. Adenine nucleotide level and RBC elongation index were greater and PF-Hb level was lower in MAP groups than NS groups (p < 0.05) after preservation and incubation. In NS, RBCs lost their deformability and became stomatocytes, and even RBC "ghosts" 48 hours after incubation, while they remained normal in MAP solution. The MAP solution helps preserve RBC morphology and function, and reduces hemolysis, possibly due to improved energy production. Therefore, MAP should replace NS during IBS.

Lactate dehydrogenase and Haemolysis Index as quality control markers of haemolysis in intra‐operative cell salvage

The aim of this investigation was to explore the potential use of the tests lactate dehydrogenase (LDH) and Haemolysis Index as haemolysis markers in intra-operative cell salvage (ICS) blood in comparison to plasma free haemoglobin levels. Quality control (QC) should be seen as a fundamental part of any ICS blood conservation programme, however, due to lack of available knowledge, familiarity and experience, QC is still a comparatively new subject. A QC pilot scheme is currently being undertaken by the Royal Cornwall Hospital in association with the UK Cell Salvage Action Group to explore potential markers that can be used to assess the quality of blood obtained from ICS. This test list should be available to all ICS users and achievable within financial budgets. Currently this proposed test list includes a full blood count, a protein marker such as urine albumin/microalbumin and heparin monitoring. Haemolysis testing is another key marker. Samples were collected from ICS processed blood and allogeneic SAGM leucodepleted red cell units and processed for plasma free haemoglobin, LDH and Haemolysis Index. There was a very strong correlation between plasma free haemoglobin and LDH (0.960), and plasma free haemoglobin and the Haemolysis Index (0.944). We have shown that the LDH and Haemolysis Index tests are suitable and reliable alternatives for measuring haemolysis from samples obtained from ICS or allogeneic blood. We have incorporated the LDH test into our Hospital's ICS QC package and recommend that this test is considered for all ICS QC samples.

In Vivo Testing of a Novel Blood Pump for Short-Term Extracorporeal Life Support

Purpose We developed a novel peristaltic-type blood pump that is preload-responsive and afterload-insensitive, generates minimal negative pressure, avoids cavitation, and can be augmented by vacuum-assisted drainage. The pump has previously been tested in vitro and in an in vivo model providing 4 hours of support. Our objective was to test the pump in a 4 to 5 day animal model, specifically examining its effects on hemolysis, thrombosis, and end-organ damage. Methods and Materials The pump was implanted in 4 adult male sheep (60.5±3.3kg) through a left thoracotomy, with drainage from the left atrium and reinfusion into the descending aorta. At the completion of the surgery, the sheep was extubated and supported for 4-5 days. Heparin was given during aortic cross-clamp (100 u/kg), but the sheep was not anticoagulated for the remainder of the study. Results Each of the 4 animals was instrumented without major complication. The sheep remained hemodynamically stable throughout the study, with mean arterial pressure of 104.08±9.19 mmHg. Average device flow was 3.42±0.24 L/min. The average pump inlet pressure was -28.39±3.15 mmHg. Plasma free hemoglobin levels decreased from a baseline of 2.03±1.52 mg/dL to 1.52±0.22 mg/dL at the completion of the study. Platelet levels slightly decreased from 244±179.32 K/μL to 174.25±111.55 K/μL. Creatinine levels remained stable from 1.00±0.18 mg/dL at baseline to 0.73±0.05 mg/dL at completion. Total bilirubin levels also remained stable, from 0.10±0 mg/dL to 0.175±0.10 mg/dL. Each animal survived without complication for the duration of the study (4-5 days), and was euthanized. On post-mortem necropsy, 1 animal had a renal infarct, but no other thromboembolic events or signs of organ damage were seen. Conclusions This pump can safely be implanted as a short-term extracorporeal support device for bridge to decision. It causes minimal hemolysis, thromboembolic phenomena, and organ damage. No manipulation of pump speed or suction is required, making it ideal for clinical use without the need for frequent adjustment by nursing.

Plasma-Free Hemoglobin Levels in Advanced vs. Conventional Infant and Pediatric Extracorporeal Life Support Circuits

Extracorporeal life support (ECLS) is a reliable method to support pediatric patients with reversible cardiorespiratory failure associated with congenital heart disease, respiratory insufficiency, or after cardiac surgery. In 2010, our institution adopted an infant/pediatric extracorporeal membrane oxygenation (ECMO) circuit that contains a magnetically levitated centrifugal pump, polymethylpentene oxygenator, and shorter tubing length (ECMO II circuit). Our prior circuit contained a nonocclusive roller pump, polypropylene oxygenator, venous compliance chamber, and hemoconcentrator (ECMO I circuit). A retrospective chart review comparing ECMO I and ECMO II daily plasma-free hemoglobin (PFH) values was conducted. We hypothesized that the PFH is similar between the two ECMO circuit groups. We reviewed medical records of children 3 years of age or younger weighing less than 13 kg who required ECLS between January 2008 and February 2012. PFH levels from 18 ECMO II patients were compared with levels in a retrospective group of an equal number of well-matched ECMO I circuit patients. There was no significant difference between ECMO I and ECMO II circuit groups regarding mean time on ECMO, age in days, and weight. There was also no significant difference in the group mean levels of PFH between ECMO I and ECMO II circuits. There was a significant increase in PFH with hours on ECMO (p &lt; .01) within and between both circuit groups (p &lt; .01) and a significantly greater increase in PFH with ECMO hours (p = .0091) in the ECMO I circuit group. Although there was no significant difference in average PFH with the change in ECMO II circuit technology, advancements such as the magnetically levitated blood pump and polymethylpentene gas exchange device has been associated with significantly fewer mechanical component change-outs (p = .0156) and less clots and fibrin build-up in the circuits (p = .0548).

