The value of ultrasonography in detecting early arthropathic changes and contribution to the clinical approach in patients of hemophilia.

PURPOSE\AIM: Hemophilia affects the blood clotting process, is a genetic disease characterized by recurrent bleeding. The hemophilia early arthropathy detection with ultrasound (HEAD-US) procedure and scoring method were designed for the detection of early changes in affected joints of patients. In this article, it was aimed to detect early arthropathic changes in the joints of hemophilia patients with the HEAD US scoring system and to investigate its clinical contribution. It was aimed to investigate the effectiveness of HEAD-US scoring in showing early joint damage in subclinical hemophilia cases and its contribution to treatment. METHODS: The present study included 50 hemophilia patients who were admitted to Departments of Pediatric and Adult Hematology for routine follow-up. During routine follow-up controls, patients were scored by physical examination and HJHS 2.1 and by ultrasonography and HEAD US. Statistical tests were used to analyze joint health status and the results of US examination in the patient group. RESULTS: A total of 294 joints (elbow n = 100, knee n = 94, ankle n = 100) were evaluated by ultrasonography. The mean HJHS and HEAD-US scores of the patients were 14.94 ± 15.18 and 15.6 ± 12.6, respectively. CONCLUSIONS: HEAD-US is accepted to be more sensitive than HJHS in detecting early signs of arthropathy. Detection of early abnormalities by ultrasonography will enable the development of individualized treatment protocols and to the prevention of arthropathy development.

Is Monitoring of Cytomegalovirus Disease Required in Nontransplant Pediatric Acute Lymphoblastic Leukemia?

INTRODUCTION: Cytomegalovirus (CMV) infections in developing countries are experienced at an early age. This study was performed to investigate the frequency of reactivation and risk factors of infection acquired at an early age of nontransplant acute lymphoblastic leukemia (ALL) patients receiving immunosuppressive therapy with weekly monitoring of CMV levels in Turkey. MATERIALS AND METHODS: This was a retrospective, single-center study of 172 pediatric patients (102 boys and 70 girls) with ALL. All patients were monitored routinely for CMV-DNA at the initial presentation of leukemia and twice a week during chemotherapy. The CMV immunoglobulin (Ig)M/IgG titers were measured at admission. RESULTS: CMV seropositivity at baseline was 90,11%. The overall prevalence of CMV infection (viremia) was 70.34%, 116 of whom were seropositive for CMV IgG and 5 of whom were negative for CMV at the time of ALL diagnosis. Reactivation was more common than de novo CMV infections (P=0.000). CMV seropositivity at the beginning of the leukemia diagnosis was found to be an independent predictor for developing CMV infection (P=0.001). A total of 60 CMV infection episodes were treated with antivirals. Four of these included organ involvement. The duration of CMV-DNA viremia episodes was longer in patients with CMV-DNA ≥1000 copies/mL (n=45) than in those with lower CMV-DNA levels (P=0.002). Infection was shown not to be associated with chemotherapy phase. CONCLUSION: This study suggests the importance of monitoring for CMV infections in developing countries because of frequent reactivations in seropositive ALL patients. It should be kept in mind that low CMV-DNA levels may also lead to organ involvement.

Successful Treatment With Total Skin Electron Beam Therapy in a Child With Isolated Cutaneous Relapsed AML.

A 9-year-old girl diagnosed with acute myeloblastic leukemia M4 developed isolated cutaneous relapse. She was given chemotherapy including idarubicin, fludarabine, and cytarabine. Although she developed very severe pancytopenia, increase in the number and size of the lesions was seen. Total skin electron beam therapy was applied to the skin lesions for a total of 18 Gy. All lesions responded to total skin electron beam therapy, some of them completely disappeared. After resolution of the skin findings, she underwent bone marrow transplantation from her matched brother. Twenty-six months after hematopoietic stem cell transplantation she is alive without any event.

Proven and probable invasive fungal infections in children with acute lymphoblastic leukaemia: results from an university hospital, 2005-2013.

