Cell saver blood transfusions may be associated with a decrease in inflammation and improved outcome measures in pediatric cardiac surgery patients.

OBJECTIVE: Cardiopulmonary bypass (CPB) is a requisite for correction of congenital heart disease by open-heart surgery and induces a systemic inflammatory response that can lead to complications such as acute lung injury and acute kidney injury. In addition, blood transfusions are commonly required for this type of surgery, and they may further exacerbate this inflammatory response and increase morbidity and mortality. We hypothesized that, in contrast to red blood cells, intraoperative cell saver (CS) blood transfusions attenuate the post-CPB proinflammatory cytokine response. METHODS: Serum cytokine concentrations of IL-10, IL-1RA, IL-6, IL-8, and TNF-α were measured at four time points (preoperatively and postoperatively on postoperative days 0, 1, and 2). RESULTS: Anti-inflammatory IL-10 levels were significantly lower in the CS group on POD 0 than in the control group (mean 1083.2 pg/mL vs 2080.2 pg/mL, 95%CI 357.4-1636.6, p = .0026). Of the clinical parameters measured, mean BUN and creatinine levels on POD 2 were significantly lower in the CS group (13.79 vs 21.88, p = .004 and 0.45 vs 0.55, p = .055, respectively). In addition, the duration of milrinone use decreased by 80% in the CS group (0.20, 95%CI 0.04, 0.94; p = .048), the median time to extubation in hours was significantly lower in the CS group (3.5 vs 6.5; 95%CI -38.00, -0.50; p = .026), and hospital length of stay was decreased by 60% in the CS group (p = .003). CONCLUSIONS: CS transfusions in children may lower postoperative anti-inflammatory IL-10 levels, possibly due to an overall decrease in proinflammatory state, and may be associated with improvements in renal and pulmonary functions.

Successful Use of Hematopoietic Stem Cell Transplantation for 2 Pediatric Cases of Glanzmann Thrombasthenia and Review of the Literature.

Glanzmann thrombasthenia is a rare platelet disorder characterized by an abnormal integrin receptor on the surface of platelets that results in the failure of platelets to aggregate. Currently, curative therapy is allogeneic hematopoietic stem cell transplantation (HSCT). The authors report 2 patients with Glanzmann thrombasthenia who successfully underwent allogeneic HSCT from unrelated donors, including one using umbilical cord blood stem cells. Although both patients had evidence of engraftment, hematopoietic recovery, and normalization of platelet aggregation, they also experienced several post-transplant complications. Allogeneic HSCT carries a significant risk of morbidity and mortality that should be considered before proceeding with the transplant.

Development of a Rapid Qualitative Screen for Anticoagulant Presence.

BACKGROUND: Direct oral anticoagulants (DOACs) and fondaparinux with stable pharmacokinetics are commonly used anticoagulants for outpatient care. Due to the lack of monitoring requirements, drug-specific assays are not available in most hospital laboratories, but drug levels are needed in some urgent/emergency situations. This study describes the development of a qualitative screen for the presence of DOAC or fondaparinux using coagulation tests found in most laboratories. METHODS: The DOAC screen is composed of a heparin anti-Xa activity assay and thrombin time (TT) assay. The STA®-Liquid-Anti-Xa assay calibrated with Stago Multi Hep® and STA®-TT were run on STA-R Max® analyzers. The anti-Xa activity and TT assays were repeated 5 times in samples of commercially available calibrators and controls for each drug: fondaparinux, dabigatran, rivaroxaban, apixaban, and edoxaban. Statistical analysis and correlations were performed for anti-Xa activity and TT results for each drug and pooled normal plasma. RESULTS: A significant correlation was found between heparin-calibrated anti-Xa levels and fondaparinux, rivaroxaban, apixiban, and edoxaban (r2 = 0.99-1.0). Dabigatran showed a strong linear correlation (r2 = 0.99) with TT. Anti-Xa levels >0.3 IU/mL and TT >25 seconds were determined as cutoffs at our lab for the detection of clinically relevant drug levels of factor Xa inhibitor and direct thrombin inhibitor, respectively. CONCLUSIONS: Our study demonstrates that commonly available heparin anti-Xa activity and TT assays can be used to qualitatively detect DOACs and fondaparinux and provides a method to establish a qualitative interpretation.

Is hyperbilirubinemia a contraindication for neonatal circumcision? A survey of practice patterns of pediatric urologists and a review of the literature.

