Impact of multidisciplinary engagement in a quality improvement blood conservation protocol for craniosynostosis.

OBJECTIVE: Patients undergoing open cranial vault remodeling for craniosynostosis frequently experience substantial blood loss requiring blood transfusion. Multiple reports in the literature have evaluated the impact of individual blood conservation techniques on blood transfusion rates during craniosynostosis surgery. The authors engaged a multidisciplinary team and assessed the impact of input from multiple stakeholders on the evolution of a comprehensive quality improvement protocol aimed at reducing or eliminating blood transfusion in patients undergoing open surgery for craniosynostosis. METHODS: Over a 4-year period from 2012 to 2016, 39 nonsyndromic patients were operated on by a single craniofacial plastic surgeon. Initially, no clear blood conservation protocol existed, and specific interventions were individually driven. In 2014, a new pediatric neurosurgeon joined the craniofacial team, and additional stakeholders in anesthesiology, transfusion medicine, critical care, and hematology were brought together to evaluate opportunities for developing a comprehensive blood conservation protocol. The initial version of the protocol involved the standardized administration of intraoperative aminocaproic acid (ACA) and the use of a cell saver. In the second version of the protocol, the team implemented the preoperative use of erythropoietin (EPO). In addition, intraoperative and postoperative resuscitation and transfusion guidelines were more clearly defined. The primary outcomes of estimated blood loss (EBL), transfusion rate, and intraoperative transfusion volume were analyzed. The secondary impact of multidisciplinary stakeholder input was inferred by trends in the data obtained with the implementation of the partial and full protocols. RESULTS: Implementing the full quality improvement protocol resulted in a 66% transfusion-free rate at the time of discharge compared to 0% without any conservation protocol and 27% with the intermediate protocol. The administration of EPO significantly increased starting hemoglobin/hematocrit (11.1 g/dl/31.8% to 14.7 g/dl/45.6%, p < 0.05). The group of patients receiving ACA had lower intraoperative EBL than those not receiving ACA, and trends in the final-protocol cohort, which had received both preoperative EPO and intraoperative ACA, demonstrated decreasing transfusion volumes, though the decrease did not reach statistical significance. CONCLUSIONS: Patients undergoing open calvarial vault remodeling procedures benefit from the input of a multidisciplinary stakeholder group in blood conservation protocols. Further research into comprehensive protocols for blood conservation may benefit from input from the full surgical team (plastic surgery, neurosurgery, anesthesiology) as well as additional pediatric subspecialty stakeholders including transfusion medicine, critical care, and hematology.

Unexpected Non-Maternally Derived Anti-PP1Pk in an 11-Week-Old Patient.

Alloantibody formation at less than 4 months of age is rare. Most antibodies identified in these patients are maternally derived. Anti-PP1Pk was detected in an 11-week-old infant that was not maternally derived. A multidisciplinary team approach led to appropriate testing, diagnosis, and transfusion management in this critically ill infant.

Pretransfusion testing practices in North America, 2005-2010: an analysis of the College Of American Pathologists Interlaboratory Comparison Program J-survey data, 2005-2010.

CONTEXT: Data collection and analysis of the College of American Pathologists (CAP) Interlaboratory Comparison Program (Proficiency Testing) J-Survey results provide insights into North American pretransfusion compatibility testing practices and trends. OBJECTIVES: To assess current North American manual testing practices for ABO grouping, rhesus (Rh) typing, antibody screening, and crossmatching using CAP proficiency testing data. DESIGN: Analysis of the CAP Interlaboratory Comparison Program J-Survey data (2005-2010) to identify laboratory methods used for ABO grouping, Rh typing, antibody screening, and crossmatching. Data were analyzed by test method using Microsoft (Redmond, Washington) Excel software. RESULTS: The method used most often in ABO grouping and Rh typing was tube testing. Many laboratories also used tube testing for antibody detection and crossmatching, but during the study period, the proportion of laboratories using gel-based methodologies increased considerably. CONCLUSIONS: Most North American CAP laboratories continue to use tube methods for ABO/Rh testing. Use of gel-based methodologies increased during the past 5 years for antibody screening and crossmatching.

Warfarin does not interfere with lupus anticoagulant detection by dilute Russell's viper venom time.

