Anemia and coagulation disorders in adolescents.

The transition of childhood to adulthood includes many changes to nearly all parts of the body and that is certainly true of blood and the coagulation system. Some disorders, like iron deficiency anemia, develop as the result of rapid growth. Approximately 10% of American adolescents are anemic and the prevalence is far greater in high-risk populations, such as urban, indigent African-American adolescents, in which 40-50% of young women are anemic. Adolescents at greater-than-average risk for developing iron deficiency anemia, such as athletes involved in lengthy, intense physical activities and pregnant adolescents, should be screened for anemia. Other blood problems are inherited but the first manifestations may not emerge until adolescence, as in the case of an adolescent girl discovered to have von Willebrand's disease during the evaluation of excessive menstrual bleeding. Besides iron deficiency anemia and von Willebrand's disease, this review focuses on management of other common hematologic disorders seen in adolescent patients, including immune thrombocytopenic purpura, hemophilia, thrombocytosis, and hypercoagulable disorders.

Embryonal adenoma of the kidney associated with polycythemia and von Willebrand disease.

PURPOSE: We studied the significance, identification and management of acquired von Willebrand disease and polycythemia associated with benign renal tumors in children. MATERIALS AND METHODS: Two patients who presented with polycythemia and a renal mass were also found to have acquired von Willebrand disease. One patient was treated with radical nephrectomy and 1 was treated with partial nephrectomy. The patients have been followed for 19 and 10 months, respectively. RESULTS: Excision of the renal mass resulted in prompt resolution of polycythemia and von Willebrand disease in each patient. Perioperatively 1-deamino-(8-D-arginine)-vasopressin was given to control bleeding. Each patient had benign embryonal adenoma of the kidney. CONCLUSIONS: Polycythemia and von Willebrand disease may be associated with benign kidney neoplasms. Children and adolescents with a renal mass may benefit from preoperative screening for coagulopathy.

Clinical features of myelokathexis and treatment with hematopoietic cytokines: a case report of two patients and review of the literature.

PURPOSE: To define the features and course of myelokathexis, a rare congenital neutropenia resulting from impaired release of granulocytes from bone marrow. METHODS: The clinical features, granulocyte function, lymphocyte function, and response to granulocyte colony-stimulating factor (G-CSF) of two patients (mother/son) with myelokathexis were studied. This experience and 14 previous reports lead to a composite description of myelokathexis. RESULTS: Both patients had chronic neutropenia, recurrent pulmonary infections, bone marrow consistent with myelokathexis, hypogammaglobulinemia, and elevated endogenous G-CSF. Patient 15 had normal granulocyte function, a rise in absolute neutrophil count (ANC) with epinephrine and hydrocortisone, and normal numbers of T- and B-lymphocytes; she also had numerous warts during childhood. Both patients experienced a transient increase in ANC with infection, a significant increase in ANC within 5 hours following a single dose of G-CSF, and fewer infections with daily G-CSF. CONCLUSIONS: Based on 16 cases, myelokathexis occurs more often in females and frequently affects multiple members of a family. The usual number of circulating granulocytes is low although function is normal. Mature marrow granulocytes are mobilized with infection, corticosteroids, epinephrine, G-CSF, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Lymphocyte number is normal but lymphocyte function is abnormal as evidenced by hypogammaglobulinemia and papillomavirus infection.

High-dose cytosine arabinoside and etoposide: an effective regimen without anthracyclines for refractory childhood acute non-lymphocytic leukemia.

The purpose of this report is to describe the tolerability and activity of the combination of high-dose cytosine arabinoside (Ara-C) given at the maximum tolerated dose of 36 g/m2, together with high doses of etoposide in relapsed and refractory childhood acute leukemias. Eighteen children with relapsed or refractory acute leukemia were treated with Ara-C 3 g/m2 every 12 h on days 1-6, followed by etoposide 400 mg/m2 on days 7-9 (HDAC/VP-16). Eight children with refractory disease received HDAC/VP-16 as salvage induction therapy after failing conventional induction regimens; four of five refractory ANLL patients (80%) had a complete response (CR) after HDAC/VP-16 therapy. Ten patients received HDAC/VP-16 as post-remission intensification therapy; five patients (four ANLL, one relapsed ALL) remain in second CR at 56, 26, 9, 5 and 2 months. Toxicities were primarily hematologic and dermatologic. Seven patients (39%) developed bacterial or fungal infections; four patients developed grade 3 or 4 acral erythema. No patient died of therapy-related toxicity. The combination of 36 g/m2 cytosine arabinoside and 1200 mg/m2 etoposide is an effective regimen for children with relapsed or refractory acute nonlymphocytic leukemia, with tolerable toxicities; the absence of anthracyclines makes this regimen suitable for patients who have previously received maximal doses of anthracyclines or who have evidence of cardiac dysfunction. Further evaluation of this regimen in acute nonlymphocytic leukemia is presently being investigated.

