Quantitative and/or qualitative deficiency of von Willebrand factor (vWF) is associated with the most common inherited bleeding disease von Willebrand disease (vWD). vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD.

OBJECTIVE: T-cell acute lymphoblastic leukemia (T-ALL) is associated with recurrent chromosomal aberrations and abnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALL this study aimed to measure the level of expression of 7 T-cell oncogenes (LMO2, LYL1, TAL1, TLX1, TLX3, BMI1, and CALM-AF10) in pediatric T-ALL patients.
METHODS: LMO2, LYL1, TLX1, TLX3, BMI1, TAL1, and CALM-AF10 expression was measured using quantitative real-time PCR in 43 pediatric T-ALL patients.
RESULTS: A high level of expression of LMO2, LYL1, TAL1, and BMI1 genes was observed in a large group of T-ALL. Several gene expression signatures indicative of leukemic arrest at specific stages of normal thymocyte development (LYL1 and LMO2) were highly expressed during the cortical and mature stages of T-cell development. Furthermore, upregulated TAL1 and BMI1 expression was observed in all phenotypic subgroups. In all, 6 of the patients had TLX1 and TLX3 proto-oncogene expression, which does not occur in normal cells, and none of the patients had CALM-AF10 fusion gene transcription. Expression of LYL1 alone and LMO2-LYL1 co-expression were associated with mediastinal involvement; however, high-level oncogene expression was not predictive of outcome in the present pediatric T-ALL patient group, but there was a trend towards a poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 protooncogene expression.
CONCLUSION: Poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 proto-oncogene expression indicate the need for extensive study on oncogenic rearrangement and immunophenotypic markers in T-ALL, and their relationship to treatment outcome.

OBJECTIVE: The aim of our study is to discuss the efficacy of low-density lipoprotein-cholesterol (LDL-C) apheresis procedure using the cascade filtration system for pediatric patients with homozygous familial hypercholesterolemia (FH), and to clarify the adverse effects and difficulties.
METHODS: LDL apheresis using the cascade filtration system was performed in 3 pediatric patients with homozygous FH. In total, 120 apheresis sessions were performed for all patients.
RESULTS: Cascade filtration therapy significantly reduced the mean LDL-C values from 418 ± 62 mg/dl to 145 ± 43 mg/dl (p<0.05). We determined an acute mean reduction in the plasma levels of total cholesterol (57.9%), LDL cholesterol (70.8%), and high-density lipoprotein (HDL) cholesterol (40.7%). Treatments were well tolerated. The most frequent clinical adverse effects were hypotension in 3 sessions (2.5%), chills/feeling cold (1.7%) in 2 sessions, and nausea and vomiting in 3 sessions (2.5%).
CONCLUSION: Our experience with three patients using the cascade filtration system were, good clinical outcomes, laboratory findings, safety of usage, minor adverse effects and technical problems.

OBJECTIVE: The aim of this study was to determine the pattern of hematological malignancies at Al-Gamhouria Teaching Hospital from 2008 to 2010.

METHODS: Hematological malignancies diagnosed at Al-Gamhouria Teaching Hospital, Department of Hematology-Oncology from January 2008 to December 2010 based on available hematological laboratory methods and histological examination were retrospectively analyzed. Clinical diagnoses were based on history and physical examination. Complete blood count was performed in all patients, bone marrow aspiration was performed in leukemia and multiple myeloma patients, and histopathological examination was performed in cases of malignant lymphoma.
RESULTS: Malignant hematological disorders were diagnosed in 300 patients aged 18-80 years (mean age: 43.6 years) with a male: female ratio of 1.23: 1. Among the male patients the most common malignant disorder was non-Hodgkin’s lymphoma, followed by Hodgkin’s lymphoma and acute myeloid leukemia. Among the female patients the most common malignant disorder was non-Hodgkin’s lymphoma, followed by acute myeloid leukemia, and Hodgkin’s lymphoma. The study provides the frequencies for the main hematological disorders and present the different subtypes of the Hodgkin’s and non-Hodgkin’s lymphomas.
CONCLUSION: The most common hematological malignancies in male patients were Non-Hodgkin’s lymphomas followed by Hodgkin’s lymphoma and acute myeloid leukemia. Gender distribution showed male predominance with striking predominance in Hodgkin’s lymphomas (M: F Ratio of 1.9: 1).

