Donor Exposure Research Articles

Platelet Transfusion - Back to Basics

As in many aspects of transfusion medicine, practices have developed based on low levels of evidence. Let’s review some assumptions and think how these might change in future:- (1) Indications. 80% of platelet transfusions are given prophylactically to patients with bone marrow failure, yet no trials have demonstrated the value of prophylaxis over treatment of bleeding alone. (2) Trigger. A trigger of 10 × 10 g/l is now accepted. Reducing this further will depend on accurate counting, challenging at this level. (3) Dose & frequency. The optimum dosing schedule has not been derived by pharmacokinetic studies, but by what can be conveniently manufactured. An adult dose of 3 × 1011 platelets is accepted, but there is wide variation in practice. (4) Manufacture. Globally, 3 methods (pooled buffy coats, platelet rich plasma and apheresis) all produce an efficacious product. Although apheresis platelets reduce donor exposure, no functional advantage has been demonstrated. (5) In vitro assessment of function. A battery of tests is recommended, but only pH has been shown to correlate with posttransfusion survival. (6) ABO matching. ABO compatible platelets give better increments, and transfusing ABO incompatible plasma can be associated with haemolysis, but ABO matching to patient is often compromised by stock management. (7) Use of platelet additive solution. A 70:30 mix of PAS:plasma would reduce reactions and perhaps TRALI but this is not standard practice. Is the plasma useful? (8) CMV safety. Overall, leucocyte depletion alone appears to provide a high degree of protection, but this is not universally accepted. (9) Assessment of response. 1 and 24 hr increments are standard, but is regression analysis the way forward? (10) Management of refractoriness. Better HLA and HPA matching is now technically possible. Should these lead to better HLA matching for all? (11) Is one product for all appropriate? 20% of platelets go to surgical patients who are bleeding. Do they need a product with a different specification?

A Comparison of Heparin Management Strategies in Infants Undergoing Cardiopulmonary Bypass

Recent investigations in adult patients have suggested that a heparin concentration-based anticoagulation protocol for heparin administration during cardiopulmonary bypass (CPB) significantly reduced hemostatic activation when compared with standard weight-based heparin doses. Reductions in hemostatic activation during CPB could be particularly beneficial in pediatric patients in whom CPB-related coagulation issues are complex and influenced by many variables. However, information regarding heparin levels during CPB and their correlation to hemostatic activation is lacking in children. In this investigation, we compared a patient-specific heparin concentration-based heparin management protocol with a standard weight-based protocol in infants <6-mo-of-age. The efficacy of these two protocols was assessed by comparisons of heparin concentration, levels of biochemical markers of hemostatic activation, and clinical outcome. Twenty-five infants <6-mo-old scheduled for primary, elective repair of a congenital heart defect were enrolled in this study. Patients were randomized to receive either 400 U/kg of heparin (control group) or a patient-specific heparin dose calculated by the Hepcon Hemostasis Management System Plus (Hepcon HMS; Medtronic, Minneapolis, MN; intervention group). Heparin concentrations were compared between the two groups at predetermined intervals. Blood samples for biochemical markers of hemostatic activation were collected before and after CPB, and measurements of clinical outcome were recorded. Infants in the intervention group received a larger total heparin dose than infants in the control group. Heparin concentrations after the initial heparin dose and 30 min into CPB were similar between groups; however, at the start of rewarming and at the termination of CPB, infants in the intervention group had significantly higher heparin concentrations than infants in the control group. Infants in the intervention group also generated less F1.2 and consumed less factor VIII than infants in the control group. Clinically, however, infants in the intervention group received one more donor exposure from the administration of blood products post-CPB. A heparin concentration-based heparin management protocol in infants <6-mo-old resulted in higher, more constant heparin concentrations during CPB than a standard weight-based protocol. Furthermore, higher heparin concentrations were associated with greater suppression of hemostatic activation, as measured by less generation of thrombin and less consumption of factor VIII. Our findings demonstrate that use of a patient-specific heparin concentration-based protocol for heparin administration during CPB in infants may attenuate hemostatic activation. However, further research is needed to determine if this protocol has clinically beneficial hemostatic effects.

