Donald L Yee

Texas Children's Hospital, Houston, Texas, United States

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Publications (27)75.67 Total impact

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    ABSTRACT: Objective To study the prevalence of hemostatic abnormalities, including bleeding disorders and risk factors, in young females referred to a multidisciplinary clinic for evaluation of heavy menstrual bleeding (HMB). Methods Retrospective chart review was undertaken for 131 post-menarchal girls with HMB, 7 to 17 years of age, enrolled in the institutional ‘Menorrhagia Data Registry’ protocol. The diagnostic approach included: (1) complete blood count, prothrombin time, partial thromboplastin time, fibrinogen, von Willebrand panel (2) platelet aggregometry, specific clotting factor assay, fibrinolytic pathway analysis, and factor XIII level as needed. The prevalence of hemostatic abnormalities and the prognostic significance of clinical variables associated with hemostatic abnormalities in young girls with HMB were evaluated. Results A hemostatic abnormality was identified in 69 (53%) young girls with HMB. Of these, 27 (21%) had an underlying bleeding disorder and 42 (32%) had a risk factor for bleeding, namely low von Willebrand factor activity. A larger number of girls with underlying bleeding disorder had personal history of other bleeding symptoms (48% vs 31%) and bleeding after surgical or dental procedure (25% vs 8%) when compared to females without hemostatic abnormality. Furthermore, girls with risk factor for bleeding (low vWF activity) were more likely to have bleeding after surgical or dental procedure (15% vs 8%) and family history of bleeding (79% vs 60%) than patients without hemostatic abnormality. Conclusions There is high prevalence of hemostatic abnormalities, including bleeding disorders and risk factors, in young girls with HMB. These findings support comprehensive and systematic hemostatic evaluation in this group of patients.
    Journal of Pediatric and Adolescent Gynecology. 09/2014;
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    ABSTRACT: Our study was developed to ascertain reference ranges of 11-dehydrothromboxane B2 (11-dhTXB2) in the urine of healthy pediatric subjects. Urine samples were analyzed using the AspirinWorks™ assay that measures levels of 11-dehydrothromboxane B2. 128 individuals (2 months to 18 years) were identified as healthy and not receiving aspirin. When adjusted as picograms/milligrams urine creatinine, there was a negative correlation between age and level of 11-dehydrothromboxane B2 (P = 0.0001). This study confirms a negative correlation between age and level of urinary 11-dehydrothromboxane B2 and provides a set of age-specific reference ranges. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 05/2014; · 2.35 Impact Factor
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    ABSTRACT: Catheter directed thrombolytic therapies (CDT) for severe pulmonary embolism (PE) have been shown to be effective and safe when compared to systemic thrombolysis in adults. Pediatric studies assessing efficacy and safety of CDT for PE are lacking. Hence our aim was to review CDT as a therapy for pediatric PE. We retrospectively reviewed charts of patients less than 18 years of age, who underwent CDT for main or major branch pulmonary artery occlusion associated with hypotension or right ventricular dysfunction secondary to PE during a three-year period, in our tertiary care academic Pediatric Intensive Care Unit. Six CDT interventions were performed on five patients with PE (median age: 16.5 years). All patients presented with chest pain and dyspnea. The predisposing factors for thrombogenesis differed in all patients and all had multiple risk factors. Five out of six procedures (83%) were accompanied by ultrasound agitation with EKOS endowave infusion system (UCDT), while one had CDT without ultrasound agitation. Complete resolution of PE occurred in four instances (67%) at 24 hours, while in two cases (33%), there was partial resolution. One patient with complete resolution underwent another successful UCDT after four months for recurrence. Clinical parameters (heart rate, respiratory rate, blood pressure, oxygen saturations) and echocardiographic findings improved post treatment in all the patients. Median duration of hospital stay was 9 days with no mortality and no treatment related complications. All patients were discharged with long-term anticoagulation. Our case series is the first that describes CDT/UCDT as an effective and safe therapy for pediatric patients with severe PE. CDT is known to accelerate fibrinolysis via focused delivery of thrombolytic agent to the thrombus site. For carefully selected patients, CDT/UCDT provides a useful treatment option for severe PE irrespective of the etiology, predisposing conditions and associated co-morbidities.
