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Autoimmune hemolytic anemia (AIHA) in childhood, including paroxysmal cold hemoglobinuria, is an uncommon, potentially life-threatening disorder. AIHA is a recognized complication of several varieties of lymphoproliferative disorders, including high-grade B-cell lymphoma, but it has not been associated with Burkitt lymphoma in people without an underlying immunodeficiency. When AIHA occurs in association with lymphoproliferative disorders, it may precede or accompany the diagnosis of malignant disease or herald relapse. We report a novel case of a previously healthy child diagnosed with paroxysmal cold hemoglobinuria 14 months preceding the development of Burkitt lymphoma.

Ischemic stroke occurs in at least 11% of patients with homozygous sickle cell anemia (SCD) by the time they turn 20 years old. High risk associated with distal intracranial internal carotid (ICA) and proximal middle cerebral artery (MCA) stenosis can be detected by transcranial Doppler (TCD). TCD screening offers the possibility of reducing the risk of first stroke significantly based on a paradigm tested and proven to be effective in a stroke prevention trial in sickle cell anemia (STOP). Children with high flow velocity in the ICA and MCA of 200 cm/s time average mean of the maximum (TAMM) or higher had a 10% per year risk of first stroke that was reduced to1% with regular red cell transfusion (reduction of hemoglobin S30%). The clinical application of the STOP results could be enhanced if criteria for treatment could be found that are based on peak systolic velocity (PSV), the measure more commonly used in vascular ultrasound practice.To compare PSV and end diastolic velocity (EDV) with TAMM for prediction of stroke and to derive PSV cutpoints for STOP protocol definitions of conditional and abnormal TCD. Using the STOP TCD and stroke outcome data to compare PSV and TAMM in terms of stroke prediction, PSV cutpoints comparable to those based on TAMM and used in STOP were derived. Because of their familiarity to the vascular ultrasound community, PSV cutpoints should be an important alternative to TAMM and may increase availability of screening and risk stratification for children with this disease.Data from 1,937 baseline TCD studies from STOP were correlated with stroke outcome in those not treated with transfusion. Stroke prediction was assessed with survival analysis using TAMM, PSV and EDV as continuous variables individually and then pair-wise in the same model, which contained 53 stroke events.PSV and EDV were highly correlated to the TAMM velocity (r=0.94). The multivariate model for prediction indicated that TAMM velocity was a better predictor than EDV, and PSV and TAMM were approximately equivalent. PSV cutpoints defining the two relevant STOP risk categories--"conditional," which should lead to increased TCD surveillance, and "abnormal," which should lead to strong consideration for treatment according to STOP--were derived taking into consideration known differences in measurements between the dedicated Doppler systems (TCD) used in STOP and the transcranial Doppler imaging (TCDI) systems commonly used in clinical practice. The recommended PSV cutpoint for conditional TCD is 200 cm/s, and for abnormal TCD triggering consideration for treatment is 250 cm/s.Assuming TCDI equipment is used and the STOP protocol is applied, a PSV cutpoint of 200 cm/s is recommended as the threshold for increased TCD surveillance (comparable to a TCD TAMM of 170 cm/s in STOP); a PSV of 250 cm/s is recommended as the cutpoint at which, if confirmed in a second examination, chronic transfusion should be considered. Assuming the STOP scanning protocol is used, PSV is at least as good as TAMM and can be used to select children with SCD for treatment or increased surveillance to prevent first stroke.

Academic medical centers have encountered increasing fiscal challenges as the paradigm in health care has shifted from traditional fee-for-service reimbursement to systems of managed care. Most academic centers have maintained primary care clinics, which have served as “educational laboratories” for students and trainees. Largely providing care to underserved patients, academic primary care clinics have been heavily dependent on Medicaid reimbursement for support. Given the realities of a rapidly changing health care environment, academic primary care clinics have been challenged to respond with innovation and creativity in order to remain viable. The pediatric primary care clinic at Rainbow Babies & Children's Hospital of University Hospitals of Cleveland initiated a reorganization program with the goal of ensuring that patients receive quality, cost efficient care and that students and pediatric residents receive first-rate ambulatory education in a fiscally responsible setting. Fundamental was the setting of priorities for patient care and service while promoting an environment conducive to medical education. Educational programs were segregated into a well-defined educational “module,” and various initiatives were advanced emphasizing patient access, consistency of care, efficient use of space and personnel resources, limitation of inappropriate use of costly after-hours resources, and identification and coordination of care for patients with chronic illness and/or at high risk for medical complications. Three years after the instituting of fundamental organizational change, objective measures of cost efficiency and selected quality measures compare quite favorably with a broad range of primary care providers throughout the region. If academic medical centers are to remain leaders in ambulatory pediatric education, energetic, proactive, and thoughtful responses to the rapidly changing global health care environment will be necessary.