Despite improvements in diagnosis and treatment, invasive fungal infections (IFIs) are still a major cause of morbidity and mortality in immunocompromised patients. The data on IFI among children with acute lymphoblastic leukaemia (ALL) are still scarce, and our aim was to estimate the risk, aetiology and outcome of proven and probable IFIs in children with ALL who did not receive primary prophylaxis over an 8-year period. Between January 2005 and February 2013, 125 children who were treated for ALL at the Pediatric Hematology Department of the Medical School of Ege University were retrospectively reviewed. Proven and probable IFIs were defined according to revised definitions of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. The proven and probable IFI incidence was 30/125 (24%). Profound neutropenia was detected in 18 (60%) patients, and prolonged neutropenia was detected in 16 (53.3%) of the patients. The most isolated agents were non-albicans Candida spp. The crude and attributable mortality was 20% and 13.3% respectively. Profound neutropenia was associated with mortality (P < 0.05). The younger patients were especially at risk for proven IFI. Prolonged neutropenia, to be in the induction phase of chemotherapy, and profound neutropenia were found to be the most common predisposing factors for IFI episodes.

The effect of inhaled nitric oxide therapy on thromboelastogram in newborns with persistent pulmonary hypertension.

UNLABELLED: Studies about the effects of inhaled nitric oxide (iNO) on bleeding time and platelet aggregation in newborns are limited in number and have inconclusive results. Thromboelastogram (TEG) shows the combined effects of coagulation factors and platelet functions. In this preliminary study, we aimed to evaluate the effects of iNO on coagulation using TEG in newborns with persistent pulmonary hypertension (PPH). TEG assays were performed in 10 term infants receiving iNO treatment for PPH and 32 healthy term infants. Samples of the iNO group were collected before and during iNO. Clot reaction time (R), clot kinetics (K), maximum amplitude (MA), and alpha angle were obtained from the TEG tracing. TEG-R values were statistically higher during iNO treatment (7.75 ± 3.34) when compared to the values before iNO (4.83 ± 1.38) and the healthy controls (3.75 ± 0.98). The alpha angle was lower in iNO treated infants at both periods (before iNO, 55.33 ± 8.58; during iNO, 42.90 ± 18.34) compared to the control group (64.95 ± 6.88). MA values before iNO treatment were the lowest (44.43 ± 14.09) and improved with the iNO treatment (48.40 ± 9.49) despite still being lower compared to the controls (53.67 ± 5.56). CONCLUSION: Both PPH and iNO may negatively effect in vitro coagulation tests. Therefore, newborns with PPH requiring iNO treatment should be closely monitored for coagulation problems.

Rabbit antithymocyte globulin treatment in childhood acquired severe aplastic anemia.

Acquired severe aplastic anemia (SAA) is a life threatening bone marrow failure characterized by pancytopenia and hypocellular bone marrow. Matched sibling donor is not available for majority of the patients and many children receive immunosuppressive therapy (IST). Although horse antithymocyte globuline (ATG) is the preferred option, our patients received rabbit ATG; since horse ATG is not available in Turkey. We reviewed the medical records of children with SAA who were treated with rabbit ATG, cyclosporine, and granulocyte colony stimulating factor (GCSF) between 2006 and 2012. Fifteen children with SAA aged between 1.5 and 17 years received rabbit ATG as first line treatment. Only two of them showed partial response and the others did not give any response at 3rd, 6th, and 12th months after the first course of IST. The second course of ATG was given to 8 of the patients; Rabbit ATG at the same dosage was used for 3 of them, and others were given horse ATG. None of the patients responded to the second course of ATG. Invasive fungal infection (IFI) which was seen in 80% of the patients was the most significant problem. Overall survival rate was 60%. The median time between the diagnosis and initiation of IST was 57 (range; 29-144) days. This delay might be significantly contributed to unresponsiveness. In our series, the use of rabbit ATG was not effective for these patients as first line treatment modality. Response rate was very low and the incidence of fungal infections was very high in the SAA patients who received rabbit ATG.

Leukapheresis in childhood acute leukemias: single-center experience.

Hyperleukocytosis in patients with leukemia is associated with early mortality, especially due to the pulmonary and neurological complications of leukostasis. The prompt use of leukapheresis may improve patients' survival in the initial treatment period. The medical records of all previously untreated acute leukemia patients were reviewed to determine whether there was hyperleukocytosis at presentation. This study summarizes a single-center experience of leukapheresis that was applied to 12 children with acute leukemia and hyperleukocytosis. The median leukocyte count at diagnosis was 589,000/mm(3) (range: 389,000-942,000/mm(3)) for ALL patients and 232,000/mm(3) (range: 200,000-282,000/mm(3)) for AML patients. A central venous catheter (CVC) was inserted, and leukapheresis procedures were repeated at 12-hour intervals. A total of 29 leukapheresis cycles were performed on 12 children. The median number of cycles of leukapheresis required by each patient was two (range: 1-4). The median absolute and percentage reductions in white blood cell (WBC) count after the first cycle of leukapheresis were 113,000/mm(3) (range: 55,000-442,000/mm(3)) and 36% (range: 16-57.4%), respectively. As a laboratory finding, mild hypocalcemia was the most frequently observed complication. No patients developed any other problem related to the procedure. Our results showed that leukapheresis is a safe and effective procedure if performed by experienced staff.

