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.

Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults.

Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.

Red cell exchange does not appear to increase the rate of allo- and auto-immunization in chronically transfused children with sickle cell disease.

BACKGROUND: Allo- and auto-antibody development is a well recognized complication of chronic red cell transfusion (RCT) in sickle cell disease (SCD). Limited matching of Rh (C, c, D, E, e) and K red cell antigens reduces the incidence of immunization. PROCEDURE: We reviewed our experience with red cell allo- and auto-immunization in pediatric SCD patients receiving chronic and/or exchange transfusions, to evaluate the rate of immunization after limited red cell antigen matching and specifically during red cell exchange (RCE) transfusion. A retrospective chart review of the patients with SCD followed at our center between 2002 and 2006, who were started on chronic RCT before or during that time period, was conducted. RESULTS: Of the 93 patients who met study criteria, 23 (24%) developed antibodies during chronic red cell transfusions. Thirty-four antibodies (15 auto-antibodies, 18 allo-antibodies) developed after the institution of limited red cell antigen matching. The rate of allo- and auto-immunization per unit of red cell exposure after limited phenotyping was 1.5%, comparable to other published data. Fifteen patients underwent RCE, utilizing a total of 2,289 packed red cell units. None developed antibodies during RCE. CONCLUSION: We conclude that limited red cell antigen matching is an effective strategy for reducing the incidence of allo- and auto-immunization in chronically transfused children with SCD. RCE does not appear to increase the risk of allo- or auto-immunization, despite exposure to more red cell units.

Defining and managing career challenges for mid-career and senior stage pediatric hematologist/oncologists.

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.

Ornithine transcarbamylase deficiency: a possible risk factor for thrombosis.

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.

Geriatric assessment of older patients with cancer in Australia--a multicentre audit.

OBJECTIVE: The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics. MATERIAL AND METHODS: This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010. RESULTS: Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70-95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation-living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM. CONCLUSION: This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians.

Gynecologic concerns in pubertal females with blood disorders.

PURPOSE OF REVIEW: The incidence and prevalence of blood disorders varies depending on the underlying etiology, age, ethnicity, family history, and presence of comorbid medical conditions. Gynecologic problems occurring around puberty may cause stress to families and patients, as well as management challenges to providers. RECENT FINDINGS: Management strategies in the setting of bleeding disorders include hormonal and non-hormonal options to address problems occurring around puberty. Management strategies in the setting of clotting disorders allow providers to address common problems occurring in adolescence, while minimizing risk of venous thromboembolism. SUMMARY: Preparedness is important at this time of life, not only to prevent unwanted gynecologic complications or hospitalizations related to specific blood conditions, but also to identify problems related to reproductive care that may be exacerbated or complicated by an underlying blood disorder.

Platelet function disorders and menorrhagia in adolescents: a review of laboratory diagnosis.

This article provides an overview of the prevalence and pathophysiology of platelet function disorders (PFDs) in adolescents with menorrhagia. In addition, this article reviews the various testing modalities employed for diagnosing PFDs including platelet aggregometry, platelet function analyzer (PFA-100), platelet electron microscopy (EM), flow cytometry, and thromboelastography (TEG), discuss their utility and drawbacks, and allude to the recent recommendations and consensus statements about some of these modalities. Finally, the authors have sketched out a diagnostic algorithm for platelet function testing, which will guide treating physicians to a step-wise approach while evaluating adolescents with menorrhagia for PFDs.

Idiopathic pulmonary hypertension causing acquired von Willebrand disease and menorrhagia.

BACKGROUND: Von Willebrand disease (VWD) maybe inherited or acquired; both etiologies can be associated with heavy menstrual bleeding. Pulmonary arterial hypertension may result in acquired VWD due to the destruction of high molecular weight von Willebrand multimers. We report a case of menorrhagia due to acquired VWD in a patient with idiopathic pulmonary hypertension. CASE: An adolescent female with known idiopathic pulmonary hypertension developed acquired VWD. Her primary disease necessitates the use of platelet inhibitors and intermittent anticoagulation. At menarche she also developed menorrhagia due to acquired VWD. She is currently controlled with stimate and progesterone-only therapy. VWD in a patient with idiopathic pulmonary hypertension causing menorrhagia. Although VWD and menorrhagia are commonly linked, the treatment and disease process in a patient with idiopathic pulmonary arterial hypertension is incredibly complex.

Rare bleeding disorders in young women.

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.

Homozygous hemoglobin Abruzzo in a North American child.

Hemoglobin Abruzzo is a stable hemoglobin variant with increased oxygen affinity, clinically causing compensatory erythrocytosis in affected patients. Heterozygosity of this variant with or without beta-thalassemia has been previously described in three Italian families, thereby suggesting a single origin of the mutation. The authors report the first case of homozygosity in a North American female infant, born to heterozygous parents as a product of consanguineous marriage.

Lymphocyte-predominant Hodgkin disease in children.

PURPOSE: To describe the clinicobiological features, treatment, treatment outcome, and sequelae of children with lymphocyte-predominant Hodgkin disease. PATIENTS AND METHODS: The authors performed a retrospective chart review of 754 patients with Hodgkin disease diagnoses at New York Medical College and St. Jude Children's Research Hospital from 1962 to 2000 to identify those with lymphocyte-predominant histology. Hematopathologists at the treating institutions reviewed stored tissue specimens and reconfirmed the histopathology of each case. RESULTS: Fifty-one children (44 boys, 7 girls) were identified. The median age was 10.5 years (range 3.2-18.5); five children were younger than age 60 months. The median duration of lymphadenopathy before diagnosis was 4 months (range 0.5-30). Thirty-six children had stage 1 disease, eight had stage 2 disease, four had stage 3 disease, and three had stage 4 disease. Fifteen children underwent staging laparotomy, and four of these were upstaged. Treatment comprised combined modality therapy (n = 27), radiation therapy alone (n = 17), and chemotherapy alone (n = 7). Four children had a Hodgkin disease recurrence. Forty-eight (94%) patients were alive and disease-free at a median follow-up of 8 years (range 0.4-32.6). Eleven patients had long-term, therapy-related adverse effects (cardiac, infertility, pulmonary, and second malignant neoplasms). Three patients died. Two died of complications of second malignant neoplasms and one died of infectious complications after Hodgkin disease recurrence. CONCLUSIONS: Children with lymphocyte-predominant Hodgkin disease respond favorably to a variety of treatment modalities and are ideal candidates for less toxic therapy.

Bacillus cereus central line infection in an immunocompetent child with hemophilia.

Bacillus species are increasingly recognized as pathogens in immunocompromised patients. The authors report a case of Bacillus cereus infection of a central line in an immunocompetent patient with hemophilia, which required line removal for complete cure.