The Prevalence of von Willebrand Disease and Significance of in Vitro Bleeding Time (PFA-100) in von Willebrand Disease Screening in the Izmir Region.

OBJECTIVE: von Willebrand disease (vWD) is the most common hereditary bleeding disorder. The purpose of this investigation was to determine the prevalence of vWD among adolescents in Izmir and to assess the sensitivity and specificity of PFA-100 as a screening method in detecting this disease. MATERIAL AND METHODS: Our study was conducted on adolescents in the city of Izmir between October 2006 and March 2007. A total of approximately 1500 high school students between 14 and 19 years of age were planned to be included in the investigation. Survey forms prepared for assessing hemorrhagic diathesis were completed by 1339 individuals (512 males, 827 females). The necessary laboratory tests were performed after having obtained written informed consent from 40 individuals suspected to have hemorrhagic diathesis. RESULTS: Based on the von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) levels and bleeding symptoms, vWD type-1 was diagnosed in 14 individuals (4 males, 10 females; prevalence: 1.04%). The most common bleeding symptom in these patients was found to be epistaxis (10/14). Screening with PFA-100 revealed prolongation in both cartridges (Col/ADP and Col/Epi) in 3 of the 14 patients. PFA-100 was determined to exhibit 21.4% sensitivity and 100% specificity in the diagnosis of vWD. CONCLUSION: The PFA-100 device was found to have high specificity but to have exhibited low sensitivity. Therefore, its utilization as a screening test may be problematic in patients with mild type-1 vWD. Specific tests (vWF:RCo, vWF:Ag) are required for the definite diagnosis of vWD. However, further studies with a large number of patients are needed. CONFLICT OF INTEREST: None declared.

Investigation of acquired von Willebrand Syndrome in children with hypothyroidism: reversal after treatment with thyroxine.

BACKGROUND: Acquired von Willebrand Syndrome (AvWS) is a rare bleeding disorder associated with various underlying conditions. Many case reports have been published so far on bleeding tendency in hypothyroidism resembling AvWS. OBJECTIVE: This study was designed to define the relationship between hypothyroidism and AvWS and to investigate the effects of L-thyroxine treatment. SUBJECTS: Twenty four hypothyroid patients were included in the study. Nineteen patients were evaluated during treatment, 5 patients were evaluated before hormone replacement. METHODS: Complete coagulation screening tests including levels of von Willebrand Factor antigen (vWF:Ag) and functional activity (vWF:RCo) were measured by thrombocyte aggregometer. RESULTS: We demonstrated low vWF:Ag and vWF:RCo in 13 patients. Two of the 13 patients were diagnosed as AvWS, while another 2 patients were diagnosed as hereditary vWD Type 1. The remaining patients are still being followed-up. CONCLUSION: We would like to attract the attention of paediatricians to the possibility of bleeding due to decreased activity of vWF in hypothyroid children.

The infection risk of visceral leishmaniasis among household members of active patients.

Human visceral leishmaniasis (HVL), caused by Leishmania infantum is mainly observed as sporadic cases in Turkey and dogs are considered as the main reservoir of the disease. The incidence of visceral leishmaniasis among members of households where a HVL infection has already been diagnosed was studied in clusters around the diagnosed cases in different regions in Turkey. A total of 47 serum samples collected from the households of 11 proven visceral leishmaniasis patients were screened for anti-Leishmania antibodies by indirect immunofluorescent antibody test (IFAT). Three and one such household members belonging to the different families were found to be seropositive and borderline, respectively. Diagnosis was confirmed with the presence of amastigotes in bone marrow aspiration samples in all seropositives while the borderline case with slight and indefinitive symptoms of VL was followed only serologically at 3-month intervals and improved spontaneously in 1 year. Household members of individuals with previously confirmed visceral leishmaniasis were found to have higher frequency of the disease suggesting the household members should be included in the risk group for visceral leishmaniasis and serological screening should be performed for the detection of possible infection.

