Seeing haemoglobin SC: Challenging the misperceptions.

Historically understudied and regarded as a mild type of sickle cell disease, HbSC can be associated with significant, progressive complications. Prospective studies are urgently needed to address treatment gaps for HbSC disease. Commentary on: Nelson et al. The clinical spectrum of HbSC sickle cell disease-not a benign condition. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19523.

Bivalirudin Monitoring in Pediatric Ventricular Assist Device and Extracorporeal Membrane Oxygenation: Analysis of Single-Center Retrospective Cohort Data 2018-2022.

OBJECTIVES: The activated partial thromboplastin time (aPTT) is the most frequently used monitoring assay for bivalirudin in children and young adults on mechanical circulatory support including ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO). However, intrinsic variability of the aPTT complicates management and risks bleeding or thrombotic complications. We evaluated the utility and reliability of a bivalirudin-calibrated dilute thrombin time (Bival dTT) assay for bivalirudin monitoring in this population. DESIGN: Retrospective analysis of clinical data (including aPTT, dilute thrombin time [dTT]) and results of residual plasma samples from VAD patients were assessed in two drug-calibrated experimental assays. One assay (Bival dTT) was validated for clinical use in VAD patients, and subsequently used by clinicians in ECMO patients. Pearson correlation and simple linear regression were used to determine R2 correlation coefficients between the different laboratory parameters using Statistical Package for Social Sciences (Armonk, NY). SETTING: ICUs at Cincinnati Children's Hospital Medical Center. SUBJECTS: Children on VAD or ECMO support anticoagulated with bivalirudin. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fifteen plasma samples from 11 VAD patients were analyzed. Both drug-calibrated experimental assays (anti-IIa and Bival dTT) showed excellent correlation with each other ( R2 = 0.94) and with the dTT ( R2 = 0.87), but poor correlation with aPTT ( R2 = 0.1). Bival dTT was selected for validation in VAD patients. Subsequently, clinically ordered results (105) from 11 ECMO patients demonstrated excellent correlation between the Bival dTT and the standard dTT ( R2 = 0.86) but very poor correlation with aPTT ( R2 = 0.004). CONCLUSIONS: APTT is unreliable and correlates poorly with bivalirudin's anticoagulant effect in ECMO and VAD patients. A drug-calibrated Bival dTT offers superior reliability and opportunity to standardize results across institutions. Additional studies are needed to determine an appropriate therapeutic range and correlation with clinical outcomes.

Impact of inflammation and steroids on anti-coagulation in children supported on a ventricular assist device.

Critically ill pediatric patients supported on ventricular assist devices (VADs) are increasingly being anticoagulated on bivalirudin, but with difficulty monitoring anticoagulation. Activated partial thromboplastin time (aPTT) has recently been shown to poorly correlate with bivalirudin plasma concentrations, while dTT had excellent correlation. However, aPTT is the more common monitoring test and dTT testing is rarely used. In addition, effects of frequent clinical VAD scenarios (such as inflammation) on the accuracy of aPTT and dTT testing remains uncertain. We reviewed the effects of clinical scenarios (infection/inflammation, chylothorax, and steroids administration) on anticoagulation monitoring in 10 pediatric VAD patients less than 3 years at Cincinnati Children's Hospital Medical Center from 10/27/2020 to 5/6/2022 using bivalirudin for anticoagulation. There were 16 inflammation/infection, 3 chylothorax, and 6 steroids events. Correlation between dTT and aPTT was significantly lower after infection/inflammation, with dTT increasing prior to inflammation/infection while aPTT remained unchanged. In addition, steroids are administered to VAD patients to reduce inflammation and thus additionally stabilize anticoagulation. However, this anticoagulation stabilization effect was reflected more accurately by dTT compared to aPTT. In children requiring VAD support utilizing bivalirudin anticoagulation, inflammation/infection is a common occurrence resulting in anticoagulation changes that may be more accurately reflected by dTT as opposed to aPTT.

Evaluation, analysis, and reporting of medication adherence for clinical trials of anticoagulants in children: guidance from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis.

