Browsing by Author "Olcay, Lale"

Now showing 1 - 14 of 14

Biochemical, Radiologic, Ultrastructural, and Genetic Evaluation of Iron Overload in Acute Leukemia and Iron-chelation Therapy
(2014) Olcay, Lale; Hazirolan, Tuncay; Yildirmak, Yildiz; Erdemli, Esra; Terzi, Yunus Kasim; Arda, Kemal; Ozturkmen, Seda; Akyay, Arzu; Kaymak-Cihan, Meric; Bicakci, Zafer; Bal, Ceylan; https://orcid.org/0000-0001-5612-9696; https://orcid.org/0000-0002-4480-7784; 23887025; B-4372-2018; ABI-7551-2020
Iron overload in hereditary hemochromatosis and hematologic malignancy has unfavorable effects on morbidity. Herein, 53 children (age 108.4 +/- 58.3 mo, 25 girls and 28 boys) with acute myeloblastic and lymphoblastic leukemia, who received 4 different chemotherapy protocols, were evaluated for iron overload throughout chemotherapy. Iron overload arose: (1) before chemotherapy, which was dependent on neither chemotherapy nor packed red blood cell transfusions and (2) after chemotherapy, which was dependent on the duration and nature of chemotherapy and partially on transfusion of packed red blood cells. Iron overload was documented in 75% of patients with a ferritin level >1000 ng/mL, by liver and heart magnetic resonance imaging, and they were administered iron-chelation therapy with success. Three of 10 radiologically iron-overloaded patients were heterozygous for H63D mutation. Aminolevulinic acid and porphobilinogen levels were normal. Light microscopic examination of the bone marrow revealed increased iron granules in erythroblasts, platelets, and megakaryocytes, iron-laden macrophages, free iron in the matrix, dyshematopoiesis, and apoptotic cells. Electron microscopic examination revealed iron-laden secondary lysosomes and autolysosomes in normoblasts and iron-laden primary granules in promyelocytes, irrelevant to the ferritin level, implying autophagia due to chemotherapy as a source of the excess iron. We think that iron overload, which is an important complication of acute leukemia, should be evaluated separately from transfusion overload, and the management principles specific to leukemia should be implemented.
Both Granulocytic and Non-Granulocytic Blood Cells Are Affected in Patients with Severe Congenital Neutropenia and Their Non-Neutropenic Family Members: An Evaluation of Morphology, Function, and Cell Death
(2018) Olcay, Lale; Unal, Sule; Onay, Huseyin; Erdemli, Esra; Ozturk, Aysenur; Billur, Deniz; Metin, Ayse; Okur, Hamza; Yildirmak, Yildiz; Buyukasik, Yahya; İkinciogullari, Aydan; Falay, Mesude; Ozet, Gulsum; Yetgin, Sevgi; 30040071
Objective: To examine granulocytic and non-granulocytic cells in children with severe congenital neutropenia (SCN) and their non-neutropenic parents. Materials and Methods: Fifteen patients with SCN and 21 non-neutropenic parents were evaluated for a) CD95, CD95 ligand, annexin V, propidium iodide, cell cycle, and lymphocyte subsets by flow cytometry; b) rapid cell senescence (of leukocytes) by senescence-associated beta-galactosidase stain; c) aggregation tests by aggregometer; d) in vitro bleeding time by PFA-100 instrument; e) mepacrine-labeled dense granule number of thrombocytes by fluorescence microscope; and f) hematomorphology by light and electron microscope. HAX1, ELANE, G6PC3, CSF3R, and JAGN1 mutations associated with SCN were studied in patients and several parents. Results: Significant increase in apoptosis and secondary necrosis in monocytes, lymphocytes, and granulocytes of the patients and parents was detected, irrespective of the mutation type. CD95 and CD95 ligand results implied that apoptosis was non-CD95-mediated. Leukocytes of 25%, 12.5%, and 0% of patients, parents, and controls showed rapid cell senescence. The cell cycle analysis testable in four cases showed G1 arrest and apoptosis in lymphocytes of three. The patients had HAX1 (n=6), ELANE (n=2), G6PC3 (n=2), and unidentified (n=5) mutations. The CD3, CD4, and NK lymphocytes were below normal levels in 16.6%, 8.3%, and 36.4% of the patients and in 0%, 0%, and 15.4% of the parents (controls: 0%, 0%, 5.6%). The thrombocytes aggregated at low rates, dense granule number/thrombocyte ratio was low, and in vitro bleeding time was prolonged in 37.5%-66.6% of patients and 33.3%-63.2% of parents (vs. 0% in controls). Under electron and/or light microscope, the neutrophils, monocytes, lymphocytes, and thrombocytes in the peripheral blood of both patients and parents were dysplastic and the bone marrow of patients revealed increased phagocytic activity, dysmegakaryopoiesis, and necrotic and apoptotic cells. Ultrastructurally, thrombocyte adhesion, aggregation, and release were inadequate. Conclusion: In cases of SCN, patients' pluripotent hematopoietic stem cells and their non-neutropenic parents are both affected irrespective of the genetic defect.
