Donor Blood Volume Research Articles

Transplantation Outcomes in Hepatitis C Virus-Positive Donor Hearts After Circulatory Death

Although the use of hepatitis C virus (HCV)-positive hearts has been shown to be safe and effective among donors with donation after brain death (DBD), it remains unknown whether such organs recovered after circulatory death (DCD) have similar outcomes. In contradistinction to recovery from DBD using cold static organ storage, DCD procurement processes typically use normothermic-perfusion transport strategies that necessitate the use of a large volume of donor blood and involve exposure to temperatures oscillating between cold to dominantly normothermic conditions. We performed a retrospective analysis of United Network for Organ Sharing (UNOS) registry data in the United States and found that clinical outcomes do not differ with respect to rates of treated allograft rejection, early and 1-year survival. Ideally, the organ-recovery source should not result in a bias in organ-offer acceptance from HCV-positive donors, although long-term outcome data are yet unavailable.

Letter to the Editor: The Concept of Real‐Time Spectroscopy for Liver Viability Assessment

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the article by Ember et al., where the investigators explored the value of Raman spectroscopy to assess liver viability in a porcine model donated after circulator death (DCD) with subsequent normothermic regional perfusion (NRP).(1) The microvascular environment was analyzed through real‐time stimulated Raman spectroscopy (SRS) and histology. Trapped erythrocytes were quantified in ischemic liver areas through the intrinsic Raman signal of hemoglobin (excitation wavelength, 532 nm).(1) The investigators found a reduction of liver congestion with less red blood cells, stuck in the sinusoids after NRP. Removal of 10% of donor blood before treatment withdrawal and circulatory death was found to be protective and resulted in healthier sinusoids with less congestion.(1) Although the article targets the hot topic of viability assessment, a few points require clarification. The investigators suggest a reduction of donor blood volume before organ donation, to decrease organ injury for transplantation. However, any donor pretreatment, including heparin administration, before withdrawal of all supportive measures, is strictly prohibited in many countries. Following treatment withdrawal, DCD donors deteriorate until circulatory death occurs, with a subsequent mandatory stand‐off period (2‐30 minutes) worldwide. Super‐rapid donor laparotomy and cannulation with cold flush or NRP are only started after donor death confirmation. Any measures, which may accelerate natural donor deterioration, including a reduction of blood volume, is therefore a violation of the donation protocol. During combined thoracic‐abdominal DCD organ procurement, the donor blood, used for normothermic ex situ heart perfusion, is obtained after circulatory death.(2) Next, although we agree that a healthy microvasculature is important, it is only one contributor to liver viability, which should target the key players of liver function: mitochondria. Ischemia leads here to metabolite accumulation and energy loss.(3) At reperfusion, reactive oxygen species and flavin mononucleotides (FMNs) are released from mitochondrial complex‐I.(4) Additionally, this autofluoresecent, mitochondrial FMN can be easily quantified from various perfusates by real‐time fluorescence spectroscopy, as recently demonstrated during hypothermic oxygenated perfusion (HOPE; Fig. 1).(4) FMN concentration in HOPE perfusates has a high predictive accuracy for graft loss and posttransplant complications and was validated by mass spectometry.(5)FIG. 1: Real‐time spectroscopy for viability assessment before liver transplantation. Real‐time viability tests are currently a hot topic in solid organ transplantation. Various spectroscopic techniques are explored on tissues and perfusates. Donor and graft assessment is a staged procedure and involves multiple unspecific tests performed from donor to recipient center.( 1‐3 ) Fluorescence spectroscopy is a valuable tool for viability assessment from perfusates, obtained during machine perfusion. Mitochondrial molecules, including FMN, are released during reoxygenation of human tissue and represent mitochondrial function and injury to predict outcomes after transplantation of high‐risk donor organs.( 4 )In summary, various spectroscopic techniques are currently tested as important tools for future viability assessment. Author Contributions M.F.C., A.S.: Conception and design. M.F.C.: Acquisition of data. M.F.C., A.S.: Analysis and interpretation of data. M.F.C.: Drafting of the article. P.M., P.D., A.S.: Critical revision for important intellectual content. M.F.C., M.M., P.M., P.D., A.S.: Final approval of the published version.

The impact of donor total estimated blood volume on nucleated cell yield in bone marrow harvests for hematopoietic stem cell transplantation