The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) demonstrated the efficacy of hydroxyurea in reducing the rate of painful crises compared to placebo. We used resource utilization data collected in the MSH to determine the cost-effectiveness of hydroxyurea. The MSH was a randomized, placebo-controlled double-blind clinical trial involving 299 patients at 21 sites. The primary outcome, visit to a medical facility, was one of the criteria to define occurrence of painful crisis. Cost estimates were applied to all outpatient and emergency department visits and inpatient hospital stays that were classified as a crisis. Other resources for which cost estimates were applied included hospitalization for chest syndrome, analgesics received, hydroxyurea dosing, laboratory testing, and clinic visits for management of patient care. Annualized differential costs were calculated between hydroxyurea- and placebo-receiving patients. Hospitalization for painful crisis accounted for the majority of costs in both arms of the study, with an annual mean of $12,160 (95% CI: $9,440, $14,880) for hydroxyurea and $17,290 (95% CI: $13,010, $21,570) for placebo. The difference in means was $5,130 (95% CI: $60, $10,200; P = 0.048). Chest syndrome was the next largest cost with a mean difference of $830 (95% CI: $−340, $2,000; P = 0.16). The hydroxyurea arm was also associated with lower costs for emergency department visits, transfusion, and use of opiate analgesics. In total, the annual average cost per patient receiving hydroxyurea was $16,810 (95% CI: $13,350, $20,270) and the annual average costs per patient receiving placebo was $22,020 (95% CI: $17,340, $26,710). The difference in means was $5,210 (95% CI: $−610, $11,030; P = 0.21). The cost of hydroxyurea with the more intensive monitoring required when using this drug appears to be more than offset by decreased costs for medical care of painful crisis and analgesic use. Although the total cost difference was not significant statistically, these results suggest that hydroxyurea therapy is cost-effective compared to placebo in the management of adult patients with sickle cell anemia. If hydroxyurea can prevent development of chronic organ damage, long-term savings may be even greater. Am. J. Hematol. 64:26–31, 2000. © 2000 Wiley-Liss, Inc.

Primary polycythemias are caused by an acquired or inborn mutation affecting hematopoietic/erythroid progenitors that results in an abnormal response to hematopoietic cytokines. Primary familial and congenital polycythemia (PFCP; also known as familial erythrocytosis) is characterized by elevated red blood cell mass, low serum erythropoietin (EPO) level, normal oxygen affinity of hemoglobin, and typically autosomal dominant inheritance. In this study we screened for mutations in the cytoplasmic domain of the EPO receptor (EPOR; exons 7 and 8 of the EPOR gene) in 27 unrelated subjects with primary or unidentified polycythemia. Two new EPOR mutations were found, which lead to truncation of the EPOR similarly to previously described mutations in PFCP subjects. The first is a 7-bp deletion (del59855991) found in a Caucasian family from Ohio. The second mutation (5967insT) was found in a Caucasian family from the Czech Republic. In both cases the EPO dose responses of the erythroid progenitors of the affected subjects were examined to confirm the diagnosis of PFCP. In one of these families, the in vitro behavior of erythroid progenitors in serum-containing cultures without the addition of EPO mimicked the behavior of polycythemia vera progenitors; however, we show that antibodies against either EPO or the EPOR distinguish the in vitro growth abnormality of polycythemia vera erythroid progenitors from that seen in this particular PFCP family. We conclude that PFCP is a disorder that appears to be associated in some families with EPOR mutations. So far, most of the described EPOR mutations (6 out of 8) associated with PFCP result in an absence of the C-terminal negative regulatory domain of the receptor.