A General Change of the Platelet Transfusion Policy from Apheresis Platelet Concentrates to Pooled Platelet Concentrates is Associated with a Sharp Increase in Donor Exposure and Infection Rates

Background: We compare the actual with the potential donor exposure and possible infection rates in the Hanover Medical School (MHH) platelet (PLT) transfusion recipients if the current MHH standard of apheresis PLT concentrate (A-PC) supply would be replaced by a pooled PLT concentrate (P-PC) transfusion regimen. Donors, Patients, and Methods: The electronic records of the MHH Institute of Transfusion Medicine and the MHH Department of Medical Controlling were evaluated to assess the development of PLT needs and supply at MHH from 2003–2006. For 2006, we evaluated all PLT transfusion recipients with respect to their overall transfusion needs, classified them for low and high PLT transfusion needs, and related them to the diagnostic groups that underlie their PLT demands. We assumed a P-PC preparation procedure using 4 whole blood-derived buffy coats for all calculations for potential donor exposure. To predict the possible infection rates of an unrecognized viral infection with low prevalence in the general population to A-PC or to P-PC recipients and the influence of neutralizing agent specific antibodies (NAB), we established a mathematical contamination/ infection model based on the current PLT transfusion mode and data about GBV-C virus infection among Hanover blood donors. Results: From 2003 to 2006, the 1,300–1,400 persons comprising MHH apheresis donor pool covered a 36% increase in PC transfusions. The exclusive use of P-PCs instead of A-PC would require a total of 36,240–49,276 whole blood donations to meet MHH demands, corresponding to a more than 1 log step increase in donor exposure. For individual hematological patients, the change to P-PCs would imply an 80–125%, for individual surgical patients a 40–50% higher donor exposure. Our infection model revealed an approximately 4 times higher infection. Conclusions: A change to P-PC would imply a more than one log step higher donor exposure, and an unrecognized infection with a prevalence around 1% leads to an up to 4 times higher infection rate. A general change in the PC transfusion policy that favors P-PCs is dangerous and must be avoided.

Use of random versus apheresis platelet concentrates

The respective use of random (RPC) and apheresis (APC) platelet concentrates is highly heterogeneous among countries, ranging from 10 to 98% RPC in countries supposed to provide a similar transfusion service to patients. Moreover, when considering each country in the past 10 years, one can observe that some have changed their policy, switching from a majority of APC to RPC or vice versa. This presentation intends to analyse which factors may impact such decisions. For many years, the only available platelet component was a RPC obtained from whole blood donation by a two centrifugation steps process, the “platelet rich plasma” or PRP method. Since the beginning of the 1970s, APCs became available, with in fact many different techniques leading to many APCs that may not be equivalent. Since the end of the 1980s, a new method of RPC preparation was developed, using the buffy-coat (BC–PC), providing a blood component with highly preserved platelet functions as compared to RPCs prepared by the PRP technique. Finally, the use of each of these components either native, or leuco-reduced, or suspended in a storage solution, or processed with a pathogen inactivation technique adds new layers of complexity to compare them. Innumerable references can be found in the literature describing in vitro functional parameters of platelet concentrates. Although it is clear that BC–RPC retain much more their in vitro functions than PRP–RPC, indicating that no one should use the latter any more, it is much more difficult to distinguish differences between other PCs. Conversely, only a very few studies have been published related to a comparison of clinical efficacy of RPC versus APC, the endpoints being mainly CCI. Similarly to the in vitro studies, although RPC prepared with the PRP method show the lowest CCIs, no clear difference exists between “modern” RPC and APC. Another factor that may impact policy decision is the occurrence of adverse reactions in recipients. When considering only comparable data, for example leuco-reduced RPC versus leuco-reduced APC, there is now evidence that the latter is more associated with adverse reactions in recipients: data from hemovigilance in France show that, although no difference is noted for febrile non haemolytic transfusion reactions, nor for bacteria contamination, the incidence of allergic adverse reactions is about four times higher with APC as compared with RPC. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC may be considered.

