Patients suffering from severe form of hemophilia (<1% factor activity) account for 60% of total hemophilia patients who may experience spontaneous bleeding into joints and muscles. The UKHCDO Dental Working Party Survey noted a similar variation in practice, with the majority of UK haemophilia centres aiming for a minimum single factor level of 50%, but with a range of pre-operative factor levels from 3060%, and with some centres giving repeat doses on a second day. ECI Webinars. Carter G, Goss A, Lloyd J, Tocchetti R . J Disab Oral Health 2009;10(4):151-55. Br Dent J 2007; 203: 389393. Keep Patient Engagement With the help of patient communication software. Mannucci P M, Tuddenham E G . Risk-based management of dental procedures in patients with inherited bleeding disorders: Development of a dental bleeding risk assessment and treatment tool (DeBRATT), Journal of Indian Society of Periodontology, http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=180&contentid=45&rptname=bleeding. Dougall A, Fiske J . Tranexamic acid mouthwash may be safely used as an adjunct but systemic treatment is best avoided when patients are treated with FEIBA due to increased risks of thromboembolic complications. The damaged teeth should be managed in a similar manner to any traumatised teeth remembering that factor cover may be required if there is significant bleeding. Menu button for Training & Technical Assistance">. This site needs JavaScript to work properly. (Treatment of Haemophilia monograph, no 45). It is the management of patients in whom the dental treatment may need modification according to their medical condition. and transmitted securely. 1983 Sep;56(3):246-51. doi: 10.1016/0030-4220(83)90004-x. Appointments should be arranged so that maximum treatment per visit can be completed to keep the number of factor infusions to a minimum. . Hemophilia A, or classic hemophilia, is are based on the amount of clotting factor in the result of a deficiency of factor VIII, or anti the blood and are expressed as a percentage hemophilicfactor. Ramstrm G, Sindet-Paedersen G, Hall G, Blombck M, Alander U . Erratum in: N Engl J Med 2001; 345: 384. The bleeding risk is difficult to assess from the level of severity of factor deficiency17 making this congenital bleeding disorder a challenge to treat. Harrington B . The timing of the planned cardiac surgery, medical status of the patient, and the It is common in dental practice to encounter patients with bleeding disorders in daily practice; therefore, it is essential to be able to identify such patients and safely manage their dental treatment.[7]. Materials Ordering System. and transmitted securely. Leal S C . Bleeding Issues (including anticoagulants) 2 . Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease. 10 Highly Influenced PDF View 4 excerpts, cites background Management of Hemophilia Patient Clinically, the tooth was fully erupted and in the line of occlusion with 18 (maxillary right 3rd molar) [Figure 1a]. Factor concentrate is administered by intravenous infusion, either by the individual or by parents and family, or by a haemophilia treater at the haemophilia centre. Women tend to be asymptomatic and men typically express diseases such as hemophilia which is X-linked. In patients with congenital bleeding disorders, the use of systemic tranexamic acid and epsilon aminocaproic acid have been demonstrated in two small randomised controlled studies in the early 1970s to control haemorrhage following dental extraction (GRADE 1B).30,31 A combination of systemic plus local tranexamic acid has been demonstrated to be associated with a reduced amount of bleeding compared to monotherapy in retrospective single-centre observational and case-control studies of dental extraction in patients with haemophilia (GRADE 2C).32,33 In a small double blind randomised controlled trial of 13 patients with all severities of haemophilia A and B conducted by Lee and colleagues,34 the use of tranexamic acid mouthwash after dental scaling was found to be as effective as factor replacement therapy in the control of gingival haemorrhage (GRADE 1B). The problems associated with the dental management of this group of patients will be discussed in a separate publication. Available at: www.gov.uk/government/publications/guidance-from-the-acdp-tse-risk-management-subgroup-formerly-tse-working-group (accessed 20 August 2013). Standard protocols of informed consent from the guardians/ parents of the selected subjects were observed. 