Purpose : This research was undertaken to determine whether obstructive sleep apnea (OSA) and/or nocturnal hemoglobin desaturations contribute to the clinical severity of sickle cell anemia (SS). Patients and Methods : Eleven patients with severe SS (group S), defined by two or more hospitalizations in the previous year for painful crises, were compared to eight patients with mild SS (group M) who had not been hospitalized for painful crises in the past year. An additional cohort of nine patients with SS who had been referred to the Sleep Disorders Center because of a clinical suspicion of OSA were studied (group R). All patients underwent full overnight polysomnography and performed standard pulmonary function tests. Results : There were no significant differences in the respiratory disturbance index (RDI ; apneas plus hypopneas per hour of sleep) or hemoglobin desaturation between the mild and severe groups, and neither RDI nor hemoglobin saturation predicted the number of painful crises. Despite a suggestive clinical presentation, only 44% of the patients in group R had OSA confirmed polysomnographically. Conclusions : In this preliminary study, unsuspected nocturnal cardiopulmonary disease and hemoglobin desaturation did not explain the variability in the severity of SS disease. However, OSA can occur in patients with SS, and when clinically suspected, the diagnosis should be confirmed with overnight polysomnography so that appropriate treatment can be instituted.

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value

We describe two patients with clinical and cytogenetic findings consistent with DiGeorge/velocardiofacial syndrome who had recurrent cytopenias at presentation. Our observations suggest that recurrent cytopenias may be part of the clinical spectrum of deletion 22q11.2. We also suggest that the diagnosis of DG/VCF syndrome be considered in patients with unexplained recurrent immune cytopenias in association with cardiac lesions, subtle craniofacial dysmorphisms, and/or learning or behavioral impairments.

Abstract 4850 Introduction: Nearly 100,000 Americans are affected by sickle cell disease (SCD), making it one of the most prevalent genetic disorders in the United States. Individuals with SCD exhibit significant morbidity and mortality related to chronic hemolysis, vasculopathy, and vascular occlusion by red cell sickling. Currently, red cell transfusions are a primary therapy for some of the acute and chronic complications of SCD, including prevention and treatment of stroke. The benefits of transfusion therapy are well known; however, transfusional iron overload is an inevitable consequence. Excess iron in the circulation leads to the formation of reactive oxygen species which ultimately causes end-organ damage. It is well established that adult SCD patients with significant iron overload have a higher mortality. As a result, exchange transfusion protocols are utilized to try to decrease overall iron overload. In our center, a modified manual exchange (MME) protocol is used which involves therapeutic phlebotomy of approximately 5–7.5ml/kg followed by the infusion of 15–20ml/kg packed red blood cells. MME is performed in the outpatient setting every 4–6 weeks with a goal hemoglobin S of less than 30%. Objective: The primary objective of our study was to describe the benefits of a MME protocol compared with a simple transfusion protocol in patients experiencing both. The effects of MME versus simple tranfusion on systemic iron overload were evaluated using serum ferritin levels, net transfusion volume, and need for iron chelation therapy. Study Design/Methods: A retrospective chart review was performed on patients with SCD (type SS) less than 18 years of age who were on chronic transfusions and transitioned from a simple to a MME protocol. All patients included were on chronic transfusions for primary/secondary stroke prevention. Exclusion criteria included all patients on automated exchange transfusion protocols and those patients who started iron chelation therapy after January 1, 2008. Demographic as well as clinical and laboratory data were collected on each patient. A simple transfusion was defined as 20ml/kg packed red blood cells transfused every 4–6 weeks. The MME protocol was defined as above. Iron overload was assessed using indicators including net volume of blood transfused, serum ferritin, and the need for iron chelation during both time periods, and differences were calculated. The Wilcoxon signed rank test was used for the change in amount of blood transfused. Slopes of ferritin levels over time were estimated for each transfusion protocol separately using mixed model methods. The need for chelation therapy was tabulated for each patient. Results: A total of six patients were included in the study, 4 boys and 2 girls. Ages ranged from 6–14 years. Four patients had been on chronic transfusions for more than 2 years prior to the start of our study. The mean net volume transfused during simple transfusion and MME was 400ml and 290ml, respectively (p=0.03). The slope of ferritin rise was 0.18 (CI: 0.11, 0.84) for MME and 1.37 (CI: 0.56, 2.17) for simple transfusion. One patient was taken off chelation therapy completely after transitioning to MME and another patient was maintained on low-dose chelation while on MME. Conclusions: MME appears to reduce the amount of blood transfused, slow the rise of ferritin, and potentially reduce the need for additional medication. MME may provide a safe and cost effective approach for delaying or preventing iron overload in patients with sickle cell disease who require long term transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

