Esther Soundar

Can phase angle determined by bioelectrical impedance analysis assess nutritional risk? A comparison between healthy and hospitalized subjects

BACKGROUND & AIMS Low phase angle (PhA) by bioelectrical impedance analysis (BIA), is associated with increased morbidity and nutritional risk. This study determined the cut-off values for PhA compared to Nutritional Risk Screening (NRS-2002) and Subjective Global Assessment (SGA) in patients at hospital admission, and evaluated the association between PhA and serum albumin. METHODS PhA was determined in patients (Men (M)/Women (W)=382/267), and healthy age-, sex- and height-matched controls. Sensitivity and specificity were calculated for PhA compared to NRS-2002, SGA and serum albumin. The cut-off values were assessed by receiver operator characteristics area under the curve (ROC-AUC). RESULTS The best PhA cut-offs were 5.0° and 4.6° in M/W. The sensitivity for NRS-2002 was 70.0/58.1% (M/W); SGA: 73.3/64.5%; albumin: 58.8/23.5%; specificity for NRS-2002: 85.1/81.7% (M/W); SGA: 76.6/76.1% and albumin: 93.2/96.6%. The PhA showed a ROC-AUC for NRS-2002 of 0.85/0.80 (M/W); SGA: 0.83/0.80 and albumin: 0.85/0.91. Patients with albumin levels <35 g/L had a relative risk of 7.5 to have low PhA compared to patients with ≥35 g/L CONCLUSIONS: The consistent sensitivity and specificity between PhA and three screening tools strengthens the validity of our study. PhA appears to be a useful screening tool to assess nutritional risk without having to measure weight or height.

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.

Validation of the procalcitonin (PCT) assay: Experience in a pediatric hospital.

OBJECTIVES Procalcitonin (PCT) is a potential early biomarker used to differentiate sepsis from systemic inflammation. Serial PCT measurement is useful in reducing the duration of antibiotic exposure without increasing treatment failure. Our aim was to establish and evaluate an automated quantitative PCT assay at Texas Childrens Hospital. METHODS We validated the analytical and clinical performance of the automated miniVIDAS B.R.A.H.M.S PCT® assay (BioMerieux®, France) at Texas Childrens Hospital. Analytical performance parameters included precision, linearity, accuracy, correlation, and effect of different common interferents (free Hb, bilirubin, triglyceride and rheumatoid factor). Also, the interference of high calcitonin (CT) on PCT assay was tested. We performed clinical correlation of PCT to blood culture, WBC counts and CRP in sepsis patients. RESULTS The PCT assay showed good precision with %CV of <5% for intra-assay and %CV of 6.5% for inter-assay precision. The assay was linear across the measurement range (0.05μg/L-200μg/L). Correlation studies showed a good correlation (r>0.9). No significant effects on PCT levels were seen with common interferents however, calcitonin concentrations of 1000ng/L or more showed cross-reactivity with PCT values. Fourteen (78%) out of the total eighteen patients with positive blood culture, showed median PCT concentrations greater than the cut-off values of 0.15μg/L. CONCLUSION The miniVIDAS PCT assay can be used for diagnostic purposes in clinical laboratories. We envision that serial PCT monitoring along with clinical correlation will be beneficial in critically ill patients.

Utility of platelet function analyzer as a screening tool for the diagnosis of Von Willebrand disease in adolescents with menorrhagia

Von Willebrand disease (VWD), and in particular, VWD type 1 and low VW factor (defined as Von Willebrand Ristocetin cofactor activity (RCoF) <30 and <50 IU/dl, respectively with normal multimers) are frequently detected in adolescents with menorrhagia and both groups benefit from similar management. Platelet function analyzer (PFA‐100®) is often used as a screening test to detect VWD. We analyzed the utility of PFA‐100® as a screening tool in the detection of VWD type 1 and low VW factor (VWF) in an exclusive adolescent population with menorrhagia.