In response to growing recognition that nonadherence prevents children, adolescents, and young adults from achieving the therapeutic benefits of anticoagulant medication, the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis convened a working party on medication adherence. The primary aim of this article was to synthesize recommendations from the larger adherence science literature to provide guidance regarding the classification, collection, and interpretation of anticoagulation adherence data. The secondary aim of this article was to evaluate the degree to which trials published from 2013 to 2023 adhered to these guidance recommendations. As less than half of all trials reported on adherence and none included all recommended elements, the proposed International Society on Thrombosis and Haemostasis Scientific and Standardization Committee guidance has the potential to enhance the rigor and reproducibility of pediatric anticoagulant research.

Barriers to medication adherence in children, adolescents, and young adults prescribed anticoagulation.

Pediatric and adolescent and young adult (AYA) thromboembolism is treated with anticoagulation, but little is known about adherence. The aims of this study were to describe barriers to adherence among children and AYAs (ages 0-25 years) prescribed anticoagulants and to explore the relationship between barriers and self-reported adherence. Nearly 75% of patients and caregivers reported barriers, and a larger number of barriers was associated with missing at least one dose in the past month per both patient (rpb  = 0.48, p = .01) and caregiver (rpb  = 0.52, p = .01) report. Limitations, clinical implications, and future directions are discussed.

A systematic review of adherence to anticoagulation regimens in pediatric patients.

Thromboembolic disease rates are increasing in pediatric patients. Anticoagulation is prescribed for treatment and prevention of thromboembolic disease. While nonadherence to anticoagulation regimens predicts poor health outcomes in adults, data in anticoagulated pediatric patients are limited. We systematically reviewed the rates, outcomes, and predictors of anticoagulation nonadherence in the pediatric population. Out of a total of 3581 unique articles identified for review, 17 studies met inclusion criteria. These studies primarily evaluated patients with cardiac disease treated with vitamin K antagonists. Overall nonadherence rates varied from 3% to 42%, based upon population, definition of adherence, and measurement strategy. Patient age, goal international normalized ratio (INR), and number of concurrent potentially interacting medications correlated with nonadherence. Data examining the relationship between nonadherence and health outcomes were included in only two studies. Limitations of current literature, as well as critical knowledge gaps that require future study, are discussed.

Results of an international survey on adherence with anticoagulation in children, adolescents, and young adults: Communication from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis.

BACKGROUND: The ISTH Scientific and Standardization Committee (SSC) Subcommittee on Pediatric/Neonatal Thrombosis and Hemostasis convened a working group on medication adherence to begin to understand the current state of clinical practice to inform priority areas for efforts to improve adherence for children, and adolescents and young adults (AYA) prescribed anticoagulants. OBJECTIVES: We sought to survey an international group of clinicians involved in anticoagulation management in children and/or AYA about perceptions of medication on health outcomes, clinical practice related to medication adherence, and barriers to assessing and improving medication adherence. METHODS: Clinicians involved in anticoagulation management in children and/or AYA were surveyed via REDCap® . Descriptive statistics were used to summarize demographic and clinical characteristics and responses to multiple choice and Likert-type questions. Free-text answers were coded based on the Behaviour Change Technique Taxonomy and the Expert Recommendations for Implement Change project. RESULTS AND CONCLUSIONS: There were 200 participants, 90% of whom were pediatric hematology/oncology physicians. Based on the results, which demonstrate that clinicians are concerned about impact of poor medication adherence and have limited resources to identify and improve adherence, the working group has identified next steps to further understand impact of medication adherence on anticoagulation-related health outcomes, address the need for validated measures to assess medication adherence for all anticoagulants prescribed to this population, and develop an intervention and implementation research agenda to improve outcomes.

The ASH-ASPHO Choosing Wisely Campaign: 5 hematologic tests and treatments to question.

Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count >10 × 103/µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.

Current practices in pediatric hospital-acquired thromboembolism: Survey of the Children's Hospital Acquired Thrombosis (CHAT) Consortium.

