Helge Schoenfeld

Blood transfusion determines postoperative morbidity in pediatric cardiac surgery applying a comprehensive blood-sparing approach

OBJECTIVE Recently we suggested a comprehensive blood-sparing approach in pediatric cardiac surgery that resulted in no transfusion in 71 infants (25%), postoperative transfusion only in 68 (24%), and intraoperative transfusion in 149 (52%). We analyzed the effects of transfusion on postoperative morbidity and mortality in the same cohort of patients. METHODS The effect of transfusion on the length of mechanical ventilation and intensive care unit stay was assessed using Kaplan-Meier curves. To assess whether transfusion independently determined the length of mechanical ventilation and length of intensive care unit stay, a multivariate model was applied. Additionally, in the subgroup of transfused infants, the effect of the applied volume of packed red blood cells was assessed. RESULTS The median length of mechanical ventilation was 11 hours (interquartile range, 9-18 hours), 33 hours (interquartile range, 18-80 hours), and 93 hours (interquartile range, 34-161 hours) in the no transfusion, postoperative transfusion only, and intraoperative transfusion groups, respectively (P < .00001). The corresponding median lengths of intensive care unit stay were 1 day (interquartile range, 1-2 days), 3.5 days (interquartile range, 2-5 days), and 8 days (interquartile range, 3-9 days; P < .00001). The multivariate hazard ratio for early extubation was 0.24 (95% confidence interval, 0.16-0.35) and 0.37 (95% confidence interval, 0.25-0.55) for the intraoperative transfusion and postoperative transfusion only groups, respectively (P < .00001). In addition, the cardiopulmonary time, body weight, need for reoperation, and hemoglobin during cardiopulmonary bypass affected the length of mechanical ventilation. Similar results were obtained for the length of intensive care unit stay. In the subgroup of transfused infants, the volume of packed red blood cells also independently affected both the length of mechanical ventilation and the length of intensive care unit stay. CONCLUSIONS The incidence and volume of blood transfusion markedly affects postoperative morbidity in pediatric cardiac surgery. These results, although obtained by retrospective analysis, might stimulate attending physicians to establish stringent blood-sparing approaches in their institutions.

Platelet activity in washed platelet concentrates

Life-threatening anaphylaxis or febrile nonhemolytic transfusion reactions after transfusion of platelet concentrates (PCs) is a serious clinical problem caused by the sensitizing of recipients to plasma components, such as immunoglobulin A, or by cytokines. There is a possible indication for washing of PCs in these throm-bocytopenic patients. However, only platelets that show activation after physiological stimulation are useful. We determined the spontaneous and induced activation of platelets before and after washing. We investigated 11 consecutive single-donor-apheresis PCs. After production and leukocyte-depletion the PCs were washed in 15% acid-citrate-dextrose-solution. The spontaneous and the adenosine diphosphate (ADP)-induced, as well as collagen-induced activation, were determined by flow cytometry. Additionally, ADP-and collagen-induced aggregation were measured. Unwashed platelets (16.1%) were activated spontaneously. The washing of PCs led to a threefold increase of spontaneous activation of platelets (47.4%). Because of increased spontaneous activation after washing we could demonstrate cytometrically a loss of induced activation of washed platelets. Furthermore, washing resulted in an impaired ADP-induced aggregability of platelets. These results have led us to reduce the frequency of washing of PCs in our institution, where the only current indication for washing of PCs is in patients with a history of severe nonhemolytic transfusion reactions.

The functional integrity of platelets in volume-reduced platelet concentrates.

Premature and low-birth-weight infants usually require small-volume platelet transfusions to treat thrombocytopenia. Also, infants undergoing open-heart surgery with extracorporeal circulation and with compromised cardiac function are at risk for excessive intravascular volume. The small-volume platelet substitution can be achieved by dispensing an aliquot from the unit of a standard single-donor platelet concentrate (PC). Alternatively, there is an indication for volume reduction of PCs to maximize the number of platelets transfused in the smallest possible volume. We determined the spontaneous and induced activation of platelets before and after volume reduction in 20 consecutive single-donor-apheresis PCs. After a mean storage time of 2 days, the PCs were plasma-depleted by centrifugation. Spontaneous, adenosine diphosphate (ADP)-induced, and collagen-induced activation were determined by flow cytometry. Furthermore, ADP- and collagen-induced aggregation were measured. A total of 33.8% of platelets in standard PCs were activated spontaneously. Volume reduction of PCs led to a mild but significant increase of spontaneous activation of platelets (43.2%). Additionally, volume reduction resulted in an impaired ADP-induced aggregability of platelets, whereas collagen induction was unaffected. Transfusion of volume-reduced PCs is an effective alternative to use of standard PCs in patients at frequent risk for excessive intravascular volume, because equal volumes increase the platelet count twice as effectively.