    Annals of Vascular Surgery 03/2014; · 0.99 Impact Factor
  • H Lindsay, A Yates, D L Yee
    Haemophilia 01/2014; · 3.17 Impact Factor
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    ABSTRACT: Platelet function defects (PFD) are reported to occur frequently in adult women with heavy menstrual bleeding (HMB). Few studies on adolescent HMB report varying incidence rates (2-44%) for PFD. We reviewed our institutional experience in detecting and managing PFD in adolescent HMB. Postmenarchial girls and adolescents with HMB seen at our institution undergo a comprehensive bleeding disorder work-up by paediatric haematology and paediatric gynaecology providers. Whole blood platelet aggregometry (WBPA) is performed as a second tier test after excluding thrombocytopaenia, coagulation factor deficiencies and Von Willebrand disease (VWD). We retrospectively reviewed the medical records of adolescents with HMB seen between June 2009 and November 2010, as approved by the Institutional Review Board. Patient demographics, clinical features, laboratory results, therapy details and patient outcome information were analysed. Overall, 114 postmenarchial girls and adolescents with HMB were evaluated; 68 patients (59%) had WBPA study performed. Nineteen patients (28%) had at least one aggregation or secretion defect; 12 (18%) had two or more such defects. Treatment included hormonal therapy (13/19; 68%), antifibrinolytic agents (8/19; 42%) and intra-nasal DDAVP (3/19; 16%). Thirteen patients (81%) had improved outcome (median follow-up - 15.6 months; range of 1-66 months). In this study, PFD were identified in nearly one-third of girls with HMB, with the majority of these having two or more defects as identified by WBPA. Further prospective studies are needed to better define the prevalence and address appropriate management of HMB and other bleeding complications of PFD in adolescents.
    Haemophilia 11/2013; · 3.17 Impact Factor
  • Donald L Yee, Sarah H O'Brien, Guy Young
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    ABSTRACT: Given the rising incidence of thrombotic complications in paediatric patients, understanding of the pharmacologic behaviour of anticoagulant drugs in children has gained importance. Significant developmental differences between children and adults in the haemostatic system and pharmacologic parameters for individual drugs highlight potentially unique aspects of anticoagulant pharmacology in this special and vulnerable population. This review focuses on pharmacologic information relevant to the dosing of unfractionated heparin, low molecular weight heparin, warfarin, bivalirudin, argatroban and fondaparinux in paediatric patients. The bulk of clinical experience with paediatric anticoagulation rests with the first three of these agents, each of which requires higher bodyweight-based dosing for the youngest patients, compared with adults, in order to achieve comparable pharmacodynamic effects, likely related to an inverse correlation between age and bodyweight-normalized clearance of these drugs. Whether extrapolation of therapeutic ranges targeted for adult patients prescribed these agents is valid for children, however, is unknown and a high priority for future research. Novel oral anticoagulants, such as dabigatran, rivaroxaban and apixaban, hold promise for future use in paediatrics but require further pharmacologic study in infants, children and adolescents.
    Clinical Pharmacokinetics 06/2013; · 5.49 Impact Factor
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    ABSTRACT: OBJECTIVE: To determine whether pediatric patients with obesity receiving weight-based dosages of unfractionated heparin (UFH) exhibit an enhanced response when dosed by actual body weight compared with nonobese patients as assessed primarily by the frequency of supratherapeutic anticoagulation. Secondary measures included UFH doses associated with therapeutic anticoagulation. STUDY DESIGN: This single-institution retrospective case-matched study included children with and without obesity, matched on a 1:1 basis, who received a weight-based continuous infusion of UFH. Therapeutic monitoring values were defined for activated partial thromboplastin time (aPTT) level (70-101 seconds) and anti-activated factor X (Xa) level (0.35-0.7 U/mL). RESULTS: The study included 50 children. The percentage of patients with supratherapeutic anticoagulation at any point in the study, as measured by either aPTT or anti-Xa level, was similar in the obese and nonobese groups (76% vs 72%; P = 1.0). However, compared with patients without obesity, those with obesity received a lower mean starting dose (17.4 vs 20.2 U/kg/hour; P = .013) and a lower mean maintenance dose (19.1 vs 24.3 U/kg/hour; P = .033) to achieve stable therapeutic monitoring test values. There was no difference in mean initial post-UFH aPTT between the 2 groups, but the mean initial anti-Xa level was higher in the obese group (0.45 vs 0.29 U/mL; P = .045). CONCLUSION: Compared with children without obesity, those with obesity who received actual body weight-based continuous UFH infusions did not exhibit a higher frequency of supratherapeutic anticoagulation, but did require lower dosages to achieve comparable anticoagulation. Our results highlight recognized discrepancies between aPTT and anti-Xa monitoring assays.
