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Two main sub-phenotypes have been described in sickle cell disease: one with higher baseline haemoglobin and a higher rate of painful crises and one with lower baseline haemoglobin, increased markers of haemolysis and a higher incidence of pulmonary hypertension, priapism and leg ulcers. We compared the patterns of response to regular automated red cell exchange transfusion over a five-year period of 21 patients with recurrent painful crises from the first group and 3 patients with pulmonary hypertension and 5 with recurrent severe stuttering priapism form the second and found them to be distinctly different. Response for pain is slow and increases gradually over years. The most pronounced clinical benefit and the one that appears first is a reduction in the severity rather than the frequency of painful crises. In contrast to the slow and gradual response we see for pain, response of patients with pulmonary hypertension and priapism is immediate with significant clinical improvement even after the first transfusion. The response appears to be directly correlated to the HbS level as the symptoms of both conditions invariably recur rapidly when transfusions are delayed or discontinued but resolve again once they are re-instituted.

Extramedullary hematopoiesis (EMH) results from the extension of hematopoietic tissue beyond the confines of the bones. Since the initiation of regular transfusion programs from an early age for all thalassemia major (ΤΜ) patients, EMH has not been considered a clinical issue anymore. The present study aims to record the prevalence of EMH in chronically transfused ΤΜ patients followed at our institution and to investigate possible risk factors associated with its occurrence. The project was designed as a retrospective, nonexperimental, descriptive, exploratory study. In total, the study enrolled 104 patients. EMH was revealed in 15/104 (14%) patients. The presence of intravening sequence (IVS)-I-6 was significantly related with the development of EMH (p < 0.05). No other demographic or biological factor studied was found to be related with the presence of EMH. The study stresses a profound incidence of asymptomatic EMH in a solid group of well-transfused ΤΜ patients. Given the high incidence of the IVS-I-6 allele in the Mediterranean and Middle Eastern region, high-quality, prospective, multicenter studies could confirm the association of EMH occurrence with the presence of the IVS-I-6 mutation and further evaluate the exact role of this mutation in the EMH process.

The most frequent enzyme abnormality of the glycolytic pathway which causes hereditary non-spherocytic hemolytic anemia is red cell pyruvate kinase (PK) deficiency.The disease is transmitted as an autosomal recessive trait. The case of a successful pregnancy in a 38 year- old woman with Pyruvate Kinase deficiency along with detection of plasminogen activator inhibitor (PAI-1) 4G/4G homozygous genotype is reported. The pregnancy was uneventful and a healthy girl was born.

Myocardial siderosis in β-thalassemia major (β-TM) remains the leading cause of death. Deferasirox (DFX), a new iron chelation treatment, has proved to be effective in reducing or preventing cardiac iron burden in thalassemic patients according to clinical trials with maximum duration of up to 3 years except one that was recently published and lasted 5 years. The aim of this study was to evaluate the efficacy of DFX in reducing or preventing cardiac iron burden in 23 patients with β-TM after 5 years of therapy. All patients had a magnetic resonance imaging (MRI) T2* evaluation of their cardiac iron load before starting DFX therapy and after a period of 5 years. Ferritin levels and left ventricular ejection fraction (LVEF) were also evaluated at the same time. Deferasirox was administered in a starting dose of 30 mg/kg/day and never increased to more than 40 mg/kg/day. The MRI T2* cardiac iron load mean values before DFX was 32.82 ± 10.86 ms, and after 32.13 ± 7.74 ms, showing a stability in MRI T2* myocardial value but a significant improvement in two patients with an intermediate iron load (12 vs. 23 ms). The mean LVEF value was 68.43 ± 7.08% before treatment with DFX and 67.95 ± 5.94% after DFX therapy without significant change. Our results confirm previous studies that DFX is considered an effective chelating agent used as monotherapy for at least 5 years and is more efficacious in moderate to severe cardiac iron loaded thalassemic patients.