Evaluation of the International Society on Thrombosis and Haemostasis and Institutional Diagnostic Criteria of Disseminated Intravascular Coagulation in Pediatric Patients

Globally, adult intensive care units routinely use the International Society on Thrombosis and Haemostasis (ISTH) scoring system for identifying overt disseminated intravascular coagulation (DIC). However, in our pediatric intensive care unit, a modified diagnostic criterion (Texas Childrens Hospital [TCH] criteria) that requires serial monitoring of the coagulation variables is employed. A retrospective analysis of 2,136 DIC panels from 130 patients who had at least 4 DIC panels during 1 admission to a pediatric intensive care unit was done to compare the diagnostic utility of the TCH criteria with the ISTH scoring method in children. Both scoring systems were evaluated against the gold standard diagnostic method of autopsy confirmation of DIC in the subset of children who died. Receiver operating characteristic analysis indicates that TCH diagnostic criteria are comparable to the ISTH scoring method (area under the curve of 0.878 for TCH and 0.950 for ISTH). On the contrary, TCH diagnostic criteria perform better, with a sensitivity significantly higher than the ISTH scoring method when tested against the gold standard (P < .05). Fibrinogen is not a significant predictor of overt DIC in both models. Sequential testing of coagulation parameters is recommended for improved sensitivity when applying ISTH criteria to pediatric populations.

Secondary Bone Marrow Fibrosis in Children And Young Adults: An Institutional Experience.

Secondary bone marrow fibrosis (BMF) is associated with many disease conditions in children, but its prevalence and characteristics have not been well elucidated. We present our experience with pediatric secondary BMF, in an attempt to characterize it in terms of underlying diagnoses, severity, and outcome. A retrospective chart review of patients diagnosed with secondary BMF by bone marrow aspirate and biopsy between January 1984 and April 2011 showed a total of 214 patients, the majority (67.1%) of whom had an underlying oncologic disease. At diagnosis, 87 patients (39.7%) had mild, 51 (23.3%) had moderate, and 33 (15.1%) had marked BMF; it was not quantified in 48 (21.9%) patients. An underlying oncologic disease was more frequently associated with marked fibrosis compared with hematologic and miscellaneous diagnoses. Follow-up posttreatment bone marrow aspirate assessments were available for 117 patients. The outcome ranges from worsening of fibrosis to complete resolution. A majority of these children (N=70/117, 60%) showed complete resolution of fibrosis. Of note, 27 patients had marked fibrosis at initial diagnosis and 16 (60%) of them showed complete resolution. These findings underscore the importance of appropriate treatment of the underlying disorder in reversing secondary BMF. Ours is the largest series of pediatric secondary BMF reported.

Diagnostic challenges in patients with bleeding phenotype and von Willebrand exon 28 polymorphism p.D1472H.

Exon 28 polymorphism p.D1472H is associated with significantly lower von Willebrand Ristocetin cofactor activity (VWF:RCoF) to von Willebrand antigen (VWF:Ag) ratio compared to normal, but has been reported as not conferring haemorrhagic risk. The impact of this polymorphism while assessing symptomatic patients for von Willebrand disease (VWD) has not been previously analysed. We retrospectively reviewed charts of children with clinically significant bleeding and abnormal VW panel who underwent VW exon 28 analysis. Twenty‐three of 63 patients studied had p.D1472H. Of these 23 patients, 6 with borderline low VWF:RCo were given provisional diagnosis of VWD type 1 by treating physicians, which could be alternatively explained as due to the effect of p.D1472H. None of the patients with low VWF:RCo, decreased VWF:RCo/VWF:Ag ratio and p.D1472H had VWD type 2M mutations identified. This study illustrates the challenge in diagnosing VWD using ristocetin‐based VW assay in symptomatic patients with p.D1472H.

Bleeding in Acute and Chronic Liver Disease

The liver plays a central role in hemostasis. In liver disease, hemostasis is deranged but precariously balanced. Different pathophysiological mechanisms form an underlying basis for bleeding in acute and chronic liver disease. In acute liver failure, there is severe reduction in circulating procoagulant and anticoagulant factor levels. However, patients with chronic liver disease more often exhibit systemic hyperfibrinolysis. The common laboratory coagulation tests such as prothrombin time/international normalized ratio (INR) are poor predictors of spontaneous bleeding or during invasive procedures in patients with liver disease. Although clinically significant spontaneous bleeding is not common, a sudden onset of massive bleeding can happen without a trigger. Therefore, the target of each coagulation parameter needs to be clearly defined to prevent catastrophic bleeding. If the patient is bleeding, appropriate therapeutic interventions including transfusions of blood components and factor concentrates are indicated without delay.