Nucleated cell yields of marrow harvests depend on factors related to donors, the procedure itself, and the volume of marrow harvested. Few attempts have been made to relate donor characteristics to harvest volume. We hypothesize that the percentage of total donor blood volume accessed for harvesting impacts the nucleated cell yield per ml of marrow collected. We investigated 481 consecutive unrelated marrow harvests from a single center. Donor characteristics including weight, body mass index (BMI), white blood cells (WBCs), hemoglobin (Hgb), and platelet counts, as well as estimated total blood volume, were recorded and compared with nucleated cell yields and harvest volumes. The percentage of donor blood volume accessed for marrow harvesting was inversely related to nucleated cell yields (r = -0.57). The donor-recipient weight differential impacted cell yields as well (r = 0.35), with heavier recipients requiring increased marrow volumes from smaller donors to satisfy their nucleated cell needs. 3.73 × 108 /kg of recipient weight could be collected with 95% certainty when harvest volumes did not exceed 16.1% of donor total blood volume. In a stepwise multiple regression analysis, 45.4% of cell yield variance was explained by blood volume percentage accessed for harvesting, donor weight, and WBC. Donor sex, BMI, and platelet counts did not contribute further to cell yield variance. Smokers had higher cell yields than nonsmokers (20.4 vs. 18.3 × 106 /ml; 95% confidence interval 0.62, 3.47) independent of other parameters. Establishing the relationship between percentage of estimated donor total blood volume and recipient cell needs can facilitate donor selection for successful hematopoietic cell (HPC) transplants.

Impact of autologous blood transfusion after bone marrow harvest on unrelated donor's health and outcome: a CIBMTR analysis.

Pre-harvest autologous blood collection from bone marrow (BM) donors is performed to meet potential post-operative transfusion needs. This study examines the impact of autologous blood transfusion on BM donor's health and safety. The study included first-time unrelated BM donors from the United States whose BM harvest was facilitated by the National Marrow Donor Program (NMDP) centers between 2006 and 2017. Examination of 7024 BM donors revealed that 60% received at least one unit of autologous blood. The donors who received autologous blood were older, had lower hemoglobin pre-harvest, underwent longer duration of anesthesia, and higher volume BM harvest. Only donors who underwent high-volume BM harvest, defined as a BM harvest volume >27% of donor's blood volume, benefited from autologous transfusion. After a high-volume BM harvest, autologous blood transfusion was shown to decrease grade 2 to 4 collection-associated toxicities within 48 h of BM donation (p = 0.010) and shorten the time to donor-reported "complete" recovery from donation-associated symptoms (p < 0.001). Therefore, autologous transfusion could be avoided as support of marrow donation in the majority of unrelated BM donors and should be limited to cases where the planned BM harvest volume is expected to exceed 27% of donor's blood volume.

The benefits of iron supplementation following blood donation vary with baseline iron status.

Whole blood donation rapidly removes approximately 10% of a donor's blood volume and stimulates substantial changes in iron metabolism and erythropoiesis. We sought to identify donors who benefit from iron supplementation, describe the nature of the benefit, and define the time course for recovery from donation. Blood samples were collected over 24 weeks following whole blood donation from 193 participants, with 96 participants randomized to 37.5 mg daily oral iron. Changes in total body, red blood cell (RBC), and storage iron, hepcidin, erythropoietin, and reticulocyte count were modeled using semiparametric curves in a mixed model. and the changes were compared among six groups defined by baseline ferritin (<12; 12-50; ≥50 ng/mL) and iron supplementation. The effect of oral iron on storage and RBC iron recovery was minimal in donors with baseline ferritin ≥50 ng/mL, but sizeable when ferritin was <50 ng/mL. Iron initially absorbed went to RBC and storage iron pools when ferritin was <12 ng/mL but went mostly to RBCs when ferritin was ≥12 ng/mL. Donors with ferritin ≥12 ng/mL had a "ripple" increase in reticulocytes ~100 days after donation indicating physiological responses occur months following donation. Thus, iron supplements markedly enhance recovery from whole blood donation in donors with ferritin <50 ng/mL. However, full recovery from donation requires over 100 days when taking iron. The findings also highlight the value of the study of blood donors for understanding human hemoglobin and iron metabolism and their usefulness for future studies as additional biomarkers are discovered.

The HPC-a Collectogram: A Useful Tool for Determining Collection Processing Volumes

Introduction Optimal mobilization is an important step in the autologous hematopoietic cell transplant procedure. Mobilization requires the administration of growth factors such as filgrastim, a granulocyte colony stimulating factor, and plerixafor, a CXCR4 antagonist, that help release hematopoietic progenitor cells (HPC) from the marrow niche. HPCs are differentiated from other cells by their expression of CD34 on the cell surface. Through monitoring of CD34+ cells, the transplant team assesses how well a donor is mobilizing and can adjust mobilization and collection plans accordingly. This enables decision-making on the use of plerixafor and the volume of whole blood to be processed (WBP). Objective We developed the HPC- A Collectogram to help determine the volume of WBP depending on the assumed collection efficiency (CE2). This tool, built in Excel utilizes embedded formulas with input variables including target CD34 dose, dosing weight, blood volume, total WBC, peripheral blood CD34%, PBCD34 count and assumed CE2 (Figure 1). The CE2 at the time of the collection is unknown however an educated guess is made based on the median CE2 for previous collections at our center. The CE2 is a measurement of the apheresis instrument's ability to separate and extract the maximum number of CD34+ cells from cells available in the peripheral blood; yet the CE2 may be heavily influenced by variables such as donor and blood characteristics, as well as apheresis machine software/program and operator adjustments. Method Utilizing the known median CE2 value as a guide, the HPC-A Collectogram can be utilized to predict collection volumes that meet exact collection goals within an acceptable range. The decision to restrict collection based on a calculated processing volume may prevent undesirable side effects of a prolonged apheresis procedure and the over-collection of HPCs. Results For example, Jane Donor, weight 69.9 Kg, height 170.2 cm, WBC 52.2 K/uL, CD34% 0.196: To use the HPC-A Collectogram to guide collection in this patient, the user should: (1) Enter values for prescribed dose and dosing weight to calculate the absolute CD34 dose. (2) Enter current height and weight into the appropriate gender column to calculate donor blood volume. (3) Enter collection day WBC and CD34% as a decimal to determine the PBCD34 and to populate WBP and the target blood volume (BV) (the number of times the donor blood volume will need to be circulated through the apheresis instrument). (4) Choose the target BV to run based on the expected efficiency. For this example, run 3.73 BVs for an expected 40% efficiency to collect 10 million CD34+ cells/kg (Figure 2). Conclusion The HPC-A Collectogram can be a useful tool to more efficiently assist transplant team members in determining the volume of WBP required to meet prescribed dosing goals for hematopoietic cell transplantation.

