Edward C.C. Wong

Hemolytic and thrombocytopathic characteristics of extracorporeal membrane oxygenation systems at simulated flow rate for neonates.

Objective: A state-of-the-art centrifugal pump combined with hollow-fiber oxygenator for extracorporeal membrane oxygenation has potential advantages such as smaller priming volumes and decreased potential to cause tubing rupture as compared with the traditional roller head/silicone membrane systems. Adoption of these state-of-the-art systems has been slow in neonates as a result of past evidence of severe hemolysis that may lead to renal failure and increased mortality. Extracorporeal systems have also been linked to platelet dysfunction, a contributing factor toward intracranial hemorrhage, a leading cause of infant morbidity. Little data exist comparing the centrifugal systems with the roller systems in terms of hemolysis and platelet aggregation at low flow rates commonly used in neonatal extracorporeal membrane oxygenation. Design: Prospective, comparative laboratory study. Setting: University research laboratory. Subjects: Centrifugal pump, roller pump, hollow-fiber oxygenator, and silicone membrane oxygenator. Interventions: Comparative study using two pumps, the centrifugal Jostra Rotaflow (Maquet, Wayne, NJ) and the roller-head (Jostra, Maquet, Wayne, NJ), and two oxygenators, polymethlypentene Quadrox-D (Maquet) and silicone membrane (Medtronic, Minneapolis, MN). Five test runs of four circuit combinations were examined for hemolysis and platelet aggregation during 6 hrs of continuous use in a simulated in vitro extracorporeal membrane oxygenation circuit circulating whole swine blood at 300 mL/min. Measurements and Main Results: Hemolysis was assessed by spectrophometric measurement of plasma-free hemoglobin. Platelet aggregation was evaluated using monoclonal CD61 antibody fluorescent flow cytometry profiles. All of the extracorporeal membrane oxygenation systems created plasma-free hemoglobin at a similar rate compared with static blood control. There was no difference in the mean normalized index of hemolysis of the centrifugal/hollow-fiber oxygenator system as compared with the roller-head/silicone membrane systems (0.0032 g/100 L vs. 0.0058 g/100 L, p ≥ .7). None of the extracorporeal membrane oxygenation systems had a significant increase in platelet aggregation above baseline. Conclusions: In a low-flow neonatal environment, a state-of-the-art centrifugal pump combined with new fiber-type oxygenators appear to be safe in regard to hemolysis and platelet aggregation.

Transfusion management strategies: A survey of practicing pediatric hematology/oncology specialists†

Little is known about the criteria used by pediatric oncologists for the transfusion of red blood cells and platelets to pediatric oncology patients.

Ceftriaxone-induced hemolytic anemia and hepatitis in an adolescent with hemoglobin SC disease.

Objectives: To describe a case of a ceftriaxone-induced hemolytic anemia and hepatitis leading to multiple organ failure and death in an adolescent with hemoglobin SC disease and to review the previous cases of this rare and potentially fatal disorder in children. Design: Case report and literature review. Setting: Intensive care unit. Patient: Adolescent with hemoglobin SC. Interventions: Emergency treatment. Measurements and Main Results: After 4 days of ceftriaxone therapy, the adolescent experienced an acute hemolytic reaction (hemoglobin decreased to 5 g/dL with hemoglobinuria) and severe hepatitis (all enzymes increasing dramatically including aminoaspartate transferase >20,000 IU/L). Renal failure and ultimately multiple organ failure ensued, and the patient died on hospital day 19. Direct antiglobulin tests on red cells obtained from the patient on hospital day 2 showed microscopic agglutination with polyspecific and anticomplement (C3) antiglobulin reagents. Plasma samples showed macroscopic agglutination reactions when incubated in the presence of ceftriaxone, many days after cessation of ceftriaxone, indicating the continued presence of ceftriaxone-dependent antibodies. Conclusions: Drug reactions leading to hemolysis are relatively uncommon, and a total of ten cases of ceftriaxone-induced hemolytic anemia have been reported in children. The present case describes an adolescent who ultimately died on hospital day 19 from multiple organ failure, although the presentation of this case seems atypical in several respects. Children with clinical syndromes that place them at risk for hemolysis and children who frequently require broad spectrum antibiotics present unique diagnostic challenges, and the possibility that hemolytic syndromes may be due to ceftriaxone must be considered.

Intravenous immunoglobulin-related hemolysis in patients treated for Kawasaki disease.

Kawasaki disease (KD) is an idiopathic, multisystem disorder characterized by vasculitis of arteries, veins, and capillaries, affecting pediatric patients, and is the leading cause of acquired heart disease in childhood. The mainstays of therapy for KD are high‐dose intravenous immunoglobulin (IVIG) and aspirin, which are thought to prevent or modify the most serious cardiac sequelae. A well‐documented complication of high‐dose IVIG infusion in adults is hemolytic anemia due to passive transfer of anti‐A and anti‐B. Risk factors for hemolysis in another case series included patient blood group (group A, B, or AB), a high cumulative dose of IVIG, and concomitant inflammation documented by one or more markers like ferritin, fibrinogen, erythrocyte sedimentation rate, or C‐reactive protein.

