Karin P.M. van Galen

Discontinuing early prophylaxis in severe haemophilia leads to deterioration of joint status despite low bleeding rates

Prophylaxis is the recommended treatment for children with severe haemophilia A, but whether prophylaxis should be continued in adulthood is still under debate. Previous studies with limited follow-up have suggested that some patients may be able to stop prophylaxis in adulthood, while maintaining good joint health. This single-centre observational cohort study examined patients with severe haemophilia A born 1970-1988 without inhibitor development, and assessed the long-term consequences of discontinuing prophylaxis. Patient-initiated changes in prophylaxis, including all switches to on-demand treatment lasting a minimum of two consecutive weeks, were recorded from the time self-infusion began until the last evaluation. Sixty-six patients were evaluated at a median age of 32.4 years: 26 % of patients had stopped prophylaxis for a median of 10 years, 15 % had interrupted prophylaxis and 59 % had continued prophylaxis. Annual joint bleeding rate (AJBR), Haemophilia Joint Health Score (HJHS-2.1; 0-124 points), radiological Pettersson score (0-78 points) and Haemophilia Activities List score (HAL; 100-0 points) were compared between patients who stopped and patients who continued prophylaxis. Although self-reported bleeding rates and functional limitations were similar in both groups (AJBR: 1.5 vs 1.2 and HAL: 84 vs 84 for those who stopped and continued prophylaxis, respectively), objective assessment of joint status showed increased arthropathy after 10 years of on-demand treatment in patients who stopped prophylaxis compared with those who continued (HJHS: 23 vs. 14 and Pettersson: 16 vs 5, respectively; P< 0.01). These results support continuation of long-term prophylaxis in adults and demonstrate the need for objective monitoring of joint status.

Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study

Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds were matched for age, sex and Factor VIII level or von Willebrand Factor activity in a nested case-control study within the Willebrand in the Netherlands study. Assessments included the Hemophilia Joint Health Score (0–124), Pettersson score (0–13 per joint X-ray), Hemophilia Activity List score (0–100), joint pain (Visual Analog Scale 0–10), and the Impact on Participation and Autonomy questionnaire (0–20). Arthropathy was defined as a Hemophilia Joint Health Score of 10 or higher, or a Pettersson score over 3 of at least one joint. We included 48 patients with verified joint bleeds (cases) and 48 controls: 60% males, mean age 46 years (range 18–80), median von Willebrand Factor activity 5 versus 8 IU/dL and Factor VIII 24 versus 36 IU/dL. Arthropathy occurred in 40% of the cases versus 10% of the controls (P<0.01). The cases reported more functional limitations compared to the controls (median Hemophilia Activity List score: 88 vs. 100, P<0.01). Arthropathy was related to joint pain and less social participation (Visual Analog Scale>3: 13 of 19 vs. 3 of 28, P<0.01, and median score on the participation questionnaire 6.1 vs. 0.9, P<0.01). In conclusion, arthropathy occurs in 40% of VWD patients after joint bleeds and is associated with pain, radiological abnormalities, functional limitations, and less social participation (Dutch trial register: NTR4548).

Maternal vitamin B12 deficiency and abnormal cell‐free DNA results in pregnancy

Whats Already Known about this Topic? Prenatal testing with cell-free DNA may incidentally identify maternal genetic anomalies and malignancies. What does this Study Add? Profound vitamin B12 deficiency with intramedullary hemolysis may cause abnormal genomic patterns that can be detected by cell-free DNA sequencing.

First report of inhibitory von Willebrand factor alloantibodies in type 2B von Willebrand disease.