Children with Iron Deficiency Anemia Have a Tendency to Hypercoagulation: An Evaluation by Thromboelastography
(2020) Kilci, Ceren; Olcay, Lale; Ozdemir, Beril; Fettah, Ali; Colak, Meric Yavuz; 0000-0002-5684-0581; 0000-0002-0294-6874; 31852173; AAK-3548-2021; AAA-4360-2021
A Common Problem in Infants: Vitamin B12 Deficiency
(2023) Kilci, Ceren; Olcay, Lale; 38204307
Background. Nutritional vitamin B12 (VB12) deficiency is characterized by anemia, the inability to gain weight, delay or decline in development. Children of mothers with VB12 deficiency have a risk of nutritional VB12 deficiency. Prevention and early treatment are necessary to prevent irreversible neurological damage. We aimed to conduct a retrospective study to understand the characteristics of patients with VB12 deficiency.Methods. Our study included patients admitted to Baskent University Faculty of Medicine Pediatric Hematology outpatient clinic between January 2015 - February 2020 for VB12 deficiency. Their clinical and laboratory characteristics were retrospectively examined through the hospital automation system.Results. Vitamin B12 deficiency was detected in 129 of the 3198 patients; 100 of them were followed regularly. The mean age at admission of our patients was 10 +/- 12 months (1 month - 7.5 years); 98% of these children were aged 0-2 years. The mean VB12 level of our patients was 171.63 +/- 51.2 pg/ml (83 - 273), mean hemoglobin 11.2 +/- 1.37 g/dl (6.3 - 13.9), mean MCV 74.5 +/- 9.1 fl (54-106.5) and mean iron level was 54 +/- 23 mu g/dl (18 - 94). At the end of one month of loading therapy (oral or intramuscular, IM), the average VB12 level was 769 +/- 537 pg/ml (post loading). One month after the loading therapy (pre-maintenance) the average VB12 level was 426 +/- 156 pg/ml. In seven cases who received IM therapy, the loading treatment was performed for the second time. The mean VB12 level of the mothers of 85 cases was 174 +/- 127 pg/ml (134 - 650). VB12 deficiency was detected in 55% of mothers, VB12 level being between 200 - 300 pg/ml in 76%, and below 200 pg/ml in the 24%. The family members of 35% of our patients (including parents) had VB12 deficiency. Conclusions. In our country, routine screening of VB12 levels in infants is not performed; however, its early diagnosis and treatment can prevent many adverse effects mainly on the central nervous system. The fact that 98% of patients were 0-2 years old indicates that its deficiency may be quite high in the young age, and routine screening of this age group for VB12 deficiency and further studies for prophylaxis may be needed.
