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  • 1
    In: Blood Coagulation & Fibrinolysis, Ovid Technologies (Wolters Kluwer Health), Vol. 24, No. 8 ( 2013-12), p. 854-861
    Type of Medium: Online Resource
    ISSN: 0957-5235
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2035229-3
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  • 2
    Online Resource
    Online Resource
    SAGE Publications ; 2012
    In:  Clinical and Applied Thrombosis/Hemostasis Vol. 18, No. 6 ( 2012-11), p. 588-593
    In: Clinical and Applied Thrombosis/Hemostasis, SAGE Publications, Vol. 18, No. 6 ( 2012-11), p. 588-593
    Abstract: Congenital factor VII deficiency is the most common form of rare coagulation factor deficiencies. This article presents a retrospective evaluation of 73 factor VII deficiency cases that had been followed at our center. The study consisted of 48 males and 25 females (2 months-19 years). Thirty-one (42.5%) of them were asymptomatic. Out of symptomatic patients, 17 had severe clinical symptoms, whereas 8 presented with moderate and 17 with mild symptoms. The symptoms listed in order of frequency were as follows: epistaxis, petechia or ecchymose, easy bruising, and oral cavity bleeding. The genotype was determined in 8 patients. Recombinant activated factor VII (rFVIIa) was used to treat 49 bleeding episodes in 8 patients after 2002. In 2 patients with repeated central nervous system bleeding prophylaxis with rFVIIa was administered. No allergic and thrombotic events were observed during both treatment and prophylaxis courses. Antibody occurrence was not detected in the patients during treatment.
    Type of Medium: Online Resource
    ISSN: 1076-0296 , 1938-2723
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
    detail.hit.zdb_id: 2230591-9
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Blood Coagulation & Fibrinolysis Vol. 26, No. 2 ( 2015-03), p. 145-151
    In: Blood Coagulation & Fibrinolysis, Ovid Technologies (Wolters Kluwer Health), Vol. 26, No. 2 ( 2015-03), p. 145-151
    Type of Medium: Online Resource
    ISSN: 0957-5235
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
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  • 4
    In: Clinical and Applied Thrombosis/Hemostasis, SAGE Publications, Vol. 24, No. 6 ( 2018-09), p. 901-907
    Abstract: Congenital factor deficiencies (CFDs) refer to inherited deficiency of coagulation factors in the blood. A total of 481 patients with CFDs, who were diagnosed and followed at our Pediatric Hematology and Oncology Clinic between 1990 and 2015, were retrospectively evaluated. Of the 481 cases, 134 (27.8%) were hemophilia A, 38 (7.9%) were hemophilia B, 57 (11.8%) were von Willebrand disease (vWD), and 252 (52.3%) were rare bleeding disorders (RBDs). The median age of the patients at the time of diagnosis and at the time of the study was 4.1 years (range: 2 months to 20.4 years) and 13.4 years (range: 7 months to 31.3 years), respectively. The median duration of the follow-up time was 6.8 years (range: 2.5 months to 24.8 years). One hundred nineteen (47.2%) of 252 patients with RBDs were asymptomatic, 49 (41.1%) of whom diagnosed by family histories, 65 (54.6%) through preoperative laboratory studies, and 5 (4.2%) after prolonged bleeding during surgeries. Consanguinity rate for the RBDs was 47.2%. Prophylactic treatment was initiated in 80 patients, 58 of whom were hemophilia A, 7 were hemophilia B, 13 were RBDs, and 2 were vWD. Significant advances have been achieved during the past 2 decades in the treatment of patients with CFDs, particularly in patients with hemophilias. The rarity and clinical heterogeneity of RBDs lead to significant diagnostic challenges and improper management. In this regard, multinational collaborative efforts are needed with the hope that can improve the management of patients with RBDs.
