Tansu Sipahi

PARVOVIRUS B19 INFECTION REMINISCENT OF MYELODYSPLASTIC SYNDROME IN THREE CHILDREN WITH CHRONIC HEMOLYTIC ANEMIA

The authors have seen transient pancytopenia with erythroid hypoplasia and striking trilineage myelodysplasia reminiscent of true myelodysplastic syndrome (MDS) in 3 children, 1 with thalassemia intermedia and the other 2 with previously undiagnosed hereditary spherocytosis. In these 3 children transient pancytopenia and myelodysplasia coincided with serological evidence of acute parvovirus B19 (PV-B19) infection, strongly suggesting their relevance. It is of interest that these 3 cases were encountered within a period of 6 months. This might be an incidental event, but it might also be concluded that acute PV-B19 infection associated transient pancytopenia with morphological appearance of MDS may occur more frequently than reported in the literature. So, PV-B19-associated nonclonal MDS should be considered in the differential diagnosis of trueclonal MDS.

Serum Interleukin-2 and Interleukin-6 Levels in IRON Deficiency Anemia

The aim of this study was to investigate the serum levels of interleukin-2 (IL-2) and interleukin-6 (IL-6) in children with iron deficiency anemia before and after iron supplementation. Twenty-five children with iron deficiency anemia 6 months to 3 years of age were included in the study. Ten age- and sex-matched healthy children constituted the control group. In the iron-deficiency group the production of IL-2 was found to be significantly lower than that in controls and became normal after iron supplementation (P < .001). But there was no difference in serum levels of IL-6 in iron deficiency anemia before and after iron supplementation (P > .05).

Coexistence of two prothrombotic mutations, factor V 1691 G-A and prothrombin gene 20210 G-A, and the risk of cerebral infarct in pediatric patients.

Several studies have evaluated the effect of the factor V (FV) 1691 G-A mutation and prothrombin (PT) 20210 G-A in patients with cerebrovascu- lar disease, particularly in patients over the age of 18, but the results are controversial (1± 3). To date, no study has evaluated the effect of these two prothrombotic mutations in pediatric patients with cerebral infarct. Thirty-twopediatriccerebralinfarctpatientsdiagnosedanddocumented with neurologic examination, laboratory examinations for the etiology of in- farct, and MRI (14 males and 18 females, ages 2 months± 13 years) were included in the study. None of the patients had any etiologic factor for cere- bral infarct, such as collagen tissue disorder, isolated angiitis, possible in- fection, congenital heart disease, sickle cell syndrome, or other inherited coagulation disorders and mitochondrial diseases. DNA was extracted by conventional methods and the mutation analysis was performed according to previously reported techniques (4± 7). Our study revealed that 9 (28.1%) ofthe patients carriedFV1691 A and7 (21.8%) of thepatientscarriedthe PT 20210 A mutation in the heterozygous state. When compared to the normal healthy population the difference was statistically important for both muta- tions respectively (p < .04; p < .0007) ((FV 1691A OR: 2.6 CI 95% 0.9± 6.3); PT 20210A OR:8.2 (CI 95% 2.5± 27.6)). Further, 2 of these patients carried both mutations (6.2%) (OR: 11.8 (CI 95% 1.0± 134.0)) (Table 1). The frequency of FV (1691 G-A) and PT (20210 G-A) mutations is 10.4 and 2.7%, respectively, in the Turkish population (6± 8). Approximately one inevery400healthyindividualsmaycarrybothmutations.Ourdataindicated that FV 1691 A and PT20210 A mutations are important risk factors for the