A multicenter pilot‐randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation

Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia. A multicenter, single-blinded pilot randomized controlled trial (RCT) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin (Hb) concentration on bleeding risk. Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups: standard transfusion strategy (transfusion of 2 units of red blood cells [RBCs] when their Hb level was less than 80 g/L) or an augmented transfusion strategy (transfusion of 2 units of RBCs when their Hb level was less than 120 g/L). Sixty patients were enrolled: 29 in the control group and 31 in the experimental group. The proportions of patients experiencing clinically significant bleeding and the time to first bleed were not significantly different between the control and experimental groups. The experimental group received more RBC transfusions (transfusions/patient-day) than the control group (0.233 vs. 0.151; relative risk, 1.56; 95% confidence interval, 1.16-2.10; p = 0.003). The proportion of patient-days with platelet (PLT) transfusions was not different between the experimental and control groups. The mean number of donor exposures (PLT and RBC transfusions) was not different between experimental and control groups. Bleeding symptoms were systematically documented. This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients.

Recombinant Erythropoietin for Anaemia of Prematurity—When Should Treatment Start?

ABSTRACTBackgroundRecombinant erythropoietin reduces blood transfusion requirements in preterm neonates weighing under 1000 g 30 days postpartum. The optimal timing of starting erythropoietin therapy to achieve this effect is unclear.AimTo ascertain the number of neonates receiving blood transfusions 30 days postpartum at an Auckland hospital.MethodIn this retrospective study, blood transfusion and donor requirements of a cohort of neonates starting treatment at 30 days of age were compared with a cohort treated at 14 days of age. Blood transfusion guidelines and treatment practices were the same for the two groups.ResultsThe two groups were comparable with regard to demographic characteristics. 16/26 (62%) neonates treated from 30 days and 14/35 (40%) neonates treated from 14 days received a blood transfusion 30 days postpartum. This 22% difference was not statistically significant. The number of neonates exposed to at least one new donor 30 days postpartum was reduced from 11/26 (42%) to 11/35 (31%) with earlier commencement of treatment (not statistically significant).ConclusionThere were trends suggesting that starting erythropoietin treatment from 14 days of age was beneficial in reducing blood transfusion and donor exposure compared to starting at 30 days. However, the differences were not statistically significant and definite conclusions cannot be reached.

Acute plateletpheresis and aprotinin reduces the need for blood transfusion following Ross operation

The effect of acute intraoperative plateletpheresis (25% platelet yield) in combination with intraoperative low-dose aprotinin (2 million units) on blood conservation was investigated in 18 young adult patients undergoing elective Ross operation. The results were compared with a group of 19 similar patients without plateletpheresis (control group). The hematological and coagulation parameters at admission and discharge were statistically similar in both groups. The total blood product transfusion requirements were significantly reduced in the plateletpheresis group compared with the control group (3.2 units and 5.1 units, respectively, P=0.036). The total blood donor exposure was also reduced significantly in the plateletpheresis group compared with the control group (3.2 and 6.9 donors/patient, respectively, P<0.001). The direct costs for the hospital for the plateletpheresis procedure, including costs for all blood products, were similar to those for blood products alone in the control group. In summary, acute plateletpheresis in combination with low-dose aprotinin significantly reduces the blood product transfusions and blood donor exposures following the Ross operation; the treatment is cost-effective.

Aprotinin Use in Cardiac Surgery Patients at Low Risk for Requiring Blood Transfusion

To determine if aprotinin is safe and effective in patients at low risk for requiring blood transfusion after cardiac surgery by evaluating whether there is any significant difference in blood product use or other significant clinical outcomes between patients who received aprotinin versus those who did not. Retrospective review. Inpatient community nonteaching hospital. Three hundred thirty-five patients who underwent primary cardiac surgery involving cardiopulmonary bypass between November 1, 2003, and December 31, 2005, and were considered at low risk for requiring postoperative blood transfusion; 162 patients received aprotinin and 173 patients received aminocaproic acid (control). Comparison of patients in the aprotinin group versus those in the aminocaproic acid group revealed no difference in total donor exposures to blood products (1.86 vs 1.16 units/patient, p=0.07), total packed red blood cells (PRBCs) received (1.25 vs 0.86 units/patient, p=0.09), postoperative donor exposures to blood products (0.91 vs 0.48 unit/patient, p=0.13), or postoperative PRBCs received (0.61 vs 0.40 unit/patient, p=0.23). No difference was noted in any other clinical outcome in the aprotinin group versus the aminocaproic acid group, including postoperative azotemia (13.0% vs 10.4%, p=0.46), new onset of atrial fibrillation (14.8% vs 15.0%, p=0.95), myocardial infarction, stroke, or death. Mean +/- SD total hospital length of stay was similar in the aprotinin group versus the aminocaproic acid group (8.1 +/- 3.8 vs 7.4 +/- 2.8 days, p=0.08), but length of stay from surgery to discharge was longer in the aprotinin group than in the aminocaproic acid group (5.9 +/- 0.17 vs 5.4 +/- 0.12 days, p=0.032). Although aprotinin appeared to be safe in this low-risk patient population, it was not more effective than aminocaproic acid in reducing blood product use after cardiac surgery. More robust evidence is needed from a controlled randomized trial to demonstrate the safety, efficacy, and pharmacoeconomic benefit of aprotinin.

