AS. Magnetic resonance imaging and joint outcomes in boys with severe hemophilia A treated with tailored primary prophylaxis in Canada.J Thromb Haemost 2012; 10: 2494-502.Summary. Background/objectives: Tailored primary prophylaxis (TPP) is a reduced-intensity treatment program for hemophiliacs with the goal of preventing arthropathy. Our primary aim was to evaluate the joint outcomes of treated subjects using magnetic resonance imaging (MRI) and physical examination as outcome measures. Methods: Ankles, elbows and knees (index joints) of 24 subjects (median [range] age at start of therapy, 1.6 [1-2.5] years) with severe hemophilia A enrolled in the Canadian Hemophilia Primary Prophylaxis Study (CHPS) were examined by MRI at a median age of 8.8 years (range 6.2-11.5 years). Subjects were treated with TPP using a recombinant factor VIII concentrate, starting once weekly and escalating in frequency and dose according to frequency of bleeding. Results: Osteochondral changes (cartilage loss/subchondral bone damage) were detected in 9% (13/ 140) of the index joints and 50% (12/24) of study subjects. Osteochondral changes were restricted to joints with a history of clinically reported joint bleeding. Soft tissue changes were detected in 31% (20/65) of index joints with no history of clinically reported bleeding (ankles 75% (12/16); elbows 19% (6/32); and knees 12% (2/17)). In these apparently Ôbleed freeÕ index joints hemosiderin deposition was detected by MRI in 26% (17/65) of joints (ankles 63% (10/16); elbows 16% (5/32), and knees 12% (2/17)). Conclusion: TPP did not completely avoid the development of MRI-detected structural joint changes in hemophilic boys in this prospective study. A longer period of follow-up is required for assessment of the longitudinal course of these early changes in hemophilic arthropathy, detected using a sensitive imaging technique (MRI).

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BackgroundThis study was undertaken to explore the longitudinal patterns of health-related quality of life (HRQoL) among youth and young adults with Hemophilia A (HA) over a 3-year period. This report presents the baseline characteristics of the study cohort.MethodsMales, 14 to 29 years of age, with predominantly severe HA were recruited from six treatment centres in Canada. Subjects completed a comprehensive survey. HRQoL was measured using: the CHO-KLAT2.0 (youth), Haemo-QoL-A (young adults) and the SF-36v2 (all).Results13 youth (mean age = 15.7, range = 12.9-17.9 years) and 33 young adults (mean age = 23.6; range = 18.4 -28.7 years) with moderate (7 %) and severe (93 %) HA were enrolled. All were on a prophylactic regimen with antihemophilic factor (Helixate FS®) during the study. The youth had minimal joint damage (mean HJHS = 5.2) compared to young adults (mean HJHS = 13.3). The mean HRQoL scores for youth were: 79.2 (SD = 11.9) for the CHO-KLAT, and 53.0 (5.5) and 52.3 (6.8) for the SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores respectively. The mean HRQoL scores for young adults were: 85.8 (9.5) for the Haemo-Qol-A, and 50.8 (6.4) and 50.9 (8.8) for PCS and MCS respectively. PCS and MCS scores were comparable to published Canadian norms, however significant differences were found for the domains of Physical Functioning and Bodily Pain. The disease-specific HRQoL scores were weakly correlated with the PCS for youth (CHO-KLAT vs. PCS r = 0.28, p = 0.35); and moderately correlated for the MCS (r = 0.39, p = 0.19). Haemo-QoL-A scores for young adults were strongly correlated with the PCS (r = 0.53, p = 0.001); and weakly correlated with the MCS (r = 0.26, p = 0.13). Joint status as assessed by HJHS was correlated with PCS scores. A history of lifelong prophylaxis resulted in better PCS but worse MCS scores.ConclusionDespite having hemophilia, the youth in this cohort have minimal joint disease and good HRQoL. The young adults demonstrated more joint disease and slightly worse HRQoL in the domains of physical functioning and pain. The data presented here provide new information to inform the selection of Health Related Quality of Life (HRQoL) instruments for use in future clinical trials involving persons with hemophilia.Trial registrationClinicalTrials.gov : NCT01034904. Study funded by CSL Behring Canada.Electronic supplementary materialThe online version of this article (doi:10.1186/s12878-016-0052-x) contains supplementary material, which is available to authorized users.

Montreal platelet syndrome (MPS), hitherto described in only one kindred, is a hereditary thrombocytopenia associated with mucocutaneous bleeding, giant platelets, and spontaneous platelet aggregation in vitro. These are features shared with some forms of type 2B von Willebrand disease (VWD); however, the MPS kindred had not been investigated for VWD. We found that all affected MPS family members had borderline to normal von Willebrand factor antigen (VWF:Ag; 0.43-0.75 U/mL), discrepantly low ristocetin cofactor activity (VWF:RCo; 0.16-0.29 U/mL), and normal factor VIII coagulant activity (FVIII:C; 0.57-1.04 U/mL). Unaffected family members all had normal VWF:Ag, VWF:RCo, and FVIII:C levels. In addition, persons with MPS, but not unaffected family members, had loss of plasma (but not platelet) high molecular weight VWF multimers, and were heterozygous for the previously reported V1316M type 2B VWD mutation. Thus, in reevaluating this kindred, we determined that patients with MPS have type 2B VWD with the V1316M VWF mutation. (Blood. 2009;113:3348-3351)