Background: A rise in hospital-acquired venous thromboembolism (HA-VTE) in children has led to increased awareness regarding VTE prophylaxis and risk assessment. Despite no consensus exists regarding these practices in pediatrics. Objective: To describe common practices in VTE prophylaxis, VTE risk assessment models, and anticoagulation dosing strategies in pediatric hospitals that are members of the Children's Hospital Acquired Thrombosis (CHAT) Consortium. Methods: An electronic survey of 44 questions evaluating practices surrounding pediatric HA-VTE risk assessment and prevention was distributed between August 9, 2021, and August 30, 2021, to the primary investigators from the 32 institutions within the CHAT Consortium. Results: The survey response rate was 100% (n = 32). In total, 85% (n = 27) of the institutions assess HA-VTE, but only 63% (n = 20) have formal hospital guidelines. Within the institutions with formal guidelines, 100% (n = 20) include acute systemic inflammation or infection and presence of a central venous catheter (CVC) as risk factors for VTE. Pharmacologic prophylaxis is prescribed at 87% (28) of institutions, with enoxaparin being the most frequent (96%, n = 27). Variability in responses persisted regarding risk factors, risk assessment, thromboprophylaxis, dosing of prophylactic anticoagulation or anticoagulant drug monitoring. A majority of providers were comfortable providing thromboprophylaxis across all age groups. In addition, the global coronavirus disease 2019 increased the providers' use of prophylactic anticoagulation 78% (n = 25). Conclusion: Practices among institutions are variable in regard to use of HA-VTE prophylaxis, risk assessment, or guideline implementation, highlighting the need for further research and a validated risk assessment model through groups like the CHAT Consortium.

Urinary 11-dehydrothromboxane B2 aspirin efficacy testing is sensitive to perioperative inflammation in pediatric solid-organ transplant patients.

BACKGROUND: Evidence for aspirin efficacy testing in pediatrics is limited, especially outside of cardiology, yet thrombotic events have high morbidity in other areas such as pediatric transplant surgery. Debates about whether thromboembolic events while on aspirin represent "aspirin resistance" or "high on-treatment platelet reactivity" persist, given the poor intertest agreement between testing platforms. PROCEDURE: This prospective observational study involved measuring aspirin efficacy using ex vivo testing of platelet aggregation (VerifyNow-Aspirin, VN) and urine 11-dehydrothromboxane B2 (AsprinWorks, UTxB2) contemporaneously at up to three time points after major noncardiac organ transplant surgery. The collection days (CD) were the second and seventh days after stable aspirin dosing and then a convalescent time point 2-9 months later. RESULTS: Fifty-five participants (age range, 0-21 years) were enrolled, having undergone total pancreatectomy with islet autotransplantation (N = 36), orthotopic liver transplantation (N = 18), and combined liver-kidney transplantation (N = 1). Platelet reactivity measured by VN remained unchanged, whereas UTxB2, which was elevated postoperatively, decreased significantly from CD1 to CD2 and CD3. Discordance in therapeutic efficacy was noted per manufacturer cutoffs, with therapeutic VN results in 86% of tests, whereas 12% of UTxB2 were therapeutic. Age-based stratification of UTxB2 results using previously published pediatric median levels increased overall UTxB2 therapeutic rates (80%) and intertest concordance (67% vs 27% if using adult range). No thrombotic events were observed. CONCLUSIONS: Our data suggest that urine thromboxane production may be an underappreciated reflection of postoperative inflammation. Validation of pediatric normal ranges for UTxB2 is a critical next step.

Case Report: Cerebral Revascularization in a Child With Mucopolysaccharidosis Type I.