1 2 The prevalence of haemophilia A (also known as classic haemophilia) is estimated at 1 in 6000 men while that of haemophilia B (or Christmas disease) has a prevalence of 1 in 30 000 men. Recommendation 2.7.7: For patients with hemophilia, the WFH recommends that dental extraction or other invasive procedures within the oral cavity (e.g., dental implantation, periodontal surgery, or gum biopsy) be performed only with a personalized plan for hemostasis management in consultation with a hematologist. Local antifibrinolytic treatment with tranexamic acid in haemophilic children undergoing dental extractions. On the 4th day, the patient returned with a complaint of uncontrolled bleeding for few hours. To support primary care teams and dental teams in the delivery of a preventive approach, evidence-based simplified prevention guides have been designed by the Department of Health39 and the Scottish Dental Clinical Effectiveness Programme (SDCEP),40,41 and are available online. The normal range of FVIII and FIX is between 50% and 150%. Figure 1 is an algorithm for dental management of patients undergoing heart valve surgery. The treatment of hemophilia may involve prophylaxis, management of bleeding episodes, treatment of factor VIII (FVIII) inhibitors, and treatment and rehabilitation of hemophilia synovitis. A. M. Anderson. What is hemophilia? There is typically an unpredictable mild bleeding tendency that may be provoked by surgery in areas with high fibrinolytic activity such as tonsillectomy and dental procedures. Guidelines for dental management of the hemophiliac patient are discussed. Internet Explorer). and JavaScript. J Clin Periodontol 2004; 31: 749757. Key words: Hemophilia, Von Willebrand disease, dental management, oral anticoagulants, antiplatelet. Haemostatic technique. In adult patients suturing and local haemostatic measures provide a useful adjunctive therapy to the augmentation of factor levels for dental extractions and invasive dental procedures.1 Both resorbable and non-resorbable sutures are acceptable. Mokhtari H, Roosendaal G, Koole R, Mauser-Bunschoten EP, van den Berg HM. Patients usually undergo an elective trial of DDAVP at the haemophilia centre to assess their responsiveness. Br Dent J. Haemophilia 2010; 16 (Suppl 4): 50 (Abs no 11S02). Mannucci P M, Ruggeri Z M, Pareti F I, Capitanio A . A number of dental procedures do not require augmentation of coagulation factor levels including examinations, fissure sealants, small occlusal restorations without the need for local anaesthesia and supragingival scaling. (Inhibit warfarin metabolism). For dental management of patients with hemophilia, it is important to know the child's type of hemophilia, the severity and their normal form of medical treatment for controlling bleeding. DDAVP: review of indications for its use in the treatment of factor VIII deficiency and report of a case. The most common diseases are periodontal disease (gum disease), dental decay and tooth wear. Bethesda, MD 20894, Web Policies 80# Aqueous Coating. Further experience in use of human antihaeomophilic globulin (H.A.H.G.) Basic Concepts of Hemophilia: Provider Guide [PDF - 680 KB] 57. Preoperative Management: 1. Haemophilia 2000; 6 (Suppl 1): 712. Hermans C, Altisent C, Batorova A et al. Fixed and removable orthodontic appliances may be used as long as enhanced preventive advice including oral hygiene instruction and demonstrations are carried out.41,44 The appliance should be designed so that the gingival and buccal mucosa cannot be damaged by sharp edges or wires. Brewer A, Correa M E . Female hemophilia gene carriers have lower quantities of FVIII compared to healthy females, but they do not manifest symptoms of hemophilia A. Accessibility A fairly common as an X-linked recessive trait. Dietary advice should routinely be given to patients to promote good oral health using four day food diaries, including advice regarding reduction in the frequency and amount of sugars, restriction of foods and drinks with a high sugar content at meal times only, and an outline of cariogenic foods and drinks such as carbonated beverages, fruit juices and cereals.43 Smoking should be strongly discouraged and NHS Stop Smoking Services are available to assist dental patients who wish to stop smoking. About 50% of male offsprings inherit the disorder due to female hemophilia A gene carriers. The following recommendations are intended to address clinical management issues that are not addressed fully within the package . The synthetic antidiuretic hormone, desmopressin, stimulates release of endogenous FVIII and vWF from stores in patients with mild haemophilia and vWD21,22 and is an established therapy for the control of bleeding associated with injury and minor general and oral surgical procedures. Life-threatening bleeding after dental extraction in a haemophilia A patient with inhibitors to factor VIII: a case report. Published by World Federation of Hemophilia. The patient was closely monitored in an ambulatory approach. Published: November 2022. The dental care of these patients should not be compromised, and this group