    Type of Medium: Online Resource
    ISSN: 1076-0296 , 1938-2723
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
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  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4933-4933
    Abstract: Background: Management of surgical procedures in people with hemophilia (PwH) has always been a major concern. Insufficient hemostatic control might be an important cause of morbidity and mortality. However, the success of surgical procedures does not only depend on appropriate replacement of the missing factor. Pre- and post-operative interventions, laboratory monitoring, care and rehabilitation of the patient are important. Therefore, surgical procedures in hemophilia patients should be performed in full-fledged hospitals capable of providing a multidisciplinary approach as a "Comprehensive Hemophilia Treatment Center". The aim of our study is to evaluate the outcomes of major surgical procedures (MSPs) among PwH who were followed at Cerrahpasa Medical Faculty. Methods: All MSPs performed on PwH between 2004 and 2017 were included. Baseline activated partial thromboplastin time (aPTT)and factor levels prior to MSP, inhibitor screening and (if any) the inhibitor titration results together with complete blood count, blood group and liver function tests were retrospectively obtained from patient files. The type of MSP, amount of factor concentrates given prior to, during and after the operation, the factor levels and aPTT results following factor replacement; complications developing during or after surgery, and information on the type of treatment modality prior to surgery (on demand vs. prophylaxis) were noted. The amount of factor concentrates administered to patients was determined in units per kilogram. Results: Of the 39 patients included in the study (37 hemophilia A and two hemophilia B) 20 were severe, 7 were moderate and 12 were mild hemophilia (Table 1). The median age at the time of MSP was 37 (20-61) years. A total of 49 MSPs were performed, two patients had 3 surgeries, six patients had 2 surgeries, and 30 patients had one surgery. Fifteen surgical procedures were performed in two, one surgical procedure was performed in three, and 33 operation procedures were performed in one operation area. There were no significant differences in complication rates between hemophilia types (A vs. B), severities (severe vs. moderate vs. mild) and number of operated regions (1 vs. 〉 1). In our study, general surgery (n=15) and orthopedic (n=10) operations were the most frequently performed MSPs (Table 2). There was no significant difference in complication rates among surgical branches. Complications were observed in a total of 6 (12%) MSPs, and one patient was deceased due to sepsis. Complication rates were 16% and 11% for MSPs done in PwH with and without inhibitors, respectively (p=non-significant). Factor consumption (U/kg) was highest in patients undergoing orthopedic surgery, followed by cardiovascular and neurosurgical operations. Factor utilization was significantly less for operations done in general surgery, urology and ear, nose and throat departments (p 〈 0.001). There was a significant positive correlation between factor consumption and duration of hospitalization (r = 0,690; p 〈 0.001). The data on the type of factor were available in 36 MSPs. Surgical procedures were carried out using plasma-derived and recombinant factor concentrates only in 26 and 5 patients, respectively. In the remaining 5, plasma-derived and recombinant factor concentrations were alternately applied. No statistically significant difference was noted with regard to the type of the factor used (plasma-derived, recombinant and plasma-derived/recombinant) and the duration of hospitalization or the complication rate. Number of days spent in the hospital were significantly higher in patients with complications than those without (16 vs. 9.5 days; p=0.003). Conclusion: The results of our retrospective study, being consistent with the current literature, clearly demonstrates that, in experienced comprehensive care centers MSPs can effectively and successfully be performed in PwH, even in those with inhibitors. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 6
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4600-4600