Nitric Oxide and cGMP Signaling in Calcium-Dependent Development of Cell Polarity in Ceratopteris richardii

Single-celled spores of the fern Ceratopteris richardii undergo gravity-directed cell polarity development that is driven by polar calcium currents. Here we present results that establish a role for nitric oxide (NO)/cGMP signaling in transducing the stimulus of gravity to directed polarization of the spores. Application of specific NO donors and scavengers inhibited the calcium-dependent gravity response in a dose-dependent manner. The effects of NO donor exposure were antagonized by application of NO scavenger compounds. Similarly, the guanylate cyclase inhibitors 6-anilino-5,8-quinolinedione and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin, and the phosphodiesterase inhibitor Viagra, which modulate NO-dependent cGMP levels in the cells, disrupted gravity-directed cell polarity in a dose-dependent manner. Viagra effects were antagonized by application of NO scavengers, consistent with the postulate that NO and cGMP are linked in the signaling pathway. To identify other components of the signaling system we analyzed gene expression changes induced by Viagra treatment using microarrays and quantitative real-time reverse transcription-polymerase chain reaction. Preliminary microarray analysis revealed several genes whose expression was significantly altered by Viagra treatment. Three of these genes had strong sequence similarity to key signal transduction or stress response genes and quantitative real-time reverse transcription-polymerase chain reaction was used to more rigorously quantify the effects of Viagra on their expression in spores and to test how closely these effects could be mimicked by treatment with dibutyryl cGMP. Taken together our results implicate NO and cGMP as downstream effectors that help link the gravity stimulus to polarized growth in C. richardii spores. Sequence data from this article can be found in the GenBank/EMBL data libraries under accession numbers BE 640669 to BE 643506, BQ 086920 to BQ 087668, and CV 734654 to CV 736151.

Clinical advantages of using mini-bypass systems in terms of blood product use, postoperative bleeding and air entrainment: an in vivo clinical perspective☆

In an effort to minimize the effect of extracorporeal circulation (ECC), mini-bypass is gaining clinical acceptance in routine coronary artery bypass grafting (CABG). These small circuits target combine the clinical advantages of reduced prime, 100% bio-coating and suction blood separation. We demonstrate that the use of mini-bypass in routine CABG reduces homologous blood product use and postoperative bleeding. Our goal was to also demonstrate that these small systems are effective in gaseous microemboli (GME) management as compared to a conventional extracorporeal system. Prospective, randomized study comparing 30 mini-bypass (Dideco ECC.O) to 30 conventional systems (n=30, Dideco 903 Avant). Study included CABG cases only, independent of preoperative coagulative status; clinic ethical committee approval and informed patient consent was obtained before initiating study. There were no statistical differences in terms of patient demographics. Statistically significant differences were seen in transfusion frequency (27% of the study group vs 43% in the control group, p=0.05), transfused volume (133.3+/-244.5 ml vs 325+/-483.1 ml, p<0.05), fresh frozen plasma (0 unit vs 3 units, p<0.001), postoperative bleeding (301.8+/-531.9 ml vs 785.5+/-1000.4 ml, p<0.05) and GME activity post-arterial filter (0.14 microl vs 5.32 microl, p<0.05). The adoption of mini-bypass significantly potentially reduces hemodilution, donor blood usage, postoperative bleeding and exposure to GME in routine CABG patients as compared to the use of conventional extracorporeal circulation circuits.