of patients can be treated in the same way as any member of the general public. A. M. Anderson,A. system to treat all patients in need. Hemophilia patients have high risk of bleeding during various dental procedures. Antibiotics should only be prescribed if there is local spread or signs of systemic infection. Guidance on the Dental management of patients with Haemophilia and congenital bleeding disorders. An alternative therapy is an activated prothrombin complex concentrate, FEIBA. To audit the success rate using 4% articaine as buccal infiltration in order to anaesthetise mandibular molars for restorative dental treatment in patients with a hereditary coagulation disorder. Alternatively, DDAVP (0.3g/kg in 50ml of normal saline) can be administered intravenously (4g/ml concentration) one hour pre-procedure as a slow intravenous infusion over 2030 minutes. Mannucci P M . The use of tranexamic acid should be avoided with FEIBA as it may increase the risk of thromboembolism. Accessibility Recombinant factor VIIa (rfVIIa, NovoSeven) is administered as a bolus injection and a treatment consists of 90g/kg every two hours for three doses. The pericoronal flap was then surgically excised using a loop and straight electrode, while hemostasis was achieved using a ball electrode [Figure 1b]. The metabolic disorder of carbohydrate metabolism due to disturbance of the normal insulin mechanism (characterized by hyperglycemia). This laboratory A survey of all United Kingdom haemophilia centres conducted in 2010 by the UKHCDO indicated that the majority of survey responders aim for a single pre-procedural factor level of 50-80% (unpublished data). Dental management of patients with inhibitors to Factor VIII or Factor IX. Clinicians typically prescribe treatment products for episodic care or prophylactic care. Epub 2012 Mar 5. There are no controlled trials on thromboprophylaxis in this group of patients, only consensus opinion was based on small case reports. The haemophilias from royal genes to gene therapy. Children with severe haemophilia requiring dental extraction will usually require a general anaesthetic and factor replacement therapy will be required to cover intubation. 1990 Aug;3(3):27-40. Google Scholar. The authors certify that they have obtained all appropriate patient consent forms. Infection control. Oral health . Dental Treatment of Patients with Inherited Bleeding Disorders [1]. The principles described therein are still appropriate for the management of patients with inhibitors to either factor VIII or factor IX. Tooth extractions in haemophiliacs. Such patients should always be managed in the setting of specialized units with appropriate clinical expertise and laboratory support. Consideration in the dental treatment of the hemophiliac patient. Fijnvandraat K, Cnossen MH, Leebeek FW, Peters M. Diagnosis and management of haemophilia. The operated area was irrigated with sterile saline and povidone-iodine. The intranasal dose is 150g to one nostril for patients weighing <50kg and to both nostrils for those weighing 50kg. 2015 Jun;19(2):195-200. doi: 10.1007/s10006-014-0476-z. The molecular genetics of hemophilia. Part 1: diagnosis and prevention, Managing direct oral anticoagulants in accordance with the Scottish Dental Clinical Effectiveness Programme guidance for patients undergoing dentoalveolar surgery, Implications for dental professionals when caring for paediatric patients, Dental care pathways for adult inpatients in an acute hospital: a five-year service evaluation, COVID-19 pandemic: the first wave - an audit and guidance for paediatric dentistry, Orofacial manifestations of sickle cell disease: implications for dental clinicians, Service evaluation of the paediatric dental general anaesthesia service in NHS Lothian, www.bcshguidelines.com/bsch_process/evidence_levels_and_grades_of_recommendations/43_grade.html, www.app.dundee.ac.uk/tuith/Static/info/warfarin.pdf, www.gov.uk/government/publications/guidance-from-the-acdp-tse-risk-management-subgroup-formerly-tse-working-group, Bleeding disorders in implant dentistry: a narrative review and a treatment guide, Intentional replantation - a clinical review of cases undertaken at a major UK dental school, Anesthetic efficacies of intrapapillary injection in comparison to inferior alveolar nerve block for mandibular premolar extraction: a randomized clinical trial, European principles of inhibitor management in patients with haemophilia, Preventing perioperative bleeding in patients with inherited bleeding disorders. factor 8 stimulant - desmopressin iv 1hr before anti-fibrinolytic - epsilon-aminocaproic acid q 6 hours for 304 days . Baudo F, de Cataldo F, Landonio G, Muti G . https://doi.org/10.1038/sj.bdj.2013.1097, DOI: https://doi.org/10.1038/sj.bdj.2013.1097. Dental providers should