Mucopolysaccharidosis (MPS) type I is a rare lysosomal storage disorder caused by an accumulation of glycosaminoglycans (GAGs) resulting in multisystem disease. Neurological morbidity includes hydrocephalus, spinal cord compression, and cognitive decline. While many neurological symptoms have been described, stroke is not a widely-recognized manifestation of MPS I. Accordingly, patients with MPS I are not routinely evaluated for stroke, and there are no guidelines for managing stroke in patients with this disease. We report the case of a child diagnosed with MPS I who presented with overt stroke and repeated neurological symptoms with imaging findings for severe ventriculomegaly, infarction, and bilateral terminal carotid artery stenosis. Direct intracranial pressure evaluation proved negative for hydrocephalus. The patient was subsequently treated with cerebral revascularization and at a 3-year follow-up, the patient reported no further neurological events or new ischemia on cerebral imaging. Cerebral arteriopathy in patients with MPS I may be associated with GAG accumulation within the cerebrovascular system and may predispose patients to recurrent strokes. However, further studies are required to elucidate the etiology of cerebrovascular arteriopathy in the setting of MPS I. Although the natural history of steno-occlusive arteriopathy in patients with MPS I remains unclear, our findings suggest that cerebral revascularization is a safe treatment option that may mitigate the risk of future strokes and should be strongly considered within the overall management guidelines for patients with MPS I.

The ASH-ASPHO Choosing Wisely Campaign: 5 hematologic tests and treatments to question.

Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count 10 × 103 /µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.

Specifications of the variant curation guidelines for ITGA2B/ITGB3: ClinGen Platelet Disorder Variant Curation Panel.

Accurate and consistent sequence variant interpretation is critical to the correct diagnosis and appropriate clinical management and counseling of patients with inherited genetic disorders. To minimize discrepancies in variant curation and classification among different clinical laboratories, the American College of Medical Genetics and Genomics (ACMG), along with the Association for Molecular Pathology (AMP), published standards and guidelines for the interpretation of sequence variants in 2015. Because the rules are not universally applicable to different genes or disorders, the Clinical Genome Resource (ClinGen) Platelet Disorder Expert Panel (PD-EP) has been tasked to make ACMG/AMP rule specifications for inherited platelet disorders. ITGA2B and ITGB3, the genes underlying autosomal recessive Glanzmann thrombasthenia (GT), were selected as the pilot genes for specification. Eight types of evidence covering clinical phenotype, functional data, and computational/population data were evaluated in the context of GT by the ClinGen PD-EP. The preliminary specifications were validated with 70 pilot ITGA2B/ITGB3 variants and further refined. In the final adapted criteria, gene- or disease-based specifications were made to 16 rules, including 7 with adjustable strength; no modification was made to 5 rules; and 7 rules were deemed not applicable to GT. Employing the GT-specific ACMG/AMP criteria to the pilot variants resulted in a reduction of variants classified with unknown significance from 29% to 20%. The overall concordance with the initial expert assertions was 71%. These adapted criteria will serve as guidelines for GT-related variant interpretation to increase specificity and consistency across laboratories and allow for better clinical integration of genetic knowledge into patient care.

Hydroxyurea Pharmacokinetics in Pediatric Patients After Total Pancreatectomy With Islet Autotransplantation.

Total pancreatectomy with islet autotransplantation is a complex surgical approach for acute recurrent or chronic pancreatitis that frequently triggers extreme thrombocytosis (platelets ≥ 1000 × 109 /L). Thrombocytosis can be prothrombotic, so cytoreductive hydroxyurea is often initiated after this surgery; however, optimal dosing strategy and efficacy are unknown. This prospective pilot study characterized the pharmacokinetics of hydroxyurea after this procedure in children. It also compared them with previously published pediatric parameters in sickle cell anemia (SCA), the disease in which pediatric hydroxyurea pharmacokinetics have primarily been studied. Plasma hydroxyurea levels were quantified in 14 participants aged 4-19 years using high-performance liquid chromatography. Blood collections were scheduled 20 minutes, 1 hour, and 4 hours after the first dose, on pharmacokinetic day 1 (PK1), and again 2-3 months later if still on hydroxyurea (PK2). Six participants had PK1 and PK2 data at all 3 postdose timed collections, 5 only had PK1 samples, and 3 only had PK2 samples. Total pancreatectomy with islet autotransplantation participants had reduced and delayed absorption compared with sickle cell anemia participant data from the Hydroxyurea Study of Long-Term Effects, regardless of timing or dosing methodology. Total pancreatectomy with islet autotransplantation participants had different pharmacokinetic profiles at PK1 versus PK2, with lower dose-normalized exposures than previously reported in sickle cell anemia. These results suggest variability exists in hydroxyurea absorption and bioavailability in total pancreatectomy with islet autotransplantation patients, suspected to be primarily because of Roux-en-Y reconstruction, and suggest that more pharmacokinetic data are needed for scenarios when hydroxyurea is prescribed to children without sickle cell anemia.

