Bülent Özgönenel

How do you treat bleeding disorders with desmopressin

Desmopressin is an analog of vasopressin that exerts a substantial haemostatic effect by inducing the release of von Willebrand factor from its storage sites in endothelial cells. It has proved useful in treating or preventing bleeding episodes in patients with von Willebrand disease, haemophilia A and platelet function defects. Its efficacy in achieving a satisfactory level of haemostasis has reduced the use of blood products to treat bleeding episodes. Clinicians need to become familiar with the use of this drug that has become a home medication for many patients with inherited bleeding disorders.

Thromboelastography identifies children with rare bleeding disorders and predicts bleeding phenotype.

Rare bleeding disorders (RBDs) comprise 3–5% of all congenital bleeding disorders. They can evade typical coagulation screening tests and there is a poor correlation between laboratory results and bleeding phenotype. Thromboelastography (TEG) measures coagulation globally in whole blood samples. The aims of this study were to evaluate the utility of TEG as an adjunct to the routine screening tests employed for the diagnosis of RBDs and to correlate TEG results with the bleeding phenotype in RBDs. TEG parameters and clot kinetics were compared to bleeding phenotypes (asymptomatic, mild, moderate and severe) in 26 RBD patients and 30 normal controls. Clot kinetics correlated strongly with RBDs and with the severity of bleeding phenotype with mean maximum rate of thrombus generation (MRTG) 15.4 mm min−1 in controls vs. 6.0 in RBDs (P < 0.0001, Wilcoxin). The mean MRTG was 7.7 in mildly symptomatic, 5.5 in moderately symptomatic and 4.1 in severely symptomatic patients (P < 0.0001, Kruskal–Wallis). Disorders that are often missed by conventional screening tests, dysfibrinogenaemia and platelet disorders displayed a distinctive TEG curve with markedly decreased maximum amplitude (MA) and low MRTG values. Factor XIII and PAI deficient patients displayed increased fibrinolysis in addition to low MRTGs. All patients with RBDs, but none of the normal controls, had abnormal clot kinetics suggesting that TEG may be an effective screening test for RBDs.

Emergency department visits in children with hemophilia

The pediatric emergency department (ED) management of bleeding and other complications of hemophilia constitutes an increasingly important component of hemophilia therapy. This retrospective study examined the overall ED use by children with hemophilia in a single center, with a particular aim to investigate visits related to injury or bleeding, and those related to blood stream infection in patients with a central venous catheter (CVC).

Pediatric EBV-positive T-cell/histiocyte-rich large B-cell lymphoma with clonal cells in the bone marrow without overt involvement

T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL) is a variant of large B-cell lymphoma only rarely encountered in children. Here we report the case of an 8-year-old African American boy with Epstein-Barr virus (EBV)-positive TCHRLBCL who initially presented with right submandibular, anterior cervical and supraclavicular lymphadenopathy. Cytogenetic analysis of the lymph node revealed a near-triploid karyotype with complex chromosomal aberrations. Although morphologically the bone marrow was normal, the same cytogenetically abnormal clone was detected. The patient responded to chemotherapy with CHOP (doxorubicin, cyclophosphamide, vincristine and prednisone) therapy, with disappearance of the abnormal clone from the bone marrow. The patient remains in remission 26 months after the initial diagnosis.

Invasive Pneumococcal Disease in Patients With Sickle Cell Disease

Background: Patients with sickle cell disease (SCD) are at risk of fatal sepsis with encapsulated bacteria, such as Streptococcus pneumoniae, because of the inherent autosplenectomy that occurs in SCD. This risk is thwarted with oral penicillin prophylaxis during the first 5 years of life, and with stringent vaccination against S. pneumoniae alongside routine childhood immunization. But compared with the general African American pediatric population, the rate of invasive pneumococcal disease (IPD) in patients with SCD still remains high, resulting in hospitalization and fatality. Methods: Patients with SCD who developed IPD from 2004 up to 2013 were identified using microbiology records. Descriptive analysis of presence of risk factors for IPD, type of SCD, pneumococcal vaccination and prophylaxis status, clinical presentation, microbiological data, and the outcome of IPD was performed. Results: Eight patients with SCD developed IPD (7 bacteremia and 1 respiratory tract infection). Three of the 8 isolates underwent serotype analysis (15 C in 2 and 15A in 1), none covered with the current vaccination program. One patient had fatal outcome (15A). Conclusions: Breakthrough cases of IPD may involve nonvaccine isolates, and seem to occur after 5 years of age when oral penicillin prophylaxis has been terminated.