Demir eksikliğinde görülen trombozun patogenezine yaklaşım: Koagulasyonun tromboelastografi ile değerlendirilmesi
(Başkent Üniversitesi Tıp Fakültesi, 2016) Kılcı, Azize Ceren; Olcay, Lale
GĠRĠġ: Demir eksikliği (DE), dünyadaki en yaygın nutrisyonel eksikliktir. Literatürde DEA zemininde tromboz gelişmiş olan birçok çocuk ve erişkin olgu sunumu ve ayrıca trombozlu hastalarda DEA sıklığının normal popülasyondan fazla olduğunu gösteren insidans çalışmaları bulunmaktadır. Ancak, DEA’nde tromboz eğilimi olduğunu kanıtlayan ve bunun mekanizmasını sorgulayan herhangi bir prospektif ve karşılaştırmalı klinik çalışmaya rastlanmamıştır. AMAÇ: Çalışmamızda koagulasyonun primer ve sekonder hemostaz ve fibrinolitik sistem bölümlerini bütün olarak değerlendiren bir cihaz olan tromboelastografi cihazı kullanılarak, Virshow triadında ifade edilen temel üç faktörden biri olan kan bileşenlerindeki değişiklikler ile DEA’nin ilişkisinin araştırılması amaçlanmıştır. YÖNTEM: Başkent Üniversitesi Tıp Fakültesi Pediatri polikliniğine başvurup DEA tanısını alan, yaşları 0-18 arasında olan 40 hasta ile 40 sağlıklı çocuktan alınan kan örnekleri tromboelastografi cihazı (TEG ® 5000 Thromboelastograph ® Hemostasis Analyzer) ile ‘düz kap testi’ kullanılarak çalışıldı. Her iki grupta tromboelastografi parametreleri olan reaksiyon (R) zamanı, pıhtılaşma (K) zamanı, alfa (α) açısı ve maksimum amplitüd (MA), 30.dakikadaki maksimum lizis (LY30) ve koagulasyon indeksi (CI) hesaplandı. BULGULAR: Tromboelastografi ölçüm sonuçları, anemi ve kontrol grubunda sırasıyla reaksiyon zamanı (R) 3.9 ± 1,41 ve 4.1 ±1,4 dk (p: 0,569); pıhtı oluşum zamanı (K) 1.45 ± 0,64 ve 1.8 ± 1,07 dk (p: 0,025); alfa açısı (α) 52.7 ± 8,34 º ve 52.7 ± 9,5 º (p: 0,876); maksimum amplitude (MA) 70.3 ± 5,41 ve 66.8 ± 8,2 (p 0,045); koagulasyon indeksi (CI) 0.96 ±1.47 ve 0.26 ± 2,14 (p: 0,12), 30.dakikadaki maksimum lizis (LY 30) 3.29±1.47 ve 2.02 ± 2.14 (p: 0,328) olarak saptandı. Tromboelastografi ve laboratuvar parametreleri arasındaki ilişkiler değerlendirildiğinde hemoglobin değeri azaldıkça, K zamanın kısalıp MA’nın arttığı, hematokrit değeri azaldıkça ve trombosit sayısı arttıkça K zamanının kısaldığı, eritrosit dağılım genişliği (RDW) değerleri azaldıkça K zamanının kısaldığı, MA ve CI değerlerinin arttığı görüldü. SONUÇ: Bu bulgular, DEA’nde hiperkoagulasyona eğilim olduğunu ve DEA’nin şiddeti arttıkça (Hb ve Hct düşüşü, RDW artışı, trombosit artışı), hiperkoagulasyon eğiliminin de arttığını göstermektedir. Elde edilen TEG verisi, bu hiperkoagulasyonun, trombosit fonksiyonlarındaki artışa ve/veya fibrinojen yüksekliğine bağlı olduğuna, DEA grubunda fibrinojen, FXIII ve diğer faktör eksikliklerinin bulunmadığına, trombositopeni, trombosit fonksiyon yetersizliği, hiperfibrinoliz bulunmadığına işaret etmektedir. Böylece DEA’nin tromboz oluşumu için hazırlayıcı bir neden olduğu laboratuvar bulguları ile kanıtlanmıştır. Patogenezde rol alan diğer mekanizmaların da belirlenebilmesi için ileri çalışmalara gerek vardır. INTRODUCTION: Iron deficiency (ID) is the most common type of nutritional deficiency in children. In literature, there are several cases reporting children and adults with thrombosis in relation with IDA. There are also incidence studies showing IDA is more common in patients with thrombosis compared with the normal population. However, there are no prospective and randomized studies to prove the relationship between IDA and its tendency to from thrombosis, or the mechanism of it. PURPOSE: In this study, tromboelastography – which can evaluate coagulation, primary and secondary hemostasis, and fibrinolytic system- was used to study the correlation between IDA and one of the three factors in Virshow triad-mainly the alterations in the constitution of blood. METHODS: Blood sampIes from 40 IDA patients at Baskent University Medical faculty pediatry clinic were taken for the study group, and was compared with 40 healthy controls. Both the study and control groups were between the ages of 0-18. Blood samples were evaluated using tromboelastography (TEG ® 5000 Thromboelastograph ® Hemostasis Analyzer) ‘plain cup test’. In both groups, reaction time (R), coagulation time (K), alpha angle ((α), maximum amplitude (MA), maximum lysis in minute 30 (LY30), and coagulation index (CI) which are parameters of tromboelastography, were evaluated. RESULTS: Tromboelastography results of the study and control groups were respectively; (R) 3.9 ± 1,41 and 4.1 ±1,4 min (p: 0,569); (K) 1.45 ± 0,64 and 1.8 ± 1,07 min (p: 0,025); (α) 52.7 ± 8,34 º and 52.7 ± 9,5 º (p: 0,876); (MA) 70.3 ± 5,41 and 66.8 ± 8,2 (p 0,045); (CI) 0.96 ±1.47 and 0.26 ± 2,14 (p: 0,12), (LY 30) 3.29±1.47 ve 2.02 ± 2.14 (p: 0,328) . The results of tromboelastography and laboratory parameters showed that as hemoglobin decreases, K time decreases but MA increases. And as heamotocrit decreases and trombocyte count