Abstract 2643 Children with sickle cell anemia (SCA) and abnormal transcranial Doppler (TCD) velocities receive chronic transfusion therapy in an effort to prevent a primary stroke. Typically the goal is maintaining sickle hemoglobin (HbS) Disclosures: Off Label Use: It will include the use of hydroxyurea in children with sickle cell anemia.

Abstract 2764 Objective: To evaluate the effectiveness and safety of rituximab in the treatment of antibody mediated hematologic disorders refractory to conventional therapy. Study Design: Retrospective chart review of 16 patients treated at Rainbow Babies and Children's Hospital with rituximab for antibody mediated hematologic disorders. Treatment effects and adverse reactions potentially attributed to rituximab therapy were recorded. Results: Patients (age range 4 months- 17 years) with the following disorders were included: autoimmune hemolytic anemia (4); chronic immune thrombocytopenia (5); autoimmune pancytopenia (4); hemophilia with inhibitor (2); acquired Factor VIII inhibitor (1). All patients received rituximab at 375mg/m2/dose, after failure to obtain a durable response to conventional therapies. The majority of patients were treated with 4 weekly dose “cycles”. One patient only received 2 doses, and two patients were maintained on prolonged weekly therapy. Two patients showed no clinical or laboratory improvement with rituximab therapy. Two patients initially responded to rituximab therapy, but relapsed 2 months after therapy. Of the remaining patients, 7 had no recurrence of disease by the end of the study period, median follow-up 14months (4mo-72mo). The remaining patients relapsed requiring repeat cycles of rituximab. Median time to relapse was 15 months (13-18mo). The most common adverse reactions were serum sickness (n=3) and hypogammaglobulinemia (n=2). Of the patients who developed hypogammaglobulinemia, one improved after a single infusion of IVIG, the other patient required chronic IVIG infusions. One patient developed chronic sinusitis and one developed acute demylinating encephalomyelitis after receiving rituximab. It is unclear if these illnesses were due to the rituximab or secondary to underlying immune dysfunction. Conclusions: Rituximab appears to be effective in a variety of antibody mediated hematologic disorders refractory to more conventional therapies in children and adolescents. The observed adverse reactions were generally mild and self-limited. Disclosures: Off Label Use: Rituximab. B cell immununosuppresion.

Diamond-Blackfan anemia (DBA) is characterized by a variable response to corticosteroid therapy. Patients poorly responsive to acceptable doses of steroid treatment require long-term transfusion therapy. We have treated three patients with DBA with the immunosuppressive agent cyclosporin A with limited success. Patients 1 (DS) and 2 (LS), half-siblings, were 13 and 9 years old, respectively, and remained transfusion independent for many years on steroid therapy. Both patients manifest steroid-associated growth failure and osteopenia, with resultant orthopedic complications. Oral cyclosporin therapy sufficient to achieve trough serum levels of 100-200 ng/ml was associated with a brisk 50-100% increase in hematocrit within 1 month of initiation of treatment and allowed for a gradual tapering of prednisone dose to approximately 20% of prior established maintenance dose. After 7-8 months, both patients developed progressive decline in hematocrit level requiring increased prednisone dose and, ultimately, transfusion support. Patient 3 (RD), a 5-year-old child with steroid refractory, transfusion-dependent DBA, was entirely unresponsive to cyclosporin therapy. No cyclosporin-associated toxicity occurred. Our observations indicated that cyclosporin A can transiently ameliorate the hematologic course of some patients with DBA. Further studies are in order to determine its mechanism of action and potential clinical utility in patients unresponsive to acceptable doses of steroid.