Адміністративна процедура у царині донорства крові та її компонентів

Адміністративна процедура у царині донорства крові та її компонентів

The Safe and Effective Plateletpheresis

At the Research and Production Center of Transfusion platelet production have mainly supported (about 99%) by apheresis. However, apheresis donations have limitations caused by donor fitness due to both their preferences and their platelet pre-count validity. So, it is important to maintain of single donor high-dose plateletpheresis by improving its efficacy and safety. The aim of study was to develop of safe-effective approaches of plateletpheresis. Donors had been attracted to the study if they had filed of informed consent for post-collection blood sampling in advance. They were selected with following criteria: male, age 18-60 years, weight ≥ 55 kg, Hb ≥ 125.0 g/L, PLTs ≥ 160.0 × 109/L. Target number of platelets need to be obtained was chosen under calculation of estimated donor post-collection platelets. Platelets were harvested by «Hemonetics MCS plus» separators with LDP protocol, blood samples were counted by «Sysmex» hematology analyzer. Thus, 16 apheresis procedures with volunteer-donors were studied. The following results are demonstrated in the present study: donor pre-collection platelets 286.0 × 109/L ± 27.2; donor blood volume calculated by separator 5481.6 mL ± 408.5; platelet yield 473.1 × 109/unit ± 47.7; donor blood processed 3190.8 mL ± 189.7; donor platelets processed 763.0 × 109 ± 55.6; actual donor post-collection platelets measured by lab 193.3 × 109/L ± 18.6; platelet collection efficacy 61.9% ± 3.0. The values of estimated postcollection platelets 199.0 × 109/L ± 21.3 were not significantly different from those with actual post-collection platelets 193.3 × 109/L ± 18.6 (χ2=0.401). Thus, plateletpheresis efficacy has to be controlled using calculation of estimated donor post-collection platelets by making sure that safe threshold of post-apheresis platelet number is provided. The further studies have to be proceeding due to small number of observations.

Collection and Processing Considerations in Haploidentical Stem Cell Transplantation Utilizing a 2-Step Methodology

