Developing an inhibitor to von Willebrand factor (VWF) is extremely uncommon. Consequently, patients with von Willebrand disease (VWD) tend not to be routinely evaluated for inhibitors, leading to the possibility of delay in inhibitor diagnosis. We present such an occurrence to raise awareness, with a view to avoiding such delays. A 1-year-old male with no family history of bleeding disorders or parental consanguinity presented with a tongue bleed lasting three days. Investigations confirmed a diagnosis of Type 3 VWD. Over the next few months, the patient received seven exposures to Humate-P (a plasma derived FVIII containing von Willebrand factor concentrate), but developed an anaphylactic reaction necessitating adrenalin and Benadryl (diphenhydramine). The reaction quickly abated and did not recur with further exposure to Humate-P. In 2013, due to recurrent epistaxis and tonsillar bleeding, the patient was commenced on prophylaxis receiving Humate-P 50 RCo U/kg twice weekly. Despite this regimen, he continued to experience recurrent epistaxis, leading to escalation of prophylaxis to 3/week. In November 2014, he showed persistent tonsillar bleeding, despite having received two doses of Humate-P (each 40 RCo U/kg) in the previous 12 hours. Testing revealed reduced VWF:Ag, VWF:RCo and FVIII:C recoveries. Further testing revealed an anti-VWF antibody (2.6 BU) of unspecified Ig type. Since diagnosis of the inhibitor, he has received 100 RCo U/kg daily for prophylaxis and immune tolerance. He is now bleed-free; however, monthly inhibitor testing shows that his inhibitor persists. Given the limited experience and literature on inhibitors in VWD, the prognosis for such cases is unknown.
Melanie Bladen, David Stephensen and Paul McLaughlin
From its humble beginnings in 1990, the UK’s Haemophilia Chartered Physiotherapists Association (HCPA) has led the development of haemophilia physiotherapy in the UK and increasingly across Europe too. Over the past 10 years, the growth of the group has centred on an annual professional meeting that facilitated educational opportunities and professional networking, and has increasingly promoted research among members. The HCPA has now established a Clinical Studies Group, an open forum designed to identify and support research needs and to promote a collaborative approach to research that will answer some of the important questions that remain about haemophilia care.
Haemophilia and associated bleeding disorders are chronic conditions that require easy, accessible, and reliable venous access for treatment. Peripheral venous access is traditionally the first option considered for prophylaxis. The initial introduction of prophylaxis to a child is during the first two years of life, and peripheral access can be problematic. Central venous catheters (CVC), for example port-a-caths, are widely used among this group; however, these devices require surgical insertion and are not without their own complications. Data were collected on venous access methods used at the paediatric centre at the Evelina London Children’s Hospital, where 242 children are registered at the comprehensive care centre, 48 of whom have a severe bleeding disorder. Of these 48, 27 have a CVC currently (PICC n=1, Port-a-Cath n=25, Hickman line n=1) and 3 have an arteriovenous fistula (AVF). Patient 1 is a 12 year-old boy with severe haemophilia A and an intracranial haemorrhage at the age of 9 months. He remains on prophylaxis and had an AVF created 5 years ago following repeated port-a-cath infections and poor venous access. Patient 2 is a 7 year-old boy with severe haemophilia B and an inhibitor, who has also had repeated port-a-cath infections. An AVF was constructed 2 years ago. Patient 3 is a 12 year-old girl with type III von Willebrand disease and an inhibitor. Due to need for regular factor treatment in the context of poor venous access, an AVF was formed. We have had a 100% success rate with all three AVFs at a follow-up period of 8-69 months. Our experience suggests AVF is a viable option of venous access in patients with haemophilia and other bleeding disorders, especially so for children with repeated CVC infections or poor peripheral venous access. However, this is not a straightforward option and further evidence on long-term use based on multicentre research will be beneficial in managing AVF in this group of patients.
Tranexamic acid inhibits fibrinolysis by competitively blocking the lysine binding sites of plasminogen, inhibiting binding between fibrin and plasminogen, and activation of plasminogen. It also competitively inhibits tissue plasminogen activator and inhibits plasmininduced platelet activation. The synthesis of tranexamic acid was first reported in 1962. It is used to treat or prevent excessive blood loss from trauma, surgery, and in various medical conditions including haemophilia and heavy menstrual bleeding. As a medicine affecting coagulation, it is listed in the World Health Organization’s List of Essential Medicines. Tranexamic acid remains a versatile and inexpensive agent with potential benefit in health services from the lowest to highest income countries. This pharmacy review focuses on the evidence base to support the use of tranexamic acid in acquired and inherited bleeding disorders to reduce bleeding complications.
Knowledge about genetic inheritance as a concept in children and young people with bleeding disorders is synonymous, in many ways, with other inherited genetic conditions. Children and young people have a more physiological understanding of inheritance, but may hold mistaken and inaccurate beliefs in understanding basic genetics. There are complex ethical and social problems in the genetic testing of youngsters with bleeding disorders to establish carrier status. Current guideline recommendations indicate circumstances where clear psychosocial and medical benefits can be demonstrated. However, children and young people have a reduced capacity to understand the tests and their implications, and in many cases family communication may impact the extent of disclosure of genetic risk factors. This paper explores the genetics of inherited bleeding disorders, including basic knowledge of the concept of inheritance and reproductive risks. Carrier status in children and young people will be considered, drawing on legal rulings that may shed light on best practice in establishing carrier status based on genetic testing. Communication patterns within families around inherited bleeding disorders and the complicated process of disclosure will also be discussed.
