Uncoupling of Bone Turnover may Compromise Skeletal Health of Young Patients With Haemophilia A.

There is evidence that bone mass is decreased and bone metabolism is dysregulated in children with haemophilia (CWH). The objective of this study was to investigate the impact of haemophilia on skeletal health in children, with regards to bone mineral density (BMD) and metabolic bone profile. This study included 51 male CWH A. Dual-energy X-ray absorptiometry (DXA) was performed to assess BMD in lumbar spine (LS) and total body less head (TBLH) and Z-scores were calculated (low BMD Z-score<-2, low-normal BMD Z-score between -1 and -2). Serum levels of osteocalcin (OC), procollagen type I C-terminal propeptide (PICP), bone alkaline phosphatase (bALP), bone tartrate-resistant acid phosphatase 5b (TRAP5b), vitamin D, parathormone (PTH), urinary calcium/creatinine (uCa/uCr) and urine deoxypyridinoline/creatinine (uDPD/uCr) were measured. Mean BMD Z-scores were lower than predicted at both sites of measurement. More specifically, 10% of CWH A had low and 20% low-normal BMD Z-scores in LS, whereas 9.1% had low-normal TBLH BMD Z-scores and there were no patients with low BMD Z-scores at this site of measurement. 36.7% of CWH had low vitamin D levels and 19.6% had a history of fracture. Also, patients with haemophilia had lower OC and higher uDPD/uCr levels while OC positively correlated to BMD Z-scores and uDPD/uCr negatively correlated to BMD Z-scores at both sites. No statistically significant differences were observed with regards to mode of treatment, number of haemorrhages and the presence of target-joints. CWH A had decreased BMD Z-scores at both sites with an uncoupling of bone turnover LS BMD seemed to be more affected than TBLH BMD.

Impact of target joint and FVIII inhibitor οn bone properties in children with haemophilia A: A peripheral quantitative computed tomography study.

BACKGROUND: Haemophilic children are prone to low bone mass accrual. OBJECTIVE: To assess bone properties in haemophilic children, using peripheral quantitative computed tomography (pQCT) and to correlate findings with clinical data. SUBJECTS/METHODS: Peripheral quantitative computed tomography scan of both radii and tibiae were performed in 31 haemophilic A children (severe 24, mean age 11.2 years). Seven subjects had a history of inhibitors. Five children had an upper extremity target-joint and 12 had at least one lower extremity target-joint. The following parameters were measured: trabecular, total and cortical bone density and content (TBD, ToBD, CBD, TbC, CC), strength-stress index (SSI), and tibial cross-sectional area (CA), outer and inner bone contour length (PERI, ENDO) and cortical thickness (CTHC). RESULTS: Mean right radius TBD was significantly higher than the left one (P = 0.015). In subjects with arm target-joint, radius TBD was significantly lower in the target than in non-target arm (186.6 ± 60.4 vs 218.6 ± 39.8, P = 0.032). Left arm target-joint subjects had significantly lower left radius TBD in comparison to subjects without arm target-joint (155.4 ± 50.3 vs 215.7 ± 37.9, P = 0.019). There were no similar differences in leg target-joint. Bone quality and geometry parameters in cortical compartment were significantly lesser in inhibitor group, with statistically significant side-to-side differences for legs and arms and left side predominance. CONCLUSION: In children with haemophilia A and a history of target-joint and/or FVIII inhibitor, abnormalities may occur in the long bones as were revealed by pQCT, where low trabecular density and weak cortical bone quality in upper and lower extremities, respectively, were confirmed.

Venous thromboembolism at uncommon sites in neonates and children.

We retrospectively analyzed the data of 24 children (whereof 11 neonates), with non-central venous line-related and nonmalignancy-related venous thromboembolism (VTE) at uncommon sites, referred to our Unit from January 1999 to January 2012. Thirty patients who also suffered deep vein thrombosis, but in upper/low extremities, were not included in the analysis. The location of rare site VTE was: portal (n=7), mesenteric (n=2) and left facial vein (n=1), spleen (n=3), lung (n=3), whereas 10 neonates developed renal venous thrombosis. The majority of patients (91.7%) had at least 1 risk factor for thrombosis. Identified thrombophilic factors were: antiphospholipid antibodies (n=2), FV Leiden heterozygosity (n=6), MTHFR C677T homozygosity (n=4), protein S deficiency (n=2), whereas all neonates had age-related low levels of protein C and protein S. All but 6 patients received low-molecular-weight heparin, followed by warfarin in 55% of cases, for 3 to 6 months. Prolonged anticoagulation was applied in selected cases. During a median follow-up period of 6 years, the clinical outcome was: full recovery in 15 patients, evolution to both chronic portal hypertension and esophageal varices in 2 children, and progression to renal failure in 7 of 10 neonates. Neonates are greatly vulnerable to complications after VTE at uncommon sites, particularly renal. Future multicentre long-term studies on neonatal and pediatric VTE at unusual sites are considered worthwhile.

Management of ligneous conjunctivitis in a child with plasminogen deficiency.

UNLABELLED: Plasminogen deficiency, a rare autosomal recessive disorder, is classified as type I (hypoplasminogenemia) or type II (dysplasminogenemia). Hypoplasminogenemia is characterized by impaired wound healing while ligneous conjunctivitis (LC) is its main manifestation presenting with redness of the conjunctivae and progression to pseudomembranes' formation on the palpebral surfaces. A 4-year-old girl with LC in her left eye and impaired vision was referred to our unit. The conjunctival membranes had been already excised twice, followed by recurrences. Soon after the third recurrence, a probable diagnosis of LC was suggested, confirmed by a reduced plasminogen activity at 20% (normal values 80-120%). Both of her parents have slightly reduced plasminogen levels (50-60%) without any relevant symptom. Fresh frozen plasma (FFP) was administered systemically and topically, initiating 2 days before surgical removal of pseudomembranes with electrocautery under general anaesthesia. Systemic FFP was administered for 12 days postoperatively, along with topical use; the later was continued thereafter for 3 months. No recurrence was noticed. The vision was improved. Two weeks after cessation of the topical treatment, pseudomembranes reappeared. Topical application of FFP was reinitiated soon thereafter, and the girl underwent a second operation to have the conjunctival pseudomembranes removed. The perioperative therapeutic management was as previously described. Systemic treatment was stopped at the end of the tenth day while topical application of FFP was being continued until now, 10 months postoperatively. No recurrence has been observed and the vision remains at 9/10. CONCLUSION: Since surgical excision of the conjunctival pseudomembranes alone in patients with LC does not protect from recurrences, the perioperative administration of FFP, both systemically and topically improves the outcome. Furthermore, the long-term application of topical FFP preparations seems to prevent recurrences and has a protective effect on the vision of these patients.