Title: Collection and Processing Considerations in Haploidentical Stem Cell Transplantation Utilizing a 2-Step MethodologyBackground: Haploidentical transplantation is an active area of research because only about one-third of patients have an HLA-matched sibling and searching for an HLA-matched-unrelated donor can delay urgent need for alloBMT. However, nearly all patients have HLA-haploidentical related donors. The incidence of graft rejection, infection, and GVHD has been minimized by improving conditioning regimens and the use of cyclophosphamide-based T-cell tolerization. There are unique collection and processing considerations associated with such transplants. We describe the unique collection considerations for the Thomas Jefferson University 2 Step regimen (TJU2) (Grosso D, Blood 2011), where the donor lymphocyte infusion (DLI) precedes the CD34+ selected hematopoietic progenitor cell (HPC) transplant.The DLI target dose in this study is fixed at 2 x 10e8 CD3+/recipient kg. The HPC collection is CD34+ cell selected. The post-selection target cell doses/recipient kg are 2-10 x10e6 CD34+ cells and < 5 x 10e4 CD3+ cells. The points to consider in determining donor blood volume to be processed during apheresis collection are:1. Although 0.14 x 10e8 CD3+/L processed/recipient kg is a median CD3+ dose collected with G-CSF mobilization (Korbling, JCA 2001), where the absolute lymphocyte count increases ~2-fold above its baseline (Holig, Blood 2009, Anderlini Transfusion 1996), the median dose for a non-mobilized collection is 0.07 x 10e8 CD3+/L processed/recipient kg (Korbling, JCA 2001). Therefore large volume DLI collection may need to be performed.2. The collection facility's lymphocyte or CD3+ collection efficiency. Donor pre-collection peripheral blood CD3+ count is typically not available.3. The collection facility's CD34+ cell collection efficiency. This can be calculated because the donor's peripheral blood CD34+ cell count is typically available.4. Higher CD34+ cell doses appear to be beneficial in haploidentical transplant (Reisner, Blood 2011). Therefore we designed the HPC collection volume to obtain a post-CD34+ cell selection target dose of 7 x 10e6/recipient kg.5. The processing facility's CD34+cell selection recovery. This typically varies from 30-100%.Methods: All procedures except one DLI (performed with the Spectra Optia CMNC) were performed using the Cobe Spectra MNC procedure (Terumo Corp). The following algorithms were used to estimate the donor blood volume ideally to be processed to ensure that target doses were reached:DLI: [(recipient kg x CD3 target/kg) / (0.6 x ALC)] / (median lymphocyte CE)0.6 is the lower limit of a normal percentage of CD3+ lymphocytesALC = donor absolute lymphocyte concentration on the day of collectionCE = collection efficiency (facility-specific median = 0.58)HPC: [(recipient kg x post-selection CD34 target/kg) / PB CD34+] / (median CD34 CE) / (minimum CD34 selection recovery)Post-selection CD34 target/kg = 7 x 10e6/kgPB CD34+ = donor peripheral blood CD34+ concentration on day of collectionCE = collection efficiency (facility-specific median = 0.45)Facility-specific minimal CD34+ selection recovery=0.31CD 34+ cell enriched products were obtained by incubation of mobilized HPC, Apheresis products with Miltenyi CD34+ reagent and subsequent positive selection on the CliniMACS Plus (Milteyi Biotec GmbH) according to manufacturer's specifications.Results: Our results in 6 donor-recipient pairs were the following:Discussion: The variability in the predictive value is due to variabilities in lymphocyte CE (range 0.38-0.94), CD34+ CE (range 0.36-0.67), and CD34+ selection recovery (range 0.31-0.81). Nevertheless, the correlation coefficients are high and as the ranges of CEs and CD34+ selection recovery are optimized and narrowed, the predictive value of these formulas will increase. Of note, all collections except one were performed with the Cobe Spectra MNC procedure. With the transition to the Optia CMNC procedure, where the collection interface is controlled by the device, the CEs are expected to become more consistent. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Plerixafor As a Salvage Regimen to Mobilize Allogeneic Stem Cells in Healthy Volunteers (NCT01954914)

Introduction: Insufficient yield of Peripheral Blood Progenitor Cells (PBPC) from healthy donors can result in higher mortality after allogeneic transplantation. Plerixafor (Mozobil®) is approved for the mobilization of PBPC in combination with G-CSF for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma. Clinical data on G-CSF and Plerixafor in healthy donors are still limited. In a prospective single arm phase 2 trial we investigated the safety and efficacy of a single dose of Plerixafor as a salvage regimen in poor mobilizing allogeneic PBPC donors (NCT01954914).Methods: We enrolled healthy unrelated PBPC donors who had received G-CSF (Lenograstim) at a targed dose of 10 µg/kg bodyweight (bw) for five days but donated less than 2x 106 CD34+ cells/kg recipient bw during the 1st apheresis on day 5 of the mobilization regimen. Plerixafor was injected subcutaneously at a dose of 240µg/kg once on day 5 in the evening before the second leukapheresis. The target for the processed blood volume during each apheresis procedure was 3x donor blood volume +/- 25%. Mobilization success was defined by a donation of more than 4.5x 106CD34+ cells/kg recipient bw. Primary endpoint was the number of mobilization successes. The null hypothesis (success rate of less than 50%) was tested with an exact single sample binomial test at a one-sided significance level of 5%.Results: Between 1/2014 and 12/2015 37 allogeneic unrelated PBPC donors (54% women, 46% men, median age 34 years) were enrolled into the study. The median donor bw was 69 kg (IQR, 61 kg to 76 kg) and the median recipient bw was 85 kg (IQR, 74 kg to 102 kg). Application of Plerixafor was well tolerated in most donors with only moderate side effects such as nausea, diarrhea and occasional vomiting. The median CD34+ count in peripheral blood was 15.4/µl (IQR, 12.0-18.3) on day 5 after G-CSF alone and 44.0/µl (IQR, 38.0-60.5) on day 6 after G-CSF plus Plerixafor. The collected total nucleated cell count was 187 x 106 (IQR, 159.9-223.4) cells per ml volume of the apheresis product on day 5 and 289 x 106 (IQR, 248.0-348.0) cells per ml volume of the apheresis product on day 6. The yield of CD34+ cells in the apheresis products was 1.05 x 108 (range, 0.21-1.80) on day 5 and 2.8 x108(range, 0.93-5.26) on day 6. The percentage of CD3+ cells per TNC was 31% (IQR 27%-40%) and 31% (IQR, 23% - 35%) on days 5 and 6, respectively.In total, a median number of 5.16 x 106 CD34+ cells (IQR 3.06-6.10) per kg recipient weight were collected during both aphereses. Twenty-one out of 37 donors reached the target cell count (56.8%, 95% confidence interval (CI) 39.5% - 72.9%) by donating a CD34+ cell dose of >4.5x 106 CD34+ cells per kg recipient bw. Nine donors had donated ≤0.8 106 CD34+ cells per kg recipient bw during their first leukaphersis after stimulation with G-CSF alone. Notably, only one out of these nine very poor mobilizing donors failed to donate at least 2.0 x 106CD 34+ cells per kg recipient bw after salvage mobilization with Plerixafor. Nevertheless, the null hypothesis (H0: rate of mobilization success <50%) could not be rejected at the 5% level (p= 0.2557).Conclusions: In this trial in poor mobilizing healthy unrelated donors the rate of mobilization success (donation of >4.5x 106 CD34+ cells per kg recipient bw) was 56.8% (95%-CI 39.5% - 72.9%) after a single dose of Plerixafor on day 5 of G-CSF administration. After injection of Plerixafor the CD34+count in the peripheral blood and the yield of CD34+ cells in the leukapheresis product increased by more than factor 2. The application of G-CSF and Plerixafor was well tolerated by most of the donors. Like for autologous donors, the administration of Plerixafor appears promising to optimize PBPC mobilization in allogeneic poor mobilizing donors. DisclosuresHoelig:Janssen Cilag GmbH: Honoraria; Therakos: Honoraria, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schetelig:Sanofi: Honoraria.