Current childhood chronic myeloid leukemia management under tyrosine kinase inhibitor treatment.

Chronic myeloid leukemia (CML) is very rare during childhood. Tyrosine kinase inhibitors (TKI) provide very good results in terms of survival. The medical records of 15 chronic phase (CP)-CML patients in a university hospital pediatric hematology department between 1997 and 2022 were reviewed retrospectively. Complete hematological response was documented in all patients between 20 and 68 (median 30) days of treatment. Major molecular response was achieved in seven patients within 6 months. Median follow-up for the study group was 79 (range 3-330) months and overall survival was 100%. Three patients (2 blastic transformation, 1 therapy resistant) underwent bone marrow transplantation (BMT) and one with blastic transformation is scheduled to undergo BMT. TKI were discontinued in three patients after a median of 86 (range 73-177) months. The complete molecular remission maintenance period before discontinuation of TKI was 81 (range 62-122) months. While no molecular relapse was seen before the last follow-up, the median overall follow-up period was 152 (range 131-300) months. In conclusion, recent advances have led to a very good prognosis for children with CP-CML. With TKI treatment, most patients continue their lives without disease progression. Additionally, in selected patients TKI can be discontinued without molecular relapse.

Relation between NT-proBNP levels, iron overload, and early stage of myocardial dysfunction in ß-thalassemia major patients.

BACKGROUND: Heart failure (HF) secondary to myocardial iron loading remains the leading cause of death in ß-thalassemia major (ß-TM) patients. The early diagnosis and treatment of HF in these patients is related to survival. We aimed to evaluate myocardial performance using conventional and tissue Doppler echocardiography and its relation to plasma NT-proBNP levels and iron overload indices in ß-TM patients with preserved systolic function. METHODS: The study population included 49 ß-TM patients (24.0 ± 4.2 years) and 48 age-matched healthy controls. Doppler-echocardiographic study was performed and blood samples for NT-proBNP measurements were drawn on the third day following blood transfusion. Patients were divided as group-1, without diastolic dysfunction: E/E' ratio < 9 and group-2, with suspected diastolic dysfunction: E/E' ratio ≥ 9. RESULTS: NT-proBNP levels and E/E' ratio were increased in patients compared with controls (P < 0.001 and P < 0.001) but did not correlate with each other. A strong positive correlation was detected between NT-proBNP levels and mean ferritin levels in ß-TM patients (r(s) = 0.939; P < 0.001). Median NT-proBNP levels were significantly higher in group-1 in comparison to controls [51.2 (41.51-113.5) vs 30.1 (17.97-68.16) ng/mL, P < 0.01]. NT-proBNP levels were also increased in group-2 in comparison to group-1 but this increase was not statistically significant. CONCLUSION: NT-proBNP secretion begins in the early phase of the disease before the increase in diastolic pressure becomes overt. While there was a strong correlation between the plasma NT-proBNP levels and iron overload, there was no correlation between NT-proBNP levels and diastolic dysfunction parameters in patients in the third decade of life.

Rare coagulation disorders: a retrospective analysis of 156 patients in Turkey.

OBJECTIVE: To retrospectively evaluate the clinical findings, laboratory data, management, and outcome in a group ofTurkish children diagnosed with rare coagulation deficiencies (RCDs) between January 1999 and June 2009. MATERIAL AND METHODS: The Turkish Society of Pediatric Hematology-Hemophilia-Thrombosis-Hemostasissubcommittee designed a Microsoft Excel-based questionnaire for standardized data collection and sent it to participatinginstitutions. RESULTS: In total, 156 patients from 12 pediatric referral centers were included in the study. The cost common RCDswere as follows: FVII (n = 53 [34%]), FV (n = 24 [15.4%]), and FX (n = 23 [14.7%]) deficiency. The most common initialfinding in the patients was epistaxis, followed by ecchymosis, and gingival bleeding. CONCLUSION: Initial symptoms were mucosal bleeding, and fresh frozen plasma (FFP) and tranexamic acid werethe most commonly used treatments. We think that prophylactic treatment used for hemophilia patients should beconsidered as an initial therapeutic option for patients with rare factor deficiencies and a severe clinical course, and forthose with a factor deficiency that can lead to severe bleeding.

