Background: In tropical countries such as Nigeria, where factor VIII (FVIII) is scarce, severe pain due to musculoskeletal bleeding complications, leading to frequent opioid prescription, is not uncommon in poorly managed people with haemophilia (PWH). The relationship between opioid use and dependence is intensively studied in other painful diseases, such as cancer and rheumatoid arthritis, but surprisingly little is known about opioid dependence in haemophilia. We hypothesise that the risk of opioid dependence among PWH in tropical countries like Nigeria is multi-factorial, encompassing demographic (age), clinical (haemophilia severity and chronic arthropathy) and biological (ABO blood groups and haemoglobin (Hb) phenotypes) factors that may directly or indirectly increase incidence of bleeding and/or pain.
Aims: To determine the prevalence of opioid dependence and relative risks (RR) associated with age, haemophilia severity, chronic arthropathy, ABO blood groups and Hb phenotypes, and to elucidate the pathophysiological roles of each risk factor in the development of opioid dependence among haemophilia-A patients in five hospitals in northern Nigeria.
Methodology: A retrospective review of the medical records of 88 PWH seen between 1996 and 2012 was used to collate data on age, sex, haemophilia severity, painful chronic haemophilic arthropathy, ABO blood group, haemoglobin phenotypes, presence or absence of opioid dependence, and the types of opioids on which the patients were dependent. The prevalence of opioid dependence among the cohort was expressed as a percentage. The frequency of each putative risk factor for opioid dependence in patients with and without opioid dependence were compared using Fisher’s exact test; RR associated with each risk factor was determined by regression analysis. P<0.05 was taken as significant.
Results: Of the 88 PWH studied,15 (17%) were shown to be opioid-dependent. Compared with PWH who were not opioid-dependent, this group had higher frequencies of severe haemophilia (86.7% vs. 49.3%: RR= 5.2, p=0.02), survival to adulthood (73.3% vs. 12.3%: RR= 9.5, p=0.0001), chronic arthropathy in one or more joints (86.7% vs. 21.9%: RR= 13.2, p=0.0004), blood group-O (80% vs. 49.3%: RR= 3.3, p=0.04), and HbAA phenotype (86.7% vs. 54.8%: RR= 4.3, p=0.04).
Conclusion: Prevalence of opioid dependence among PWH treated at five hospitals in northern Nigeria was 17% during the study period. Significant risk factors were directly or indirectly associated with increased rates of bleeding and/or pain, which can only be prevented or treated through optimal application of FVIII. There is a need for the Nigerian government to establish standard haemophilia care centres with adequate FVIII for optimal prophylaxis and treatment in order to minimise painful complications, thereby helping to prevent undue opioid use and dependence.
Experience of surgery during prophylaxis with emicizumab is currently limited, but the information available suggests that it is associated with a low risk of complications. This case study describes the surgical management of a patient with haemophilia A and inhibitors, managed with emicizumab prophylaxis, who underwent parathyroidectomy. The plan to manage bleeding risk during surgery involved prophylaxis with oral tranexamic acid 1g six-hourly and recombinant Factor VIIa (rFVIIa), prescribed at the discretion of the consultant haematologist. Preoperatively, rFVIIa 45 mcg/kg (3 mg) was administered immediately, and repeated every three to four hours after surgery depending on clinical presentation. There was no unexpected or excessive bleeding during surgery and no clinical need for additional haemostatic medication. Postoperatively, rFVIIa 3 mg was administered at three and ten hours after the first dose. Two further doses were administered on the morning and evening of the first postoperative day. There was no unexpected or excessive bleeding requiring additional treatment, and satisfactory haemostasis resulted in optimal wound healing. The patient reported no bleeding episodes and also an improved quality of life. This case study demonstrates the successful use of emicizumab in conjunction with rFVIIa.
Michelle Lavin, Rezan A Kadir, Sylvia von Mackensen, Debra Pollard and Anna Tollwé
Prolonged menstrual bleeding interferes with daily life and causes marked blood loss, resulting in anaemia and fatigue. Treatment centres should address the issue of heavy menstrual bleeding (HMB) with pre-pubertal girls in advance of their first period, in order to best prepare them. It is common for a bleeding disorder to be overlooked in primary care and in gynaecology clinics, and women sometimes struggle to get a correct diagnosis. There are cultural taboos that inhibit open discussion of menstruation, and women tend to minimise the severity of their symptoms. Health professionals should work to destigmatise the issue and seek an accurate account of bleeding severity, with diagnosis and treatment provided in a joint clinic combining gynaecology and haematology expertise. Treatment should be individualised, taking into account personal, social and medical factors, with the aim of improving quality of life. Great care is needed with regard to choice of language when talking about treatment, and treatment centres should consider offering open access to women who need support in dealing with adverse effects. National member organisations have an important role to play in educating people with bleeding disorders, health professionals and the wider public about the burden of HMB associated with bleeding disorders.