Antibodies to von Willebrand factor (VWF) in patients with congenital von Willebrand disease (VWD) are rare; the prevalence in type 3 VWD patients is 6–10%. These antibodies are associated with loss of haemostatic response to VWF concentrates and allergic reactions, even anaphylactic, in rare cases. The majority of these alloantibodies occur in patients with large VWF gene deletions, although VWF antibodies have also been described in patients with nonsense or frameshift mutations (James et al, 2013). There are no reported cases of VWF alloantibodies in non-type 3 VWD. We report the first case of VWF antibodies with inhibitor activity in a 35-year-old woman with type 2B VWD. Anti-VWF antibodies are mostly characterized as polyclonal IgG class alloantibodies (Berntorp et al, 2013). Target specificity has been demonstrated towards the GP1b-binding A1 and the collagen binding A3 domain of VWF in selected cases (Van Genderen et al, 1994; Tout et al, 2000). In addition, some antibodies have been reported to partially inhibit factor VIII (FVIII) coagulation activity (FVIII:C). To date, no single common epitope has been shown to be involved (L opez-Fern andez et al, 1988; Batlle et al, 1997; Tout et al, 2000). We further analysed the properties of the VWF alloantibody in the presented type 2B VWD patient. A 35-year-old woman was previously diagnosed with type 2B VWD; mutation analysis revealed a 3922C>T nucleotide substitution in VWF, resulting in a R1308C amino acid substitution in exon 28 coding for the VWF-A1 domain (Verweij et al, 1988; Ahmad et al, 2013). Incidental treatment consisted of desmopressin and tranexamic acid, she had received cryoprecipitate once in childhood. The current

Antifibrinolytic therapy for preventing oral bleeding in people on anticoagulants undergoing oral or dental procedures

This is the protocol for a review and there is no abstract. The objectives are as follows: We aim to assess the efficacy of antifibrinolytic agents for preventing bleeding complications in people on oral anticoagulants undergoing oral or dental procedures. Secondary objectives are to assess if antifibrinolytic agents can eliminate the need for the discontinuation or a dose reduction of oral anticoagulants before and during oral or dental procedures.

Long-Term Outcome after Joint Bleeds in Von Willebrand Disease Compared to Haemophilia A: A Post Hoc Analysis

Long-term outcome after joint bleeds in von Willebrand disease (VWD) (von Willebrand factor activity ≤ 30 IU/dL) could differ from moderate or severe haemophilia A (HA) (factor VIII [FVIII] 1-5 IU/dL or FVIII < 1 IU/dL). We performed a post hoc analysis on Haemophilia Joint Health Score (HJHS, 0-124), X-ray Pettersson scores (PS, 0-13/joint) and the Haemophilia Activities List (HAL, 0-100), using multivariable regression to adjust for age (rate ratio [RR] or odds ratio [OR] [95% confidence interval]). We included 48 VWD (median age, 47 years, type 3 VWD, n = 19), 39 moderate HA (median, 39 years) and 59 severe HA patients (median, 25 years) with documented joint bleeds. VWD patients suffered repeated bleeding (lifetime > 5/joint) less often than moderate and severe HA patients (52% vs. 77% vs. 98%). HJHS and PS in VWD were similar to moderate HA (median HJHS 5 vs. 6, RR 0.9 [0.5-1.4] and PS > 3 of ≥ 1 joint OR 0.3 [0.1-1.4]), but better than in severe HA patients (median HJHS 5 vs. 9, RR 1.8 [1.1-2.9]; PS > 3 in any joint OR 0.1 [0.0-0.3]). Self-reported limitations in activities were comparable across VWD, moderate HA (HAL score < 95: 67% vs. 49%; OR 1.4 [0.5-3.6]) and young adults with severe HA (67% vs. 48%; OR 1.7 [0.7-4.4]). Despite fewer joint bleeds, joint outcome after joint bleeds was similar in VWD and moderate HA patients. Type 3 VWD patients had worst joint outcome, comparable to younger intensively treated severe HA patients. Limitations in activities occurred as often in VWD as in both moderate and severe HA.

Letter From van Galen et al Regarding Article, “Cardiac Amyloidosis: A Treatable Disease Often Overlooked”

To the Editor: Recently, Falk pointed toward the importance of an early diagnosis of cardiac AL (light-chain) amyloidosis (CA) in view of the increasing number of treatment options. Unfortunately, the efficacy of an implantable cardioverter-defibrillator (ICD) to prevent sudden cardiac death (SCD) was considered to be negligible.1 Nevertheless, SCD severely threats CA patients. We fear that, on the basis of scarce literature only, ICD use in CA is becoming a nonissue undeservedly. From our own clinical practice and a critical review of literature, we believe that selected patients could possibly benefit from an ICD. First, potential SCD was prevented in 2 CA patients, diagnosed at the VU University Medical Center, …