BACKGROUND: The dilute Russell's viper venom time (DRVVT) test is part of the diagnostic armamentarium used to detect lupus anticoagulant (LA). When testing patients on warfarin therapy, there is some concern of false positive results due to their low Factor X levels. We studied the diagnostic performance of the DRVVT ratio (DRVVT-R) to confirm the presence of LA in thrombophilia patients receiving warfarin therapy, and compared those results with a control group receiving warfarin for cardiac conditions but without thrombosis. METHODS: The DRVVT (screen, confirm, and ratio), Factors II and X assays, and PT/INR were performed in patients receiving warfarin for thrombosis and in patients with cardiac conditions but no thrombosis (control group). RESULTS: Patients on warfarin in the thrombosis group (n=22) were positive for LA by DRVVT-R (ratio >1.27 was considered positive) whereas none of the patients in the control group (n=13) were positive for LA. The median DRVVT-R was significantly higher in the thrombosis group (1.60, range 1.29-1.92) as compared to controls (1.13, range 0.79-1.23, p<0.001) even though the INRs were comparable (median 2.3 for thrombosis group versus median of 2.2 for controls, p<0.05). Similarly, FX and FII levels were not significantly different in these two groups. CONCLUSIONS: We conclude that the use of the DRVVT-R allows for diagnosis of LA in patients receiving warfarin with therapeutic INR despite their decreased Factor X levels.

Transfusion of platelets containing ABO-incompatible plasma: a survey of 3156 North American laboratories.

CONTEXT: Hemolytic transfusion reactions due to platelet transfusions containing ABO-incompatible plasma (ie, group O platelets into a non-group O patient) have been reported in the literature. However, limited data describe the extent to which transfusion services manage such platelet transfusions or the methods used to limit the risk of such reactions. OBJECTIVE: To determine transfusion services' current practices regarding the use of platelets containing ABO-incompatible plasma. DESIGN: In a College of American Pathologists' Transfusion Medicine Proficiency Testing Survey, supplemental questions asked participants whether a policy existed for the use of platelets containing ABO-incompatible plasma and, if a policy existed, what elements were part of the policy. RESULTS: Of 3156 laboratories that transfused platelets, 3152 responded to the question of whether they had a policy. Of these respondents, 83% (n = 2623) had a policy. One or more elements were reported for transfusions in adults: only ABO-compatible plasma products (n = 1363); only ABO-compatible plasma and platelet products (n = 679); notification of medical director (n = 646); notification of ordering physician (n = 637); volume limit of ABO-incompatible plasma allowed (n = 255); volume-reduction of ABO-incompatible products (n = 168); screening for critical titer of anti-A or anti-B (n = 53). A total of 529 laboratories indicated that they did not have a policy. CONCLUSIONS: A majority of laboratories have a policy, but most do not include a method to limit the risk of hemolysis if platelets containing ABO-incompatible plasma must be transfused. When such platelets are used, there does not appear to be consensus on a specific method to minimize the transfusion of anti-A or anti-B.

Evolution of surveillance methods for detection of bacterial contamination of platelets in a university hospital, 1991 through 2004.

BACKGROUND: Platelet (PLT) bacterial contamination (PBC) is the most common transfusion-associated infection. It is important to understand the impact of interventions addressing this problem. STUDY DESIGN AND METHODS: PBC was studied by prospective (active) and transfusion-reaction triggered (passive) surveillance from July 1991 to December 2004. Active surveillance, utilized for 10 years, included bacterial culture of all or 4- and 5-day-old PLTs at issue and intermittent use of Gram stain, pH measurements, and early (24-hr) culture of single-donor plateletpheresis (SDP) units. RESULTS: Active surveillance detected 38 instances of PBC, 7 in SDP units (1:2213) and 31 in random-donor PLT units (1:2090 units, p = 0.89; or 1:418 pools of 5 units, p < 0.001). Contaminants were coagulase-negative staphylococci (CONS; n = 27), Staphylococcus aureus (4), Bacillus cereus (1), Serratia marcescens (2), streptococci (2 S. bovis, 1 S. uberis), and CONS with viridans group streptococcus (1). Only one instance of contamination, caused by Pseudomonas aeruginosa, was detected by passive surveillance, with fatal outcome. Colony counts of contaminants ranged from 0.5 x 10(2) to 4 x 10(11) colony-forming units per mL at time of issue. PBC was interdicted before transfusion in 6 cases through Gram stain screening. Transfusion reactions occurred in 13 of 32 recipients (41%), with 9 severe reactions (28%) and 3 deaths (9%). pH testing failed to detect 5 contaminated units and resulted in discard of nearly 2 percent of units, whereas culture of SDP units at 24 hours failed to identify a contaminated unit. CONCLUSION: Improved active surveillance methods for detecting PBC are needed to improve the safety of PLT transfusions.

Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2.

Mutations in LMAN1 (ERGIC-53) or MCFD2 cause combined deficiency of factor V and factor VIII (F5F8D). LMAN1 and MCFD2 form a protein complex that functions as a cargo receptor ferrying FV and FVIII from the endoplasmic reticulum to the Golgi. In this study, we analyzed 10 previously reported and 10 new F5F8D families. Mutations in the LMAN1 or MCFD2 genes accounted for 15 of these families, including 3 alleles resulting in no LMAN1 mRNA accumulation. Combined with our previous reports, we have identified LMAN1 or MCFD2 mutations as the causes of F5F8D in 71 of 76 families. Among the 5 families in which no mutations were identified, 3 were due to misdiagnosis, with the remaining 2 likely carrying LMAN1 or MCFD2 mutations that were missed by direct sequencing. Our results suggest that mutations in LMAN1 and MCFD2 may account for all cases of F5F8D. Immunoprecipitation and Western blot analysis detected a low level of LMAN1-MCFD2 complex in lymphoblasts derived from patients with missense mutations in LMAN1 (C475R) or MCFD2 (I136T), suggesting that complete loss of the complex may not be required for clinically significant reduction in FV and FVIII.

Acute hemolytic transfusion reaction in a pediatric patient following transfusion of apheresis platelets.

The practice of transfusing ABO-incompatible platelets, driven primarily by concerns about inventory management, has been considered generally safe because the accompanying plasma is usually diluted in the recipient's total blood volume. However, if the platelet product contains a large volume of plasma or a high concentration of incompatible isoagglutinin, there may be hemolysis of the recipient's red cells. Patients with a small blood volume, such as babies and children, are considered to be at particular risk for such a complication. We describe the case of a baby who suffered massive hemolysis of her group A red cells after transfusion of group O Apheresis Platelets containing a high-titered anti-A isoagglutinin. We also offer a review of the literature on this subject and recommendations to avoid acute hemolytic reactions as a result of platelet transfusion.

North American pretransfusion testing practices, 2001-2004: results from the College of American Pathologists Interlaboratory Comparison Program survey data, 2001-2004.

CONTEXT: Pretransfusion testing of whole blood and red blood cell recipients is regulated by the federal government under the authority of the Clinical Laboratory Improvement Amendments of 1988. Regulated tests include determination of ABO group, Rh D type, antibody detection, antibody identification, and crossmatching. A wide variety of methods and reagents are available for these regulated tests. During 2001-2004, the College of American Pathologists (CAP) Interlaboratory Comparison Program (Proficiency Testing) J-Survey collected data from more than 4000 laboratories regarding their pretransfusion testing practices. Those data are presented in this report. OBJECTIVE: To assess current testing practices for ABO grouping, Rh D typing, antibody detection, and crossmatching in North America. DESIGN: Data collected for the CAP Interlaboratory Comparison Program (Proficiency Testing) J-Survey were analyzed for trends in laboratory testing practice during 2001- 2004. The data were grouped for analysis by peer group (testing method used) for ABO grouping, Rh D typing, antibody detection, and crossmatching and then analyzed. SETTING, PATIENTS, OR OTHER PARTICIPANTS: Subscribers to the CAP Interlaboratory Comparison Program Transfusion Medicine J-Series. RESULTS: The most common testing schemes used in North America during 2001-2004 are as follows: ABO grouping (most laboratories perform tube testing: 97.6% in 2000 and 91.1% in 2004); Rh D typing (most laboratories perform tube testing: 97.7% in 2001 and 91.1% in 2004); antibody detection (most laboratories perform tube testing: 69.7% in 2001 and 55% in 2004, most frequently with the low ionic strength solution anti-human globulin [AHG] method, 48.3% in 2001 and 39.9% in 2004; as of 2004 slightly more laboratories use the gel AHG method [42%] than the low ionic strength solution AHG tube method); crossmatching for alloimmunized patients (most laboratories perform tube testing using a low ionic strength solution AHG method; 55.8% in 2001 and 47.6% in 2004); and crossmatching for nonalloimmunized patients (tube testing using an immediate spin method; 42% in 2001 and 40.4% in 2004). CONCLUSIONS: Most North American laboratories currently favor tube methods when performing ABO grouping, Rh typing, antibody screening, and crossmatching. However, there has been a significant increase in the use of gel-based methods in recent years, especially for antibody detection and crossmatching. Data collection and data analysis of CAP Interlaboratory Comparison Program Survey results allow for assessment of laboratory proficiency and provide insights into current North American practice trends in pretransfusion compatibility testing.

