Women who are pregnant and have mechanical prosthetic heart valves (MPHV) pose a major therapeutic dilemma for clinicians responsible for providing care. Two issues seem clear. Pregnancy in women with MPHV is very uncommon in the UK-the UKOSS study reports an occurrence in 0.0037% of pregnancies-one case in every 27 000 maternities, so very few UK practitioners will have direct experience in caring for these women. Pregnancy is a hypercoagulable state and women with MPHV require therapeutic dose anticoagulation throughout pregnancy to reduce the risk of valve thrombosis and its complications. A highly contentious issue is what constitutes the 'optimal' anticoagulant regi-men. Some clinicians (Regitz-Zagrosek et al. Eur Heart J 2011;32:3147-97) strongly favour continuing vitamin K antagonists, such as warfarin, throughout pregnancy, arguing that they are the most effective, albeit not 100% effective, at preventing thromboem-bolic complications (TEC). However, these drugs freely cross the placenta and are teratogenic. Warfarin embry-opathy is reported in up to 12% of infants exposed in the first trimester. Warfarin fetopathy (fetal loss, stillbirth and neurological problems) is reported in up to 25% women exposed to war-farin in later pregnancy. Much has been made of a 'safe' warfarin dose but there is no dose that prevents adverse fetal outcomes (McLintock Best Pract Res Clin Obstet Gynecol 2014;28:519-36). This has prompted the demand for alternative approaches to anticoag-ulation. Low-molecular-weight heparin (LMWH) does not cross the placenta, is not teratogenic and its use is associated with live birth rates of 95% in women with MPHV. Although it is not as effective at preventing TEC, the best outcomes are achieved if women are able to comply with twice daily injections of LMWH and have regular anti-Xa levels to guide dose adjustments as pregnancy progresses. Critical to the clinical efficacy of LMWH is ensuring adequate levels of anticoagu-lation. Peak anti-Xa levels will predict the maximum anticoagulant effect of LMWH and risk of bleeding. Trough levels ensure that anticoagulation is within a therapeutic threshold. Whether targeting peak and trough levels is associated with lower risks of TEC has not been tested in a large prospective study. The UKOSS study highlights an inconsistent and inadequate approach to anticoagulant management. Practitioners did not seem to appreciate the complexities inherent in providing safe anticoagulation or the high risk of these pregnancies. One in five women were not referred for specialist care at any stage during their pregnancy. Of the women who chose 'therapeutic dose' LMWH throughout pregnancy, data on anti-Xa monitoring was available in just over half, with alarming variations in the frequency and timing of testing, and target anti-Xa levels. Inappropriate LMWH dosing and poor compliance were associated with poor maternal outcome. Given the inadequacies in clinical care, it is not surprising that clinical outcomes in the cohort overall were poor and it is uncertain if...

Fifty adults aged 35.12±14.7 with mild (n = 12), moderate (n = 10), or severe (n = 28) haemophilia A (70%) or B (30%) from four haemophilia centres across the United Kingdom participated in the study. A total of 64% were overweight/obese according to their BMI; median orthopaedic joint scores using the WFH Orthopaedic Joint Score (OJS) were 6 (range 0-48). On a VAS pain scale (range of 0-10), patients reported mean score of 5.66 ± 2.4. 36% of participants reported not doing any sport, mainly due to their physical condition. However, 64% of participants reported undertaking sporting activity including contact sports, mostly twice per week in average 4 h week(-1) . Participating in sport did not have a statistically significant impact on HRQoL; except in the domain 'sport and leisure' of the Haem-A-QoL. Patients doing more sport reported significantly better HRQoL than those doing less sport (P < 0.005). Those doing sport for more than 4 h week(-1) had a significantly better physical performance than patients doing less sport (assessed with Hep-Test-Q). Encouraging physical activity and sport in older patients with haemophilia may have a direct impact on their HRQoL; thus, education about sport activity should be incorporated into routine haemophilia care.

Introduction: Nuwiq â [human cell line-derived recombinant factor VIII (human-cl rhFVIII)] is a new generation rFVIII protein, without chemical modification or fusion to any other protein, produced in a human cell line. Aim/methods: This prospective, open-label, multinational phase III study assessed the efficacy and safety of human-cl rhFVIII in 32 adult previously treated patients (PTPs) with severe haemophilia A during standard prophylaxis for ≥6 months and ≥50 exposure days. Efficacy in treating bleeds and during surgical prophylaxis was also assessed. Results: Prophylactic efficacy, based on mean monthly bleeding rate, was rated as 'excellent' or 'good' in 97% of patients for all bleeds and in 100% of patients for spontaneous bleeds. Mean (SD) annualized bleeding rate was 2.28 (3.73) [median = 0.9] for all bleeds, 1.16 (2.57) [median = 0] for spontaneous bleeds and 1.00 (1.79) [median = 0] for traumatic bleeds. There were no bleeds in 50% of patients and there were no major, life-threatening bleeds. Efficacy was 'excellent' or 'good' in treating 28 (100%) of 28 bleeds. Overall efficacy was rated as 'excellent' during four surgical procedures (three major, one minor) and 'moderate' during one major surgery. Incremental in vivo recovery (IVR) data were comparable with the one-stage and chromogenic assays. IVR was >2.0% per IU kg À1 for all measurements and stable over 6 months. No patients developed FVIII inhibitors and there were no treatment-related serious or severe adverse events. Conclusion: These results in adult PTPs indicate that human-cl rhFVIII is effective for the prevention and treatment of bleeds in adults with severe haemophilia A.

1 The effect of low dose steady state warfarin (0.2 mg and 1 mg daily) on clotting factor activity and vitamin K1 metabolism was studied in seven healthy volunteers. 2 Steady state plasma warfarin concentrations were 41‐99 ng ml‐1 for the 0.2 mg dose and 157‐292 ng ml‐1 for the 1 mg dose. 3 There was a significant prolongation of the mean prothrombin time (0.9 s) after 1 mg warfarin daily, but no significant change in prothrombin time after 0.2 mg warfarin daily. There was no significant change in individual clotting factor activity (II, VII, IX or X) with either dose of warfarin. 4 Following the administration of a pharmacological dose of vitamin K1 (10 mg), all seven volunteers had detectable levels of vitamin K1 2,3‐epoxide with both doses of warfarin (Cpmax 31‐409 ng ml‐1). 5 Both the Cpmax and the AUC for vitamin K1 2,3‐ epoxide were significantly greater on 1 mg of warfarin daily than 0.2 mg daily (P less than 0.01). 6 The apparent dissociation between inhibition of vitamin K1 2,3‐epoxide reductase and reduction of clotting factor activity, produced by warfarin, may reflect the insensitivity of functional clotting factor assays to a small reduction in clotting factor concentration.