Erectile dysfunction in patients with haemophilia.

INTRODUCTION: Patients with haemophilia (PWH) are experiencing a nearly normal life span with safe factor replacement therapy and effective antiviral treatments for co-infections. As a result, many ageing-related health issues are starting to emerge. One rarely discussed health issue is erectile dysfunction (ED). ED can affect overall well-being and predict future cardiac events, but is not well studied in PWH. AIM: This prospective study aims to examine the prevalence and risk factors for ED in PWH using the validated International Index of Erectile Function (IIEF) questionnaire. METHODS: Patients with haemophilia A and B at all severities were invited to participate in IIEF questionnaire at the provincial Hemophilia Treatment Centre. Risk factors for ED including cardiovascular risk factors, prior surgeries, viral infections, medications and haemophilia-specific factors were obtained. Fasting laboratory tests including but not limited to renal function, haemoglobin, lipid profile, glucose and CRP were performed the same day. Blood pressure and anthropomorphic indices were measured. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD and hyperaemic velocity time integral [VTI]). RESULTS: Out of the 56 subjects approached, 44 completed the IIEF. Median age was 49 years. About 38.6% of the cohort reported ED symptoms. There was no significant difference in endothelial function measured by FMD and VTI between patient with ED and without. IIEF score correlated with age in multivariable analysis. CONCLUSION: Erectile dysfunction symptoms appear prevalent in PWH, particularly in the older group. This disorder along with the underlying causes needs to be explored further in future larger observational study.

Patient powered prophylaxis: A 12-month study of individualized prophylaxis in adults with severe haemophilia A.

INTRODUCTION: Adults with severe haemophilia A (SHA) may experience breakthrough bleeds despite standard weight-based FVIII prophylaxis three times weekly. Individualized prophylaxis has evolved to optimize patient outcomes. AIMS: This study aimed to evaluate the impact of a standardized approach to individualized prophylaxis on annualized bleeding rates (ABR), factor utilization, physical activity and quality of life in adults with SHA. METHODS: In this prospective cohort study, patients with baseline FVIII:C <2% and ABR >3 on weight-based prophylaxis received a standardized approach to individualized prophylaxis. Changes in ABR, annualized FVIII consumption and adherence from the 12-month prestudy and 12-month intervention period were compared. Changes in Haemo-QoL-A total score, Physical Functioning (PF) subscale and physical activity level measured by accelerometry were also examined. RESULTS: Eighteen patients participated (median age 26 years). Individualized prophylaxis decreased total bleeds in the population by 69% and traumatic bleeds by 73%. The median ABR decreased from 7.5 to 2 (P<.001). Annualized factor consumption increased by 7.3%, as a result of 66% reduction in factor utilization for treatment of bleeds and 25% increase in factor utilization for prophylaxis. Adherence scores for frequency and dosing did not change. There was a significant increase in the Haemo-QoL-A total score (P=.02) and PF score (P=.01) from baseline to 4 months but no change in physical activity. CONCLUSION: Patients with SHA who switched from standard to individualized prophylaxis show reduced ABR and increased FVIII consumption, and also improved their health-related quality of life. The mechanism is independent of adherence to prescribed prophylactic regimen.

The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.

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.

Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy.

Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an autosomal dominant syndrome characterized by platelet abnormalities and a predisposition to myelodysplasia (MDS) and/or acute myeloid leukemia (AML). The disorder, caused by inherited mutations in RUNX1, is uncommon with only 14 pedigrees reported. We screened 10 families with a history of more than one first degree relative with MDS/AML for inherited mutations in RUNX1. Germ- line RUNX1 mutations were identified in 5 pedigrees with a 3:2 predominance of N-terminal mutations. Several affected members had normal platelet counts or platelet function, features not previously reported in FPD/AML. The median incidence of MDS/AML among carriers of RUNX1 mutation was 35%. Individual treatments varied but included hematopoietic stem cell transplantation from siblings before recognition of the inherited leukemogenic mutation. Transplantation was associated with a high incidence of complications including early relapse, failure of engraftment, and posttransplantation lymphoproliferative disorder. Given the small size of modern families and the clinical heterogeneity of this syndrome, the diagnosis of FPD/AML could be easily overlooked and may be more prevalent than previously recognized. Therefore, it would appear prudent to screen young patients with MDS/AML for RUNX1 mutation, before consideration of sibling hematopoietic stem cell transplantation.

Long term platelet responses to Helicobacter pylori eradication in Canadian patients with immune thrombocytopenic purpura.

This prospective Canadian pilot study assesses the platelet response rate in H. pylori positive and negative patients and evaluates potential mechanisms to explain response. Patients with ITP received H. pylori eradication therapy and platelet counts at day 56 were used to assess response. Gastric permeability, stool H. pylori antigen and serum CagA anti-body were done at baseline and at day 60. Twenty-two patients were enrolled with an overall response rate of 27% (6/22). The prevalence of H. pylori was 18% (4/22). Seventy-five percent of the H. pylori positive patients (3/4) achieved a response compared to 17% (3/18) of the H. pylori negative patients (P < 0.05). Seventy-five percent of complete responders have demonstrated long-term ongoing responses at 48 months of follow-up. A trend towards lower post-eradication gastric permeability in responders was seen. Although the prevalence of H. pylori is low, H. pylori positive Canadian patients with ITP may benefit from a trial of H. pylori eradication therapy as a safe and effective means to achieve long term platelet response.

Prophylaxis in older Canadian adults with hemophilia A: lessons and more questions.

BACKGROUND: Although prophylaxis is a standard of care for young children in developed countries, known to reduce the severity of hemophilic arthropathy, older adults with existing arthropathy have not traditionally used prophylaxis. Recent studies have shown that adults with hemophilia A are increasingly adopting prophylaxis but the characteristics of this treatment in older adults are not well understood. This multicenter observational study was conducted to describe how secondary/tertiary prophylaxis is being used in older adults (≥40 years of age) in comparison to younger adults with severe hemophilia A. METHODS: Eligible adult (≥18 years of age) Canadian males with baseline FVIII:C ≤2% from the participating centres were observed over a 2 year period. RESULTS: Of the 220 adult severe hemophilia patients enrolled, 70% (155/220) used prophylaxis during the observational period. Only 27% (60/220) are older adults with very few >60 years of age. A lower proportion of older adults use prophylaxis compared to younger adults (58% vs. 75%, p = 0.016), with most patients in both groups using continuous prophylaxis (92 and 94% respectively). When considering all treatment modalities together, younger subjects use more factor concentrate than older subjects (2437 u/kg/year vs. 1702 u/kg/year, p = 0.027); however, older subjects on prophylaxis use 3447 u/kg/year and had an ABR of 12 while those on demand use 560 u/kg/year and had an ABR of 13. CONCLUSION: A significant number of older adults use secondary/tertiary continuous prophylaxis in Canada, accounting for a significant fraction of factor concentrate utilization.

2B or not to be--the 45-year saga of the Montreal Platelet Syndrome.

Over 45 years ago, Montreal Platelet Syndrome was first described as a rare inherited platelet disorder characterised by macrothrombocytopenia with spontaneous platelet clumping, abnormal platelet shape change upon stimulation and a defect in platelet calpain. This syndrome has now been reclassified as type 2B von Willebrand disease with the V1316M VWF mutation in the only kindred ever reported. We herein revisit the historical platelet characteristics originally described in Montreal Platelet Syndrome in light of the new diagnosis. This paper will review the 45-year saga of Montreal Platelet Syndrome, a story that highlights the value of revisiting a rare diagnosis to look for a more common explanation.