Hypercoagulability in Children with Thalassemia Major

Objective: We wished to determine the role of various factors causing hypercoagulability in thalassemia patients. Methods: Forty-six homozygous β-thalassemia patients were investigated. Protein C, protein S, and antithrombin (AT) levels were measured and lupus anticoagulants (LA) were screened. D-Dimer and fibrinopeptide A ( FPA) levels were measured to show the activation of the fibrinolytic system. Ten healthy children served as controls. Results: There was a marked decrease in protein C activity in 44.4% and in protein C antigen in 53.8% of the patients. Although no significant differences was noted between the mean values for protein S in the patient and control groups, protein S activity was <60% in 40% of the patients. AT levels were always normal. D-Dimer and FPA levels were increased, indicating the ongoing coagulation activation and fibrinolysis. Three patients had LA; which reflect the expression of phosphatidylserine on the outer surface of the erythrocyte membrane. Conclusions: In thalassemic patients, there is activation of the coagulation and fibrinolytic system which is believed to be secondary to an underlying mechanism. The presence of LA in some patients, probably due to the expression of PS on the outer surface of the erythrocyte membrane, may be the initiating event. Key Words: Thalassemia-Hypercoagulability-Protein C—Protein S—Antithrombin—Antiphospholipid antibodies.

Bloody nipple discharge in 2 infants with interesting cytologic findings of extramedullary hematopoiesis and hemophagocytosis.

Bloody nipple discharge in the infantile period is an uncommon finding. Despite its stressful course to the parents, it is generally a benign condition with a spontaneous resolution. The approach to bloody nipple discharge in the infantile period is well documented in the literature even though the number of these cases is limited. We report 2 infants with unilateral bloody nipple discharge. Their physical examination, laboratory, and ultrasound findings were normal but the cytologic examinations of the discharge revealed signs of extramedullary hematopoiesis and hemophagocytosis. These extraordinary findings made us brainstorm on the probable ongoing processes in the infantile breast tissue.

Cerebral infarct associated with prothrombin gene G 20210 A variant in a Turkish child with cystic fibrosis: an unusual coexistence.

To the Editor: Cystic fibrosis (CF) is an autosomal recessively inherited disease characterized with pancreatic insufficiency and chronic lung disease (1). Coagulation abnormalities may sometimes occur in CF and generally manifest as bleeding symptoms, related to decreased vitamin K dependent factors and in a lesser frequency due to increased fibrinolytic activity (2, 3) . Here we describe an unusual case with CF who developed a cerebral infarct, which seemed to be contributed by the presence of prothrombin gene G 20210 A variant, that has recently been shown to be a genetic risk factor for thromboembolism (4-7). A 14-month female infant was presented as unconscious. She had experienced an abrupt onset of convulsions 4 d before presentation. She was given diazepam and luminalized in a local hospital and referred to our center when she had become unconscious. In her past history she had meconium ileus at birth. Her parents were unconsanguineous. At the age of 2.5 months she was admitted to our hospital because of repeated pulmonary infections and diarrhea. The diagnosis of CF was established on the basis of sweat chloride concentrations > 100 mEq/l(13O-160 mEq/l) on numerous occasions. She was given supplemental pancreatic enzymes, fatsoluble vitamins and prophylactic antibiotic therapy. On this admission, although she seemed to be unconscious she was responsive to painful stimuli caused by moving her extremities. The pupils were isochoric and responsive to light. Except for her neurologic compromise all other physical examination findings were normal. There was no notified event such as a recent trauma or a family history that might have been relevant to her neurological status. Complete blood count findings, determination of serum electrolytes, glucose and calcium levels, liver and renal function tests, urine and cerebro-spinal fluid (CSF) analysis were all normal. Blood, urine and CSF cultures were sterile. Cardiac examination and echocardiography showed no abnormality. An electroencephalograph record showed active paroxismal activity originating from the left occipital region. Cerebral MRI revealed an infarcted area in the right parietotemporal region. Since neither evidence of a mass effect as seen in an acute infarct nor a volume loss due to encephalomalasia as defined in a chronic infarct was present, the lesion seen in MRI was diagnosed to be a subacute infarct (Fig. 1). In coagulation screening her PT was 11.40 s (N=11-14 s) and her APTT was 32.60 s (N=2540 s); protein C, protein S, antithrombin I11 and fibrinogen were all found to be normal. Anticardiolipin antibodies were negative. Heterozygosity for prothrombin gene G 20210 A variant was found by amplification of prothrombin gene (Factor 11) by polymerase chain reaction (PCR) and using a method described elsewhere (4). Over the following days her neurologic status improved partially. She was put on prophylactic coumadin therapy and discharged with some residual neurologic compromise, with an invitation to periodic controls. Coagulation abnormalities may sometimes occur in patients with CF. In patients with advanced pulmonary disease who have impaired liver functions and/or hepatosplenomegaly and malabsorption, decreased levels of vitamin K dependent factors (prothrombin and factor VII-X complex) may contribute to prolonged PT and PTT. Increased fibrinolytic activity and a mild thrombocytopenia due to hypersplenism were also reported in some children with CF (2). Coagulation abnormalities generally manifest as bleeding symptoms, and a thromboembolic phenomenon is quite uncommon in CF. Although protein C and protein S are also vitamin K dependent natural anticoagulants, thromboembolism related to their deficiency is not a defined complication in CF. In our patient the disease (CF) has been succesfully controlled. She was put on a supplemental therapy consisting of pancreatic enzymes