Improved donor safety in high-volume apheresis collections.

Separators use 1960s sex-based nomograms to estimate apheresis donor blood volume and to calculate the 15% maximum extracorporeal and collection volumes. As US body habitus changes, proportional overestimation of the maximum safe collection volume may become clinically significant with large-volume collections. We correlated 2 years of vasovagal reaction (VVR) data with 148,416 Trima apheresis procedure parameters to identify trends. Only platelet/plasma with or without red blood cell (RBC) procedures yielded collection volumes of at least 900 mL with no saline replacement. Vasovagal events of any severity were correlated by sex with actual collection volume and donor estimated blood volume (EBV). We performed multivariable analysis incorporating the factors that influence VVR rates to assess the significance of EBV and collection volume. VVR rates nearly doubled in male donors who had collection volumes greater than 1050 mL. No reaction threshold could be identified in female donors. This was confirmed in multivariable analysis that included donor sex, age, donation experience, draw time, and reporting location. Limiting apheresis collections to the lesser of 1050 mL or 15% EBV may reduce VVR rates. Further confirmation of this finding by other collection centers is desirable.

Side effects of blood donation by apheresis

Apheresis is a method of obtaining one ore more blood components by machine processing of whole blood in which the residual components are returned to the donor or patient during or at the end of the process. To prevent clotting, immediately next to the needle, the donor’s/patient’s whole blood is mixed with an anticoagulant solution (usually trisodium citrate) in a specific whole blood to anticoagulant ratio. For apheresis techniques, specially developed machines which are classified as medical devices are used. Special disposables are available for each type of apheresis and each type of machine. The sterile disposable, incorporating collection bags, bacterial and/or separation filters and/or centrifuge chambers, etc., is placed in the machine. The disposable is classed as an open or closed system. To separate the requested blood component from the nonrequested components various techniques can be used, such as filtrationor centrifugation techniques, or a combination of both. Besides these two techniques, also elutriation and absorption techniques are applied. The apheresis procedure can be performed using a continuous flow technique or a discontinuous flow technique. In continuous flow techniques the blood is drawn, processed and returned at the same time. Two venipunctures are needed. In discontinuous flow techniques only one venipuncture is needed. Modern apheresis machines are computer-controlled devices with multiple safety features for both the donor/patient and collected product. Examples are monitoring the pressure in the draw/return line to the donor/patient during draw and return phase. If the pressure exceeds predetermined values set by the manufacturer the process stops and sounds an alarm. This prevents a too low or too high pressure in the vein of the donor. With many machines with the same sensors the pressure in the disposable, and therefore the possibility for wrong installation of the disposable on the machine or leakage of the disposable is monitored. Other sensors (with or without combination of cameras) take care of the collection of the intended blood components. Also one or more air detectors are included in the apheresis equipment. If a sensor detects air in the tubing the procedure stops and an alarm will sound. This prevents any risk of air entering the donor’s vein. The volume of donor blood processed and collected by the machine is accurately monitored. In procedures where the donor’s/patient’s height and weight are entered into the machine’s software, the donor is protected by the apheresis machine from removal of more than 15% of the donor’s total blood volume. The volume of anticoagulant during an apheresis procedure added to the donor blood is closely monitored. Fluid leakage in a centrifuge chamber is detected by sensors. If leakage occurs the process stops and an alarm sounds. S7 Side effects of blood donation by apheresis M. Neyrinck, H. Vrielink. AZ Delta hospital, Roeselare, Belgium; Sanquin Blood supply, Amsterdam, The Netherlands

Assessment of five formulae to predict post-transfusion packed cell volume in cats.