Cochrane review: Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants

Cochrane review: Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants

Calculating the required transfusion volume in children

The traditional method of calculating blood volume for pediatric transfusion in the UK is weight (kg) x aimed increment in hemoglobin concentration (Hb; g/dL) x the transfusion factor, usually quoted at 3 or 4. This equation is without evidence base. The aim was to assess how the volume of red cells (RBCs) affects the increase in serum Hb in children and to devise a formula that allows accurate volume calculation. All pediatric intensive care charts for 2 years were examined retrospectively. The immediate pre- and posttransfusion Hb estimations and the precise volumes of RBC transfused were recorded. Fluid boluses and hemorrhagic loss during the transfusion were documented. A total of 7679 patient charts were examined with a total of 564 transfusions. All patients who were bleeding, had drain losses, or had concurrent colloid infusions were excluded, giving 379 data points. The correlation gradient between mL per kg blood transfused and increase in Hb was 5.02. There was no significant association between effect and patient weight, age, starting Hb, transfusion time, or sex. No significant difference was found in Hb at 1 and 7 hours posttransfusion. The following equation should be used to calculate transfusion volumes: weight (kg) x increment in Hb (g/dL) x 3/(hematocrit [Hct] level of RBCs). This predicts that with a UK standard Hct of 0.6, 10 mL/kg gives an increment of 2 g/dL. Care must be taken not to risk hypervolemia, while minimizing donor exposure. Hb estimation 1 hour after transfusion is the same as 7 hours after transfusion.

Platelet count has no influence on traumatic and bloody lumbar puncture in children undergoing intrathecal chemotherapy

British Committee for Standards in Haematology, Blood Transfusion Task Force (2003) produced guidelines suggesting a platelet count of ≥50 × 109/l to safely proceed with lumbar puncture (LP). This has led us to review our institute's policy of a platelet count of ≥30 × 109/l as a safety cutoff for LP procedures and administration of intrathecal chemotherapy. There is obvious concern because a low platelet count may be associated with devastating neurological complications due to spinal bleeding. Furthermore, on presentation if a traumatic tap occurs, leukaemic cells circulating in the blood may be introduced into the cerebrospinal fluid (CSF), thereby possibly worsening the patient's prognosis (Gajjar et al, 2000). Howard et al (2000) reported a large retrospective analysis of 4309 LPs performed in 959 children, including 941 procedures with platelet count of <50 × 109/l with no neurological haemorrhagic complications. This article recommended that a platelet count of 10 × 109/l or higher would be adequate to perform routine LP. The authors (Howard et al, 2002), found that platelet counts of below 100 × 109/l were associated with increased risk of traumatic or bloody tap, but this risk was not different across platelet categories once the platelet count reduced below this threshold. Our aim in this retrospective cohort study was to review the available literature, ensure the safety of our practice and determine if the platelet count had any influence on the rate of traumatic LP performed. We report a review of 54 consecutive paediatric patients, 29 male and 25 female, age range 3 months to 17 years (median 7 years), with haematological malignancy who underwent a total of 738 LP procedures at Royal Manchester Children's Hospital between March 2001 and June 2005. All patients underwent LP and intrathecal chemotherapy under general anaesthetic conditions and procedures were performed by experienced clinicians (Consultant or Specialist registrar) according to the national guidelines. Patients underwent between 1 and 25 (median 11) procedures LPs from diagnosis. For each LP, the platelet count and number of red blood cells (RBCs) within CSF was recorded. Traumatic LP was defined as an LP in which cerebral fluid contained at least 10 RBCs/μl and bloody LP which the CSF contained at least 500 RBCs/μl. Of the 738 LPs performed, 65 (9%) were traumatic and 30 (4%) were bloody. No bleeding or neurological complications observed in any of the patients. Regression curve analysis showed no correlation with platelet count and red cell count in the CSF (R2 = 0.004). There appeared to be no increase in the incidence of traumatic or bloody taps in patients with a lower pre-procedure platelet count (Fig 1). Incidence of traumatic and bloody taps dependant on platelet count (×109/l). Within this cohort of patients with platelet count <50 × 109/l we observed no bleeding complications, and no increase in traumatic or bloody CSF. These findings support previous published data. These results indicate a significantly less traumatic rate than previously reported (Howard et al, 2000). At our institute we attribute the low rate of red cell contamination to experienced clinicians, dedicated general anaesthetic lists, and specific LP 24-guage needles. This study and existing evidence in the literature would support the safety of performing LPs with platelet counts ≥30 × 109/l. This policy enabled 27 of 738 patients (3.6%) to avoid a platelet transfusion, and thus reduced donor exposure, platelet-associated infections, delay in procedure, as well as reducing costs and making better use of platelet resources.