Therapeutic apheresis in pediatrics: technique adjustments, indications and nonindications, a plasma exchange focus.

Therapeutic Apheresis procedures are associated with multiple and unique challenges in children. The procedures are often performed using evidence or experience extrapolated from adult clinical practice, which may not be evidenced based. In addition to the clinical challenges, relevant psychological issues, modification of protocols and technical hardware are often necessary for safe and effective treatment in children. The following review addresses these aspects of therapeutic apheresis in children as presented at the Therapeutic Apheresis Academy in September 2011. Because of the variety of therapeutic apheresis procedures that can be performed in children, for the purposes of this review, an emphasis will be on the performance of plasma exchange in children. J. Clin. Apheresis, 2012.

AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections.

Transfusion‐transmitted cytomegalovirus (TT‐CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life‐threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT‐CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV‐serology and leukoreduction to prevent TT‐CMV for at‐risk patients. Other approaches may also be feasible to prevent TT‐CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large‐scale clinical trials will be performed to determine whether leukoreduction, CMV‐serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV‐safe blood components.

Extracorporeal photopheresis practice patterns: An international survey by the ASFA ECP subcommittee

Although many apheresis centers offer extracorporeal photopheresis (ECP), little is known about current treatment practices.

Report of the ASFA apheresis registry study on Wilson's disease

Wilsons disease is a rare autosomal recessive genetic disorder that results in accumulation of copper in the liver, brain, cornea and kidney. Therapeutic plasma exchange (TPE) has been used to remove copper and provide a bridge to liver transplantation. We report here the collective experiences through the ASFA apheresis registry on Wilsons disease.

Rapamycin increases fetal hemoglobin and ameliorates the nociception phenotype in sickle cell mice

Fetal hemoglobin-inducing therapies are disease-modifying and ameliorate the pain phenotype in sickle cell disease (SCD). Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, increases HbF in erythroid precursor cells in vitro. We hypothesized that rapamycin would increase HbF levels and improve nociception phenotype in SCD mice. We used sine-wave electrical stimulation to examine nocifensive phenotype and evaluate myelinated [2000Hz (Aβ-fiber) and 250Hz (Aδ-fiber)] and unmyelinated (5Hz C-fibers)] sensory fiber function. Rapamycin significantly increased γ-globin mRNA and HbF levels [+2.3% (0.7, 3.9), mean increase (95% confidence interval, CI), p=0.006]. In homozygous (sickling) mice, long- (16 weeks), but not short-term (6 weeks), rapamycin treatment increased 2000Hz and 250Hz current thresholds in a pattern that varied according to sex. In male, but not female mice, rapamycin (compared with vehicle) was associated with increases in 2000Hz [21Units (7, 35), mean difference (95% CI), p=0.009 for sex∗treatment interaction] and 250Hz [9Units (1, 16), p=0.01] current thresholds. In rapamycin-treated homozygotes, HbF levels directly correlated with myelinated [2000Hz(Aβ-fiber, r=0.58, p=0.01) and 250Hz(Aδ-fiber, r=0.6, p=0.01)] but not unmyelinated sensory fiber current thresholds. These findings suggest that in SCD mice, rapamycin increases HbF and modulates current thresholds of myelinated fibers. Therefore, mTOR signaling might be implicated in the pathobiology of SCD.

Effect of temperature on thromboelastography and implications for clinical use in newborns undergoing therapeutic hypothermia

Background:Encephalopathic neonates undergoing therapeutic hypothermia have increased risk for coagulopathy secondary to perinatal asphyxia and effects of cooling on the coagulation enzyme cascade. Thromboelastography (TEG) allows for a comprehensive assessment of coagulation that can be regulated for temperature. TEG has not been previously evaluated in newborns undergoing hypothermia treatment.Methods:Encephalopathic neonates treated with systemic hypothermia were enrolled in this prospective observational study. Daily blood specimens were collected for standard coagulation tests and platelet counts during hypothermia and after rewarming. Concurrent TEG assays were performed at 33.5 and 37.0 °C for comparison.Results:A total of 48 paired TEGs from 24 subjects were performed. Forty percent of the subjects were males, the mean (± SD) birth weight was 3.2 ± 0.7 kg, and the mean gestational age was 38.4 ± 1.4 wk. TEG results differed significantly between assays performed at 37.0 vs. 33.5 °C, indicating more impaired coagulation at 33.5 °C. TEG parameters clot kinetics, angle, maximum amplitude (MA), and coagulation index were significantly associated with clinical bleeding (P < 0.05). These remained significant (except for MA) after controlling for transfusion therapy.Conclusion:TEG results are affected by temperature, consistent with the known association of hypothermia with coagulopathy. Several TEG parameters are predictive of clinical bleeding in newborns undergoing hypothermia. Selected cutpoints to predict bleeding risk are temperature dependent.