be aware of the patient's hematologic status and related risks of bacteremia and excessive bleeding. Scottish Dental Clinical Effectiveness Programme. A total of 86 patients were selected from May 2009 to September 2010 and they underwent 144 different dental procedures including full mouth scaling, class II fillings, root canal treatment and extractions. The objective of this guidance, which is largely consensus-based, is to assist dental practitioners in primary and secondary care to provide routine dental care for patients of all ages with congenital bleeding diatheses in order to improve overall access to dental care. 31 terms. Hemophilic patients usually visit dental clinics with exten-sive dental treatment and complex management needs.14 Long waiting lists at the hospital as well as the high cost of traveling and treatment could be obstacles to seeking treatment earlier. Randall C (ed). Dental management of the hemophilic patient Vibhuti Kaul Oral manifestations of blood disorders Arsalan Wahid Malik Hemorrage in oral surgery Mohammad Akheel Haematology for Dental Students - Bleeding Disorders Shashidhar Venkatesh Murthy DENTAL MANAGEMENT OF THE MEDICALLY COMPROMISED PATIENT DENTAL MANAGEMENT OF. Arruda VR, Doshi BS, Samelson-Jones BJ. Emphasis is placed on the importance of regular dental follow-up, with fluoride varnish (5%) placed three to four times per year, and the principles of toothbrushing to prevent dental caries and periodontal disease by removal of the biofilm of dental plaque. Hematologic management of the patient should be directed by the patient's oncologist, and consultation with the medical team is necessary to determine the need for prophylactic interventions prior to dental treatment. In adults, local anaesthetic infiltration using a slow injection technique and modern fine gauge single-use needles can usually be used without the need for factor replacement therapy.1,43,44,45 In children there are differing views and advice should be sought from the paediatric haemophilia centre; for children on regular prophylaxis a dose of factor replacement therapy may be administered before infiltration. Print Copy Information: 98 pages. Department of Health and British Association for the Study of Community Dentistry. Would you like email updates of new search results? Postoperative instructions were reinforced. Hemophilia A and B) as well as of the alterations on platelets consequence of the use of certain medication (anti-platelet and anticoagulant drugs), and their dental management. In the case reported by the authors, using electrocautery helped the patient to some extent in minimizing the unnecessary postsurgical complication. Dental Management and Prevention Prevention is essential in managing the dental health of the child with hemophilia. Genotype analysis identifies the cause of the royal disease. @article{Katz1988DentalMO, title={Dental management of the patient with hemophilia. Total number of bleeding episodes (24 months) Soft tissue hemorrhages Extremity Trunk Head or neck Abdominal Hemarthroses Knee Ankle Elbow Other Lacerations Dental bleeding (including extractions) Hematuria . Lee A, Boyle C A, Savidge G F, Fiske J . Geneva: World Health Organization, 1996. Understanding this complex entity is very important for a. There are two main types of haemophilia: haemophilia A is the commonest, accounting for approximately 85% of all cases of haemophilia (incidence 1:5,000 live male births), and characterised by a deficiency of factor VIII (FVIII). More than 400,000 males are affected by hemophilia A, many of whom remain undiagnosed in developing countries. Received 2018 Jul 17; Accepted 2018 Sep 19. Primary dental care of patients with haemophilia. The dental man- agement of such indiviuals presents a signif- icant challenge; however, the onus is very much on the dental practitioner to maintain clear and frequent communication with the patient's primary physician, hematologist or both to assess the risk and plan appropriate management. Strategies for elective and emergency treatment planning. There is evidence from the literature that antifibrinolytic therapy plus factor replacement therapy is more effective than factor replacement therapy alone (GRADE 1B),30,31 and that antifibrinolytics and attention to local haemostasis are also of benefit49,50,51,52,53(GRADE 2C). Patients may be on prophylactic factor regimens. The distribution of orally administered versus tranexamic acid mouthwash has been compared in plasma and saliva samples of 30 healthy volunteers in a study by Sindet-Paedersen.23 Following oral tablet administration, peak plasma levels occurred after two hours but with no detectable levels in saliva. At each routine haemophilia follow-up visit there should be written documentation about the patient's oral health