Clopidogrel-Related Refractory Bleeding after Coronary Artery Bypass Graft Surgery: A Rationale for the Use of Coagulation Factor Concentrates?

Clopidogrel, an irreversible ADP-receptor antagonist, inhibits platelet aggregation mediated by reduced activation of glycoprotein receptor IIb/IIIa. Clopidogrel in combination with aspirin has been shown to be superior to aspirin alone for treating unstable angina, but clopidogrel recipients have shown increases in blood loss, transfusion requirements, and rate of reoperation after cardiac surgery. We describe a patient who had taken clopidogrel 75 mg daily until the day prior to coronary artery bypass graft surgery. Severe postoperative bleeding developed and was refractory to conventional hemostatic therapy consisting of 19 units of packed red blood cell concentrates, 16 of fresh frozen plasma, 8 of platelet apheresis concentrates plus high-dose treatment with aprotinin (500.000 kallikrein-inhibiting units/h) and administration of 0.3 microg/kg 1-deamino-8-D-arginine vasopressin (DDAVP). Two reoperations were performed, but surgical hemostasis was not achieved, so 100 microg/kg recombinant activated factor VII was applied to generate sufficient thrombin to stop the bleeding. This treatment approach reduced the bleeding. Then, to promote clot formation and firmness, 2 g of fibrinogen and 1250 IU of factor XIII were administered, and the bleeding finally stopped. No further transfusions were required, and the patient was discharged from the hospital on day 10 after the operation. This case suggests that in clopidogrel-related bleeding refractory to conventional hemostatic therapy, hemostasis may be achieved by a stepwise administration of coagulation factor concentrates.

SOCIOECONOMIC FACTORS, HAZARDOUS ALCOHOL CONSUMPTION, AND SMOKING IN PATIENTS WITH MINOR TRAUMA IN AN INNER-CITY EMERGENCY DEPARTMENT

Emergency Department (ED) patients show a high prevalence of hazardous alcohol consumption and smoking. The objective of this study was to determine if socioeconomic factors and smoking status help to optimize screening for hazardous alcohol consumption (HAC) in patients with minor trauma. A survey was conducted in an ED in an inner-city university hospital. A total of 2562 patients with minor trauma were screened for HAC (≥ 8 points in men and ≥ 5 points in women on the Alcohol Use Disorders Identification Test), smoking status, and socioeconomic factors. The median age of participants was 32 years, with 62.1% being male. A total of 84.2% of patients had an Injury Severity Score of 1, indicating minor trauma. Overall, 23.5% of patients showed a pattern of HAC, whereas 46.2% were current smokers. Compared to patients without HAC, those with HAC were characterized by lower incomes, no partnership, living in a single-household, and being unemployed. The strongest discriminative variable for HAC for patients aged ≤ 53 years was smoking status. Gender differences played a role only in patients older than 53 years. Although socioeconomic factors showed a non-equal distribution in patients with respectively without HAC, solely age, gender, and smoking status may provide a successful stratification for alcohol screening and intervention in these patients.

Evaluation of immunohematologic routine methods using the new erythrocyte-magnetized technology on the QWALYS 2 system.

BACKGROUND: QWALYS 2 is a fully automated system for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS). Its new erythrocyte‐magnetized technology (EMT) is based on the use of magnetic nanoparticles and avoids centrifugation and washing steps.

Red Blood Cell Storage Duration Is Associated with Various Clinical Outcomes in Pediatric Cardiac Surgery

Background: Recommendations on the use of fresh red blood cells (RBCs) in pediatric patients undergoing cardiac surgery are based on limited information. Furthermore, the RBC storage time cut-off of fresh units remains unknown. Methods: Data from 139 pediatric patients who underwent cardiac surgery and received RBCs from a single unit within 14 days of storage were analyzed. To identify the optimal cut-off storage time of RBCs for transfusion, multiple multivariate analyses aimed at different outcome parameters were performed. Results: 26 patients received RBC units stored for ≤3 days, while 126 patients received RBCs that were stored for 4-14 days. The latter group required more RBC transfusions and fresh frozen plasma (FFP) than the former group (19 vs. 25 ml/kg, p = 0.003 and 73% vs. 35%, p = 0.0006, respectively). In addition, the odds for the administration of FFP increased with the transfusion of RBCs stored for more than 4 days. The optimal cut-off for post-operative morbidity was observed with a storage time of ≤6 days for length of ventilation (p = 0.02) and peak of C-reactive protein (CRP; p = 0.008). Conclusions: The obtained results indicate that the hazard of blood transfusion increased with increasing storage time of RBCs. The results of this study suggest that transfusion of fresh RBCs with a storage time of ≤2 or 4 days (concerning transfusion requirements) or ≤6 days (concerning postoperative morbidity) may be beneficial in pediatric patients undergoing cardiac surgery. However, further prospective randomized studies are required in order to draw any final conclusions.