Impact of exogenous antithrombin on low molecular weight heparin anti-Xa activity assays in a pediatric and young adult leukemia and lymphoma cohort with variable antithrombin levels.

BACKGROUND: Low molecular weight heparin (LMWH) remains the most commonly prescribed pediatric anticoagulant. There is debate whether LMWH anti-Xa assays with or without exogenous antithrombin (AT) best reflect anticoagulation effect, and how much discrepancy exists between assay types. OBJECTIVES: We assessed the effect of variable AT activity on LMWH anti-Xa levels in plasma samples from anticoagulated pediatric and young adult acute lymphoblastic leukemia and lymphoma (ALL/L) patients, using two instruments and their commercial kits with and without exogenous AT (ie, four platforms). METHODS: We analyzed LMWH anti-Xa levels on 60 plasma samples with known AT activity from 12 enoxaparin-treated ALL/L patients, using four commercial kits from Siemens and Stago containing AT or not, on Siemens BCS and Stago STA R Max, respectively. RESULTS: Of 236/240 samples with interpretable results, mean AT activity was 80% (46-138%). Correlation was acceptable for published kit ranges of LMWH anti-Xa levels when comparing kits containing AT (r = 0.82, P < .0001), or not (r = 0.93, P < .0001), and within a manufacturer (Berichrom to Innovance, r = 0.92, P < .0001; Stachrom to STA-Liquid Anti-Xa r = 0.98, P < .0001). LMWH anti-Xa levels were lower in platforms without added AT (P < .0001). For Stago kits, this effect increased when AT < 70% (P = .001, n = 19, mean 56%). Assay variability, measured as mean percent difference, was less pronounced with Stago kits (14.7%, n = 49) than Siemens (41.9%, n = 50). CONCLUSIONS: Although LMWH levels from anti-Xa assays with added AT trend higher than in those without, correlation was fairly good between platforms in pediatric ALL/L plasmas, even when AT activity was <70%.

Tricuspid regurgitation velocity and other biomarkers of mortality in children, adolescents and young adults with sickle cell disease in the United States: The PUSH study.

In the US, mortality in sickle cell disease (SCD) increases after age 18-20 years. Biomarkers of mortality risk can identify patients who need intensive follow-up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3-20 years into an observational study in 2006-2010 and followed 497 patients for a median of 88 months (range 1-105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality. Estimated survival to 18 years was 99% and to 25 years, 94%. Causes of death were known in seven of 10 patients: stroke in four (hemorrhagic two, infarctive one, unspecified one), multiorgan failure one, parvovirus B19 infection one, sudden death one. Baseline TRV ≥2.7 m/second (>2 SD above the mean in age-matched and gender-matched non-SCD controls) was observed in 20.0% of patients who died vs 4.6% of those who survived (P = .012 by the log rank test for equality of survival). The baseline variable most strongly associated with an elevated TRV was a high hemolytic rate. Additional biomarkers associated with mortality were ferritin ≥2000 µg/L (observed in 60% of patients who died vs 7.8% of survivors, P < .001), forced expiratory volume in 1 minute to forced vital capacity ratio (FEV1/FVC) <0.80 (71.4% of patients who died vs 18.8% of survivors, P < .001), and neutrophil count ≥10x109 /L (30.0% of patients who died vs 7.9% of survivors, P = .018). In SCD children, adolescents and young adults, steady-state elevations of TRV, ferritin and neutrophils and a low FEV1/FVC ratio may be biomarkers associated with increased risk of death.