This retrospective study aimed to identify the most accurate formula for estimating the increase in packed cell volume (PCV) after whole blood transfusion of cats, as several formulae have been reported but not validated. Forty cats, of varying breeds and gender, were included from two referral institutions after database searches over a 13 year period. Five formulae were used to calculate an estimated post-transfusion PCV based on the re-working of formulae for determining the volume of donor blood to be transfused; three formulae were derived from those previously reported in the feline literature and two from human paediatric medicine, where a similar mean blood volume has been described. Cats were subdivided into two groups, the first consisting of 17 cats with non-regenerative anaemia and the second consisting of 23 cats with ongoing losses such as haemolysis and haemorrhage; it was hypothesised that formulae could be more accurate for group 1 cats, whereas formulae applied to group 2 cats could have overestimated the post-transfusion PCV. Bland-Altman analysis was performed for all cats to compare the actual increase in PCV with the calculated increase for the five formulae. Formula 1 (PCV % increase = volume of blood transfused in ml/2 × bodyweight in kg) performed best overall and is easy to calculate; however, no single formula was highly accurate at predicting the PCV increase after whole blood transfusion in cats and, owing to the wide confidence intervals, these formulae should be applied judiciously in the clinical setting.

A Tale of Two Hospitals: The Evolution of Phototherapy Treatment for Neonatal Jaundice

* Abbreviations: Rh — : Rhesus factor TSB — : total serum bilirubin Phototherapy was developed in the late 1950s and is today considered the mainstay of managing neonatal jaundice. Yet prominent academic leaders continued to promote the older approach of exchange transfusion well into the 1970s, despite the considerable risks involved. This article explores why phototherapy took so long to be embraced, and how pediatric residents were caught in the middle of the controversy.—Jeffrey P. Baker, MD, PhDSection Editor, Historical Perspectives The chief rationale of treating newborn jaundice is the prevention of kernicterus, a devastating and often fatal outcome attributed to bilirubin’s effects on the basal ganglia. Infants so affected commonly develop a characteristic choreoathetoid form of cerebral palsy accompanied by severe intellectual disability.1 In the mid-20th century, pediatric researchers scored a breakthrough by demonstrating the efficacy of exchange transfusion in preventing this devastating syndrome. The majority of infants thus treated were Rhesus factor positive (Rh+) children born to Rh– mothers exposed to the Rh factor during a previous pregnancy. Maternal antibodies to neonatal red blood cells caused extensive hemolysis, causing the total bilirubin level to rise rapidly and overwhelm the liver’s ability to process and excrete it. Exchange transfusion, rarely performed today, was a challenging procedure that might keep physicians up all night, patiently withdrawing the infant’s blood through an umbilical venous catheter in small increments by syringe and replacing them with an equal volume of donor blood. The procedure was technically difficult and fraught with the possibility of a fatal electrolyte or fluid imbalance.2 In the late 1950s, phototherapy emerged as another potential treatment of jaundice. In 1956 at Rochford General Hospital in Essex, England, Sister J. Ward noted that sunshine decreased neonatal jaundice. Meanwhile, hospital biochemists noted erroneously low bilirubin levels in samples sitting in sunlight before processing.3 Soon afterward came the first evidence … Address correspondence to Elliott Mark Weiss, MD, 550 First Ave #NBV 8S4-11, Department of Pediatrics, NYU School of Medicine, New York NY 10016. E-mail: elliottmweiss{at}gmail.com

Faint and pre‐faint reactions in whole blood donors: predictive value of pre‐donation measurements

Background A small proportion of blood donors have adverse reactions. The purpose of this study was to determine predictors of faint and significant hypotensive reactions that could serve as targets for interventions to reduce reactions, thus improving the blood donation experience for those at higher risk of reactions and reducing the risk of serious adverse events.Methods The records of 422,231 allogeneic whole blood donations from a 9‐month period were assessed for adverse reactions. Incidents related to needle insertion, such as hematoma were excluded. Demographic, biometric, and clinical measurements were collected. Reactions were analyzed by multivariate logistic regression analysis comparing donors with any adverse reaction to donors without reactions and by stratified rates according to reaction severity.Results The overall reaction prevalence was 1·43%. Of the reactions, 63%, 29% and 8% were classified as mild, moderate and severe, respectively. Markers of reactions were: age, gender, race, blood volume, blood pressure, pulse and body mass index. Compared to donors without reactions, the strongest predictor of a reaction was a donor's blood volume &lt;3500 ml (OR 2·9, 95% CI 2·57–3·23). Age and first time status were also associated with a significantly higher risk of reaction with 17–18 years olds (OR 2·8, 95% CI 2·59–2·98) and 19–24 year olds (OR 2·39, 95% CI 2·23–2·56) at higher risk compared to 25–65 year olds, and first time donors at higher risk compared to repeat donors (OR 2·2, 95% CI 2·07–2·33). Using a lower weight limit of 50 kg does not prevent donors from giving more than 15% of their blood volume.Conclusion The results of this study are helpful in identifying donors at risk for adverse reactions and in understanding the contributors to reactions. Donor blood volume was a strong predictor of reaction. Selecting donors using blood volume, not weight, should reduce the frequency of reactions.