    The Journal of pediatrics 02/2013; · 4.02 Impact Factor
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    ABSTRACT: OBJECTIVE: To determine if using actual body weight to dose enoxaparin in obese pediatric patients results in higher anti-Xa levels compared with non-obese pediatric patients. STUDY DESIGN: This was a retrospective case-matched study of obese and non-obese pediatric patients receiving treatment doses of enoxaparin in a tertiary care children's hospital. Patients were included if they were initiated on treatment doses of enoxaparin, had appropriate anti-Xa levels drawn, and were between 2 and 18 years of age. Patients with renal insufficiency, hyperbilirubinemia, goal anti-Xa level <0.5 or >1 unit/mL, or receiving mechanical circulatory support were excluded. Obese patients who met study criteria were matched on a 1:1 basis with non-obese patients. RESULTS: All baseline characteristics were similar except for body mass index percentile (98.2 ± 2 vs 48.7 ± 15, P < .01). Obese patients had higher initial anti-Xa levels (0.67 ± 0.27 vs 0.53 ± 0.24 unit/mL, P = .028). Over time, obese patients required a lower mean dose to achieve therapeutic anti-Xa levels than non-obese patients (0.81 ± 0.19 vs 1.1 ± 0.4 mg/kg, P = .005). CONCLUSIONS: The mean initial anti-Xa level was higher in obese pediatric patients compared with non-obese pediatric patients, but a dosage adjustment was not required. Obese patients may need closer monitoring over time to avoid supratherapeutic levels and possible bleeding events.
    The Journal of pediatrics 09/2012; · 4.02 Impact Factor
  • Zhou Zhou, Donald L Yee, Prasenjit Guchhait
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    ABSTRACT: Intravascular hemolysis is a major component of anemia in sickle cell disease (SCD). Plasma extracellular hemoglobin (ECHb) liberated by intravascular hemolysis has deleterious effects on the vasculature. ECHb scavenges nitric oxide (NO) and promotes the pathogenesis of several clinical events including pulmonary hypertension, priapism and non-hemorrhagic strokes. ECHb reduces the bioavailability of NO which down-regulates platelet activation, leading to platelet aggregation and vascular clot formation. Recently we have identified an additional mechanism whereby increased hemolysis can lead to a prothrombotic state in SCD by increasing the activity of von Willebrand factor (VWF), a multimeric plasma glycoprotein secreted by the endothelium. Our studies show that ECHb binds to the A2-domain on VWF at the proteolytic site of the metalloprotease, ADAMTS13, and blocks VWF cleavage in vitro. Elevated ECHb is associated with high levels of ultralarge and hyperactive VWF multimers in SCD patients' plasma. A sub-population of VWF multimers, bound to ECHb is hyperactive, and exists in greater quantity in SCD patients' plasma compared to normal controls. These results suggest a possible role for plasma ECHb in the accumulation of hyperactive VWF multimers in vivo that may mediate thrombotic and vasoocclusive complications in SCD patients.
    Current Vascular Pharmacology 01/2012; · 2.91 Impact Factor
  • Donald L Yee
    The Journal of pediatrics 01/2012; 160(1):73. · 4.02 Impact Factor
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    ABSTRACT: The incidence of thromboembolic disease is increasing in children. New anticoagulants have been licensed in adults and need to be studied in children. This report describes the first prospective study of fondaparinux in children. The purpose of the study was to determine the dosing, pharmacokinetics, and safety of fondaparinux in children with deep vein thrombosis (DVT) or heparin-induced thrombocytopenia (HIT). Hospitalized children between 1 and 18 years of age with DVT or HIT received fondaparinux 0.1 mg/kg once daily. Fondaparinux-based anti-factor Xa levels were assessed at 2, 4, 12, and 24 hr following the first dose, and peak levels were measured twice weekly thereafter. Detailed pharmacokinetic analyses were performed. Twenty four subjects in 3 age cohorts were enrolled and completed the study. Pharmacokinetic modeling demonstrated that a once-daily dose of fondaparinux at 0.1 mg/kg resulted in similar concentrations known to be efficacious in adults. Safety was demonstrated with only two bleeding events: one which may have pre-dated study drug administration and one which led only to temporary discontinuation of study drug. Dosing of fondaparinux at 0.1 mg/kg once daily in children resulted in PK profiles comparable to those in adults receiving standard dosing. Fondaparinux can be considered an attractive alternative to LMWH given its once-daily dosing, acceptable safety data, and other favorable properties.