Extreme Thrombocytosis after Pediatric Pancreatectomy with Islet Autotransplantation Is Unique Compared to Other Postsplenectomy States.

BACKGROUND: Hematologic trends after pancreatectomy with islet autotransplantation (IAT), which involves splenectomy, have been rarely studied. Reactive thrombocytosis (RT, platelets ≥500 K/µL) often occurs postoperatively, similar to other postsplenectomy states, but the degree of similarities and true incidence are unknown. STUDY DESIGN: A single-site, retrospective, observational cohort study of patients who underwent total splenectomy between 2010 and 2018 was performed. Thrombocytosis incidence and pharmacologic management strategies were evaluated, including cohort-based analyses for IAT versus other splenectomy indications. RESULTS: Analyses included 112 patients overall, 42 of whom underwent IAT. RT occurred frequently (93.8%) despite most patients having normal preoperative platelet counts. IAT patients had significantly higher peak platelet counts compared to non-IAT patients and the rate of platelet rise for IAT patients was significantly faster. IAT was uniquely predictive of developing extreme thrombocytosis (ExT, platelets ≥1000 K/µL, 90% vs. 15.7%, risk ratio 4.11, P < 0.0001) despite standardized hydroxyurea use. Thrombotic events were infrequent and did not differ between groups. CONCLUSIONS: RT was common regardless of splenectomy indication but ExT was uniquely associated with IAT despite cytoreductive pharmacotherapy. These results strongly suggest that splenectomy is unlikely to be the sole contributor to post-IAT RT but further investigations into this phenomenon are needed. LEVEL-OF-EVIDENCE RATING: Treatment study, Level III (retrospective comparative study).

Thrombopoietin Contributes to Extreme Thrombocytosis After Pediatric Pancreatectomy With Islet Autotransplantation.

OBJECTIVE: This study aims to explore the role of thrombopoietin (TPO) production in extreme thrombocytosis that is often observed after pancreatectomy with islet autotransplantation (IAT) and the effectiveness of hydroxyurea in thrombocytosis management. METHODS: Retrospective chart review was performed for all patients who underwent pancreatectomy with IAT at our institution between April 1, 2015, and December 31, 2016. Data evaluated included demographics, platelet counts, TPO levels, and thrombocytosis management strategies. RESULTS: Twelve total and 1 subtotal pancreatectomy with IAT cases were reviewed. All operations included splenectomy. No major surgical or thrombotic complications occurred. Thrombopoietin levels, normal preoperatively, rose significantly (median, 219 pg/mL) soon after surgery, peaking on median postoperative day 3. Platelet counts, also normal preoperatively, increased within a week of surgery, with 92% over 1000 K/µL (median peak platelet count, 1403 K/µL). Platelet counts and TPO levels dropped after hydroxyurea initiation in most patients. CONCLUSIONS: After pancreatectomy with IAT, patients experienced marked TPO rise and subsequent thrombocytosis, and both decreased significantly after hydroxyurea initiation. These data suggest that TPO elevation and associated increased platelet production may be one driver of early extreme post-total pancreatectomy with islet autotransplantation thrombocytosis, and this process may be modulated by hydroxyurea.

Capped antithrombin III dosing is cost effective in the management of asparaginase-associated thrombosis.

Asparaginase therapy induces a transient antithrombin III (ATIII) deficiency, which contributes to the risk of asparaginase-induced thrombosis. At Cincinnati Children's Hospital Medical Center, management of asparaginase-induced thrombosis includes ATIII supplementation during therapeutic anticoagulation with enoxaparin. Due to the expense associated with ATIII, a capped dosing approach for ATIII was evaluated in this population. Peak ATIII levels were obtained following capped doses to evaluate response. In this pilot evaluation, 11 patients received a total of 138 capped doses for a total cost savings of $803 782. This pilot evaluation represents the first reported analysis of capped ATIII dosing in oncology patients.