Abstract 262 Introduction: The most common cause of neurological injury in sickle cell anemia is silent cerebral infarcts (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) cohort, we sought to identify risk factors associated with SCI. Patients and Methods: In this cross-sectional study, we evaluated the clinical history, baseline laboratory values and performed magnetic resonance imaging of the brain. For those children with SCI-like lesions, a pediatric neurologist examined the child and neuroradiology and neurology committees adjudicated the presence of SCI. Children between the ages of 5 and 15 years with hemoglobin SS or S-beta° thalassemia and no history of overt strokes or seizure were evaluated. Results: A total of 542 children were evaluated; 173 (31.9%) had SCI. The mean age of the children was 9.3 years, with 280 males (51.7%). In a multivariate logistic analysis, two covariates were significant: a single systolic blood pressure (SBP) obtained during a baseline well-visit, p = 0.015 and hemoglobin F (Hgb F) level obtained after three years of age, p = 0.038. Higher values of SBP and lower values of Hgb F increased the odds of SCI; Figure. Baseline values of white blood cell count, hemoglobin level, oxygen saturation, reticulocytes, pain, or ACS event rates were not associated with SCI. Conclusion: SBP and Hgb F level are two previously unidentified risk factors for SCI in children with sickle cell disease. Modulation of SBP and Hgb F levels might decrease the risk of SCI. Disclosures: No relevant conflicts of interest to declare.

The follow-up Stroke Prevention Trial (STOP II) attempts to optimize tx therapy for primary stroke prevention in children with SCD who are at increased risk due to an abnormal Doppler ultrasound. A survey of participating investigators (PIs) was performed in order to assess tx practices; 12 PIs out of 26 responded. To begin chronic tx, 42 % of the PIs preferred erythrocytapheresis (ECP), partial or total exchange to bring hemoglobin (Hb) S 30%. Most PIs had a post-tx target hematocrit (Hct) 35–36%, but a third of them did not have one. Pre-tx Hct and/or Hb S (but not post-tx values) were used to predict the timing of the next tx by 83% of the group. When performing ECP, the PIs participated in the decision of how much to exchange pts only 33% of the time; generally ECP was planned by a blood bank physician and/or by machine programming. Chelation began either after 12–30 months of tx (median 18 months), or after serum ferritin 1000–2500 ng/ml (median 2000). 67% of the PIs obtained liver biopsies in all or some of the STOP II pts. Indications for liver biopsies were cited as routine for transfused pts (5 PIs) or depending on ferritin values (6 PIs). Deferoxamine 25–50 mg/kg was infused subcutaneously over 8–10 hours 5–7 nights a week in all pts. Eight PIs reported the use of central venous lines (ports) in some pts to facilitate IV access. Barriers cited to effective chronic tx were: pt compliance with chelation (7 reported it as most important), IV access, pt compliance with tx schedule, hypersplenism, and alloimmunization. We conclude that hematologists :(1) Administer leucoreduced Rh and Kell compatible, S negative PRBC to keep pre-tx Hb S levels

We have studied a number of cell surface, enzyme, and protein markers in the human leukemic K562 cell line. We have confirmed previous observations that these cells accumulate human embryonic hemoglobins after exposure to hemin. In addition, our results demonstrated that these cells possess in the "ininduced" state i surface antigen, lactate dehydrogenase isoenzymes characteristic of embryonic or fetal erythroid cells, fetal and embryonic globin chains, and globin mRNAs. The levels if i antigen, embryonic globin chains, and embryonic globin mRNA increased substantially after exposure of the cells to hemin in suspension culture. In contrast, K562 cells lacked several surface, enzymatic, and functional properties typical of granulocytes, lymphocytes, monocytes, or adult erythroblasts, including HLA surface antigens, surface immunoglobulins, sheep erythrocyte rosetting, phagocytosis, terminal deoxynucleotidyl transferase, carbonic anhydrase, ABO and Rh blood groups, and adult hemoglobins. The K562 cell line therefore exhibits phenotypic properties of embryonic erythroid progenitor cells and a quantitative increase in the expression of some of these properties can be achieved by exposure of the cells to hemin.