Upper-extremity deep venous thrombosis after whole blood donation: Report of three cases from a single blood center

There are two upper‐extremity deep venous thrombosis (UEDVT) cases after whole blood donation reported in the English medical literature. Three additional UEDVT cases after whole blood donation were reported to our blood center within a 13‐month period.

Bacteremia in febrile children with sickle cell disease.

To the Editor: We read with great interest the article by Narang et al,1 where they reported a low rate (1%) of true positivity in blood cultures drawn from febrile children with sickle cell disease (SCD), spanning from the period 1997 to 2006. We also observed a similar low rate of bacteremia among our patients with SCD on reviewing their electronic medical records during the whole year of 2010. We identified 531 distinct blood cultures (drawn at least 48 h apart) obtained from 242 febrile children with SCD, including 36 cultures that were drawn from 9 patients with central vein catheters (CVCs). Fever was considered to be a body temperature elevation of Z38.01C, at home and/or at the hospital. Sixteen blood cultures were positive; however, 11 of these were considered contaminated. Five blood cultures from 4 patients were considered true positives (0.9% of all blood cultures). Of the blood cultures drawn from patients without a CVC (n=495), only 2 (0.4%) were considered true positive. However, of the blood cultures drawn from patients with a CVC (n=36), 3 (8.3%) were true positive. The rate of true bacteremia was therefore B21 times higher in blood cultures drawn from patients with CVC compared with those without (P=0.0026 by Fisher exact test). There was only 1 patient with bacteremia secondary to Streptococcus pneumoniae. This was a 7-year-old boy who had previously received 4 doses of the heptavalent pneumococcal conjugate vaccine and 2 doses of the 23-valent pneumococcal polysaccharide vaccine. Serotyping was not done in this patient’s case. The other isolated organisms included Serratia plymuthica, Staphylococcus aureus, Stenotrophomonas maltophila, and Escherichia coli. From a larger database that went back to 2006, we were able to identify 3 additional patients with SCD who developed pneumococcal bacteremia despite immunization, and in 2 of these a nonvaccine serotype, type 15c, was isolated at Centers for Disease Control and Prevention, Atlanta, GA. This observation was consistent with the report by McCavit et al,2 wherein a recent surge in invasive pneumococcal infection due to nonvaccine isolates was described. Our findings of low rates of bacteremia in febrile patients with SCD corroborate with those obtained by Narang and colleagues, a tribute to the state-of-the-art care in SCD. In the subgroup of patients with CVCs, however, the rate of bacteremia persists at higher levels, because of the added risk for bloodstream infections posed by the CVCs. Pneumococcal bacteremia, although rare, still occurs even in fully immunized patients and may be due to nonvaccine isolates.

Vacuolated neuroblastoma cells mimicking FAB L3 lymphoblasts in bone marrow aspirates

Abundant cytoplasmic vacuolation of neuroblasts has been noted on bone marrow aspirate (BMA) smears of two patients with metastatic neuroblastoma. Occasional tumor cells were dispersed as individual cells as well as in clumps. These cells had basophilic cytoplasm and several nucleoli, reminiscent of L3 lymphoblast morphology. Flow cytometric analysis of the bone marrow mononuclear cells and neuron‐specific enolase staining of the bone marrow biopsy samples further distinguished the cells as neuroblasts. Cytoplasmic vacuolations of neuroblasts may be a feature of metastatic neuroblastoma cells in BMA smears. Pediatr Blood Cancer 2007;48:227–229.