OBJECTIVE: At present in Turkey, centers that are able to give reliable RQ-PCR BCR-ABL results are limited in number. We aimed to describe a cost-effective, in-house method for BCR-ABL quantification and to illustrate an example for RQ-PCR validation tests.
METHODS: BCR-ABL and ABL target sequences were cloned into pJET1.2 vectors; from which calibrators were prepared and used as templates in RQ- PCR reactions to generate standard curves. Dilutions of K562 cells (representing an in vitro simulation of BCR-ABL transcript reduction) were analyzed.
RESULTS: Previously determined standard curves were used to calculate the BCR-ABL and ABL copy numbers. Linear BCR-ABL results were obtained. Repetitive experiments showed that our methodology is able to detect one BCR-ABL positive cell in a total of 1x105 cells.
CONCLUSION: The approach described in this manuscript is suitable for implementation into any RQ-PCR instrument and/or kit aiming to quantify BCR-ABL transcripts.

OBJECTIVE: The aim of this study was to assess the prognostic value of CD49d expression in Turkish chronic lymphocytic leukemia patients.

METHODS: Data for 118 patients from a single center were evaluated. In all, the study included 73 patients for whom complete clinical follow-up data, and flow cytometry test results for CD5/19, CD23/43, CD38, Zap- 70, Kappa, and Lambda light chains, and CD49d were available. The effect of the level of CD49d expression on overall survival (OS) and time to treatment (TTT) was investigated retrospectively.
RESULTS: Patients with high CD49d expression (≥30%) had more advanced disease at the time of diagnosis (median Rai stage 3 vs. Rai stage 1, P = 0.03). Patients resistant to treatment had higher CD49d expression than patients that responded to treatment (mean CD49d expression of 58% vs. 46%, P = 0.08). The level of CD49d expression was not associated with OS or TTT.

CONCLUSION: The study’s findings show that the patients with high CD49d expression at the time of diagnosis had more advanced disease and poorer response to therapy; however, their overall survival did not differ from that of the patients with advanced disease stage, but lower levels of CD49d expression.

OBJECTIVE: Ankaferd Blood Stopper (ABS) comprises a mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum ve Urtica dioica. ABS has been used as a topical haemostatic agent because of its antihaemorrhagic effect. Its haemostatic mechanism of action remains to be investigated. ABS does not affect individual levels of the coagulation factors II, V, VII, VIII, IX, X, XI and XIII. The aim of this study was to investigate the effects of ABS on endothelium and immune response. So, we investigated the possible changes in EPCR and PAI-1 without and with LPS-challenge inside HUVECs.
METHODS: 10 μL and 100 μL ABS is given to HUVECs in 5 min., 25 min., and 50 min.,6 hour and 24 hour time periods. 10 μg/ mL LPS has been added for one hour to observe the effects of LPS challenge on HUVECs and then the cells have been treated with ABS for the time period of 5 min., 25 min., 50 min. and 6 hours to observe ABS-effects on HUVECs. Total RNAs were isolated from HUVECs and then EPCR ve PAI-1 mRNA expression levels were investigated.
RESULTS: It was microscopically observed that cells arised from the surface and adhered to each other after the ABS application to the HUVECs. Also, after 24 hours cells returned the normal growth and physiology. It suggests that the adhesive cellular functions of ABS may be reversible. 10 µl ABS have negative effect on EPCR and PAI-1 expressions. Moreover the effects increases with 100 µl ABS. EPCR and PAI-1 expression increased by time with LPS and 10 µl ABS. Expressions were very low during the first hour when LPS and 100 µl ABS were given but at the end of 6 hour, EPCR and PAI-1 expression increased similar to LPS and 10 µl ABS experiment.
CONCLUSION: In this study, we observed that Ankaferd has dual diverse dynamic reversible actions depend on dose and concentration on EPCR and PAI-1 inside vascular endothelial cells in the model of HUVEC. ABS might have a role on numerous cellular mechanisms as well as its hemostatic actions.