Hypertension is a well-known risk factor for ischaemic heart disease and cerebrovascular events. Globally, there is a drive to try to reduce salt intake. In an older population, where hypertension is likely to have a high prevalence, are health care professionals aware of the sodium content in replacement factor?
Chandra Khyati, Mavinakote Gowda Triveni, Rini Gopal, Ab. Tarunkumar, Suresh Hanagavadi and Dhoom Singh Mehta
Haemophilia is a rare blood clotting disorder, characteristic features of which include extemporaneous and post-traumatic subcutaneous bleeding and mucosal haemorrhages. Genetic deficiency of coagulation factor VIII results in haemophilia A, while deficiency of factor IX leads to haemophilia B. The most common treatment for haemophilia A is administration of recombinant or plasma-derived factor VIII concentrate, to raise the levels of the deficient factor VIII. Tranexamic acid is also used as an anti-fibrinolytic agent that inhibits plasminogen activators present in oral secretion and stabilises the clot. Administration of factor IX is required in haemophilia B. Treatment leads to increased longevity and quality of life for patients. Dental conditions and treatments are more complicated and uncertain in patients with haemophilia due to bleeding risk, thus restorative dental care is of paramount importance for those with haemophilia. The fear of bleeding during treatment procedures is the primary cause of lack of proper dental care for people with haemophilia in countries with limited health care resources. This case report highlights the significance of clinical examination and investigation, and the importance of proper interaction between a haematologist and the periodontist for correct multidisciplinary and uneventful management of periodontal health of a patient with haemophilia.
Umma A. Ibrahim, Sagir G. Ahmed, Modu B. Kagu and Usman A. Abjah
Haematuria is not uncommon in people with haemophilia and is mainly caused by spontaneous haemorrhage or trauma. The frequency and clinical significance of urinary schistosomiasis in the aetiology of haematuria among haemophiliacs in schistosomiasis endemic countries such as Nigeria have not been previously studied. We retrospectively analysed the clinical and laboratory data of 45 haemophiliacs with haematuria in Nigeria with the aim of determining the frequency of urinary schistosomiasis and other causes of haematuria among haemophiliacs, the haematological profiles of haemophiliacs with haematuria and the severity of schistosomal haematuria relative to non-schistosomal haematuria. Haematuria was due to spontaneous haemorrhage in 23 (51.1%) patients, trauma in 14 (31.1%) patients and schistosomiasis in 8 (17.8%) patients. There were no significant differences in mean values of haematological parameters between patients with spontaneous and traumatic haematuria. However, compared to patients with spontaneous and traumatic haematuria, patients with schistosomal haematuria had significantly lower mean Hb concentration (8.5 vs.11 and 11.5g/dL; p<0.05) and significantly higher mean eosinophil count (0.42 vs. 0.21 and 0.2×109/L; p<0.05). This study revealed that schistosomiasis was responsible for 17.8% of cases of haematuria in northern Nigerian haemophiliacs. Schistosomal haematuria was severe and caused significant anaemia in contradistinction to spontaneous and traumatic haematuria that were mild and did not cause significant anaemia. A superimposed pro-haemorrhagic host-parasite relationship was responsible for the severe haematuria seen in haemophiliacs with schistosomiasis, a situation that would potential increase their risk of iron deficiency and its attendant consequences including childhood cognitive impairment. Haemophiliacs with haematuria in schistosomiasis endemic countries should be investigated by urinalysis for early detection and treatment. Haemophiliacs who present with haematuria in association with eosinophilia should evoke the strongest clinical suspicion for schistosomiasis. Parents of haemophiliacs should be counseled on how to protect their children from exposures to infected waters.
In a recent editorial published in Haemophilia, Millar asks ‘Why and how do we classify von Willebrand disease?’ . This may seem like a philosophical question, but two case reports in this edition of The Journal of Haemophilia Practice illustrate good practical answers to both parts of the question.
The Verpleegkundigen & Verzorgenden Nederland Verpleegkundig Specialisten (V&VN VS), the Dutch professional organisation representing nurse practitioners, has introduced a requirement for advanced practice (registered) nurses (APRN) who wish to be eligible for reregistration within five years to participate in a peer review group for at least eight hours per year. In 2013, five APRNs caring for people with haemophilia and other bleeding disorders in the Netherlands formed a peer review group. As no framework was available, research was undertaken through reviewing literature and engaging in exploratory discussions within the profession in order to identify best practice in establishing such a group. The initial meeting of the new peer review group agreed possible methodologies and established meeting rules. After four meetings, some initial conclusions can now be drawn on the benefits of this specialised haemophilia peer review group. Overall, it is clear that participation in a forum in which knowledge and expertise are shared, contributes to the professionalism of the APRN.