    Abstract: Introduction and Objectives: For patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP), four baseline prognostic scores are commonly used including the Sokal score and the most recently introduced EUTOS long-term survival (ELTS) score. The ELTS score was shown to be superior to the Sokal score for predicting survival. The aim of the study is to evaluate the value of ELTS score on predicting disease progression and survival in Turkish pts with CML-CP. Material and Method: Demographic, laboratory and clinical features, disease responses to tyrosine kinase inhibitor (TKI) therapy and survival of CML-CP pts, who received upfront imatinib (IM) between 2003 and 2018 were analyzed retrospectively. Treatment responses were reevaluated according to European LeukemiaNet 2013 recommendations. Risk groups analysis, discrimination and hazard ratios (HRs) were evaluated with Cox regression and Kaplan-Meier survival analysis. Receiver operating characteristic (ROC) analysis was performed to examine the effects of scores on predicting overall survival (OS) and progression-free survival (PFS). Results: A total of 185 pts were included, of which 103 (55.7%) were male and median age was 47 years (range, 16 - 81 years) (Table 1). The percentages of pts with low-, intermediate-, and high-risk ELTS scores were 60.5%, 25.9%, and 13.5%, respectively. For the Sokal score, these percentages were 37.3%, 40.5%, and 22.2% respectively. For Sokal high-risk pts, only 46.3% were classified as high-risk according to the ELTS score. Similarly, 44% of pts with intermediate Sokal risk had low-risk ELTS score (Fig. 1). Seventy-seven pts (41.6%) had at least one comorbidity, and the most common comorbidities were hypertension (21.6%), diabetes mellitus (13%), and ischemic heart disease (12.4%) (Table 1). The median durations of IM therapy and follow-up were 2728 (range, 14 - 6320 days) and 3473 (range, 71 - 6320 days) days, respectively. Complete hematologic and early molecular (BCR-ABL1 IS & lt;10% at 3 months) responses at 3 months were 95.6% and 75.9%, respectively. Complete cytogenetic and major molecular response rates at 6 and 12 months were 72.3% and 86.1% and 45.4% and 54%, respectively. Thirty-five pts (18.9%) switched to second-generation TKI therapy and 6 pts (3.2%) progressed to advanced-phase disease during the follow-up (Table 1). For PFS, with reference to the low-risk Sokal score, the HR of high-risk groups was 9.301 (95% CI: 1.086-79.656, p=0.042) (Fig. 2A). Similarly, with reference to the low-risk ELTS score, the HR of intermediate- and high-risk groups were 4.744 (95% CI: 0.43-52.314, p=0.204) and 14.642 (95% CI: 1.523-140.791, p=0.020) (Fig. 2B). Regarding OS, with reference to the low-risk Sokal score, the HR of the intermediate- and high-risk groups were 1.835 (95% CI: 0.564-5.964, p=0.313) and 6.412 (95% CI: 2.11-19.489, p=0.001), respectively (Fig. 2C). With reference to the low-risk ELTS score, the HR of the intermediate- and high-risk groups were, 3.263 (95% CI: 1.242-8.576, p=0.016) and 7.258 (95% CI: 2.762-19.074, p & lt;0.001) respectively (Fig. 2D). In the ROC analysis, the ELTS score was superior than the Sokal risk score for both predicting PFS (AUC=0.820 vs. AUC=0.818) and OS (AUC=0.762 vs. AUC=0.744). During the follow-up, 27 (14.6%) pts died, of which 6 died due to CML progression and causes of death were unrelated to CML in 21. Conclusion: In our study, we showed that the ELTS score could successfully predict high-risk pts compatible with the literature. With higher hazard ratios and better risk group stratifications, the ELTS score outperformed the Sokal score. The ELTS score can help clinicians to better discriminate poor prognostic pts and can promote optimal treatment strategies for these pts with potentially worse prognosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 7
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4541-4541