Efficacy of continuous midazolam infusion and mortality in childhood refractory generalized convulsive status epilepticus.

PURPOSE: Continuous midazolam infusion is commonly used for the management of status epilepticus (SE). The purpose of this study was to assess the efficacy of midazolam and mortality in childhood refractory generalized convulsive SE. METHODS: We included 27 children with refractory generalized convulsive SE. Midazolam was given 0.2 mg/kg as bolus, followed by 1-5 microg/kg/min as continuous infusion. Clinical data and response to treatment were recorded for each patient. RESULTS: Acute symptomatic SE accounted for 52%, and central nervous system (CNS) infections were the most frequently associated etiologic condition (44%). Complete control of seizures was achieved with midazolam infusion in the 26 (96%) children within 65 min; at a mean midazolam infusion rate of 3.1 microg/kg/min. Adverse effects such as hypotension, bradycardia or respiratory depression did not occur during midazolam infusion. In one (4%) patient with acute meningoencephalitis, SE could not be controlled. Five (19%) patients died; four had acute symptomatic aetiology and one had progressive encephalopathy. CONCLUSION: Midazolam is effective and safe in the control of refractory generalized convulsive SE. The response to treatment and mortality were related to the underlying aetiology.

Effect of carbamazepine and valproate on bone mineral density.

The objective of this study was to examine the effect of carbamazepine and valproate monotherapy on bone mineral density in children. Femoral neck area bone mineral density was measured by dual-energy x-ray absorptiometry in 31 healthy children and 33 children with idiopathic epilepsy treated with either carbamazepine (n = 17) or valproate (n = 16) for more than 6 months. There were no significant differences between the control and study patients in age, height, weight, and physical activity. No patient had dietary restrictions or neurologic impairment. Serum levels (as mean +/- S.D.) of valproate and carbamazepine were 53.75 +/- 23.94 microg/mL and 6.26 +/- 2.00 microg/mL, respectively, and the duration of treatment for each drug was 24.38 +/- 10.58 months and 31.76 +/- 16.33 months, respectively. Calcium intake in the diet was similar in both the control and study groups. In the valproate-treated group, 25% of the patients were hypocalcemic, 6% had elevated alkaline phosphatase levels, and 50% were hypophosphatemic. In the carbamazepine-treated group, 17.6% of the patients were hypocalcemic and 35.3% were hypophosphatemic. Children treated with valproate had 31.9% reduction in bone mineral density at the femoral neck area (P < 0.05); the 20% reduction in bone mineral density in this anatomic location in carbamazepine-treated children was not significant. In conclusion, valproate monotherapy, but not carbamazepine therapy, significantly reduces femoral neck area bone mineral density in children with idiopathic epilepsy.

Acquired Hemophilia in Pediatric Population.

The development of acquired inhibitors against the factor VIII protein in childhood period, is a very rare disorder in nonhemophiliac persons but may be clinically important condition due to potential serious bleedings. We have investigated acquired hemophilia development frequency in children with potential high risk groups. Totally 483 nonhemophiliac children including healthy controls were enrolled the study. Age range was 2 to 20 years and mean age was 11 ± 5.4 years. Risk groups for acquired hemophilia were selected among sick children with transfusion dependent ß- thalassemia major (n= 75), children with malignancy (n= 55), asthma bronchiale (n= 65), type I insulin dependent diabetes mellitus (n= 63), collagen tissue disorders (n= 35). Age-matched 190 healthy children were selected as for healthy control group. Inhibitor tests were performed by the method of Bethesda assay. We have found only two patients who had acquired factor VIII inhibitor among 483 children. These two patients were solid tumor (osteosarcoma) and type I insulin dependent diabetes mellitus. Other risk groups and healthy controls have not inhibitor positivity. As a conclusion, acquired inhibitors should be considered for the differential diagnosis of unusual bleeding episodes in patients who had risk factors of all age groups including childhood period.