Faint and prefaint reactions in whole‐blood donors: an analysis of predonation measurements and their predictive value

A small proportion of blood donors have adverse reactions. The purpose of this study was to determine predictors of faint and significant hypotensive reactions that could serve as targets for interventions to reduce reactions, thus improving the blood donation experience for those at higher risk of reactions and reducing the risk of serious adverse events. The records of 422,231 allogeneic whole-blood donations from a 9-month period were assessed for adverse reactions. Incidents related to needle insertion, such as hematoma, were excluded. Demographic, biometric, and clinical measurements were collected. Reactions were analyzed by multivariate logistic regression analysis comparing donors with any adverse reaction to donors without reactions and by stratified rates according to reaction severity. The overall reaction prevalence was 1.43 percent. Of the reactions, 63, 29, and 8 percent were classified as mild, moderate, and severe, respectively. Markers of reactions were age, sex, race, blood volume, blood pressure, pulse, and body mass index. Compared to donors without reactions, the strongest predictor of a reaction was a donor's blood volume of less than 3500 mL (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.57-3.23). Age and first-time status were also associated with a significantly higher risk of reaction with 17- to 18-year-olds (OR, 2.8; 95% CI, 2.59-2.98) and 19- to 24-year-olds (OR, 2.39; 95% CI, 2.23-2.56) at higher risk compared to 25- to 65-year-olds and first-time donors at higher risk compared to repeat donors (OR, 2.2; 95% CI, 2.07-2.33). The results of this study are helpful in identifying donors at risk for adverse reactions and in understanding the contributors to reactions. Donor blood volume was an unexpectedly strong predictor of reaction. Potential interventions to reduce the frequency of reaction are discussed.

Simulated Sequential Laser Therapy of Twin–Twin Transfusion Syndrome

Sequential laser therapy of twin–twin transfusion syndrome (TTTS) includes laser obliteration of arteriovenous (AV) anastomoses from donor to recipient (AVDR) before obliterating AV anastomoses from recipient to donor (AVRD). This strategy allows for a beneficial intra-operative transfusion of blood from the hypervolemic recipient to the hypovolemic donor. In the present study, we sought to analyze the benefits and risks of sequential laser therapy with our computational model to aid its more widespread introduction. We simulated an equally shared placenta with an AVDR and a smaller diameter AVRD causing TTTS at 20 weeks. Laser coagulation and various volumes and directions of inter-twin transfusion were simulated at 21 weeks. A typical result is that when an AVDR is coagulated first, and 10 min later the AVRD with inner diameter of about 1 mm, an inter-twin transfusion of 25 ml may result from the recipient to the donor, based on literature data of AV flow versus diameter. This procedure causes a simulated loss of 50% of the recipient's blood volume. The opposite coagulation sequence, thus coagulating the AVRD first, 10 min later followed by the AVDR of 1 mm inner diameter, causes a loss of the donor's blood volume of 64%. In conclusion, our simulations support the concept of sequential laser therapy for TTTS and suggest directions for an improved safety and efficacy of this strategy.

Volunteer Unrelated Donor PBSC Collection Efficacy and Recipient Outcomes: Results of a Prospective National Marrow Donor Program (NMDP) Trial, 1999–2003.

In spite of limited multi-institutional outcome data and concern about high rates of chronic GVHD, PBSC has become the most frequently used unrelated donor stem cell source. We present an analysis of 1178 non-T-cell depleted donor/recipient pairs enrolled on a prospective trial conducted by the NMDP (1999–2003; med f/u 762 d). Multivariate analysis revealed that younger donors, heavier donors, or donors with higher pre-apheresis CD34+ cell numbers gave significantly higher CD34+ yields. The median time to neutrophil and platelet engraftment >50K was 14 and 24 days, respectively. Recipients were more likely to have neutrophil engraftment by day 25 if the pre-BMT Karnofsky score was ≥90 (OR 0.31 for <90, p<0.001) or if the donor blood volume processed was about 24 L (OR 2.88 for 24L vs. <19L, p=0.006). Recipients were more likely to engraft platelets by day 60 if their Karnofsky score was ≥90 (OR 0.66 for <90, p=0.006), they were CMV seronegative (OR 0.66 for CMV+, p=0.004) or the number of CD34+ cells/kg recipient wt in the infused product was higher (OR 2.94 for >9.5x106 CD34+ cells/kg vs <3.6, p<0.001). Surprisingly, a higher incidence of grade II-IV aGvHD at 100 days was noted in pediatric compared to adult patients (58% vs. 45%, p = 0.009), although rates of grade III-IV aGvHD were similar (31 vs. 26%, p= 0.28). Adjustment for the lower rate of reduced intensity conditioning (RIC) performed in children (15% vs. 45%) plus a higher mismatch rate (14% vs. 10%) explained some but not all of this effect (RR decreased from 1.62 to 1.29). Lower rates of grade II-IV aGVHD were also noted for HLA matched vs mismatched (45 vs. 56%, p = 0.017), and RIC vs. myeloablative patients (39 vs. 51%, p < 0.0001). FK506 was superior to CsA-based regimens in preventing grade II-IV aGvHD (RR 0.73, p=0.003). Of note, higher total WBC in the infused product was found to be associated with a lower risk of developing grade III-IV aGvHD (<45 x 109 vs ≥ 91 x 109, RR 0.64, p=0.009). Among 565 recipients who developed cGvHD (cumulative incidence 50% in adult and 58% in pediatric recipients at 2 yrs), 110 (19%) had limited and 455 (81%) extensive involvement. Chronic GvHD occurred more often with CsA vs. FK506 (RR 0.64 for FK506, p<0.001). An advantage in survival at one year was noted for early vs. intermediate vs. high risk disease (1yr OS 57 vs. 45 vs. 33%, p < 0.0001) and 6/6 HLA matched vs. mismatched groups (1yr OS 48 vs. 38%, p = 0.007). At latest follow up, the risk of dying was higher in recipients who had a Karnofsky score <90 (RR 1.56, p<0.001), were CMV seropositive (RR 1.23, p=0.006), had an HLA-mismatched donor (RR 1.46, p=0.001), or received a myeloablative transplant (RIC RR 0.73, p<0.001). In addition, smaller product volume or lower platelet count in the product also resulted in poorer survival (high vs. low RR of 0.70 (volume ) and 0.82 (platelets), p=0.005). In conclusion, unrelated donor PBSC results in rapid engraftment and acceptable long-term survival outcomes, but cGVHD occurs in >50% of recipients. Better outcomes are associated with use of FK-506, 24L of collection, higher product cell counts, RIC regimens, matched donors, low risk disease and high Karnofsky scores. Pediatric recipients have similar or worse GvHD outcomes compared to adults.