Gene therapy in haemophilia: literature review and regional perspectives for Turkey.

Haemophilia is an X-linked lifelong congenital bleeding disorder that is caused by insufficient levels of factor VIII (FVIII; haemophilia A) or factor IX (FIX; haemophilia B) and characterized by spontaneous and trauma-related bleeding episodes. The cornerstone of the treatment, factor replacement, constitutes several difficulties, including frequent injections due to the short half-life of recombinant factors, intravenous administration and the risk of inhibitor development. While extended half-life factors and subcutaneous novel molecules enhanced the quality of life, initial successes with gene therapy offer a significant hope for cure. Although adeno-associated viral (AAV)-based gene therapy is one of the most emerging approaches for treatment of haemophilia, there are still challenges in vector immunogenicity, potency and efficacy, genotoxicity and persistence. As the approval for the first gene therapy product is coming closer, eligibility criteria for patient selection, multidisciplinary approach for optimal delivery and follow-up and development of new pricing policies and reimbursement models should be concerned. Therefore, this review addresses the unmet needs of current haemophilia treatment and explains the rationale and principles of gene therapy. Limitations and challenges are discussed from a global and national perspective and recommendations are provided to adopt the gene therapies faster and more sufficient for the haemophilia patients in developing countries like Turkey.

A rescue therapy with a combination of caspofungin and liposomal amphotericin B or voriconazole in children with haematological malignancy and refractory invasive fungal infections.

Combination treatment of paediatric invasive fungal infections (IFIs) has rarely been reported. A total of 17 children with 19 IFI episodes were enrolled in the study. The median age of the patients was 5.3 (range 0.5-17) years. IFI was classified as proven in 4, probable in 12 and possible in 3 episodes. These patients received empiric antifungal treatment, which consisted of liposomal amphotericin B (LAmB) monotherapy for a median duration of 12 days (range 3-69 days). All patients were refractory to LAmB; therefore, caspofungin was added to the therapy in 11 patients. In the remaining six patients, LAmB was ceased and a combination of caspofungin and voriconazole was started. Among the patients who received caspofungin + LAmB, four did not show favourable response and the combination was switched to caspofungin + voriconazole. The median (range) and total duration of the therapy were 7 (3-14) days and 91 patient days for LAmB + caspofungin combination and 49 (7-126) days and 516 patient days for caspofungin + voriconazole combination. We found a favourable response rate of 68.4% in 16 proven or probable IFI episodes. Twelve-week survival rate of these patients was 75%. No serious side effect was observed among the patients. Our data suggest that combination antifungal therapy is safe and effective in children with haematological malignancies.

Experience of pandemic influenza with H1N1 in children with leukemia.

It is not exactly known the risks from infection with pandemic influenza (H1N1) 2009 in children with leukemia. Here the authors present their experience in 5 children with leukemia. Pandemic influenza (H1N1) 2009 was detected in 5 patients (F/M: 3/2) at their institution. The ages of these patients were between 2 and 16 years. Four had acute lymphoblastic leukemia (ALL) and 1 acute myeloblastic leukemia (AML). Three of the ALL patients had the diagnosis of pandemic influenza (H1N1) 2009 at the same time as they were diagnosed with ALL. The remaining 2 patients were receiving intensive chemotherapy. All patients had fever, rhinorrhea, and cough. Although bronchopneumonia was seen in 3 patients, only 1 revealed respiratory distress. Stomach ache and diarrhea was seen in the patient who had no pneumonia. All treated as inpatients, but none of them required hospitalization in intensive care unit. One to 3 days after the symptoms of influenza appeared, oseltamivir (Tamiflu) was given to all patients in combination with broad-spectrum antibiotics. Fever declined to normal ranges in 1 to 3 days after treatment was started. The patients received oseltamivir for 5 to 7 days. Cell culture tests were found to be positive for influenza A and polymerase chain reaction (PCR) revealed H1N1 for all 5 patients. Although this is a very small case series, pandemic influenza (H1N1) 2009 did not seem to be very dangerous for children with leukemia if the oseltamivir treatment was given early when symptoms of influenza appeared.

Cost of hemophilia A in Turkey: an economic disease burden analysis.