Development of a Multifunctional Detoxifying Unit for Liver Failure Patients

Background/Aims: Extracorporeal blood detoxification strategies aimed at supporting impaired liver function have been explored because of the imbalance between donor organs and waiting patients. A limited number of artificial devices are now available clinically, and these are characterized by the use of multistage adsorption procedures in conjunction with hemodialysis, but these features simultaneously increase system complexity and treatment costs. Methods: The authors developed a simpler strategy for liver dialysis based on the use of a multifunctional filter, which enables plasma separation and perfusion in a single unit. Results: Liver dialysis treatments were successfully performed using the devised unit when bovine blood containing uremic and hepatic toxins was circulated. Removal of the solutes under investigation was significant, and reduction ratios of 78% for urea, 98% for creatinine and 91% for bilirubin were achieved. Plasma free hemoglobin levels were reasonably maintained despite prolonged blood recirculation for 5 h, and platelet, hematocrit and hemoglobin levels remained uniform throughout liver dialysis sessions. Conclusion: The devised liver support unit may offer a straightforward and efficient means of cleansing blood for patients with hepatic failure.

Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study

IntroductionThe increasing number of reports on the relation between transfusion of stored red blood cells (RBCs) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied.MethodsThirty patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb, haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120 minutes and 24 hours after transfusion. Differences were compared using Pearson's chi-square test or Fisher's exact test for dichotomous variables, or an independent-sample t test or Mann-Whitney U test for continuous data. Continuous, multiple-timepoint data were analyzed using repeated one-way analysis of variance or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson correlation.ResultsStorage duration correlated significantly with fHb concentrations and NO consumption within the storage medium (r = 0.51, P < 0.001 and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly increased circulating fHb and NO consumption in the recipient (P < 0.001 and P < 0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage duration of the blood products did not correlate with changes in fHb and NO consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations.ConclusionThese data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO consumption in the recipient. This finding may contribute to the potential pathophysiological mechanism underlying the much-discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.

Retrospective Hemolysis Comparison Between Patients With Centrifugal Biventricular Assist and Left Ventricular Assist Devices

Little is known about the hemolysis rate in the case of concomitant implantation of two continuous flow pumps for the treatment of biventricular heart failure. We present a retrospective study comparing the hemolysis parameters in patients supported with one implantable centrifugal pump of the type HeartWare HVAD used as a left ventricular assist device (LVAD) and with two pumps as a biventricular assist device (BiVAD). A total of 20 consecutive patients who received HeartWare BiVAD (n = 10) and LVAD (n = 10) support at our institution between September 2009 and September 2010 were examined. Hemolysis- and anemia-related parameters were analyzed after 2 weeks, 5 weeks, 3 months, and 6 months of support. Preoperative levels of hemoglobin, lactate dehydrogenase (LDH), and total bilirubin were similar in both groups. There were no differences in LDH, plasma-free hemoglobin (fHB), or total bilirubin levels postoperatively for up to 6 months. Only the haptoglobin level was lower in BiVAD recipients up to 3 months after surgery: 2nd week (63.5 [range: 8-237] mg/dl vs. 151 [range: 11-263] mg/dl, p = 0.05), 5th week (67 [range: 8-196] mg/dl vs. 215 [range: 56-292] mg/dl, p = 0.046), and after 3rd month (42 [range: 8-205] mg/dl vs. 220 [range: 157-256] mg/dl, p = 0.048). Our retrospective analysis of BiVAD HeartWare and LVAD HeartWare recipients showed a lack of a clinically important degree of hemolysis when two centrifugal HeartWare pumps are used for biventricular support.

Hemolysis at Different Vacuum Levels during Vacuum-Assisted Venous Drainage: A Prospective Randomized Clinical Trial

There are several reports on the application of variable degrees of vacuum pressure to hardshell venous reservoirs. The aim of the current study was to compare the hemolytic effects of vacuum-assisted venous drainage (VAVD) at two different vacuum levels with the classical gravity siphon method. A prospective, equally randomized (1: 1: 1), parallel group study was performed in elective coronary artery bypass grafting (CABG) operations. (n = 162) were divided into three groups: gravity siphon (group 1, n = 55), VAVD at -40 mmHg (group 2, n = 55) and VAVD at -80 mmHg (group 3, n = 52). Hemolysis tests were performed at 2, 24 and 48 h following the operations. There were no deaths in this study. Plasma-free hemoglobin (PfHb) levels showed a difference at 2 h (p < 0.001) compared to 24 h (p = 0.02) between the groups. Haptoglobin (Hp) levels also revealed hemolysis in groups 2 and 3 at all sampling times. Constant negative suction at -80 mmHg during elective coronary bypass operations caused more hemolysis. We do not recommend a constant suction of -80 mmHg for VAVD.