Blood volume regulation in donors undergoing intermittent‐flow plasmapheresis involving a high extracorporeal blood volume

Intermittent-flow plasmapheresis (IFP) often involves a large extracorporeal blood volume (ECV) of donors during donation. Depending on equipment and donor characteristics, ECV can exceed 20 percent of a donor's blood volume (BV). It was the aim of this study to delineate mechanisms of BV regulation associated with these volume shifts. Parameters of BV regulation were recorded in 60 donors (30 men, 30 women) undergoing IFP, who were randomly selected after stratification for sex and BV. Shock index (SI), stroke volume (SV), cardiac index (CI), and thoracic fluid content (TFC) were determined at the beginning of the procedure and when maximum ECV (ECV(max)) was reached with noninvasive techniques. In a control investigation, donors were kept in reclined position for the duration of an IFP session without actually donating. SI increased significantly during IFP (+0.18; p < 0.0001). SV decreased significantly (-14.3 mL/stroke; p < 0.0001). CI did not decrease significantly (-0.07 L/min/m(2) body surface area; p = 0.33). Preservation of CI was due to a significant rise in heart rate (+13.4 beats/min; p < 0.0001). TFC decreased significantly during IFP (-0.77 kOmega(-1); p < 0.0001), indicating the development of an intravascular volume deficit. The changes of SI, heart rate, and TFC weakly correlated with ECV(max). The hemodynamic response during IFP is consistent with a hypovolemic challenge of the donors and is sufficient to maintain cardiac function. ECV(max) during donation does not reliably predict the degree of hypovolemic stress, as long as it remains below 20 percent. This might warrant reevaluation of collection limits based on ECV(max).

A new method to determine the feto-placental volume based on dilution of fetal haemoglobin and an estimation of plasma fluid loss after intrauterine intravascular transfusion.

(1) To calculate the feto-placental volume (FPV), using the haematocrit (Ht) values and the percentages of fetal haemoglobin (HbF), before and after red blood cell transfusion. (2) To estimate the transfusion-induced loss of plasma fluid. Retrospective analysis of data of 42 anaemic fetuses at the first transfusion [gestational age (GA) 19-36 weeks]. Department of Obstetrics, Leiden University Medical Centre, The Netherlands. Fifteen hydropic and 27 non-hydropic fetuses. Donor blood volume (V(donor)) and Ht (Ht(donor)), fetal pre- and post-transfusion Ht values (Ht(initial), Htfinal) and percentages of HbF (HbF(initial) and HbF(final)) were used to calculate the FPV. The total red cell volume after transfusion (RCV(final)) and Ht(final) were used to estimate the plasma fluid loss. Feto-placental blood volume and loss of plasma fluid. The equations that use Htfinal over-estimate the FPV when the formula does not account for the difference between donor and post-transfusion Ht (FPV(Ht) = 21.36 * GA, - 390; r = 0.89). FPV is underestimated (FPV(Ht) = 9.90 * GA - 172; r = 0.84) when the blood volume increases with a volume less than the added donor blood volume. The calculation of FPV, using HbF percentages and the initial fetal RCV, is independent of volume changes (FPVHbF = 15.10 * GA - 279; r = 0.85). Comparing RCV(final) and Ht(final) values showed that 31.1 +/- 14.5% of the transfused volume was lost. Results of the hydropic fetuses did not differ from those of the non-hydropic fetuses. FPV values based on Ht values are less reliable than those based on RCV and HbF findings. When, for practical reasons, Ht values have to be used, we propose an adapted equation for the calculation of the necessary volume of donor blood: V(donor) = FPV(HbF) * (Ht(final) - Ht(initial) / (Ht(donor) - 0.70 * Ht(final)).