    Abstract: Introduction: The prognosis of classical Hodgkin lymphoma (cHL) is generally inferior in elderly patients (pts) than in younger pts. Tolerance of conventional therapy decreases in elderly pts, and in addition, treatment-related toxicities and death are more common. While the 5-year overall survival (OS) of pts with cHL is 86.6%, this rate is 57.5% in elderly pts. Objective and Methods: The aim of this study was to retrospectively evaluate the demographic, histopathological, clinical, and laboratory features, prognosis determination according to German Hodgkin Study Group (GHSG) in early-stage, International Prognostic Score (IPS)-3 and IPS-7 in advanced-stage, ECOG (Eastern Cooperative Oncology Group) performance scale (PS), Cumulative Disease Rating Score (CIRS) , Charlson Comorbidity Index (CCI), Adult Comorbidity Evaluation-27 (ACE-27) values, treatment responses, toxicities, and survival among cHL pts aged 50 years and older who were diagnosed between 1999 and 2020. Results: There were 101 pts in total, of which 52 were between 50-59 years of age, and 49 pts were ≥60 years. Sixty-two pts were male, and the most common histopathological subtype was mixed cellularity CHL with 58.4%. Fifty-four pts had advanced-stage disease, while there were 31 and 16 pts with early-stage unfavorable and favorable diseases, respectively. Sixty-one pts (60.4%) had B symptoms (Table 1). ECOG PS, CIRS, CCI, and ACE-27 scores were significantly higher in pts aged ≥60 years than those of 50-59 age group (Table 2). While all pts aged 50-59 years received ABVD as first-line therapy, 79% (n=39) of pts aged ≥60 years had ABVD. Among pts receiving ABVD as a first-line treatment, 82% (n=41) of pts aged 50-59 years and 73.2% (n=30) of pts aged ≥60 years had complete response following first-line treatment (p=0.312). Overall, at interim evaluation, response rates to first-line therapy were significantly higher in pts with IPS-7 value 0-3 (71.8%) than those with IPS-7 value 4-7 (42.9%) (p=0.028). While full-dose treatment was administered to 71 pts (70.3%), 30 pts (29.7%) needed a dose reduction. The percentage of pts needed a dose reduction was 38.8% among pts ≥60 years, whereas this was 21.2% for pts aged 50-59 years (p=0.053). During the follow-up, grades 3-4 hematological and non-hematological toxicities were observed in 50 (49.5%) and 15 pts (14.9%), respectively. Age groups were comparable in terms of hematological and non-hematological toxicities (p=0.369, p=0.127, respectively). None of the pts in the ≥60 age group had received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDC with AHSCT)/allogeneic hematopoietic stem cell transplantation (allo-HSCT). On the other hand, 8 pts (15.4%) diagnosed between 50-59 years of age underwent HDC with AHSCT, in one patient (1.9%) allo-HSCT was performed, and one patient (1.9%) received both HDC with AHSCT and allo-HSCT (p=0.004). There was no significant difference in terms of OS between those with and without transplantation (p=0.069). In the multivariate analysis, the risk of progression was higher in pts with lymphocyte ≤600/mm 3 and the risk of mortality was higher in pts with B symptoms (p=0.002, p=0.012, respectively). In addition, progression-free survival (PFS) was inferior in pts who were unresponsive to first-line treatment, and worse OS was associated with higher age and CIRS (p & lt;0.001, p=0.001, p=0.038, respectively) (Fig. 1A-C). During their follow-up, 26 pts (25.7%) died, and the causes of death could be determined in 19 of them. The most common cause of death was treatment complications (n=7). Secondary malignancies were detected in 5 pts, of which 3 died. In 2 pts, the cause of death was HL-related, and 7 pts died due to other causes. Conclusion: Although not statistically significant, the percentage of pts needing a dose reduction was higher in pts aged ≥60 years, on the other hand, treatment responses and toxicities were similar in both groups, most probably due to personalized treatment selection and dose reduction according to age, comorbidities, and the performance status. Pts undergoing a transplant had a more favorable outcome than pts without a transplant, but the difference did not reach statistical significance. Response to first-line therapy was associated with superior PFS, and pts with higher age and CIRS had inferior OS. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 8
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 97-97