Luisa Durante, Martin Sedmina, Alexandra Vaskova, Baiba Ziemele and Anna Tollwé
Figures in the World Federation of Hemophilia (WFH) global annual survey indicate, by their absence, that there is under-recognition of bleeding disorders in women. The WFH and its national member organisations (NMOs) are working to raise awareness and improve the diagnosis of care of women with bleeding disorders globally, regionally and locally. WFH initiatives include a global programme focused on improving the diagnosis, care and treatment of women with von Willebrand disease (VWD), and programmes involving education and training in conjunction with NMOs in countries including Honduras and Malaysia. NMOs in Slovakia, Latvia and Sweden describe their local activities. The Slovak Hemophilia Society is in the process of establishing a Women’s Committee and considers peer support and network building as essential tools in addressing the issues faced by women with bleeding disorders. In Latvia, access to resources is difficult and von Willebrand factor is not available. There is concern in the Latvia Hemophilia Society that the fundamental human right of access to healthcare is not being met. It supports WFH initiatives through education and advocacy, and believes that the voices of women with bleeding disorders will be better heard through working together. The Swedish Hemophilia Society’s Women’s Project has worked since 2006 to promote better care for women with bleeding disorders and to raise public awareness. Despite resistance, their campaign to increase the identification of girls and women with VWD, improve diagnosis and care, and raise awareness has been well received by healthcare professionals and has had extensive media coverage.
Fatos Dilan Atilla, Ahmet Alp Unat, Hale Bulbul, Murat Ulukus, Zuhal Demirci, Guray Saydam and Fahri Sahin
Acquired haemophilia A (AHA) is a rare, autoimmune disease, presenting as sudden haemorrhages without any personal or family history. Anti-factor VIII (FVIII) is the most commonly recognised autoantibody resulting in decreased factor activity. The aetiology and pathophysiology of these antibodies remains unclear. Approximately 50% of reported cases are idiopathic; the rest are associated with other conditions, mainly underlying malignancies, autoimmune diseases (eg rheumatoid arthritis (RA), systemic lupus erythematosus), drug administration and postpartum period. A 74-year-old woman presented to our institution with haematochezia and haematuria. She had a medical history of cervix carcinoma; total abdominal hysterectomy and bilateral salpingo-oophorectomy with postoperative chemoradiotherapy was performed in 2011. She had also been followed up for 20 years for deforming and severe RA, which was in low-disease activity with methotrexate and corticosteroid. Laboratory investigations for abnormal bleeding revealed prolongation of activated partial thromboplastin time (APTT). APTT prolongation was not corrected by 50:50 plasma mixing studies, and a confirmatory factor assay demonstrated FVIII deficiency (1.4 IU/dL; normal range 50-150 IU/dL). Positive FVIII antibodies on Bethesda testing confirmed a diagnosis of AHA. A rectosigmoid mass and fistula between rectum and bladder were discovered by computed tomography (CT). Bleeding was controlled with recombinant activated factor VII (rFVIIa) after two weeks. Eradication of the inhibitor was achieved with high-dose pulse methylprednisolone for two days and then 2mg/kg daily over four weeks.
Karolina Dańko, Piotr Dańko, Ewelina Soroka, Véronique Petit and Marcin Olajossy
The progress of medicine in the recent decades has strongly improved perinatal care, especially its somatic-related aspects. Pregnancy and childbirth have become much safer, but the mental strain and stress have remained the same. The models of motherhood and the number of children in a family have changed, giving rise to significant requirements concerning the quality of life of the offspring. These changes have brought about new psychological challenge for women and a team of psychiatrists and gynaecologists – obstetricians. The aim of this study is to look at the affective disorders affecting women during pregnancy and postpartum: the postpartum depression and so-called baby blues, which were both compiled in the form of a table in the final part of this work to illustrate the differences between these two mental disorders.