To the Editor, Pyrimidine 5’-nucleotidase (P5N) is an intra-erythrocytic isoenzyme that catalyzes the dephosphorylation of pyrimidine ribonucleotides, which are the product of DNA catabolism. A reduction in P5N reactivity leads to accumulation of pyrimidine products in erythrocytes, which increases its life span, resulting in hemolytic anemia and intense basophilic stippling [1]. P5N deficiency is inherited in an autosomal recessive fashion and is one of the most important causes of inherited non-spherocyte anemia, as well as G-6PD and pyruvate kinase deficiency. P5N deficiency is characterized by hemolytic anemia, splenomegaly, and intense basophilic stippling. There are several reports in the literature concerning reduced P5N reactivity in patients with intermediate and heterozygous β-thalassemia; however, the co-existence of P5N deficiency in a patient with α-thalassemia is a rare event [2,3,4]. We report the clinical and hematological findings in a 25-year-old female that was screened for hemoglobinopathies due to her pregnancy (6th week).Based on her medicalrecords, she was known to be a carrier of 5PN deficiency. The proposita’s hematological parameters were as follows: Hb: 10.7 g dL—1; Hct: 34%; RBC: 4.35 x 106; MCV: 77 fL; MCH: 24.7 pg; RDW: 16.2%; reticulocytes: 3.97%; ferritin: 30 (normal range=20-81ngr/Ml). Microscopic examination of a stained peripheral blood smear showed severe anisocytosis, microcytosis, and basophilic stippling. Biochemical analysis of hemoglobin using high-performance liquid chromatography (HPLC) showed normal values for hemoglobin A2 (HbA2: 2.4%) and hemoglobin F (HbF: 0.5%). No abnormal hemoglobins were detected. Due to an unclear hematological picture in the proposita’s husband, who was thought to be heterozygous for thalassemia, genetic analysis of the proposita’s DNA was performed. Molecular analysis showed that she was heterozygous for the mild mutation of α-thalassemia (-α3,7/ NI). In conclusion, mismatch between the hematological parameters of the presented pregnant patient and the usual hematological phenotype associated with α-thalassemia (-α 3,7/NI) were due to the lack of P5N (P5N: 1.88 U g–1 of Hb).The patient never required blood transfusion. The co-existence of hereditary P5N deficiency and heterozy-gous α-thalassemia is extremely interesting due to the fact that to the best of our knowledge this is the first report of such a case. Conflict of Interest Statement The authors have no conflicts of interest, including specific financial interests, relationships, and/or affiliations, relevant to the subject matter or materials presented.

Blood transfusion many times works in a life-saving way when a patient is facing a critical situation. However, some patients, such as Jehovah’s Witnesses, may refuse their administration because it opposes to their religion beliefs. Thus, clinicians are forced to respect patients’ preferences and seek other treatments in order to overcome the obstacle of the transfusion. In 1989, recombinant human erythropoietin (rHuEPO) was approved by the United States Food and Drug Administration (FDA) for the treatment of anemia associated with chronic renal failure. This is an amino acid glycol-protein that stimulates red blood cell production in the same manner as endogenous erythropoietin. Other treatment indications approved by the FDA include anemia due to chronic kidney disease, anemia secondary to zidovudine therapy in patients with human immunodeficiency virus infection, and anemia secondary to cancer chemotherapy. The drug also has been used for many off-label indications. Many Jehovah’s Witnesses have accepted rHuEPO as a treatment option to maintain and enhance erythropoiesis. This paper reports the case of a 57-year-old Jehovah’s Witness man, who was diagnosed with severe anemia due to aggressive non Hodgkin lymphoma and refused transfusion of blood; thanks to the treatment with rHuEPO he has managed to complete chemotherapy and has survived a life threatening situation.

