Anemia in patients undergoing chronic therapeutic plasma exchange.

Therapeutic plasma exchange is known to be an extracorporeal treatment procedure with few adverse effects. Anemia in chronically exchanged patients is not a well-recognized adverse effect. Our aim is to find if adult patients develop anemia while undergoing prolonged TPE treatments and to determine the time of onset of anemia. We retrospectively reviewed all outpatients that have undergone TPE at least once a week from July 2017 to March 2020. Kaplan-Meier time-to-event analysis was employed to calculate the time taken for development of anemia and time to reduction of hemoglobin by 1 g/dL from baseline in uncensored patients. A total of 14 patients met inclusion criteria receiving chronic TPE for neurological disorders including myasthenia gravis (MG). Eleven patients had once a week procedure. Study patients underwent a total of 113 (IQR, 84-227) TPE procedures and the duration of TPE was 4 (IQR, 2-6.5) years. Anemia was prevalent in 29% of this patient cohort before the initiation of TPE with a median hemoglobin of 9.4 (IQR, 8.1-11.0) g/dL. All patients regardless of hemoglobin levels prior to therapy had a decrease of 1 g/dL in hemoglobin in 6 (IQR, 3-8) weeks after initiation of chronic TPE. Anemia occurred in all non-anemic patients who underwent chronic TPE within a short period of ten weeks. Patients who were moderately anemic prior to initiation of TPE progressed to severe anemia within six weeks of TPE. Our results suggest that anemia is a consequence of chronic TPE. Baseline and follow-up laboratory studies are vital for early diagnosis.

Primed for change: The effect of a blood prime on peripheral blood stem cell collection and accuracy of a prediction tool in pediatric patients.

Pediatric apheresis collection of peripheral blood stem cells for autologous transplantation often requires use of a blood prime. We evaluated the relationship between pre-apheresis blood CD34+ counts and final CD34+ yield with use of a blood prime. Forty patients underwent apheresis stem cell collection in a 5 year period in our hospital, of which 27 required blood priming of the apheresis machine. Despite the blood prime group having significantly higher pre-apheresis CD34+ cell counts, this group processed a relatively higher volume of blood due to a higher dilutional effect and collected significantly less than predicted CD34+ cell yield. Use of weight-specific collection efficiencies and dilution-adjusted pre-apheresis CD34+ counts will help in accurately estimating the whole blood volume to process for PBSC collection and therefore increase efficiency and decrease the overall cost of collection.

Characteristics of thawed pooled cryoprecipitate stored at refrigerated temperature for 24 hours.

BACKGROUND: The need for thawed cryoprecipitate is growing. However, according to current guidelines, the shelf-life of pooled thawed cryoprecipitate at room temperature is limited because of possible bacterial contamination and loss of clotting factor activity. Here we assessed microbial growth and retention of clotting activity in cryoprecipitate stored at 4 °C after thawing to see whether its shelf life could be safely extended. MATERIALS AND METHODS: Pooled thawed cryoprecipitate units (n=10) were maintained at room temperature for 6 hours and then placed at 1-6 °C for 18 hours after thawing. We examined the cryoprecipitate pools for fibrinogen, factor VIII, and von Willebrand factor activity at the following time points: 0 hours (immediately after thawing), after 6 hours at room temperature, and after 24 hours at 1-6 °C. A 5-mL aliquot from each pool was collected for aerobic and anaerobic bacterial cultures at the 24-hour time point. RESULTS: Mean fibrinogen concentration and von Willebrand factor activity were similar at each time point, but factor VIII activity decreased significantly over the storage period. Bacterial growth was not detected in any cultured pooled sample. DISCUSSION: Extended storing of thawed cryoprecipitate at 1-6 °C does not appear to increase the risk of bacterial contamination or affect coagulation factor activity.

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.

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 Children's 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 Children's 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 Children's 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.

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 µg/L [30.7-76.0] vs 18.7 µg/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 µg/L [786-3,090] vs 398 µg/L [296.8-990.8]; p = 0.00), and D-dimer (3.0 µg/mL [1.9-11.5] vs 1.5 µg/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.

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/mm(3) 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.

Plasma is ineffective in correcting mildly elevated PT-INR in critically ill children: a retrospective observational study.

BACKGROUND: Fresh frozen plasma transfusion is widely utilized in pediatric clinical practice to correct mild coagulopathy. Several studies on adult population have shown that transfusion of plasma cannot effectively correct mild coagulopathy when international normalized ratio (INR) is ≤1.5. Much controversy exists about the generalization of this finding for pediatric populations, especially since pediatric dosages often exceed those in adults. The aim of this study is to determine the prevalence of plasma transfusion with mild coagulopathy (INR ≤ 1.5) and its effectiveness in a pediatric setting. METHODS: In our tertiary referral hospital, we retrospectively reviewed the electronic medical records of all patients who received plasma (April to October 2011) for mildly elevated prothrombin time (PT)-INR levels (≤1.5) and had post-transfusion PT-INR measurements; patients who received intraoperative, ECMO, or plasma exchange-related plasma transfusions were excluded from this study. We abstracted demographic data and pre- and post coagulation test results for the patients included in our study. RESULTS: Among 468 plasma transfusions administered to 285 patients from April to June 2011, 60 plasma transfusions (12.8%) were given to patients with PT-INR ≤ 1.5 (range 1.3-1.5). Forty-one patients [median age 2.5 years (IQR, 0.14 to 13.75 years), median weight of 16.0 kg (IQR, 8.0 to 69.3 kg)] who received 41 single plasma transfusions [median dose 11 mL/Kg (IQR, 6-15)] had post-transfusion PT-INR measurements and were included in our study. There was no significant difference in their PT-INR values (p = 0.34) pre- and post-transfusion. Of our study, only 15.4% patients showed post-transfusion normalization [median change in PT-INR 0.15 (IQR, 0.1-0.2)] and were not different from the remaining 85% in age, plasma dose, and bleeding status. CONCLUSIONS: The prevalence of plasma transfusion for correction of mildly elevated PT-INR levels in critically ill children is high (12.8%). Plasma transfusion showed no significant effect in correcting minor prolongation of PT-INR in pediatric patients regardless of age, volume of plasma transfused per kilogram (dosage), or bleeding status.

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 Children's 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.

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

BACKGROUND: 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. METHODS: The study population consisted of adolescents with menorrhagia who had simultaneously drawn blood samples for VWD and PFA-100®. Abnormal PFA-100® was defined as values >183 seconds for collagen/epinephrine and/or >126 seconds for collagen/ADP. RESULTS: Of a total of 235 patients tested, 23 patients had RCoF <50 IU/dl and normal multimer patterns. Statistical analysis of the utility of PFA-100® in detecting RCoF <50 IU/dl with normal multimers yielded sensitivity, specificity, positive predictive, and negative predictive values of 52%, 89%, 34%, and 95%, respectively. CONCLUSIONS: Based on our results, PFA-100® was not sufficiently sensitive to detect RCoF values <50 IU/dl with normal multimer patterns in teen-aged women with menorrhagia. We conclude that in the setting of adolescent menorrhagia, PFA-100® does not have utility as an initial screening test for the diagnosis of VWD and in particular, low VWF and that clinicians need to be aware of this limitation of PFA-100® while evaluating adolescents with menorrhagia.

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.