Feeding practices and other risk factors for developing transfusion-associated necrotizing enterocolitis.

AIMS: The objective of this study is to determine the incidence of and risk factors for necrotizing enterocolitis (NEC) and transfusion-associated NEC (TANEC) in very-low-birth-weight (VLBW) infants pre/post implementation of a peri-transfusion feeding protocol. STUDY DESIGN: A retrospective cohort study was conducted including all inborn VLBW infants admitted to the Duke intensive care nursery from 2002 to 2010. We defined NEC using Bell's modified criteria IIA and higher and TANEC as NEC occurring within 48h of a packed red blood cell (pRBC) transfusion. We compared demographic and laboratory data for TANEC vs. other NEC infants and the incidence of TANEC pre/post implementation of our peri-transfusion feeding protocol. We also assessed the relationship between pre-transfusion hematocrit and pRBC unit age with TANEC. RESULTS: A total of 148/1380 (10.7%) infants developed NEC. Incidence of NEC decreased after initiating our peri-transfusion feeding protocol: 126/939 (12%) to 22/293 (7%), P=0.01. The proportion of TANEC did not change: 51/126 (41%) vs. 9/22 (41%), P>0.99. TANEC infants were smaller, more likely to develop surgical NEC, and had lower mean pre-transfusion hematocrits prior to their TANEC transfusions compared with all other transfusions before their NEC episode: 28% vs. 33%, P<0.001. Risk of TANEC was inversely related to pre-transfusion hematocrit: odds ratio 0.87 (0.79-0.95). CONCLUSIONS: Pre-transfusion hematocrit is inversely related to risk of TANEC, which suggests that temporally maintaining a higher baseline hemoglobin in infants most at risk of NEC may be protective. The lack of difference in TANEC pre-/post-implementation of our peri-transfusion feeding protocol, despite an overall temporal decrease in NEC, suggests that other unmeasured interventions may account for the observed decreased incidence of NEC.

Transfusion-related biologic effects and free hemoglobin, heme, and iron.

BACKGROUND: Red blood cell (RBC) transfusion is common in intensive care unit (ICU) patients and is associated with complications that appear related to the duration of blood storage. We hypothesize that hemolysis of stored RBCs results in increases in the availability of non-heme-bound iron, which inhibits macrophage activation. STUDY DESIGN AND METHODS: RBCs were sampled at multiple time points to evaluate hemolysis and iron release. Activation of THP-1 monocytic cells was assessed in the presence of plasma from aged RBCs. Age of transfused blood in our pediatric intensive care unit (PICU) from 2001 to 2006 was analyzed to assess relevance to our patient population. RESULTS: Hemolysis increased significantly during storage time as demonstrated by increases in free heme and hemoglobin. While there was a trend toward elevated levels of non-heme-bound iron, this was not significant (p = 0.07). THP-1 cell activation was inhibited by exposures to both plasma and a ferric compound; the effect of plasma on macrophage activation was not reversed by the iron chelator desferroxamine. Thirty-one percent of our PICU patients received blood older than 2 weeks. CONCLUSION: Hemolysis products increased significantly over time in our stored RBCs. Ferric compounds and plasma from stored blood inhibit THP-1 cell activation. Plasma inhibition does not appear to be due primarily to increased iron. Further studies are needed to define the inhibitory effect of stored blood plasma on macrophage function. Complications related to blood storage are relevant to our PICU patients.

Storage age of transfused platelets and outcomes after cardiac surgery.

BACKGROUND: The relationship between duration of platelet (PLT) storage, currently limited to 5days, and surgical outcomes has not been established. We tested the hypothesis that PLT storage age was associated with adverse outcomes. STUDY DESIGN AND METHODS: A retrospective cohort of aortocoronary bypass (CABG) surgery patients from January 1996 to January 2005 receiving one or more PLT transfusions was selected for study. The composite primary ("short-term") outcome was 30-day mortality or prolonged hospital stay. Secondary outcomes included complications and survival to annual follow-up. Multivariable logistic regression models and Cox proportional hazards regression analysis evaluated the association between PLT storage age and outcomes, expressed as an odds ratio (OR) or hazard ratio with 95% confidence intervals (CIs), respectively. RESULTS: PLT transfusion was administered to 3272 of 10,275 CABG patients and 2578 received units of known storage age, which ranged between 2 and 5days (median, 4days; 25th percentile, 3days; 75th percentile, 5 days). The mortality rate for the 1637 patients receiving a single plateletpheresis transfusion was 3.8%, while 21.6% experienced a prolonged hospital stay or death. After adjusting for the number of PLT and red blood cell (RBC) units transfused, RBC storage age, and preoperative mortality risk, there was no association between PLT storage age and short-term outcome (OR, 1.01; 95% CI, 0.90-1.14), survival (hazard ratio [HR], 1.04; 95% CI, 0.96-1.13), or postoperative infections. CONCLUSIONS: PLT storage age was not associated with adverse short-term outcomes, decreased long-term survival, or infections after cardiac surgery.