Efficacy of Prothrombin Complex Concentrate (PCC) for Reversal of Warfarin Effect.

In the United States supratherapeutic INRs are typically reversed with fresh frozen plasma (FFP). This requires transfusion of large volumes (10–15 ml/kg) with therapeutic delay, volume overload, risk for TRALI (transfusion related acute lung injury) and multiple donor exposures. Our Blood Utilization Review Committee recommends PCC as the preferred product for warfarin reversal. Profilnine (Alpha Therapeutic Corp, Los Angeles, CA) is PCC containing vitamin-K dependent clotting factors and dosed by FIX content. FII, VII and X content is no more than 150%, 35% and 100% of the FIX amount, respectively. The manufacturer's suggested dose for warfarin reversal is 15–50 U/kg. The dose of PCC and need for vitamin K or FFP is determined by the clinician after consultation with the transfusion service. Sixty-five patients received PCC; 25 for reduction of INR prior to surgery or other interventions and 40 for treatment of a supratherapeutic INR (>5.0) with bleeding or risk of bleeding. Twenty-three patients with supratherapeutic INRs received low dose PCC (mean 25 U/kg) and 17 received high dose (mean 50 U/kg). The average admission INR was 9.0 (5.2–15.0) for the low-dose group and 8.6 (5.3–15) for the high-dose group. Repeat INR measurements occurred after PCC and again if FFP was transfused. Twenty patients had samples frozen for analysis of FII, VII, IX and X with a mean time between PCC infusion and sample draw of 2 hours (0.5–8.1). Ten of these were stable at the time of PCC infusion and were used to calculate relative factor recovery. The INR corrected (decreased to ≤3) in 55%(6/11) of cases following treatment with low-dose PCC, while high-dose PCC corrected the INR in 43%(3/7). Combination of PCC and FFP (mean 2 units, ~5–7 mL/kg) corrected the INR in 89% (16/18) and 87%(13/15) of cases for low and high-dose PCC, respectively. PCC dose, with or without FFP, had no effect on the likelihood of INR correction (Chi-square, p> 0.05). The addition of low dose FFP, however, significantly increased the response rate (Chi-square, p<0.05) for both doses. The average factor increment is summarized in Table 1. Differences in factor levels between the PCC and PCC plus FFP groups were not significant(ANOVA, p>0.05). Based on PCC dose the median recovery of factor IX was 100% with a median recovery for FII, VII and X of 168%, 32%, and 100% of the factor IX increment. When FFP was added to the treatment regimen the recovery of factor IX was 106% of the PCC dose. FII, VII, and X were 182%, 46%, and 119% of the FIX increment. Only FVII recovery was significantly higher in the PCC plus FFP group (Mann-Whitney, p< 0.05). In conclusion, treatment with Profilnine increases factor levels compatible with the manufacturer's insert, but PCC plus FFP causes a larger FVII increment. Treatment with low or high dose PCC results in similar rates of INR correction. However, addition of FFP increases the rate of INR correction for both doses. Profilnine alone is, therefore, unable to reliably correct a supratherapeutic INR, and supplementation with small amounts of FFP is necessary to provide additional FVII. A PCC product with a higher content of FVII is a better therapeutic option but is not readily available in the United States.Factor increments following PCC infusionINRF II(%)F VII(%)F IX(%)F X(%)PCC onlyPre8.3±4.511±107±710±106±3Post2.6±1.453±2114±1028±1931±12PCC plus FFPPre12.2±5.05±11±112±1912±19Post1.9±0.876±2820±1245±2253±19mean±SD