increases, K time decreases. As red cell distribution width (RDW) decreases, K time decreases but MA and CI increase. CONCLUSIONS: These results showed that in IDA, there is a tendency for hypercoagulation to occur, and the severity of IDA (decreased Hb and Hct, increased RDW and trombocyte count) is positively correlated with the hypercoagulation. According to TEG results, this coagulation is related to the increased trombocyte function and/or the increase in fibrinogen. It also showed there is no deficiency of fibrinogen or factors - FIVI or other in the study group. It also meant thrombocytopenia, trombocyte function deficiency or hyperfibrinolysis were absent. In conclusion, with these laboratory findings, it was proved that IDA is an underlying cause for thrombosis formation. There is need for more prospective randomized studies for determining its pathogenesis.
Hemolytic anemia caused by non-D minor blood incompatibilities in a newborn
(2019) Tugcu, Ali Ulas; Ince, Deniz Anuk; Turan, Ozden; Belen, Burcu; Olcay, Lale; Ecevit, Ayse; 31692740
Hyperbilirubinemia is one of the most widely seen cause of neonatal morbidity. Besides ABO and Rh isoimmunization, minor blood incompatibilities have been also been identified as the other causes of severe newborn jaundice. We report a newborn with indirect hyperbilirubinemia caused by minor blood group incompatibilities (P1, M, N, s and Duffy) whose hemolysis was successfully managed with intravenous immunoglobulin therapy. A thirty-two gestational weeks of preterm male baby became severely icteric on postnatal day 11, with a total bilirubin level of 14.66 mg/dl. Antibody screening tests revealed incompatibility on different minor groups (P1, M, N, s and Duffy (Fya ve Fyb)). On postnatal day thirteen, the level of bilirubin increased to 20.66 mg/dl although baby was under intensive phototherapy. After the administration of intravenous immunoglobulin and red blood cell transfusion, hemoglobin and total bilirubin levels became stabilised. Minor blood incompatibilities should be kept in mind during differential diagnosis of hemolytic anemia of the newborn. They share the same treatment algorithm with the other types hemolytic anemia. New studies revealed that intravenous immunoglobulin treatment in hemolytic anemia have some attractive and glamorous results. It should be seriously taken into consideration for treatment of minor blood incompatibilities.
Homozygous c.130-131 ins A (pW44X) mutation in the HAX1 gene as the most common cause of congenital neutropenia in Turkey: Report from the Turkish Severe Congenital Neutropenia Registry
(2019) Olcay, Lale; 31321910
Background Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. Method Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. Results The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (+/- mean standard error) follow-up period was 129.7 +/- 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. Conclusion In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.
The Impact of Iron Overload in Acute Leukemia: Chronic Inflammation, But Not the Presence of Nontransferrin Bound Iron is a Determinant of Oxidative Stress
(2017) Olcay, Lale; Serteser, Mustafa; Kolay, Murat; Balci, Havva F.; Yildirim, Ulku M.; Tekgunduz, Sibel A.; Hazirolan, Tuncay; Terzi, Yunus K.; https://orcid.org/0000-0002-5684-0581; https://orcid.org/0000-0001-5612-9696; 28731917; AAK-3548-2021; B-4372-2018
In the literature, studies on the oxidant effects of nontransferrin bound iron [NTBI (eLPI assay)] during chemotherapy of acute lymphoblastic leukemia and acute myeloblastic leukemia are lacking. We established NTBI and oxidative stress determinants (OSD), iron parameters, high-sensitive C-reactive protein (hs-CRP) levels, liver tests, cumulative chemotherapeutic doses, and transfused blood in 36 children with acute leukemia throughout chemotherapy. These parameters were determined at the beginning and end of chemotherapy blocks (11 time points) and in 20 healthy children using enzyme-linked immunosorbent assay, and colorimetric and fluorometric enzymatic methods. In acute lymphoblastic leukemia, NTBI, OSD, and hs-CRP were higher than controls at 4/11, 7/11, and 9/11 time points (P<0.05). At 3 time points, NTBI and OSD concurrently increased. Ferritin, soluble transferrin receptor, serum iron, and transferrin saturation were higher than in controls at 5 to 11/11 time points (P<0.05). Those with NTBI had higher iron parameters than those without NTBI (P<0.05), but showed similar OSD, hs-CRP, liver enzymes, cumulative chemotherapeutics, and transfused blood (P>0.05). OSD did not correlate with NTBI, but correlated with hs-CRP. In conclusion, NTBI is a poor predictor of OSD in acute leukemia possibly because of the heterogeneity of NTBI and chronic inflammation. Further studies are needed to delineate the pathophysiology of these diseases.