The relationship of plasma transfusion from female and male donors with outcome after cardiac surgery.

OBJECTIVE: Pulmonary dysfunction is common in transfused patients recovering from heart surgery. Plasma transfusion from female donors has been linked with rare catastrophic lung injury, but its relationship with outcome after cardiac surgery is poorly understood. We examined whether plasma donor gender is related to postcardiac surgery pulmonary dysfunction and death or prolonged hospitalization. METHODS: In this retrospective case-control study, cardiac surgery candidates who received plasma perioperatively from only female donors were compared with male-only recipients who were matched for the number of units transfused and surgery date. RESULTS: In a dataset of 2157 recipients, there were no blood bank-reported complications, but escalating plasma transfusion was associated with increased 30-day mortality (odds ratio, 1.52 per unit; P = .0001). From the 1069 recipients receiving plasma exclusively from female or male donors, 390 matched pairs were identified. Recipients of female compared with male donor plasma had a lower incidence of pulmonary dysfunction (5.9% vs 10.8%; P = .01) and death or hospitalization more than 10 days (9% vs 16.4%; P = .002) but similar long-term survivals. CONCLUSIONS: Escalating plasma transfusion was associated with 30-day mortality, but female donor plasma recipients had less pulmonary dysfunction and fewer poor outcomes compared with male-only recipients. Although our retrospective study findings neither support nor refute a strategic policy to exclude female donor plasma to reduce catastrophic transfusion-related acute lung injury, they raise concern that such a policy may have unanticipated effects on outcome in patients undergoing cardiac surgery and highlight a need for additional studies in this and other patient groups.

A prospective, double-blind, randomized clinical feasibility trial of controlling the storage age of red blood cells for transfusion in cardiac surgical patients.

BACKGROUND: Recent evidence demonstrates an association between duration of storage of red blood cells (RBC) and morbidity and mortality after cardiac surgery. We studied the feasibility of two different schemes for categorizing and randomizing age of RBC units transfused in cardiac surgical patients. STUDY DESIGN AND METHODS: In Phase 1, 20 subjects were randomly assigned to standard of care (SOC) versus no RBCs with more than 21 days' storage duration. In Phase 2, 23 subjects were randomized to RBCs of 7 +/- 4 versus 21 +/- 4 days' storage duration. The age of study RBC units was masked. RESULTS: In Phase 1, no patients received RBCs 31 days or older in SOC, and there was overlap in storage age shared in both arms so the predefined feasibility criteria were not met. In Phase 2, it was feasible to deliver specified age RBCs to the 7-day arm (achieved in 100% of subjects), but feasibility was not demonstrated for the 21-day arm (only 50% of subjects transfused with target age RBCs). Significant differences, however, were observed between the 7 +/- 4- and 21 +/- 4-day arms with respect to age of all RBC units (6 +/- 2 vs. 18 +/- 7, p = 0.0002) and maximum age (7 +/- 2 vs. 20 +/- 7, p < 0.0001). CONCLUSION: Given the current storage age distribution of available RBC inventory, use of a SOC arm in future studies is unlikely to result in a large exposure to "old" blood. It is feasible to randomize patients to "younger" RBCs (3-11 days) but design strategies are needed to provide "intermediate-aged" or "old" blood as a comparator.

ABO blood group and bleeding after coronary artery bypass graft surgery.

Low circulating von Willebrand factor levels increase the risk of bleeding after cardiac surgery. Patients with blood group O may be at greatest risk owing to lower baseline levels of von Willebrand factor compared with patients with other blood groups, and perioperative hemodilution during cardiac surgery may reduce von Willebrand factor to critical levels in these patients. This study tested the hypothesis that patients with blood group O are at increased risk for postoperative bleeding following cardiac surgery, and determined whether the blood group affected perioperative assessment of primary hemostasis. Using multivariate linear regression models that included preoperative and intraoperative covariates, the risk factors for postoperative bleeding were evaluated in 877 patients undergoing primary, nonemergent coronary artery bypass surgery at a university hospital. In a subset of these patients, we measured perioperative in-vitro bleeding times (PFA-100 analyzer) to determine whether there were measurable differences in primary hemostasis between patients with blood type O and those with other blood groups. Patients with blood group O did not have increased bleeding after cardiac surgery compared with patients with other blood types. In addition, while blood group O patients had laboratory evidence for abnormal primary hemostasis before surgery, there were no measurable differences in postoperative primary hemostasis in patients with different blood types. In conclusion, although we identified clinical and procedural factors that were independently associated with bleeding, blood group was not one of these factors.