    Pediatric Blood & Cancer 02/2011; 57(6):1049-54. · 2.35 Impact Factor
  • Source
    Cristyn N Camet, Donald L Yee
    Pediatrics in Review 01/2011; 32(1):31-3. · 0.82 Impact Factor
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    ABSTRACT: Although von Willebrand disease is the most common inherited bleeding disorder, platelet function disorders are less well recognized as a cause of bleeding. We report a case of menorrhagia caused by an unsuspected platelet secretion defect. A 13-year-old Asian female, with unknown family history, presented with menorrhagia not responsive to intravenous conjugated estrogens, requiring transfusion of 7 units of packed red blood cells. Initial screening tests for bleeding disorders were normal; however, due to high clinical suspicion, further specific testing with platelet aggregometry was performed, which revealed a platelet secretion defect. The prevalence of platelet secretion defects in adolescents with menorrhagia is unknown, but may be higher than currently recognized. When screening tests are normal, yet suspicion remains high for an underlying hemostatic disorder, platelet aggregometry must be performed.
    Journal of pediatric and adolescent gynecology 12/2010; 24(2):e35-8. · 0.90 Impact Factor
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    ABSTRACT: A workshop at the 2008 ASPHO Annual Meeting functioned as the first step in a systematic needs assessment of the particular challenges to satisfaction and success in the middle and senior phases of career development for pediatric hematologist/oncologists (PHOs). The 61 ASPHO members who attended were randomly distributed to small discussion groups based on self-identified career stage. Groups completed challenge forms for each issue identified as pertinent to their own stage of professional development. A total of 71 forms with useable data were generated by the groups. The largest number of challenges described (26) clustered around themes of Work-Life Balance followed by Transition and Succession (18), Management and Finances (15), and Keeping up to Date (13). Mid-career groups were more likely to identify Work-Life Balance challenges while senior stage groups were more likely to articulate Succession and Management challenges. The article describes the demographics of the workshop participants, summarizes the content of challenge themes and the associated suggestions for management. It is hoped that this effort will assist educational and career planning efforts by individuals, institutions, and ASPHO as a professional society.
    Pediatric Blood & Cancer 12/2010; 55(6):1180-4. · 2.35 Impact Factor
  • Lakshmi Venkateswaran, Donald L Yee
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    ABSTRACT: Rare bleeding disorders can cause significant bleeding in children and adolescents. These encompass rare clotting factor deficiencies, and fibrinolytic pathway defects. Vascular anomalies can cause recurrent and refractory bleeding, and are included in this review of rare causes of abnormal bleeding in children and adolescents. Menorrhagia is often reported as a manifestation of these conditions. Succinct knowledge about these disorders, their clinical presentation, diagnostic work-up, and therapeutic options are crucial to the accurate diagnosis and optimal management of affected patients. This review provides an overview of these infrequently encountered disorders, discusses their recognition based on results of suggested screening tests and offers a general guideline for approach to therapy.
    Journal of pediatric and adolescent gynecology 10/2010; 23(6 Suppl):S38-42. · 0.90 Impact Factor
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    ABSTRACT: Recent guidelines discourage routine use of thrombolytic agents for treatment of venous thromboembolism (VTE) in pediatric patients, but actual practice patterns are unknown. An electronic survey was emailed to all active and trainee members of the American Society of Pediatric Hematology/Oncology in April 2008. Respondents were asked a series of multiple-choice questions based on hypothetical case scenarios describing pediatric VTE, pertinent to the implementation of thrombolytic therapy and other professional demographic information. Two hundred eighty-five evaluable responses were obtained (22% response rate) which varied greatly with respect to all spheres of questioning. Tissue plasminogen activator (tPA) was the thrombolytic agent chosen by most respondents, but no clear consensus emerged as to appropriate indications (although preference for thrombolytic therapy increased with severity of the posed clinical scenario), mode of tPA delivery (systemic vs. catheter-directed), dose (high-dose vs. low-dose regimen) or a suitable maximum duration of therapy (range: 1-168 hr; varied according to specific dosing regimen chosen). Expertise in pediatric thrombosis, years out from fellowship training and volume of experience with cases of pediatric thrombosis were not largely associated with respondent choices; however, institutional experience with pharmacologic thrombolysis exhibited the most notable association of the professional demographic factors analyzed. The survey results support that clinical practice pertaining to use of thrombolytic agents in pediatric VTE varies widely but also provide useful benchmarks to aid clinical decision-making and future clinical trial design. Such varied practices stem from the lack of strong evidence supporting one therapeutic approach versus another.
