Nihal Ozdemir

Bleeding risk of surgery and its prevention in patients with inherited platelet disorders. The Surgery in Platelet disorders And Therapeutic Approach (SPATA) study

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series.

Development of inhibitors is the most serious complication in haemophilia A treatment. The assessment of risk for inhibitor formation in new or modified factor concentrates is traditionally performed in previously treated patients (PTPs). However, evidence on risk factors for and natural history of inhibitors has been generated mostly in previously untreated patients (PUPs). The purpose of this study was to examine cases of de novo inhibitors in PTPs reported in the scientific literature and to the EUropean HAemophilia Safety Surveillance (EUHASS) programme, and explore determinants and course of inhibitor development.

Successful management of hepatic mucormycosis in an acute lymphoblastic leukaemia patient: a case report and review of the literature.

We present a case of hepatic mucormycosis in a 9‐year‐old boy with acute lymphoblastic leukaemia. Despite long‐term use of combined liposomal amphotericin B and posaconazole therapy, the lesion persisted and could only be treated by surgical excision. After surgery, antifungal treatment was continued with posaconazole. On follow‐up, the patient had two episodes of ascending cholangitis which were responsive to intravenous antibiotics. He is doing well at the moment in remission for 2.5 years. Mucormycosis was long regarded as a fatal infection with poor prognosis. With early medical and surgical management, survival rates increase. Isolated hepatic mucormycosis is rare and only seven cases were reported in the literature up to now. We wanted to emphasise the role of early surgery in patients with hepatic mucormycosis in view of the literature.

A 17-year experience with ALL-BFM protocol in acute lymphoblastic leukemia: prognostic predictors and interruptions during protocol.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and despite the intense combination chemotherapy, cure rates are less than 90%. Several prognostic parameters, including nonneoplastic hematologic cell counts during induction phase, are suggested to predict outcome in ALL. We analyzed 242 ALL patients treated in our center to investigate individual prognostic parameters and the impact of delays on disease outcome. Age at diagnosis, risk groups, extramedullary involvement, t(9;22), prednisone response, bone marrow response at days 15 and 33, day 15 platelet count, day 33 lymphocyte, monocyte, and platelet counts, treatment delay, sepsis, and omission of day 64 cyclophosphamide were valuable predictors of survival in univariate analysis. However only the age, CNS involvement, omission of cyclophosphamide, and total delay during treatment were associated with survival in multivariate analysis. Omission of second cyclophosphamide dose had no impact on survival of standard risk group patients, but adversely affected the long term survival of medium risk group (MRG) patients. The second dose might be given with the first dose on day 36 to MRG patients to prevent delays. Day 15 and 33 platelet counts are promising predictors of survival in low income countries where assessment of minimal residual disease is difficult, but this data needs further consolidation.

Voriconazole Induced Bradycardia

Voriconazole is a triazole antifungal drug that is used to treat invasive fungal infections, especially aspergillus. Here, we report two children who had severe bradycardia associated with voriconazole at a dose of 12 mg/kg per day. Bradycardia resolved in 24 hours in both after decreasing the dose to 10 mg/kg per day. Heart rates were in normal limits on follow-up. Bradycardia may be a side effect of voriconazole treatment in children under immunosuppressive treatment. Heart rate should be monitored in patients receiving voriconazole and other triazole treatments.

Successful management of bilateral total hip replacement in a patient with von Willebrand's disease and developmental hip dysplasia

formation of electrostatic contacts between the preferred guanidyl group of Arg at the P1 position in the substrate. The proband showed a compound (or double) heterozygous mutation in prothrombin gene. In 1954 Dr. van Creveld, who was a fellow-countryman of the family we described, proved for the first time that prothrombin deficiency was a hereditary disease and stated: prothrombin is a very complex protein, with many unknown characteristics [4]. To date, almost 60 years later, this is still true from a medical and biochemical point of view. In naturally occurring mutations, a clear genotype–phenotype relation is not often identified. Also there often is a discrepancy between the clinical severity of this disease and the in vitro determined coagulant activity [5]. New mutations, especially those of a type II phenotype, can help to understand the mechanisms and the role of prothrombin in haemostasis and thrombosis.

Effect of prothrombotic mutations on factor consumption in children with hemophilia.