Uncommon presentation of craniopharyngioma with anemia in an adolescent

To the Editor: Craniopharyngioma most commonly presents with symptoms related to increased intracranial pressure, such as headache and vomiting [1,2]. Less common presenting symptoms are secondary to the invasion of the neighboring structures, which include the pituitary, the hypothalamus, the optic pathways, and the third ventricle. Visual and endocrine abnormalities are usually present at initial evaluation although only a minority of patients seeks medical attention because of symptoms related to these abnormalities [1,3,4]. Anemia is a common, nonspecific finding in the ambulatory pediatric practice but constitutes an unusual initial presentation for craniopharyngioma. We present the case of a 13-year-old female who was referred for the evaluation of mild normocytic anemia and whose further investigation led to the diagnosis of panhypopituitarism secondary to craniopharyngioma. The patient’s academic performance had deteriorated over the last 6 months, which instigated the investigation for anemia. She also reported fatigue, constipation, and weight gain of 5 pounds in the last 6 months despite a poor appetite. She denied headache or visual symptoms. Hermenarche had occurred a year prior to her presentation and her menstrual periods were regular but lasted only 2 days and consisted of spotting. The birth and past medical history were unremarkable. She was not taking any medications. The family history was significant for hypothyroidism in a 29-year-old sister and was otherwise negative. Aside from delayed puberty (Tanner stage II for breasts and Tanner stage I for pubic and axillary hair), the physical examination was essentially unremarkable, with no focal neurologic findings. White blood cell count was 4,800/mm with a differential of 29% neutrophils, 58% lymphocytes, 8% monocytes, and 5% eosinophils. Hemoglobin was 10.9 g/dl and the red blood cell count was 3.71 million/mm. The platelet count and the absolute reticulocyte count were within normal range. Red blood cells were normocytic and the other red cell indices were normal. Sedimentation rate, serum aminotransferases, bilirubin, blood urea nitrogen, and creatinine were within normal range. Our patient’s symptoms (weight gain despite loss of appetite, fatigue, worsening school performance, amenorrhea and constipation) suggested the presence of hypothyroidism. Serum levels of free thyroxine and total thyroxin were low (0.5 ng/dl and 3.8 mg/dl, respectively) in the face of a normal thyroid stimulating hormone (TSH) level (1.94 m IU/ml). The anti-thyroglobulin and antimicrosomal antibodies were negative. The inappropriate TSH response to low thyroxine levels, coupled with other abnormal findings (delayed puberty and lymphocyte predominance in the white blood cell differential) further led to a clinical suspicion of hypopituitarism in our patient. Serum levels of A.M. cortisol, insulin like growth factor-1 (IGF-1), IGF binding protein-3, follicle stimulating hormone, and luteinizing hormone levels were also low, establishing a diagnosis of hypopituitarism. Serum prolactin level was within normal range. The radiological bone age revealed mild delay in skeletal maturity. Urine and serum osmolality were not suggestive of diapedes insipidus. A magnetic resonance imaging of the brain revealed a sellar/suprasellar lesion, 2.5 cm in diameter, demonstrating hyperintense signal in T1-weighted images, most likely representing a craniopharyngioma. The sella turcica was widened and a normal pituitary and infundibulum were not seen. A subsequent computerized tomographic scan showed a rim of calcification within the lesion. Automated perimetry using Humphrey field analyzer revealed bitemporal hemianopia. The patient underwent bifrontal craniotomy and total resection of the tumor. The histologic examination of the tumor revealed dense fibrous tissue and cystic spaces lined by squamous epithelial cells with peripheral palisading mimicking adamantinoma of the jaw, characteristic of craniopharyngioma. Post-operatively the patient developed diabetes insipidus and monocular diplopia. She was started on oral thyroxine, hydrocortisone, and desmopressin supplementation and the hemoglobin rose from 10.9 to 12.2 g/dl 3 months after surgery. Although an uncommon presenting symptom for craniopharyngioma, anemia may be commonly discovered