Liver Transplant in a Patient With Hemophagocytic Lymphohistiocytosis
(2019) Soy, Ebru H. Ayvazoglu; Alam, Humaira; Olcay, Lale; Baris, Zeren; Yildirim, Sedat; Torgay, Adnan; Haberal, Mehmet; https://orcid.org/0000-0002-0993-9917; https://orcid.org/0000-0002-5684-0581; https://orcid.org/0000-0002-5735-4315; https://orcid.org/0000-0002-6829-3300; https://orcid.org/0000-0002-3462-7632; 30777561; AAC-5566-2019; AAK-3548-2021; AAB-4153-2020; AAF-4610-2019; AAJ-5221-2021; AAJ-8097-2021
Hemophagocytic lymphohistiocytosis is a rare and life-threatening systemic disease that can cause hepatic infiltration and present as acute liver failure. Here, we report a case of a 3-year-old pediatric patient who presented with acute liver failure and hepatic encephalopathy secondary to hemophagocytic lymphohistiocytosis. She had left lateral segment liver transplant from her father. After 27 months, she had bone marrow transplant from her sister. At the time of reporting (36 months after liver transplant), she showed normal liver function and blood peripheral counts. We found that liver transplant can be a curative treatment for this type of rare disorder, not only to improve the quality of life but also to prolong survival.
Myelodysplastic features and cellular senescence in autoimmune disorders: a pilot study on patients with collagen tissue disorders and immune thrombocytopenic purpura
(2015) Olcay, Lale; Billur, Deniz; Erdemli, Esra; Baskin, Sidika Esra; Balci, Havva Fatma; Yetgin, Sevgi; 26281349
Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors
(2017) Turan, Ozden; Anuk-Ince, Deniz; Olcay, Lale; Sezer, Taner; Gulleroglu, Kaan; Yilmaz-Celik, Zerrin; Ecevit, Ayse; 0000-0002-4369-2110; 0000-0002-2232-8117; 0000-0002-7707-1881; 0000-0002-2278-1827; 0000-0003-1434-3824; 0000-0002-5684-0581; 29168367; I-6746-2016; AAJ-4616-2021; AAJ-2333-2021; AAJ-5931-2021; AAJ-8833-2021; AAK-3548-2021
Cerebral sinovenous thrombosis (CSVT) is a rare disease in the neonatal period and also the greatest risk of neonatal mortality and morbidity. In this report, we presented two cases with CSVT and different risk factors. One of these cases had methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism and the other case had both MTHFR A1298C homozygous polymorphism, plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and elevated lipoprotein a. Early diagnosis and prompt initiation of therapy of neonatal CSVT may prevent neonatal mortality and poor long-term neurodevelopmental outcomes.
Successful Bone Marrow Transplantation After Orthotopic Liver Transplantation in A Child With Familial Hemophagocytic Lymphohistiocytosis
(2018) Aksu, Tekin; Olcay, Lale; Ozcay, Figen; Ozbek, Namik Y.; https://orcid.org/0000-0002-5684-0581; https://orcid.org/0000-0002-5214-516X; AAK-3548-2021; ABG-5684-2020
Turkish National Severe Congenital Neutropenia Registry
(2016) Olcay, Lale; https://orcid.org/0000-0002-5684-0581; AAK-3548-2021
Type 3 Gaucher disease presented with cardiac manifestations
(2019) Gumus, Ersin; Tokel, Kursad; Karhan, Asuman Nur; Demir, Hulya; Ozen, Hasan; Temizel, Inci Nur Saltik; Olcay, Lale; Yuce, Aysel; 0000-0002-6759-1795; AAF-3253-2021