OBJECTIVE: Hemophilia A is the second most common bleeding disorder causing patients to have lifelong follow-up and treatment. Despite being a rare disease, hemophilia A has a high economic burden on individuals and the public. The purpose of this study was to estimate the total disease cost of hemophilia A in Turkey. MATERIALS AND METHODS: Data used in this analysis were collected through literature review, including studies conducted in Turkey in December 2018. A disease burden analysis was performed by modeling hemophilia A-related costs among patients, their relatives, and the social security system. Two expert panels were held to evaluate real-world data sources and to provide further information. All direct medical and non-medical costs were calculated annually from the Social Security Institution of the Republic of Turkey perspective, while indirect costs were estimated from the patient and community perspective. RESULTS: For the calendar year of 2018, the number of hemophilia A patients in Turkey were estimated to be 5,055, with an average weight of 64.7 kg. The average annual direct medical, direct non-medical, and indirect costs of hemophilia A were calculated as €93,268 ($109,286; ₺502,717), €2,533 ($2,968; ₺13,655), and €7,957 ($9,323; ₺42,888) per patient, respectively, with a total annual cost of €103,759 ($121,578; ₺559,259). For the management of patients with inhibitors (4.9%), the average annual total cost was calculated to be €325,439 ($381,330; ₺1,754,117) per patient. The total annual disease burden of hemophilia A in 2018 was estimated to be about €524 million ($614 million; ₺2.82 billion), which corresponded to 1.6% of the total health expenditure in Turkey. CONCLUSION: The most important reason hemophilia A has a significant economic burden in Turkey is that replacement therapy is expensive. The major cost contributor was identified as factor replacement therapy. With inhibitor development, the average annual cost increased more than 3-fold.

Impact of the HEAD-US Scoring System for Observing the Protective Effect of Prophylaxis in Hemophilia Patients: A Prospective, Multicenter, Observational Study

Objective: This study aimed to observe the preventive effect of prophylactic treatment on joint health in people with hemophilia (PwH) and to investigate the importance of integration of ultrasonographic examination into clinical and radiological evaluation of the joints. Materials and Methods: This national, multicenter, prospective, observational study included male patients aged ≥6 years with the diagnosis of moderate or severe hemophilia A or B from 8 centers across Turkey between January 2017 and March 2019. Patients were followed for 1 year with 5 visits (baseline and 3th, 6th, 9th, and 12th month visits). The Hemophilia Joint Health Score (HJHS) was used for physical examination of joints, the Pettersson scoring system was used for radiological assessment, point-of-care (POC) ultrasonography was used for bilateral examinations of joints, and the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score was used for evaluation of ultrasonography results. Results: Seventy-three PwH, of whom 62 had hemophilia A and 11 had hemophilia B, were included and 24.7% had target joints at baseline. The HJHS and HEAD-US scores were significantly increased at the 12th month in all patients. These scores were also higher in the hemophilia A subgroup than the hemophilia B subgroup. However, in the childhood group, the increment of scores was not significant. The HEAD-US total score was significantly correlated with both the HJHS total score and Pettersson total score at baseline and at the 12th month. Conclusion: The HEAD-US and HJHS scoring systems are valuable tools during follow-up examinations of PwH and they complement each other. We suggest that POC ultrasonographic evaluation and the HEAD-US scoring system may be integrated into differential diagnosis of bleeding and long-term monitoring for joint health as a routine procedure.

Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations

Objective: Hemophilia A (HA) is the most severe X-linked inherited bleeding disorder caused by hemizygous mutations in the factor 8 (F8) gene. The aim of this study is to determine the mutation spectrum of the F8 gene in a large HA cohort from Turkey, and then to establish a phenotype-genotype correlation. Materials and Methods: All HA cases (270 patients) analyzed molecularly in the Ege University Pediatric Genetics Molecular Laboratory between March 2017 and March 2018 were included in this study. To identify intron 22 inversion (Inv22), intron 1 inversion (Inv1), small deletion/insertions, and point mutations, molecular analyses of F8 were performed using a sequential application of molecular techniques. Results: The mutation detection success rate was 95.2%. Positive Inv22 was found in 106 patients (39.3%), Inv1 was found in 4 patients (1.5%), and 106 different disease-causing sequence variants were identified in 137 patients (50.6%). In 10 patients (3.7%), amplification failures involving one or more exonic regions, considered to be large intragenic deletions, were identified. Of 106 different F8 mutations, 36 were novel. The relationship between F8 genotype and inhibitor development was considered significant. Conclusion: A high mutation detection rate was achieved via the broad molecular techniques applied in this study, including 36 novel mutations. With regard to mutation types, mutation distribution and their impact on clinical severity and inhibitor development were found to be similar to those previously reported in other hemophilia population studies.