Introduction: In hemophilia A, factor activity usually correlates with clinical severity; however, there are patients with severe hemophilia who have bleeding less than expected. Aim: The aim of this study is to evaluate the impact of prothrombotic mutations on annual factor consumption in children with hemophilia. Methods: Factor V Leiden (FVL) G1691A, Prothrombin (PT) G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T and A128C mutations were evaluated in children with moderate–severe hemophilia A (n = 51) and controls (n = 25). Results: None of the cases and controls carried the FVL and PT G20210A in homozygous state. There was no difference in factor consumption between carriers of FVL, PT mutations, and noncarriers. Patients who were homozygous for MTHFR C677T were found to have increased factor consumption compared to noncarriers, and this was a negative association. No decrease in factor consumption was noted in patients with hemophilia having MTHFR A1298C mutation. Conclusion: We could not demonstrate a significant decrease in factor concentrate consumption in children with hemophilia having prothrombotic mutations.

Reduced early prophylaxis of children with haemophilia in a developing country, Turkey

CB and KK have received reimbursement for travel expenses and speaking honoraria by Biotest AG. CEE has acted as a paid speaker to Biotest AG and has received reimbursement for attending symposia as well as fees for consulting. WK has received research funding from Biotest AG. CM has received reimbursement for attending symposia and speaker fees from Biotest AG. LN has received fees for speaking and reimbursement for attending symposiums from Biotest AG.

PSEUDOPROGRESSION AFTER RADIOTHERAPY WITH CONCURRENT TEMOZOLOMIDE IN A CHILD WITH ANAPLASTIC ASTROCYTOMA

In their article “Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiaton with temozolomide,” Walter Taal et al. [1] describe tumor progression in patients with malignant glioma treated with concurrent temozolomide (TMZ) and radiotherapy (RT). Of 85 patients treated with this regimen, 18 (50%) were diagnosed with pseudoprogression. Recently, Brandes et al. [2] published data regarding correlation of pseudoprogression with O6-methylguanine-DNA methyltransferase (MGMT) methylation status. It was also postulated that, on average, 7 months was required for clinical resolution of pseudoprogression and there is diffuculty in clinically distinguishing pseudoprogression from true progression. We recently treated a 5-year-old boy with anaplastic astrocytoma (AA) who deteriorated after approximately 4 weeks of RT with concurrent TMZ. He was first admitted with a 1-month history of intermittent bouts of generalized headache, often accompanied by vomiting. Initial cranial magnetic resonance imaging (MRI) scan showed a bilateral thalamic tumor with obstructive hydrocephalus. Debulking surgery with ventriculoperitoneal shunt was performed and histopathology revealed a highly cellular AA with increased mitotic figures (World Health Organization [WHO] Grade III). Cerebrospinal fluid (CSF) was positive with abundant tumor cells. He was treated by RT concomitant with vincristine and triple intrathecal (IT) injections (methotrexate [12 mg], cytarabine [30 mg], and prednisone [10 mg]). As CSF continued to be positive for tumor cells and there was no clinical

Parvovirus B19 infection mimicking juvenile myelomonocytic leukemia

We read with great interest ‘‘Transient leukoerythroblastosis in a very low birth weight infant with parvovirus B19 infection’’ by Duran et al. The authors describe a preterm infant with transient leukoerythroblastosis associated with a parvovirus B19 infection. Parvovirus B19 is a widespread virus, which shows tropism to bone marrow, particularly erythroid progenitor cells. In immunocompetent children, parvovirus B19 is the cause of erythema infectiosum. Transient hemolytic crisis is seen in those who have an underlying hemolytic disease. Parvovirus B19 is also a cause of cytopenia in children who have a congenital or acquired immune deficiency, such as organ transplant recipients and cancer patients. Leukoerythroblastosis is a rare disease that is characterized by leukocytosis and the presence of erythroid and myeloid blasts in the peripheral blood. The most common causes in children are viral infections and juvenile myelomonocytic leukemia (JMML). It can also be observed following osteopetrosis, myelofibrosis, and neuroblastoma. We report the case of a 2-month-old baby with a parvovirus B19 infection who initially presented with features of JMML. The patient was a twin pair male, born to non-related parents, weighing 2400 g. The prenatal and birth histories were unremarkable. He developed vomiting and reduced sucking on day 3 of life and was admitted to the neonatal intensive care unit with a diagnosis of sepsis. He was referred to our Pediatric Gastroenterohepatology Department with a distended abdomen and hepatosplenomegaly, which developed on follow-up.