SummaryHaemophilia A and B has been associated with increased prevalence of low bone mass (67–86%). The aim of this study was to estimate the prevalence of bone disease in haemophiliacs and its association with potential risk factors. Adult patients with haemophilia A and B followed-up in the Haemophilia Centre of Northern Greece were included. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) in lumbar spine (LS), femoral neck (FN), total hip (TH) and great trochanter (GT). One-hundred four male patients (aged 45.8 ± 15.1 years) and 50 controls (aged 44.9 ± 12.8 years) were screened. Low BMD was diagnosed in 28 patients (26.9%) and 10 controls (20%) (p=0.0001). Patients had lower BMD in TH (p=0.007), FN (p=0.029) and GT (p=0.008) than controls, without differences in LS. BMD was positively associated with the severity of haemophilia, history of herpes virus C or human immunodeficiency virus and level of physical activity, and negatively with the level of arthropathy. In multiple-regression analysis, only the level of physical activity and 25-hydroxyvitamin D [25(OH)D] significantly predicted BMD. Half of the patients had vitamin D deficiency. In conclusion, our study showed increased prevalence of low BMD in haemophiliacs. The levels of physical activity and 25(OH)D independently predicted low BMD.

Introduction Conflicting data exist regarding the role of leptin in bone metabolism. The purpose of the present study was to investigate serum leptin concentrations in male patients with haemophilia A and B, a disease known to be associated with low bone mass. Material and methods Eighty-one male patients, aged 45.4 ±15 years, were screened. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) in lumbar spine (LS), femoral neck (FN) and total hip (TH). Results Low bone mass was diagnosed in 20 patients (24.7%). Serum leptin concentrations were strongly associated with body weight (r s = 0.457, p = 0.0001) and body mass index (BMI) (r s = 0.491, p = 0.0001). In unadjusted analysis leptin was inversely associated with BMD in LS (r s = -0.255, p = 0.023), but not in FN and TH (r s = -0.205, p = 0.068 and r s = -0.191, p = 0.090, respectively). However, after adjusting for BMI and body weight, leptin was inversely associated with BMD in FN (F 1,76 = 7.727, p = 0.007, β = -0.371, ΔR (2) = 0.089) and TH (F 1,76 = 4.533, p = 0.036, β = -0.290, ΔR (2) = 0.054), but not in LS (F 1,75 = 2.076, p = 0.154, β = -0.202, ΔR (2) = 0.026). No association was found between age, presence of HBV, HCV or HIV infection or alkaline phosphatase and leptin levels. Conclusions Our study showed a negative association between circulating leptin levels and bone mass in males, independently of body weight and BMI.

Aim Hemophilia A and B has been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) is unknown. The aim of this study was to evaluate bone metabolism in men with hemophilia and investigate associations between BTM and bone disease. Methods Serum N- (NTX-I), C-terminal telopeptide of type I collagen (CTX-I) and tartrate-resistant acid phosphatase band-5b (TRAP-5b), as bone resorption markers, and osteocalcin (OC) and bone-specific alkaline phosphatase (b-ALP), as bone formation markers, were assessed. Results Seventy men (mean age 45.4±14.7 years) with hemophilia A (n=59) or B (n=11) were studied. Patients with low BMD had significantly higher b-ALP concentrations compared with those with normal BMD, without any differences in the other BTM. NTX-I and CTX-I concentrations were negatively associated with estradiol concentrations and hip BMD and positively with HIV infection, number of affected joints and arthropathy scores. B-ALP and OC concentrations were negatively associated with hip BMD, severity of hemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations. In men with low BMD, NTX-I, TRAP-5b and b-ALP concentrations were positively correlated with the number of affected joints, whereas TRAP-5b concentrations were positively associated with arthropathy scores and negatively with the level of physical activity. Conclusion Increased bone metabolism exists in men with hemophilia and low BMD. Arthropathy, low physical activity and low estradiol concentrations are associated with increased bone resorption and may contribute to the pathogenesis of low BMD in these patients. Disclosures: No relevant conflicts of interest to declare.