An unusual cause of multiple organ dysfunction syndrome in the pediatric intensive care unit: hemophagocytic lymphohistiocytosis.

OBJECTIVE: To report our experience in children with primary or secondary hemophagocytic lymphohistiocytosis (HLH) presented with multiple organ dysfunction syndrome (MODS) in pediatric intensive care unit (PICU). DESIGN: The records of patients with a diagnosis of HLH and MODS between January 2005 and January 2008 were reviewed. The patients' characteristics, treatment modalities, and outcomes were assessed. SETTING: PICU of Ege University Hospital. PATIENTS/SUBJECTS: Twelve children who were hospitalized in the PICU met the diagnostic criteria for HLH, and presented with MODS were entered into the study. RESULTS: The median age of the patients was 3 years (range, 2 months-15.5 years). Six patients had a history of parental consanguinity and two had an affected sibling. Five of the patients were classified as primary HLH. All of the patients had hepatosplenomegaly, elevated ferritin levels, hypofibrinogenemia, anemia, thrombocytopenia, and hemophagocytosis in bone marrow examination at presentation. The median Pediatric Logistic Organ Dysfunction score of the patients at onset was 51 (range, 12-62). Four patients had six, four had five, two had four, and the remaining two had three organ dysfunctions. Organ dysfunction, other than hematologic dysfunction which was present in all patients, was most commonly seen in hepatic (n = 11, 91.7%), respiratory (n = 11, 91.7%), and cardiovascular systems (n = 10, 83.3%). Although nine patients showed neurologic dysfunction including convulsion and coma, renal failure was detected in five patients. Eleven patients were supported with mechanical ventilation and four patients required hemodialysis. Eight patients were treated according to the HLH 2004 treatment protocol, consisting of cyclosporine A, etoposide, and dexamethasone. The remaining four patients received only intravenous immunoglobulin and supportive treatment. Seven of the patients died. CONCLUSION: HLH is a frequently lethal disease and with a clinical presentation similar to severe sepsis, MODS, disseminated intravascular coagulation, or septic shock, which are frequent diagnoses in the PICU. In the PICU, HLH should be considered in the case of prolonged fever, splenomegaly, cytopenia, and MODS. It is important for pediatricians and particularly pediatric intensivists to know the diagnostic criteria and possible clinical presentations of HLH so treatment is initiated promptly.

Extended Half-Life Coagulation Factors: A New Era in the Management of Hemophilia Patients

Despite effective factor replacement and various treatment schedules, there remain several challenges and unmet needs in the prophylactic treatment of hemophilia limiting its adoption and thereby posing an increased risk of spontaneous bleeding. In this regard, extended half-life (EHL) recombinant factor VIII (rFVIII) and factor IX (rFIX) products promise optimal prophylaxis by decreasing the dose frequency, increasing the compliance, and improving the quality of life without compromising safety and efficacy. EHL products might lead to higher trough levels without increasing infusion frequency, or could facilitate the ability to maintain trough levels while reducing infusion frequency. This paper aims to provide a comprehensive review of the rationale for developing EHL coagulation factors and their utility in the management of hemophilia, with special emphasis on optimal techniques for half-life extension and criteria for defining EHL coagulation factors, as well as indications, efficacy, and safety issues of the currently available EHL-rFVIII and EHL-rFIX products. Potential impacts of these factors on quality of life, health economics, and immune tolerance treatment will also be discussed alongside the challenges in pharmacokinetic-driven prophylaxis and difficulties in monitoring the EHL products with laboratory assays.

Fertility in Patients with Thalassemia and Outcome of Pregnancies: A Turkish Experience

Objective: In recent years, the rates of marriage and pregnancy are increasing in patients with thalassemia major. The aim of the present study was to investigate the fertility rate of thalassemic patients and the course of pregnancies in terms of mother and infant health. Materials and Methods: In this observational study patients with major hemoglobinopathy were evaluated regarding marital status, the need for assisted reproductive techniques, fertility rate, iron status, and pregnancy complications. Results: Seventeen female patients gave birth to 21 healthy infants. About one-third of the patients needed assisted reproductive techniques. Thalassemia major patients showed increased serum ferritin levels from 1203±1206 µg/L at baseline to 1880±1174 µg/L at the end of pregnancy. All babies are still alive and healthy. Conclusion: Pregnancy in patients with thalassemia can be safe for the mother and newborn with close monitoring and a multidisciplinary approach.