Shiu-Ki Hui

Multidisciplinary team learning in the management of the morbidly adherent placenta: outcome improvements over time

BACKGROUND: Morbidly adherent placenta (MAP) is a serious obstetric complication causing mortality and morbidity. OBJECTIVE: To evaluate whether outcomes of patients with MAP improve with increasing experience within a well‐established multidisciplinary team at a single referral center. STUDY DESIGN: All singleton pregnancies with pathology‐confirmed MAP (including placenta accreta, increta, or percreta) managed by a multidisciplinary team between January 2011 and August 2016 were included in this retrospective study. Turnover of team members was minimal, and cases were divided into 2 time periods so as to compare 2 similarly sized groups: T1 = January 2011 to April 2014 and T2 = May 2014 to August 2016. Outcome variables were estimated blood loss, units of red blood cell transfused, volume of crystalloid transfused, massive transfusion protocol activation, ureter and bowel injury, and neonatal birth weight. Comparisons and adjustments were made by use of the Student t test, Mann‐Whitney U test, χ2 test, analysis of covariance, and multinomial logistic regression. RESULTS: A total of 118 singleton pregnancies, 59 in T1 and 59 in T2, were managed during the study period. Baseline patient characteristics were not statistically significant. Forty‐eight of 59 (81.4%) patients in T1 and 42 of 59 (71.2%) patients in T2 were diagnosed with placenta increta/percreta. The median [interquartile range] estimated blood loss (T1: 2000 [1475‐3000] vs T2: 1500 [1000‐2700], P = .04), median red blood cell transfusion units (T1: 2.5 [0‐7] vs T2: 1 [0‐4], P = .02), and median crystalloid transfusion volume (T1: 4200 [3600‐5000] vs T2: 3400 [3000‐4000], P < .01) were significantly less in T2. Also, a massive transfusion protocol was instituted more frequently in T1: 15/59 (25.4%) vs 3/59 (5.1%); P < .01. Neonatal outcomes and surgical complications were similar between the 2 groups. CONCLUSION: Our study shows that patient outcomes are improved over time with increasing experience within a well‐established multidisciplinary team performing 2−3 cases per month. This suggests that small, collective changes in team dynamics lead to continuous improvement of clinical outcomes. These findings support the development of centers of excellence for MAP staffed by stable, core multidisciplinary teams, which should perform a significant number of these procedures on an ongoing basis.

Granulocyte Transfusions for Children with Infection and Neutropenia or Granulocyte Dysfunction

Transfusions of granulocytes can be used as an adjunct therapy to antimicrobials in patients with infection and neutropenia or granulocyte dysfunction. However, there is a lack of strong clinical evidence to support the use of this treatment strategy, particularly in children. We retrospectively reviewed the medical records of children who received granulocytes at our institution from April 2009 to October 2012, with emphasis on primary indication for the transfusion and clinical outcome in terms of infection. The patients had granulocyte dysfunction or severe neutropenia, defined as absolute neutrophil count (ANC) < 500 cells/mm3 due to chemotherapy or hematopoietic stem cell transplant (HSCT), and reasonable hope for bone marrow recovery or engraftment. Eighteen children received granulocytes during 20 distinct episodes: 62% (n = 13) for acute infection, 29% (n = 5) for unresolved chronic infection during the time of HSCT, and 9% (n = 2) for other clinical conditions such as typhilitis and appendectomy. Overall, 92% (n = 12) of the episodes of acute infection had complete or partial resolution, as determined by review of vital signs, physical exam findings and discontinuation of antimicrobials. A substantial number (46%) of children who received granulocytes for acute infection developed respiratory adverse events, but all of these recovered. We conclude that granulocyte transfusions continue to be primarily used in neutropenic patients with acute infections, and that its use in this group of patients is reasonable. However, a prospective randomized clinical trial is needed to evaluate safety and whether the use of granulocytes is superior to antimicrobial-only therapy.

Age-based difference in activation markers of coagulation and fibrinolysis in extracorporeal membrane oxygenation.