status and advice should be provided on preventive care. Lancet. ), In adult patients undergoing dental extractions, bleeding may be minimised by the use of either resorbable or non-resorbable sutures and additional local measures such as Surgicel, Gelfoam, cyanoacrylate tissue adhesives and surgical splints (consensus opinion). Dental management is the same for the equivalent categories of patients with haemophilia, as outlined in Table 1. Br Dent J 2003; 195: 495501. (Professor)12 Spiral Bound. [1] Hemophilia is an X-linked recessive disorder caused by insufficiency in coagulation factors, clinically characterized by prolonged clotting time. [9,10] According to a study conducted by the World Federation of Hemophilia, almost 50% of the world's hemophilia population lives in India, and over 70% of people with hemophilia do not have adequate knowledge or access to treatment.[11]. Patients with hemophilia A face many barriers to oral health care. In the majority of patients with type 1 vWD, treatment with desmopressin is used (Section 2.2) and type II and type III vWD usually require the administration of coagulation factor replacement therapy with a FVIII concentrate rich in vWF. As a result, individuals may avoid the dentist until extensive treatment needs arise. The presence of such an inhibitor poses Hemophilia Hemophilia A and B are genetic disorders of clotting factors VIII and IX, respectively. MeSH Scottish Dental Clinical Effectiveness Programme. Hewson I D, Daly J, Hallett K B et al. 2007 Apr-Jun;18(2):48-54. doi: 10.4103/0970-9290.32419. The delivery of dentistry has moved away from a treatment-focused approach to a preventive model of care. about navigating our updated article layout. Where possible, evidence from the literature is graded according to the 'GRADE' system (www.bcshguidelines.com/bsch_process/evidence_levels_and_grades_of_recommendations/43_grade.html); however, overall there is a lack of robust data and most studies have methodological limitations. Bleeding generally occurs only after trauma or surgery in mild hemophilic individuals (6%49% factor activity). This local anaesthetic has been described for infiltration as an alternative to inferior dental block in the restoration of mandibular molars, removing the need for pre-operative factor cover.46,47. ISSN 0007-0610 (print), Guidance on the dental management of patients with haemophilia and congenital bleeding disorders, Acquired bleeding disorders through antithrombotic therapy: the implications for dental practitioners, Guidelines relevant to paediatric dentistry do foundation dentists and general dental practitioners follow them? The treatment needs of adults with inherited bleeding disorders. Local haemostatic measures include oxidised cellulose, Surgicel, resorbable gelatine sponge, Gelfoam, cyanoacrylate tissue adhesives and surgical splints.37 A number of novel haemostatic agents Lyostpt and Ankaferd Blood Stopper38 may also be of use. General measures to reduce accidental trauma and minimise damage to oral mucosa should be employed at all times including careful use of saliva ejectors, careful removal of impressions and care in the placement of radiographic films.1,43. Factor XI deficiency differs from haemophilia A and B by the lack of bleeding into joints and muscles. One of the most haemophilic patient's concern about dental treatment is the possibility of oral bleeding, which could be spontaneous due to gum/periodontal disease or caused by some more invasive clinical procedures, such as endodontic treatment, periodontal surgery, or tooth extraction [4 4 Othman NA, Sockalingam SN, Mahyuddin A. Rasaratnam L, Chowdary P, Pollard D, Subel B, Harrington C, Darbar UR, et al. Ideally this should be given two hours pre-operatively, and continued for up to 7-10 days post-procedure. 8600 Rockville Pike Keila S . Tranexamic acid mouthwash a prospective randomized study of a 2-day regimen vs 5day regimen to prevent postoperative bleeding in anticoagulated patients requiring dental extractions. If prolonged bleeding is encountered discuss with a consultant in paediatric dentistry who can liaise with a consultant paediatric haematologist. Service Coordination/Case Management Resources. This is especially relevant in patients with mild forms of congenital bleeding disorders, or those who live geographically a long distance from the haemophilia centre. Oral Surg Oral Med Oral Pathol 1988; 66: 139144. dental care for individuals with vwd includes a comprehensive medical and dental health history review, including the documentation of vital signs; oral health screening; notation of current prescription therapies and allergies to any drugs used in dental care; assessment of the potential for substance abuse; and identification of other potential Oral Surg Oral Med Oral Pathol 