Beta-thalassemia trait is a frequent cause of microcytic anemia in Mediterranean children. Because striking age-related changes occur in hemoglobin and mean corpuscular volume during childhood, we assessed developmental hematologic characteristics of 132 patients less than or equal to 18 years of age with beta-thalassemia trait. Thirty-nine kindred were studied to examine intrafamilial correlations of hematologic abnormalities. Patients with beta-thalassemia trait demonstrated Hgb values about 2 gm/dl below normal standards, with a progressive rise with age paralleling normal trends. Thalassemic MCV values showed a far greater deviation from normal than Hgb levels. In contrast to normal developmental trends which show a sharp increase in the first five years of life, the MCV in thalassemia trait showed no age-related increase prior to adolescence. No age-related changes in hemoglobin A2 levels were noted. Kindred studies demonstrate a correlation of the degree of anemia, microcytosis, and elevated hemoglobin A2 levels in affected family members (r = 0.318 P0.004, r = 0.525 P0.001, r = 0.416 P0.0015, respectively). Our findings support the use of electronically determined MCV values as an initial screening procedure for children with beta-thalassemia trait. Values of70 fl prior to adolescence and75 fl during adolescence were present in nearly all thalassemic subjects. Intrafamilial correlations of Hgb, MCV, and hemoglobin A2 levels suggest that these characteristics are genetically determined.

Adrenal cortical carcinoma is an uncommon neoplasm in children. Only a handful of congenital adrenal cortical carcinoma cases have been described. A newborn who had metastatic adrenal cortical carcinoma (skin metastases and cerebral lesions) is described. This patient underwent surgical resection of the right adrenal primary, but no further treatment was given. Hemihypertrophy developed in this patient by 2 months of age, and at 4 months of age spontaneous regression of all skin nodules and central nervous system (CNS) lesions was observed. Follow-up at 1 year shows the patient to be alive, well, and disease-free. Evaluation of the tumor included DNA ploidy analysis that showed the tumor to be polyploid, a pattern recently associated with nonmetastasizing adrenal cortical neoplasm. The observation of apparent metastatic disease that regressed spontaneously highlights the prognostic value of DNA ploidy analysis and raises the possibility of an adrenal tumor with properties similar to those of Stage IV-S neuroblastoma.

after one year (Table II). In the PM group the total number of recurrences and of recurrences per patient was significantly less in either sex than in the EC group (Table II). The first recurrence in six of nine (all boys) in the PM group was due to PM. In the EC group, seven of eight recurrences were due to EC. DISCUSSION This study revealed a number of characteristics of initial UTI due to Proteus mirabilis. Most patients were male, relatively young, and had fewer clinical findings, fewer abnormalities of urine or urinary tract structure, and a relatively benign course. The predominance of PM infection among boys (58%) in our series is comparable to that in previous observations (59%), ~ but varies with that in other reports of 2% 3 to 32% 5 . The basis for the male predilection to PM infection is not known. Age seems to influence sex distribution. In the study showing a very low incidence (2%) among boys, ~ the mean age was much higher (9 years) than in our group (2.7 years). The relative paucity of symptoms in patients with PM infection may also be related in part to age, since many were too young to verbalize complaints. The observation of a less acid, or even alkaline, urinary pH has been previously described? Structural abnormalities were less common among the patients with PM infection than in the EC group and than in a prior series 2 of males patients with Proteus infection. The recurrence rate (31%) in the male patients with PM infection may be compared with the 36% reported in a previous study, ~ which included some patients with EC and with urinary tract abnormalities. The number of recurrences per patient and their relative rarity after one year suggest a favorable outlook. The frequency of stone formation associated with PM infection seems to be variable. During the initial episode it may be low as in this series (a single patient) or totally absent, as in a previous study. ~ Its prevalence, however, may be higher with persistent and/or chronic infection.' It may be concluded that Proteus mirabilis, the most prevalent pathogen in boys in this series, predominantly involves younger patients and is associated with fewer clinical signs and urinary findings, higher urinary pH, a relatively benign course, and a low incidence of structural abnormalities of the urinary tract. REFERENCES