Objective: Coagulation system activation in extracorporeal membrane oxygenation results in hemostatic derangements. Thrombin generation markers like prothrombin fragment 1+2 and thrombin-antithrombin complex are sensitive markers of hypercoagulability. Plasmin-antiplasmin complex is a sensitive marker for fibrinolysis. D-dimers reflect thrombin generation and fibrinolysis. The aim was to identify the extent of hemostasis activation during extracorporeal membrane oxygenation by measuring thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer. Design: Prospective cohort study. Setting: Tertiary care academic center. Patients: Children placed on extracorporeal membrane oxygenation from April 2011 to January 2013. Interventions: Prothrombin fragment 1+2, thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer were measured on days 1 and 5 of extracorporeal membrane oxygenation. Measurements and Main Results: Data presented as median (interquartile range); nonparametric tests were done using SPSS. Twenty-nine children (52% < 30 d old [neonates], median extracorporeal membrane oxygenation length 151 hr) were studied. Complications included thrombosis in 14%, bleeding in 45%, and thrombosis and bleeding together in 10%. Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels were high on day 1 and remained increased on extracorporeal membrane oxygenation. In neonates, all levels were higher on day 5 compared with day 1: thrombin-antithrombin complex (55.6 &mgr;g/L [30.7–76.0] vs 18.7 &mgr;g/L [10.9–34.6]; p = 0.03), prothrombin fragment 1+2 (2,038 pmol/L [1,093–4,018.5] vs 377.5 pmol/L [334.3–1,103.0]; p = 0.00), plasmin-antiplasmin complex (2,160 &mgr;g/L [786–3,090] vs 398 &mgr;g/L [296.8–990.8]; p = 0.00), and D-dimer (3.0 &mgr;g/mL [1.9–11.5] vs 1.5 &mgr;g/mL [0.6–2.9]; p = 0.01). Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels did not correlate with anti-Xa activity or heparin dose. In bleeders older than 30 days, plasmin-antiplasmin complex stayed elevated on day 5, but in patients with no bleeding complications, plasmin-antiplasmin level showed a declining trend. In neonates, plasmin-antiplasmin levels increased over the course of extracorporeal membrane oxygenation irrespective of bleeding. Conclusion: Despite our best efforts at adequate anticoagulation with unfractionated heparin, neonates showed persistent increase in coagulation activation on extracorporeal membrane oxygenation. Fibrinolysis activation may contribute to bleeding in patients older than 30 days. Different anticoagulation protocols should be individualized based on age.

Neonatal transfusion models to determine the impact of using fresh red blood cells on inventory and exposure.

BACKGROUND Data on age of blood and its impact on donor exposure and inventory in the paediatric setting are lacking. The standard of practice of reserving a specific red blood cell (RBC) unit for neonates who may require repeat transfusions is unique to the paediatric setting. Requiring transfusion of fresher RBC units may increase the exposure of neonates to multiple units and negatively affect the supply of fresh RBC. We constructed a transfusion model based on a 6 months of retrospective neonatal transfusion data at our institution. MATERIALS AND METHODS All neonates (≤4 months old) at Texas Childrens Hospital who received a RBC transfusion from June to November 2011 were included and RBC transfusion data were compiled. The age of blood at the time of each RBC transfusion was recorded. These data were reviewed to calculate exposure and inventory impact if each transfusion had been restricted to RBC either ≤7 or ≤14 days old at transfusion. RESULTS A total of 216 neonates received 938 RBC transfusions. Of these, 393 (42%) were fresh RBC (≤14 days old), even without a required age guideline. Requiring fresh (≤14 days) RBC for all transfusions in this period would have resulted in 70 additional fresh units and one or more additional exposures in 44 patients. Requiring fresher (≤7 days old) RBC would have resulted in an additional 147 units and. one or more additional exposures in 54 patients. DISCUSSION The more conservative model of fresh (≤7 days old) RBC would greatly increase fresh RBC inventory requirements, and 25% of transfused neonates would require additional RBC exposure. Based on retrospective data and the two transfusion models, it can be concluded that requiring RBC ≤14 days old for neonatal transfusion would best balance the use of fresher RBC with the smallest increase in patient exposure (20%) and minimum impact on the RBC inventory.

Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.

It was recently reported that factor H, a regulatory component of the alternative complement pathway, is stored with von Willebrand factor (VWF) in the Weibel-Palade bodies of endothelial cells. If this were to be the case, it would have therapeutic importance for patients with the atypical hemolytic-uremic syndrome that can be caused either by a heterozygous defect in the factor H gene or by the presence of an autoantibody against factor H. The in vivo Weibel-Palade body secretagogue, des-amino-D-arginine vasopressin (DDAVP), would be expected to increase transiently the circulating factor H levels, in addition to increasing the circulating levels of VWF. We describe experiments demonstrating that factor H is released from endothelial cell cytoplasm without a secondary storage site. These experiments showed that factor H is not stored with VWF in endothelial cell Weibel-Palade bodies, and is not secreted in response in vitro in response to the Weibel-Palade body secretagogue, histamine. Furthermore, the in vivo Weibel-Palade body secretagogue, DDAVP does not increase the circulating factor H levels concomitantly with DDAVP-induced increased VWF. Factor I, a regulatory component of the alternative complement pathway that is functionally related to factor H, is also located in endothelial cell cytoplasm, and is also not present in endothelial cell Weibel-Palade bodies. Our data demonstrate that the factor H and factor I regulatory proteins of the alternative complement pathway are not stored in Weibel-Palade bodies. DDAVP induces the secretion into human plasma of VWF —- but not factor H.