OBJECTIVE: Coagulation tests are influenced by pre-analytic conditions such as blood collection systems. Change of glass collection tubes with plastic ones will cause alteration of the test results.
The aim of this study was to compare three plastic blood collection tubes with a standard glass blood collection tube and each plastic collection tube with the other two for possible additional tube-to- tube differences.
METHODS: A total of 284 blood samples were obtained from 42 patients receiving warfarin during their routine controls, besides 29 healthy volunteers. Subgroup analyses were done according to health status.
RESULTS: Our study demonstrated that different blood collection tubes have a statistically significant influence on coagulation tests. The magnitude of the effect depends on the tube used. However most of the tests performed on samples obtained from any tube correlated significantly with results obtained from other tube samples.
CONCLUSION: Although blood collection tubes with different brands or properties will have distinct effects on coagulation tests, the influence of these blood collection tubes may be relatively small to interfere with decision-making on dose prescription, therefore lack clinical importance. Correlations between the results showed that, one of these plastic blood collection tubes tested in our study, can be used interchangably for a wide variety of coagulation assays.

OBJECTIVE: To investigate the prognostic significance of cytogenetic abnormalities, staging, patient factors, and the serum p53 protein concentration in Chinese non-Hodgkin lymphoma (NHL) patients.
METHODS: The study included 43 patients with NHL that were identified between August 2003 and December 2008. Patient clinical characteristics patients were determined based on morphological, immunohistochemical, and cytogenetic analysis, and the serum p53 protein concentration was measured quantitatively.
RESULTS: Following conventional chemotherapy, the complete/partial remission (CR/PR) rate was significantly higher and overall survival (OS) was significantly longer in the patients with early-stage (stage I-II) lymphoma, normal karyotype, and a low serum p53 protein concentration than in those with advanced-stage (stage III-IV) lymphoma, cytogenetic abnormalities, and a high serum p53 protein concentration (≥0.35 U/mL). Bone marrow infiltration was also a predictor of poor response and OS. There weren’t any significant differences in disease remission between the male and female patients, older and younger patients (aged <70 years vs. ≥70 years), or B-cell lymphoma and T-cell lymphoma patients.
CONCLUSION: Staging is an effective means of assessing the severity of NHL. Cytogenetic examination can provide useful information for diagnosis, staging, and prognostication. The serum p53 protein level may be a potential prognostic marker in patients with NHL.

OBJECTIVE: Immunoglobulin free light chain (FLC) abnormalities are frequent in patients with monoclonal gammopathies and kidneys are the most affected organs in these patients. Immunoassays which provide quantitative measurement of FLC in serum, indicate monoclonal FLC production by the presence of an abnormal κ to λ FLC ratio. The aim of this study was to assess the serum FLC measurement as a diagnostic tool for detecting plasma cell dyscrasias to compared with standart assays and ascertain its sensitivity and specificity in patients with acute renal failure (ARF).
METHODS: Sera from 82 patients with ARF were assessed by serum protein electrophoresis (SPE), serum immunofixation electrophoresis (SIFE) and FLC measurements. The sensitivity and specificity of the FLC ratio for identifying patients with multiple myeloma (MM ) and ARF was compared with SPE and SIFE results.
RESULTS: Of 82 patients who were presented with ARF, seven diagnosed multiple myeloma by using serum protein electrophoresis, immunofixation electrophoresis, and bone marrow biopsy tecniques. Of cases 8 patients had not have κ/λ ratio within the published reference range (0.26-1.65); κ/λ ratio based on FLC measurements had 96 % specificity, 71% sensitivity and 62.9 % positive predictive and 97.3% negative predictive value for myeloma diagnoses.
CONCLUSION: Patients with MM who were presented with acute renal failure had low sensitivity and specificity for к/λ FLC ratio compared to SPE and SIFE. As a consequence of making a more accurate comment about this method, prospective, well-designed and more patient population studies are needed.

Fludarabine monophosphate is an effective drug for the treatment of lymphoid malignancies. Myelosuppression, opportunistic infections, and autoimmune hemolytic anemia are the most common side effects of fludarabine. Herein we report a 55-year-old female that presented with fever and dyspnea after completing her third cycle of FMD (fludarabine, mitoxantrone, and dexamethasone) chemotherapy for stage IV non-Hodgkin follicular lymphoma. Chest X-ray revealed bilateral pneumofibrotic changes and chest CT showed bilateral diffuse interstitial changes with fibrotic alterations. No evidence of infectious agents was noted. The patient had a reduced carbon monoxide transfer factor (45%). Her symptoms and radiographic findings resolved following treatment with prednisolone. The literature contains several cases of fludarabine-associated interstitial pulmonary toxicity that responded to steroid therapy. Fludarabine-induced pulmonary toxicity is reversible with cessation of the drug and administration of glucocorticosteroids.