Relapsed thrombotic thrombocytopenic purpura presenting as an acute cerebrovascular accident.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon but severe disorder that classically presents with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and fluctuating neurological changes. Previously, it was impossible to make a diagnosis of TTP in the absence of thrombocytopenia or microangiopathic hemolysis (MAHA). We describe two cases of relapsing TTP that presented with acute cerebrovascular accident (CVA) without concurrent thrombocytopenia or MAHA after initial classical presentation of TTP. In both cases, the diagnosis of TTP as the cause of the CVA was attributed to severe deficiency of the von Willebrand factor cleaving protease, ADAMTS13 in plasma (11 and 12%, normal 79-127%). Each patient had a dramatic clinical improvement in response to therapeutic plasma exchange. The experience in these two cases suggests that TTP should be considered as a potential cause among patients presenting with a CVA, particularly if the patients have a history of TTP.

Effect of ABO blood group on the collagen-binding assay for von Willebrand factor.

von Willebrand disease (VWD) is the most common congenital bleeding disorder and is caused by a quantitative or qualitative abnormality of von Willebrand factor (VWF). Ristocetin cofactor (RCoF) assay is used to evaluate VWF activity, but it does not assess collagen-binding activity. Normal values of RCoF and VWF antigen vary with ABO blood group type. The collagen-binding assay (CBA) measures VWF activity; however, its relationship with ABO blood group has not been completely explored. We performed CBA on plasma samples from 131 healthy volunteers to determine if CBA values correlated with blood type. Individuals with blood group O had a mean CBA value of 94 +/- 28%, which was significantly different from the mean of 117 +/- 33% in persons with non-O blood groups (P = 0.0001). Thus, CBA values appear to correlate with ABO blood type in a manner similar to RCoF.

Advances in pretransfusion infectious disease testing: ensuring the safety of transfusion therapy.

The public expects a zero-tolerance policy for the transmission of infectious agents by blood transfusion. Although unrealistic, the efforts to reach this goal have produced an extremely safe albeit costly blood supply [82]. Blood collecting agencies, the FDA, physicians, and scientists have over the past 20 years created a complex system of layers of protection to interdict transfusion-transmitted infections (Fig. 2). As new, exotic, potentially blood transmittable infectious agents evolve [83], new barriers will be erected to [figure: see text] interdict these agents. In the interim, the US blood supply is the safest in the world.

Ultralarge von Willebrand factor multimers and normal ADAMTS13 activity in the umbilical cord blood.

INTRODUCTION: Recent studies demonstrate that deficiency of ADAMTS13, the metalloprotease that cleaves von Willebrand factor (VWF) in a shear-dependent manner, causes thrombotic thrombocytopenic purpura (TTP). Previously, ultralarge multimers of VWF were detected in the fetuses, the umbilical cords and the newborns. However, the significance of this finding is unknown. MATERIALS AND METHODS: The activity of ADAMTS13 and the multimer pattern of VWF in the cord blood, as well as the VWF antigenic and ristocetin cofactor levels, were analyzed using previously published methods. The presence of ultralarge multimers was determined by densitometric analysis. RESULTS: On the average, the level of VWF antigen and ristocetin cofactor activity are slightly increased in the newborns (mean+/-standard deviation, 1.66+/-0.76 and 1.45+/-0.64 U/ml, respectively). Ultralarge VWF multimers are detected in 11 of 17 umbilical cord plasma samples. However, the ADAMTS13 is normal (0.99+/-0.15 U/ml) in all but one sample in which it is mildly decreased (0.71 U/ml). CONCLUSIONS: Since ADAMTS13 activity is normal, we speculate that the presence of ultralarge multimers in the umbilical cord blood may be due to the low levels of shear stress in the umbilical circulation. These results may have important implications for understanding the manifestation of ADAMTS13 deficiency during the neonatal period.