Lyophilised plasma: evaluation of clotting factor activity over 6 days after reconstitution for transfusion

Aims Little is known about long-term stability of clotting factors in dissolved human lyophilised plasma. This study evaluated clotting factor and inhibitor activity in reconstituted lyophilised plasma after storage for up to 6 days at 4°C. Methods Five samples from different lots of pooled lyophilised plasma (LyoPlas; German Red Cross Blood Transfusion Service West) were reconstituted. The activity of fibrinogen, factor II (FII), FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII, antithrombin, plasmin inhibitor, von Willebrand factor antigen, free protein S and protein C were determined immediately and at 2, 4, 6, 24, 48, 72, 96, 120 and 144 h after reconstitution. Tests for bacterial contamination were performed after 12, 72 and 144 h from each plasma bottle. Results Storage at 4°C for 6 h led to a decrease in the activity of FVIII (Δ −14.9%), FIX (Δ −6.9%) and FXI (Δ −6.3%), and an increase in the activity of plasmin inhibitor (Δ +10.2%). Storage for up to 6 days resulted in a further decrease in activity of FVIII (Δ −24.3%), FIX (Δ −13.4%) and FXI (Δ −22.9%), and, additionally, a decrease in the activity of FV (Δ −15.0%), fibrinogen (Δ −6.9%) and plasmin inhibitor (Δ −17.5%). Other factors and inhibitors, with exception of protein C (Δ +8.2%), remained almost unchanged over time. Blood cultures were sterile and showed no bacterial growth. Conclusions The activity of all measured coagulation factors and inhibitors in a time course of up to 6 days met required quality standards. Further in vivo testing is required to demonstrate safety and efficacy of extended clinical use of refrigerated reconstituted lyophilised plasma.

Thawed solvent/detergent-treated plasma: too precious to be wasted after 6 hours?

BACKGROUND Coagulopathy associated with trauma and bleeding requires early administration of haemostatic agents. Solvent/detergent-treated plasma (S/D-plasma) requires thawing and its availability for clinical use is, therefore, delayed. The long-term stability of clotting factors in thawed S/D-plasma has not been thoroughly investigated. The purpose of this study was to evaluate stability of clotting factors and inhibitors in thawed S/D-plasma stored at 4 °C for 6 days. MATERIALS AND METHODS Clotting factor levels and bacterial contamination were investigated using 20 units of S/D-plasma. Fibrinogen, factor (F) II, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII, antithrombin, von Willebrand antigen (VWF-Ag), plasmin inhibitor, protein C and free protein S were analysed over time. RESULTS After 6 days of storage the results were as follows: fibrinogen 270 mg/dL (-10 mg/dL, p=0.0204), FII 75% (-5%, p<0.0001), FV 88% (-14%, p<0.0001), FVII 81% (-24%, p<0.0001), FVIII 70% (-16%, p<0.0001), FIX 96% (-8, p<0.0001), FX 92% (-1%, p<0.0001), FXI 119% (-4%, p=0.3666), FXII 94% (-2%, p=0.3602), FXIII 89% (-1%, p 0.0019), free protein S 76% (-4%, p<0.0001), protein C 96% (+1%, p=0.0371), antithrombin 92% (-3%, p<0.0001), plasmin inhibitor 29% (-4%, p<0.0299), VWF-Ag 137% (+2%, p=0.2205). FVII and FVIII showed a critical drop of more than 20% or approached the lower quality assurance threshold after storage for more than 24 hours. No S/D-plasma showed bacterial contamination. CONCLUSION All clotting factors in thawed S/D plasma remained stable for up to 24 hours when stored at 4 °C. Storage of thawed S/D plasma may improve the availability of this product in emergency situations.

Validation of a hospital-laboratory workstation for immunohematologic methods.

BACKGROUND: The FREELYS Nano system (Diagast) is a manual workstation for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS) for immunoglobulin G (IgG) antibodies only and works with the erythrocyte‐magnetized technology (EMT). The principle of EMT is based on magnetization of red blood cells and avoids centrifugation and washing steps.