    Abstract: Abstract 97 Von Willebrand Factor (VWF) is a multimeric glycoprotein that maintains hemostasis in the vascular system. VWF is secreted mainly from endothelial cells. During its biosynthesis VWF undergoes a series of post-translational modifications and some of the newly synthesized protein is released constitutively. The remainder of the protein is stored for regulated release from cytoplasmic storage granules, Weibel Palade Bodies. Abnormalities in the biosynthetic pathway or increased clearance of plasma VWF are likely to contribute to decreased plasma VWF levels. Inherited partial deficiency of VWF is classified as Type I von Willebrand disease (VWD). Clinical diagnosis of Type I VWD is complicated due to incomplete penetrance and variable expressivity of the abnormal VWF phenotype. The molecular basis of Type 1 VWD remains incompletely understood. The purpose of this study is to explore the effect of four VWF missense mutations (p.M771I, p.L881R, p.P1413L, p.Q1475X), that were reported as candidate mutations in Type I VWD patients in the ISTH SSC VWF Database. The focus of these studies is on the intracellular biosynthetic processing and localization of VWF in a heterologous cell system. For this purpose, selected VWF gene variations were generated in a VWF cDNA expression vector by in vitro site directed mutagenesis. The effect of the candidate mutations on the intracellular localization were analyzed in HEK293 cells by immunoflourescence antibody staining and confocal microscopy. In addition, the effect of the mutations on the biosynthesis of the recombinant VWF was analyzed in COS-7 cells The expression vectors WT-cDNA (wild type) and the expression vector carrying the candidate mutations were transiently transfected into COS-7 cells alone or together to generate wild-type, mutant homozygous and heterozygous genotypes, the latter situation mimicking the status in type 1 VWD patients. To determine whether the mutant recombinant protein was retained within the cell or was efficiently secreted, VWF:Ag levels were assayed in cell lysates and in the conditioned media using ELISA. Confocal analysis of the transfected HEK293 cells demonstrated impaired intracellular localization of recombinant VWF having p.M771I and p.Q1475X variations. On the other hand, a normal pattern of intracellular storage was observed for the VWF variants having p.L881R and p.P1413L changes. Expression studies for the p.P1413L and p.Q1475X mutations are currently in progress. Transient transfection of COS-7 cells with the VWF expression vector carrying p.M771I mutation revealed that secretion of the recombinant VWF protein was decreased by 73% (P=0.013, n=3) in the homozygous state, and by 47% (P=0.013, n=3) in the heterozygous state relative to the secretion of wild-type recombinant VWF protein. Intracellular levels of the mutant recombinant protein was increased by 212% in the homozygous state (P=0.005, n=3) and by 69% in the heterozygous state (P=0.255, not significant, n=3). This study demonstrated that p.M771I mutation causes increased intracellular retention of the protein and it has a dominant negative effect on the processing of the wild type protein. Transient transfection of COS-7 cells with the VWF expression vector carrying p.L881R mutation revealed that secretion of the recombinant VWF protein was decreased by 10% (P=0.61, not significant, n=3) in the homozygous state, and increased by 47% (P=0.36, not significant, n=3) in the heterozygous state relative to the secretion of wild-type recombinant VWF protein. Intracellular levels of the mutant recombinant protein were increased by 58% in the homozygous state (P=0.925, not significant, n=3,) and decreased by 35% in the heterozygous state (P=0.405, not significant, n=3). This study demonstrates that in contrast to the findings with the p.M771I mutant, the p.L881R mutation has little effect on VWF biosynthesis and secretion and does not show a dominant negative effect on the wild type VWF. The pathogenetic mechanism responsible for the type 1 VWD phenotype associated with the p.L881R mutation requires additional evaluation but may involve enhanced protein clearance. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 9
    In: Hematology, Informa UK Limited, Vol. 23, No. 4 ( 2018-04-21), p. 212-220
    Type of Medium: Online Resource
    ISSN: 1607-8454
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2035573-7
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  • 10
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 19, No. 7 ( 2019-07), p. e377-e384
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 2540998-0
    detail.hit.zdb_id: 2193618-3
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