Is neutropenia a clue for early diagnosis of X-linked agammaglobulinemia?

Neutropenia is a prominent finding in the primary immunodeficiency syndromes including X-linked agammaglobulinemia (XLA), hyper IgM syndrome, common variable immunodeficiency (CVID), IgA deficiency, cartilage–hair hypoplasia, and reticular dysgenesis [1]. Here, we would like to emphasize that in the infancy period, in addition to recurrent infections, neutropenia could have also alerted physicians to the diagnosis of XLA. Our patient with recurrent pulmonary infection and growth retardation was referred to our hospital when he was 7 months old. He was a term, 1500-g baby, delivered by cesarean section after an uneventhful pregnancy. He has a healthy twin brother. His parents were relatives and his family history was unremarkable for immunodeficiency. On admission, his weight was 4480 g (<5th percentile), his height was 55 cm (<5th percentile), and his head circumference was 34.5 cm (<5th percentile). On auscultation of the chest, crepitan rale was noted and chest radiography showed bilateral pulmonary infiltration. Laboratory studies revealed Hb level 9.7 g/dL, leukocyte count 1600/mm3 (18% PMNL, 70% lymphocytes, 12% monocytes), absolute neutrophil count 288/mm3, platelet count 233,000/mm3, and CRP (C-reactive protein) 43 mg/dL. The other biochemical parameters were normal. A series of laboratory tests was carried out to evaluate the etiology of recurrent pulmonary infection. Alpha-1 antitrypsin level, sweat test, urine, and blood amino acid chromatography were found to be normal, whereas IgG, IgA, IgM, IgE levels were below the 95% confidence limits for appropriate ageand sex-matched controls. After the immunologic evaluation was performed; hypogammaglobulinemia, neutropenia, and low peripheral B-cell numbers supported the diagnosis of XLA. Hypogammaglobulinemia (usually <100 mg/dL total immunoglobulin), hypoplasia of adenoids, tonsils, and peripheral lymph nodes is the rule;

Alpha-1 antitrypsin deficiency: an overlooked cause of late hemorrhagic disease of the newborn.

To the Editor:We read with interest the neonatal case of α1-antitrypsin deficiency with fatal intracranial hemorrhage reported by Israels and Gilfix in your journal (1). The diagnosis of late hemorrhagic disease of the newborn can mainly be established with the observation of minor bleeding from the

Coffee beans pica causing iron and zinc deficiency

A case of coffee beans pica is reported that was associated with zinc deficiency and iron deficiency anemia. Both deficiencies showed a good response to iron and zinc therapy. J. Trace Elem. Exp. Med. 10:205–208, 1997.