ABO-incompatible deceased donor pediatric liver transplantation: Novel titer-based management protocol and outcomes

ABO‐ILT have re‐emerged as an alternate option for select patients awaiting transplant. However, treatment protocols for children undergoing deceased donor ABO‐ILT are not standardized. We implemented a novel IS protocol for children undergoing deceased donor ABO‐ILT based on pretransplant IH titers. Children with high pretransplant IH titers (≥1:32) underwent an enhanced IS protocol including plasmapheresis, rituximab, IVIG, and mycophenolate, while children with IH titers ≤1:16 received steroids and tacrolimus. We retrospectively assessed our outcomes of ABO‐ILT with ABO‐compatible recipients of similar age and diagnosis over a 2‐year period. Ten children with median age of 8.9 months underwent ABO‐ILT, 4 of 10 patients underwent enhanced IS due to high IH titers. Rates of complications (rejection, infections, biliary, and vascular) at both 1 year and up to 3 years post‐transplant were comparable between the groups. Patients with ABO‐ILT had good graft function with 100% survival at a median follow‐up of 3.3 years. In conclusion, IS tailored to pretransplant IH titers in pediatric deceased donor ABO‐ILT is feasible and can achieve outcomes similar to ABO‐CLT at 1 and 3 years post‐transplantation.

Deficiency of complement factor H-related proteins and autoantibody-positive hemolytic uremic syndrome in an infant with combined partial deficiencies and autoantibodies to complement factor H and ADAMTS13

ABSTRACT A 3-month-old male infant developed an extremely severe episode of atypical hemolytic uremic syndrome (aHUS) associated with partial deficiencies of full-length complement factor H (FH; ∼15% of infant normal) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) (39% of normal) and autoantibodies reactive with both proteins. His FH and ADAMTS13 genes were normal, indicating that the partial deficiencies were acquired, probably as the result of autoantibodies against full-length FH and ADAMTS13. The child also had a homozygous deletion of the complement factor H–related (CFHR)3–CFHR1 portion in the complement factor H (CFH) gene cluster. He therefore had deficiency of CFHR proteins and autoantibody-positive hemolytic uremic syndrome (DEAP-HUS) with an unusual early onset associated with a partial deficiency of ADAMTS13 and an anti-ADAMTS13 autoantibody. His clinical episode of aHUS responded to plasma infusion and subsequent treatment with mycophenolate and rituximab. We believe that this is the first report of DEAP-HUS in an infant with partial deficiencies in both ADAMTS13 and full-length FH acquired in association with autoantibodies to both proteins.

Retrospective surveys of obstetric red cell transfusion practice in the UK and USA

To examine whether professional guidance promoting a policy of restrictive blood transfusion is being followed.

Stability and Sterility of Enoxaparin 8 mg/mL Subcutaneous Injectable Solution

BACKGROUND: Enoxaparin is often diluted to accurately deliver doses to neonatal and infant patients. Current recommendations for dilutions may not be adequate for the smallest patients. METHODS: Review of dosing at our institution occurred, and an 8 mg/mL concentration of enoxaparin was chosen. A concentration of 8 mg/mL was compounded by diluting 0.4 mL of enoxaparin (100 mg/mL) into 4.6 mL of sterile water for injection into an empty sterile vial. Four syringes of the 8 mg/mL concentration were prepared by 5 technicians (20 total syringes). Stability and sterility testing occurred a 0, 7, 14, and 30 days. One-way repeated-measures analysis of variance was used to detect significant differences in Anti-Factor Xa concentrations at the testing time points. RESULTS: The dilution of enoxaparin was sterile at 30 days but exhibited significant degradation at the 30-day point (p < 0.05). CONCLUSION: A dilution of enoxaparin 8 mg/mL is stable and sterile for 14 days refrigerated but is not stable at 30 days.

Von Willebrand Disease Laboratory Workup

The accurate subtyping of von Willebrand disease (VWD) relies heavily on the appropriate laboratory workups. An algorithmic approach to laboratory workup for VWD not only improves efficiency, but also avoids unnecessary testing. This chapter will discuss the various assays that are used for laboratory evaluation of VWD including the routinely performed tests like von Willebrand factor (VWF) antigen, VWF ristocetin cofactor assay, factor VIII assay, and VWF multimer analysis along with second-tier tests such as factor VIII binding assay, 2B binding assay, ristocetin-induced platelet aggregation, and collagen-binding assay. Finally, the role of the more esoteric VWF assays, VWF propetide assay and VWF gene analysis, will also be considered.