INTRODUCTION AND OBJECTIVE: 50-80% of term newborns develop jaundice, or hyperbilirubinemia (HB), in their first week. The vast majority have benign etiologies, including physiologic jaundice of the newborn and breast milk/breastfeeding jaundice, which do not affect the synthetic capacity of the liver, thus conferring a low risk of peri-procedural bleeding. Though uncommon, HB in the setting of sepsis, biliary obstruction, or metabolic disease, may increase procedural bleeding risk. Circumcision of neonates with HB has not been well studied. We sought to characterize practice patterns among Society of Pediatric Urology (SPU) members and to explore whether HB confers increased bleeding risk for newborn circumcision. METHODS: An anonymous survey of 14 multiple-choice questions was sent to members of the SPU listserv. Questions regarding circumcision and HB were presented. We performed a literature review regarding whether HB confers increased surgical bleeding risk. RESULTS: 100/234 (43%) SPU members completed the survey. The majority (79/100) perform neonatal circumcision and use the Gomco© clamp (68%). 24/79 (30%) factor total bilirubin (Tbili) level in their decision prior to performing circumcision. Of those who consider HB a factor, 11/24 (46%) had cutoff Tbili levels at which they await improvement prior to proceeding. The most common cutoff level was Tbili level of 10-15 mg/dL (6/11, 55%). DISCUSSION: Existing data suggest a possible increased bleeding risk isolated to cases of HB in the setting of biliary obstruction or other associated relevant findings (ill infant, recent infection, congenital syndromes) or known personal/family history (fulminant liver disease, familial bleeding diatheses). While literature from Jewish Mohels and Talmudic discussion suggest that elevated Tbili may be a contraindication to circumcision, no scientific studies exist directly assessing the impact of HB on bleeding risk with circumcision. A review of the scientific literature suggests that isolated HB in otherwise healthy newborns does not increase bleeding risk. CONCLUSIONS: 30% of pediatric urologists survey respondents consider HB a potential contraindication to neonatal circumcision. Despite varied practices in circumcising jaundiced babies, neonatal jaundice rarely confers increased bleeding risks. While deferring circumcision is appropriate in an ill infant with HB, or in those with a genetic/congenital syndrome or with family history of coagulopathic, review of the scientific literature suggests that in otherwise healthy neonates, elevated Tbili likely represents benign causes and is unlikely to increase bleeding risk.

Perinatal Arterial Ischemic Stroke.

Perinatal arterial ischemic stroke (PAIS) is a common cause of seizures, encephalopathy, altered mental status, and focal neurologic deficits in the neonatal period. It is the leading known cause of cerebral palsy. Other long-term risks include the development of epilepsy and impairment in cognition, language, and behavior. This article will review the known risk factors for PAIS, as well as the evaluation, management, and prognosis. Long-term neurodevelopmental surveillance is recommended, along with intensive therapies to reduce morbidity.

Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies.

Pediatric Acute Liver Failure (PALF) is a rapidly progressive clinical syndrome encountered in the pediatric ICU which may rapidly progress to multi-organ dysfunction, and on occasion to life threatening cerebral edema and hemorrhage. Pediatric Acute Liver Failure is defined as severe acute hepatic dysfunction accompanied by encephalopathy and liver-based coagulopathy defined as prolongation of International Normalized Ratio (INR) >1.5. However, coagulopathy in PALF is complex and warrants a deeper understanding of the hemostatic balance in acute liver failure. Although an INR value of >1.5 is accepted as the evidence of coagulopathy and has historically been viewed as a prognostic factor of PALF, it may not accurately reflect the bleeding risk in PALF since it only measures procoagulant factors. Paradoxically, despite the prolongation of INR, bleeding risk is lower than expected (around 5%). This is due to "rebalanced hemostasis" due to concurrent changes in procoagulant, anticoagulant and fibrinolytic systems. Since the liver is involved in both procoagulant (Factors II, V, IX, XI, and fibrinogen) and anticoagulant (Protein C, Protein S, and antithrombin) protein synthesis, PALF results in "rebalanced hemostasis" or even may shift toward a hypercoagulable state. In addition to rebalanced coagulation there is altered platelet production due to decreased thrombopoietin production by liver, increased von Willebrand factor from low grade endothelial cell activation, and hyperfibrinolysis and dysfibrinogenemia from altered synthetic liver dysfunction. All these alterations contribute to the multifactorial nature of coagulopathy in PALF. Over exuberant use of prophylactic blood products in patients with PALF may contribute to morbidities such as fluid overload, transfusion-associated lung injury, and increased thrombosis risk. It is essential to use caution when using INR values for plasma and factor administration. In this review we will summarize the complexity of coagulation in PALF, explore "rebalanced hemostasis," and discuss the limitations of current coagulation tests. We will also review strategies to accurately diagnose the coagulopathy of PALF and targeted therapies.