Surface-mediated reactions of clotting were compared in 21 black children with homozygous sickle cell disease, 12 age-matched controls, and 15 adults. Both the coagulant and antigen titers of Hageman factor (factor XII) were decreased in asymptomatic patients compared with those in the control groups. These findings were associated with slight but significant reductions in the plasma titers of prekallikrein and high molecular weight kininogen. A further decrease from the initially low titers of these contact factors was observed during vaso-occlusive crises. Additionally, we observed a disparate relationship between Hageman factor coagulant activity and its antigen titers. These data provide evidence for reduction of the contact factors in patients with homozygous sickle cell disease.

The most common initial manifestations of Hodgkin's disease in children are cervical or supraclavicular adenopathy or a mediastinal mass. Axillary and inguinal lymph node involvement are much less frequent. Epitrochlear involvement is very unusual, even in the presence of generalized disease and is extremely rare as an initial and isolated manifestation of Hodgkin's disease. Report of a Case .—A healthy 6-year-old girl, had a firm, painless, 4-cm, right epitrochlear mass. There was no history of the systemic symptoms (ie, fever, sweats, weight loss, or pruritus), local infection, animal bites or scratches, or medications. The physical examination was otherwise unremarkable. An excisional biopsy specimen demonstrated nodular sclerosing Hodgkin's disease. Clinical assessment included complete blood cell count, sedimentation rate, liver function tests, chest tomography, gallium scan, liver-spleen scan, bipedal lymphangiography, intravenous pyelogram and bilateral posterior iliac crest bone marrow aspirates, and biopsy specimens, all of which showed no evidence of lymphoma. A

MULTIPLICITY of tumors is being recognized with increasing frequency. The association of pheochromocytoma with Recklinghausen neurofibromatosis is a well-known but infrequent phenomenon. To the best of our knowledge, neither has been reported as occurring together with Burkitt lymphoma. We report the unusual occurrence of Burkitt lymphoma, pheochromocytoma, and Recklinghausen neurofibromatosis in a single person and comment on possible interrelationships. Report of a Case In July 1973, a 20-year-old woman underwent curetting of a mass growing at the site of a prior dental extraction. Histologic examination suggested an anaplastic malignant process. In the course of her evaluation, multiple cafe-au-lait spots were noted on the trunk and extremities along with numerous 0.5-cm, spongy, subcutaneous nodules on the abdomen and lower back. Findings from a bone marrow aspiration and biopsy were compatible with iron deficiency anemia. Over the next two months, an expanding mass, which was lytic on roentgenograms, developed in the posterior

Evidence supporting the existence of intravascular coagulation in homozygous sickle cell (HbSS) disease has been reported. In this study, surface-mediated reactions of clotting were compared in 21 black children with HbSS disease and 12 age-matched controls. Both the coagulant and antigen titers of Hageman factor were decreased (mean coagulant titer 0.49 ± S.D. 0.29 u/ml; mean antigen titer 0.77 ± 0.27 u/ml) in asymptomatic HbSS patients compared to the control group (mean coagulant titer. 1.01 ± 0.39 u/ml; mean antigen titer 0.94 ± 0.25 u/ml). A disparate relationship between the Hageman factor coagulant and antigen titers were observed in HbSS patients. These findings were associated with a slight decrease in the plasma titers of prekallikrein and HMW kininogen (mean 0.78 ± 0.14 and 0.75 ± 0.15 u/ml respectively in HbSS patients compared to 1.05 ± 0.22 and 0.86 ± 0.09 u/ml respectively in the control group). A further reduction from the initially low titers of these contact factors was observed during vaso-occlusive crises (mean Hageman factor titer 0.32 ± 0.15 u/ml; mean prekallikrein titer 0.38 ± 0.18 u/ml; mean HMW kininogen titer 0.56 ± 0.17 u/ml). These data indicate that the initial participants of the intrinsic pathway of coagulation are consumed in patients with HbSS disease. Further, these processes appear to accelerate during vaso-occlusive crises.