Transfusions for VLBW infants

Kirpalani et al report a large randomized controlled trial demonstrating that transfusion for low versus high hemoglobin levels had no effect on outcomes. However, fewer infants randomized to the lower transfusion level ever received a transfusion. In an accompanying editorial, Ed Bell contrasts these new results with a smaller trial from Iowa demonstrating fewer brain injuries diagnosed by ultrasound and less apnea in similar infants with hemoglobin levels that were higher than the high transfusion group in the study by Kirpalani et al.In general, infants have received fewer transfusions than in the past for numerous reasons that include the use of arterial catheter less frequently, more permissive approaches to ventilation resulting in fewer blood gas measurements, and multiple trials indicating little benefit from transfusions to high hemoglobin in all of medicine. The use of polypacks for transfusions has strikingly decreased donor exposures for infant transfusions, and some clinicians use erythropoietin and iron therapy to both decrease transfusions and increase hemoglobin levels. When all is said and done, there are no firm guidelines for transfusion of infants. The trial by Kirpalani et al establishes two transfusion goals that definitively are not different in terms of clinically relevant outcomes. Kirpalani et al report a large randomized controlled trial demonstrating that transfusion for low versus high hemoglobin levels had no effect on outcomes. However, fewer infants randomized to the lower transfusion level ever received a transfusion. In an accompanying editorial, Ed Bell contrasts these new results with a smaller trial from Iowa demonstrating fewer brain injuries diagnosed by ultrasound and less apnea in similar infants with hemoglobin levels that were higher than the high transfusion group in the study by Kirpalani et al. In general, infants have received fewer transfusions than in the past for numerous reasons that include the use of arterial catheter less frequently, more permissive approaches to ventilation resulting in fewer blood gas measurements, and multiple trials indicating little benefit from transfusions to high hemoglobin in all of medicine. The use of polypacks for transfusions has strikingly decreased donor exposures for infant transfusions, and some clinicians use erythropoietin and iron therapy to both decrease transfusions and increase hemoglobin levels. When all is said and done, there are no firm guidelines for transfusion of infants. The trial by Kirpalani et al establishes two transfusion goals that definitively are not different in terms of clinically relevant outcomes.

Renal Dysfunction After Thoracic Aortic Surgery Requiring Deep Hypothermic Circulatory Arrest: Definition, Incidence, and Clinical Predictors

The purpose of this study was to evaluate renal dysfunction (RD) after thoracic aortic surgery (TAS) requiring deep hypothermic circulatory arrest (DHCA), to determine the influence of definition on RD after TAS-DHCA, to determine univariate predictors of RD after TAS-DHCA, and to determine multivariate predictors for RD TAS-DHCA. RD was defined in 3 ways: (1) >25% reduction in creatinine clearance, (2) >50% increase in serum creatinine, and (3) >50% increase in serum creatinine with an abnormal peak serum creatinine (>1.3 mg/dL for men and >1.0 mg/dL for women). Retrospective and observational. Single large university hospital. All adults requiring TAS-DHCA in 2000 and 2001. The cohort size was 144. Antifibrinolytic exposure was 100%: aprotinin 66% and aminocaproic acid 34%. The incidence of RD TAS-DHCA was 22.9% to 38.2%, depending on the definition. The incidence of renal replacement therapy was 2.8%. Multivariate predictors for RD after TAS-DHCA were sepsis, aprotinin exposure, preoperative hypertension, age, and donor exposures. Although RD after TAS-DHCA varies substantially because of definition, it is still very common. Its multivariate predictors merit further focused research to enhance perioperative protection of the kidney.

Untreated Rejection in 6-Month Protocol Biopsies Is Not Associated with Fibrosis in Serial Biopsies or with Loss of Graft Function