1985; 59: 69. J. Based on the total amount of clotting factors in a human blood, hemophilia is classified into mild, moderate, and severe. This report describes the dental/medical management provided to an 8.10-year-old patient suffering . Management options for dental extraction in hemophiliacs: a study of 55 extractions (2000-2002). This will involve detailed liaison with the haemophilia centre. For patients with inhibitors to FVIII and FIX, it may be advisable to extract only one tooth at a time and to observe the patient for a 24-hour period after the extraction. Hemophilia is a rare, inherited blood disorder that causes your blood to clot less, which results in an increased risk of bleeding or bruising. J Am Dent Assoc 2007; 138: 11041112. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Severe hemophilia often manifests in the first months of life, whereas mild or moderate hemophilia will present later in childhood or adolescence often incidentally or following trauma. A bleed management plan should be developed and managed in close coordination with appropriate staff of the patient's HTC, including physicians/advanced practice providers, nurse coordinators, and pharmacy staff. In the meantime, to ensure continued support, we are displaying the site without styles Complications in HIV-infected and non HIV infected haemophiliacs and other patients after oral surgery. Ambados F . Treatment planning is essential for good outcome and should involve liaison between the dentist and the haemophilia centre. Local anesthesia rushda087 This report describes the dental/medical management provided to a 23-year-old patient suffering from uncontrolled bleeding after an electrosurgical procedure (operculectomy) in relation to the mandibular right third molar, in which hemophilia was a true accidental finding. After topical application of anesthesia, the area was infiltrated with lidocaine HCL 2% and epinephrine 1:100,000. There are three subtypes of vWD (Table 2) and patients in each subtype may be categorised into mild, moderate and severe at the time of diagnosis. The hemophilia). Desmopressin (DDAVP) is used to achieve a transient increase in factor VIII level through the release of en-dogenous factor VIII in patients with hemophilia A and von . Manton S, Martin A, Bhuta B . They are not intended to replace regular evaluation and treatment by the hemophilia treatment centre. Ryan White was an American hemophiliac who was infected with HIV from a contaminated blood treatment (factor VIII). A major anxiety of patients with congenital bleeding disorders is the risk of bleeding either during or after treatment, as well as concerns about dentists' understanding of their bleeding condition and its management.3,6 Many patients also worry when their gingivae bleed on brushing and so avoid brushing, which exacerbates the problem, especially if preventive dentistry is difficult to access in a primary care setting. }, author={Jerald O. Katz and G{\'e}za T. Ter{\'e}zhalmy}, journal={Oral surgery, oral medicine, and oral pathology}, year={1988}, volume={66 1}, pages={ 139-44 } } Access to special care dentistry, part 5. DOI: 10.1016/0030-4220(88)90081-3 Corpus ID: 43328331; Dental management of the patient with hemophilia. Management of bleeding in these patients during & after surgery is the biggest challenge for dental. It is an autosomal dominant condition, and affects both males and females. A significant number of patients have also experienced the refusal of treatment by general dental practices. Adornato M C, Penna K J . Effectiveness in controlling haemorrhage after dental scaling in people with haemophilia by using tranexamic acid mouthwash. HHS Vulnerability Disclosure, Help With clinical and laboratory findings, the patient was diagnosed as having mild hemophilia A. Following extraction, packing with Gelfoam rolled in thrombin powder (Thrombostat) or use of Surgicel may aid haemostasis. Dundee: Scottish Dental Clinical Effectiveness Programme, 2011. Epub 2009 Jun 5. Some mild hemophiliacs may remain undiagnosed until late adulthood. Patients with mild hemophilia A need pre-operative cover for invasive procedures where bleeding is likely. The use of a new haemostatic agent: Ankaferd Blood Stopper in haemophiliacs. Lockhart P B, Gibson J, Pond S H, Leitch J . In children, the routine exfoliation of primary teeth does not routinely require factor replacement therapy. { Katz1988DentalMO, title= { dental management of the patient was closely monitored in ambulatory! Only be prescribed if there is local spread or signs of systemic infection occurs! J, Pond s H, Roosendaal G, Blombck M, Alander U haemophilia centre disorder a challenge treat! And to both nostrils for those weighing 50kg, Gibson J, Pond H! 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