    Pediatric Blood & Cancer 07/2009; 53(6):960-6. · 2.35 Impact Factor
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    ABSTRACT: Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. Thromboembolic complications have not heretofore been linked with this diagnosis. We describe four patients with neonatal-onset OTC deficiency who developed vascular thromboses. One patient had arterial thrombosis; the rest developed venous thromboses. Multiple pro-thrombotic risk factors were identified. Low plasma arginine levels were observed in all patients at the time of thrombosis. Arginine deficiency and the resultant nitric oxide insufficiency may contribute to thrombotic risk. Careful normalization of plasma arginine and citrulline levels and increased surveillance for thrombotic complications should be considered in patients with OTC deficiency.
    Pediatric Blood & Cancer 05/2009; 53(1):100-2. · 2.35 Impact Factor
  • Jennifer E Dietrich, Donald L Yee
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    ABSTRACT: As Virchow's triad suggests, a fine balance exists between the vascular wall, intravascular contents, and dynamic blood flow, such that a shift in this balance predisposes to thrombosis. Although thromboembolic events (TEs) are relatively infrequent in adolescents, the morbidity and mortality associated with TEs can be significant. Over the past 15 years, TEs and inherited and acquired thrombophilic conditions underlying them have become increasingly recognized in teens at risk, with combined hormonal contraception constituting one of the most significant of these risk factors. Therefore, managing gynecologic problems in teens who have thrombophilic conditions can be challenging. It is important to have a clear understanding about safe options available to help address adolescent gynecologic concerns in this setting and to manage situations collaboratively with a hematologist.
    Obstetrics and Gynecology Clinics of North America 04/2009; 36(1):163-75. · 1.45 Impact Factor
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    ABSTRACT: Current literature suggests that acquired von Willebrand syndrome associated with Wilms tumor (AVWS-WT) occurs infrequently and usually has little clinical significance. Treatment strategies are thus poorly defined. We describe two patients with AVWS-WT and profuse bleeding who required intensive multimodal therapy, including aggressive blood component and factor replacement and plasmapheresis. They achieved adequate surgical hemostasis only after the renal vessels were ligated, with resolution of the coagulopathy upon tumor removal. Our experience suggests that AVWS-WT is not always benign. A careful bleeding history should always be obtained in patients with suspected renal tumors for consideration of pre-operative screening for AVWS.
    Pediatric Blood & Cancer 12/2008; 52(3):392-4. · 2.35 Impact Factor
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    ABSTRACT: Although "aspirin resistance" (AR-inadequate platelet inhibition as suggested by in vitro testing of aspirin-treated patients) has been widely studied in adults and linked to increased risk of adverse outcomes, its prevalence and clinical significance are largely unknown in children. To determine AR prevalence in children and its relationship to assay methodology, we undertook a cross-sectional study of 44 children (1-17 years, 24 male) on aspirin for various indications and considered three published definitions of AR in adults: platelet aggregation >/=70% to 10 microM adenosine diphosphate and >/=20% to 0.5 mg/ml arachidonic acid (AA), normal PFA-100(R) closure time and elevated urinary 11-dehydro thromboxane B(2) (11dhTxB(2)) concentration. Six subjects exhibited AR according to at least one of the criteria (5 by PFA-100(R), 1 by aggregometry and 11dhTxB(2) criteria); nearly all subjects had low levels of 11dhTxB(2) compared with controls. Subjects studied prior to therapy showed pronounced changes in AR parameters after aspirin dosing (e.g., mean aggregation to AA decreased from 82% to 6%, P < 0.001), confirming an aspirin effect. Subjects with AR did not differ from aspirin responsive subjects in terms of age, race, platelet count, or aspirin dose, indication or therapy duration. There was minimal correlation between assays. In this initial prevalence study of a clinically diverse group of pediatric patients, frequencies of AR were assay-dependent; however, the prevalence of true AR is likely low in children (2.3%; 95% CI 0.1-10.7%), in agreement with adult studies. To better define the clinical relevance of AR in children, multicenter, prospective cohort studies are imperative.
    Pediatric Blood & Cancer 07/2008; 51(1):86-92. · 2.35 Impact Factor

Publication Stats

212 Citations
75.67 Total Impact Points

Institutions

  • 2012–2014
    • Texas Children's Hospital
      Houston, Texas, United States
  • 2004–2014
    • Baylor College of Medicine
      • • Department of Pediatrics
      • • Section of Hematology/Oncology
      • • Thrombosis Research Section
      Houston, Texas, United States