Donor age, calcineurin inhibitor nephrotoxicity, and acute rejection are the most significant predictors of chronic allograft nephropathy. Protocol biopsies, both in deceased- and living-donor renal grafts, have shown that cortical tubulointerstitial fibrosis correlates with graft survival and function. The impact of not treating subclinical acute rejection (SAR) is less clear. In this study, 126 de novo renal transplant recipients were randomly assigned to receive area-under-the-curve-controlled exposure of either a cyclosporine or a tacrolimus-based immunosuppressive regimen that included steroids, mycophenolate mofetil, and basiliximab induction. Protocol biopsies were taken before and 6 and 12 mo after transplantation. The prevalence of SAR was determined retrospectively. Fibrosis was evaluated by quantitative digital analysis of Sirius red staining in serial biopsies. Donor age correlated significantly with tubulointerstitial fibrosis in pretransplantation biopsies and inferior graft function at month 6 (rtau = -0.26; P = 0.033). Acute rejection incidence was 11.5%, and no clinical late rejection occurred. The prevalence of SAR at 6 mo was 30.8% but was not associated with differences in serial quantitative Sirius red staining at 6 or 12 mo, proteinuria, or progressive loss of GFR up to 2 yr. No differences were found in donor variables, histocompatibility, rejection history, or exposure of immunosuppressants. Controlled individualized calcineurin inhibitor exposure and subsequent tapering resulted in a low early acute rejection rate and prevented late acute rejection. Because, by design, we did not treat SAR, these results provide evidence that asymptomatic infiltrates in 6-mo surveillance biopsies may not be deleterious in the intermediate term. There is need for reliable biomarkers to prove that not all cell infiltrates are equivalent or that infiltrates may change with time.

Automated red cell collection – quality and value

Automated red cell collection was initially used largely for therapeutic purposes. New technology has rendered the procedure safer for donors and easier for machine operators. Optimal additive solution can be automatically added and the red cells filtered to provide a leucodepleted product. Two units of red cells may be collected during a single procedure from individuals who have a high enough red cell mass, whilst a single unit of red cells plus platelets or plasma can be collected from smaller donors. In vitro studies suggested that red cells collected by automated methods would be of better quality than those collected by gravity. This was not confirmed in vivo, but red cells collected by automated methods have the major advantage of consistency in terms of haemoglobin content, volume and haematocrit, compared with red cells collected by gravity. This standardised product is of particular value for transfusion dependent patients as the patient's haemoglobin can be maintained within narrow limits. The use of a double dose red cell product for transfusion to a single patient also confers benefit in terms of reduction in donor exposure.

Transfer of Chlorfenapyr Among Workers of &lt;I&gt;Reticulitermes flavipes&lt;/I&gt; (Isoptera: Rhinotermitidae) in the Laboratory

The potential for transfer of chlorfenapyr among subterranean termites was investigated using a donor-recipient (5:95 ratio) experiment. In one experiment, workers of Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae) were exposed to treated sand at 0, 50, 100, 250, and 500 ppm chlorfenapyr (wt [AI]/wt sand). Exposed workers were allowed to interact with untreated nestmates for 14 d, after which mortality was assessed. The three colonies responded differently to the treatments in this experiment. For two colonies, donor exposure rates of 500 ppm (as well as 250 ppm for colony B) chlorfenapyr resulted in significantly greater recipient mortality than controls. For colony C, donor chlorfenapyr exposure did not significantly influence recipient mortality. In a second experiment examining donor mortality over time, donor termites exposed to all test concentrations of chlorfenapyr (except for 0 ppm) suffered 100% mortality within 5 d. Analysis of donor termite body washes using gas chromatography indicated a linear uptake of chlorfenapyr by termites over the concentration range studied. Thus, for this concentration range, no upper limit (saturation plateau) of termite uptake for chlorfenapyr was reached.

Transfer of Chlorfenapyr Among Workers of Reticulitermes flavipes (Isoptera: Rhinotermitidae) in the Laboratory

The potential for transfer of chlorfenapyr among subterranean termites was investigated using a donor–recipient (5:95 ratio) experiment. In one experiment, workers of Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae) were exposed to treated sand at 0, 50, 100, 250, and 500 ppm chlorfenapyr (wt [AI]/wt sand). Exposed workers were allowed to interact with untreated nestmates for 14 d, after which mortality was assessed. The three colonies responded differently to the treatments in this experiment. For two colonies, donor exposure rates of 500 ppm (as well as 250 ppm for colony B) chlorfenapyr resulted in significantly greater recipient mortality than controls. For colony C, donor chlorfenapyr exposure did not significantly influence recipient mortality. In a second experiment examining donor mortality over time, donor termites exposed to all test concentrations of chlorfenapyr (except for 0 ppm) suffered 100% mortality within 5 d. Analysis of donor termite body washes using gas chromatography indicated a linear uptake of chlorfenapyr by termites over the concentration range studied. Thus, for this concentration range, no upper limit (saturation plateau) of termite uptake for chlorfenapyr was reached.