Both leukocytoclastic vasculitis and metastatic pulmonary calcification are conditions that rarely occur during the course of multiple myeloma. We present a multiple myeloma patient that had severe dyspnea due to metastatic pulmonary calcinosis, and ulceronecrotic skin lesions caused by leukocytoclastic vasculitis. After 3 courses of standarddose chemotherapy all skin and pulmonary lesions disappeared. Autologous peripheral stem cell transplantation was performed and during 1 year of follow-up the patient was in complete remission; after 1 year, laboratory test results indicated disease relapse. Although the patient was treated with bortezomib and dexamethasone, the disease progressed. Non-myeloablative allogeneic stem cell transplantation was performed, but despite of all treatment the patient died due to disease progression.

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening condition. Uncontrolled proliferation of activated lymphocytes secreting high amounts of inflammatory cytokines seems to be the main pathogenesis. The diagnosis of HLH can often be difficult. It may presents in many forms such as fever of unknown origin, hepatitis, acute liver failure, and sepsis-like illness. Here we present a newborn galactosemia case presented with HLH. Close monitoring of the diagnostic criteria of HLH during the course of galactosemia-associated hemophagocytosis, both before and after dietary treatment, should be performed in order to fully determine if the triggering mechanism is infection or accumulation of metabolites.

The outcome in patients with chronic myeloid leukemia (CML) has dramatically improved over the last decade due to the widespread use of novel tyrosine kinase inhibitors such as imatinib. As overall survival has improved, the number of women with CML that wish to become pregnant has increased. As such, attending physicians are faced with a dilemma-continue life-prolonging medication to treat the cancer, or interrupt its use due to its potential teratogenicity. Herein we describe 2 CML patients that gave birth. Case 1 was managed via substitution of imatinib with interferon. The patient’s child underwent genetic evaluation at age 3 years, achieved normal developmental milestones, and despite being shorter than his peers was proportional. In terms of morphology, the child had clinodactyly, short fifth fingers, and slightly downward slanting palpebral fissures, but otherwise appeared normal. In case 2 imatinib was continued throughout the pregnancy. This patient’s child underwent postpartum evaluation by a geneticist and was observed to be morphologically normal, except for clinodactyly and low-set ears.

Currently, Steroid refractory severe gastrointestinal (GI) GVHD is one of the important complications in patients undergoing allogeneic transplantation and there has been no standard therapeutical approach of disease yet. We report here the results related to the application of intramesenteric steroid in two cases with steroid refractory GI GvHD. In both cases, the frequency and volume of diarrhea were completely resolved soon after intramesenteric methylprednisolone (MP) injection. In conclusion, intra-arterial steroid injection might be an alternative approach especially steroid refractory GI GvHD.

Nasal-type natural killer (NK)/T-cell lymphoma (NKTL) is a rare disease strongly associated with Epstein-Barr virus and is often localized to the upper aerodigestive tract at presentation. Extranodal NKTL may involve any extranodal site and disease beyond the nasal cavity is highly aggressive, with short survival time and poor response to therapy. Herein we present a 57-year-old male that had been treated with systemic chemotherapy and cranial radiotherapy for nasaltype NKTL in the palate with skin, right eye, and right peroneal nerve involvement. He was given salvage chemotherapy consisting of 3 cycles of ICE and his response to the therapy was satisfactory, except for persistent right drop foot. About 6 weeks later, the patient presented with bilateral total loss of vision and proptosis; therefore, DHAP chemotherapy was started. Unfortunately, after 1 cycle of the second salvage chemotherapy, he died due to severe fungal infection of the hard palate.
Despite the fact that involvement of any extranodal site is possible, concurrent involvement of many systems in NKTL patients is unusual. Nasal-type NKTL has a poor prognosis, despite local radiotherapy and systemic chemotherapy. Physicians should be aware of this rare disorder than can only be diagnosed after extensive immunohistochemical studies.