Central venous catheter infection in haemophiliacs undergoing prophylaxis or immune tolerance with clotting factor concentrate.

The risk of infection in individuals with haemophilia using central vascular access devices for administration of clotting factor concentrates for prophylaxis or immune tolerance is unknown. We conducted a survey of US haemophilia treatment centres to determine the incidence and clinical characteristics of infection associated with the use of central venous catheters. Seventy (38.3%) of 183 patients using central lines developed device-associated infection, including 30 (28.0%) on prophylaxis and 40 (52.6%) on immune tolerance, P < 0.005. Over half (54.8%) the infections occurred in those 3 years of age. Implanted/tunnelled devices (port catheters) were more likely to become infected in the first 30 days after insertion, 11 of 41 (26.8%), than external catheters (broviac/hickman), none of 29 (0%), P= 0.00003. The median time to infection from initial device placement, 124 days, varied with age, 57 days in those 2 years of age vs. 161 days in those > 2 years of age, P= 0.0008, but not with type of device or treatment. Staphylococcal infections were more common with implanted devices (ports), 30 (73.2%), than external catheters, 12 (41.4%), P < 0.01, and Gram-negative infections were more common with external catheters, 17 (58.6%), than tunnelled devices, 7 (17.1%), P < 0.005. In summary, the rate of infection with central venous access devices in haemophiliacs is high, and alternative approaches to venous access should be explored.

Long-term granulocyte-macrophage colony-stimulating factor and immunosuppression in the treatment of acquired severe aplastic anemia.

PURPOSE: Seven children with newly diagnosed acquired severe aplastic anemia (SAA) were treated with a combination of long-term granulocyte-macrophage colony-stimulating factor (GM-CSF) and immunosuppression to assess the potential for GM-CSF to induce sustained neutrophil recovery, reduce the incidence of infection, and enhance the therapeutic efficacy of immunosuppression. METHODS: Patients received a 14-day course of i.v. antithymocyte globulin 15 mg/kg/day with oral prednisone 1 mg/kg/day, long-term daily oral cyclosporine A 10 mg/kg/day, and long-term daily s.c. GM-CSF 5 micrograms/kg/day. RESULTS: All seven children recovered an absolute neutrophil count of > 1.0 x 10(9)/L within 3.5 months of diagnosis (mean 60 days). Of the six children followed throughout their entire illness (follow-up 10-27 months), five are platelet and red cell transfusion independent (three off-therapy, two on tapering therapy) and one continues on therapy with a diminishing transfusion requirement. Compared with seven children treated previously with immunosuppression alone, children who received GM-CSF spent fewer days in the hospital and were less likely to develop infection. CONCLUSIONS: The addition of GM-CSF to immunosuppressive therapy appears to be beneficial in the treatment of children with acquired SAA with GM-CSF stimulating granulopoiesis. The children are better protected from infectious complications while immunosuppressive agents achieve full therapeutic potential.

Intravenous corticosteroids versus intravenous gammaglobulin in the treatment of acute immune thrombocytopenic purpura.

Debate continues over the most appropriate treatment for children with acute immune thrombocytopenic purpura (ITP). An institutional review of all admissions for acute ITP between 1986 and 1991 found 61 children treated with intravenous (i.v.) IgG or i.v. steroids with a bone marrow aspirate consistent with ITP, an age of 21 years or younger, and an admission platelet count of < or = 20,000/mm3. The efficacy of these two agents was compared in the described population. A response was defined as achieving a platelet count of > or = 50,000/mm3. A significantly greater percentage of patients responded to i.v. IgG compared to i.v. steroids during the first 36 hr of therapy; however, by 72 hr of treatment there was no significant difference. The cost of hospitalization was 3 1/2 times greater for the patients responding to i.v. IgG vs. i.v. steroids.

Applications of neutron activation analysis to the study of age-related neurological diseases.

Although the etiology and pathogenesis of Alzheimer's disease, Pick's disease, and amyotrophic lateral sclerosis are still unknown, it has been suggested that perturbations in element metabolism may play a role. Even if not causative factors, these imbalances may prove to be markers that could aid in diagnosis. We have employed a sequential neutron activation analysis (NAA) procedure to determine elemental concentrations in brain, hair, fingernails, blood, and cerebrospinal fluid (CSF) of these patients and age-matched controls. Samples are first irradiated with accelerator-produced 14-MeV neutrons for determination of nitrogen and phosphorus, then with reactor thermal neutrons for the instrumental determination of 16-18 minor and trace elements, and, finally, reactor-irradiated again, followed by a rapid radiochemical separation procedure (RNAA) to determine four additional elements. Major advantages of NAA are: (1) its simultaneous multielement capability; (2) the relative freedom from reagent and laboratory contamination; (3) the absence of major matrix effects; and (4) an adequate sensitivity for most elements of interest. Ranges of concentrations by INAA and RNAA in selected control tissues and interelement correlations in control brain are presented to illustrate results obtained by the procedure. Longitudinal studies of tissues from Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) patients are still in progress.