During childhood growth, bone undergoes modelling involving separate osteoblastic and osteoclastic processes. Markers of bone turnover circulate at high concentrations, parallel the childhood growth curve and correlate with height velocity. The aim of this study was to compare serum markers of bone turnover in children with haemophilia and normal bone mineral density (BMD) vs. those with low BMD. In a cross-sectional study, 69 children with haemophilia were evaluated, 45 children with normal spine BMD vs. 24 with low BMD. Lumbar spine BMD was determined using dual X-ray absorptiometry and Z-scores were calculated. Serum samples of markers of bone turnover, osteocalcin (bone formation) and C-telopeptide of type I collagen (bone resorption) were measured using ELISA. The mean BMD (g cm(-2) ) in the normal group was 0.656 ± 0.15 vs. 0.558 ± 0.12 in those with low BMD (P = 0.007), osteocalcin levels in children with normal BMD were 9.29 ± 4.97 vs. 7.06 ± 2.17 ng μL(-1) in the low BMD group (P = 0.012). C-telopeptide levels in the normal group were 1.06 ± 1.4 vs. 0.74 ± 0.3 ng mL(-1) in the low BMD group (P = 0.169). Our results showed that low osteocalcin levels predominated in the group with low BMD, which indicates a diminished osteoblastic bone formation activity while there were no differences with regard to bone resorption markers. Moreover, osteocalcin levels explain 10% of the variation of lumbar spine Z-score.

BackgroundThe Functional Independence Score in Hemophilia (FISH) is a performance‐based assessment tool used to measure the patients functional ability so far only used in patients with severe hemophilia. Its aim is to determine if FISH is useful in patients with mild and moderate disease.ProcedureIn a cross‐sectional study 90 children 60 hemophilic and 30 sex‐, race‐, and age‐matched healthy males were assessed. Patients between 5 and 16 years of age were selected each patient was evaluated in seven activities under three categories: self‐care (grooming and eating, bathing, and dressing), transfers (chair and squat), and locomotion (walking and step climbing). Each activity was graded from 1 to 4 according to the amount of assistance required to perform the activity with total scores ranging from 7 to 28.ResultsAs a whole, the mean age of the patients was 10.0 ± 3.4 years with a mean FISH of 25.8 ± 3.6 (range 15–28). There were no differences in the FISH between healthy males and patients with mild hemophilia; however, the score was significantly higher in patients with mild hemophilia (28 ± 0) than patients with moderate (26.2 ± 2.5; P = 0.004) or severe hemophilia (24.0 ± 4.7; P = 0.0006). The most affected activities were squatting, walking, and step climbing.ConclusionsA significant decrease in functional ability was demonstrated according to the severity of hemophilia, especially for those activities involving weight‐bearing demands like locomotion and step climbing. Of seven activities evaluated, changes were observed in the group with moderate and severe hemophilia, but no changes detected in patients with mild disease. Pediatr Blood Cancer 2010;54:394–397. © 2009 Wiley‐Liss, Inc.

In Mexico, 15% of haemophilia A (HA) patients develop inhibitory alloantibodies in response to replacement therapy with factor VIII (FVIII), requiring bypass therapy such as activated prothrombin complex concentrate (APCC). Because bypass therapy has not been broadly available in Mexico even in recent years, this study aimed to evaluate the thrombin generation assay (TGA) in assessing the response to FVIII or APCC treatment in patients with severe HA positive to inhibitors. We studied 189 patients with severe HA. Clinical severity was verified by one-stage APTT-based clotting assay. Inhibitors to FVIII were investigated by the Nijmegen-Bethesda (N-B) method, and type of inhibition was assessed through serial plasma dilutions. Thrombin generation was measured with the calibrated automated thrombogram in inhibitor-positive plasmas previously spiked and incubated with FVIII or APCC. Data were analysed using anova, Student or Fisher's exact tests. We detected 47 (24.9%) subjects with high-titre (5-1700 N-B U mL(-1)) and 25 (13.2%) subjects with low-titre inhibitor antibodies (0.6-4.7 N-B U mL(-1)). We found an association between kinetic behaviour and clinical response to FVIII (P = 0.0049) or vs. FVIII response evaluated with TGA (P = 0.0007). Global concordance between clinical and in vitro response was 70%. By evaluating the capacity of thrombin formation in a plasma sample, TGA predicts the response to FVIII or APCC therapy and allows individual optimization of resources in patients with severe HA and high-titre inhibitors. The inhibition pattern of the antibodies to FVIII:C correlated with the TGA parameters and showed an association with the clinical response to FVIII.

BackgroundThe pathophysiology of hemophilic arthropathy is complex and not completely understood. In this study, we aimed to identify biomarkers that can affect the hemophilic arthropathy severity.MethodsFifty patients were analyzed for biomarker frequencies; in 37 patients, articular symptoms were evaluated based on the physical joint examination score, and in 18, it was based on magnetic resonance imaging. Eight polymorphisms, namely FV 1691G>A, FII 20210G>A, MTHFR 677C>T and 1298A>C, TNFα‐308G>A and ‐238G>A, ACAN VNTR, and IL1RN*2‐VNTR were identified.ResultsPatients with the MTHFR 677TT genotype showed a higher number of affected joints (1.83 ± 0.9 vs. 0.55 ± 0.7 for CC; p = .023), whereas those with the MTHFR 1298AC genotype exhibited higher effusion according to two radiologists (0.90 ± 0.31/1.20 ± 0.63 vs. 0.38 ± 0.52/0.50 ± 0.53 for AA genotype; p = .043/0.036, respectively). In addition, patients with the TNFα‐308GA genotype had more subchondral cysts (0.75 ± 0.95 vs. 0.07 ± 0.26 for GG genotype; p = .041).ConclusionsThe distribution of risk genotypes for MTHFR and TNFα‐308GA suggests their association with clinical parameters of hemophilic arthropathy. Cohort studies are essential to verify these associations.

Introduction Development of inhibitors is the most serious complication in patients with haemophilia (PWH). The prevalence of inhibitors in patients with severe haemophilia A (HA) is approximately 25%‐30%. Inhibitor prevalence differs among populations. Some studies report a prevalence of almost twice in Hispanic as compared to Caucasian patients. Most data available, on the prevalence of inhibitors and their predisposing factors, originate from centres in developed countries. Aim Establish the prevalence of inhibitors of FVIII and FIX in Mexico. Methods This was an observational, cross‐sectional and descriptive study. The records of all patients diagnosed with haemophilia A (HA) or B (HB), with and without inhibitors, were included. Clinical and demographical characteristics of patients with inhibitors were assessed. Statistical analysis was performed using IBM SPSS version 22. The Ethics Committees of the various participating institutions approved this study. Results A total of 1455 patients from the 20 participating centres were recruited, from which 1208 (83.02%) had HA and 247 (16.97%) were diagnosed with HB. The presence of inhibitors in severe HA was reported in 93/777(11.96%), and 10/162 (6.17%) in severe HB. Of them, 91.7% exhibited high titres in HA and 100% in HB. Conclusion In Mexico, the general prevalence of inhibitors varies considerably among centres. This study established a basis of comparison for future development and advances in the treatment and follow‐up of patients. These findings also augment our understanding of risk factors related to inhibitor development.