Over the last five decades, haemophilia treatment has advanced considerably. Patients with haemophilia can now have almost normal life expectancy and quality of life. However, the sudden pandemic of COVID-19 has posed a challenge to the management of patients with haemophilia [10]. In this study, we performed follow-up observations in 265 patients with haemophilia during the COVID-19 pandemic, and the results showed that the frequency of bleeding events was stable and unchanged from the pre-pandemic levels. In patients with bleeding, the major manifestation was a joint hematoma, and the rate of bleeding events was significantly higher in adults than in children. Compared with 66.5% of adults, 85% of children reduced social intercourse and actively isolated themselves at home to prevent COVID-19 infection. At the same time, the proportion of individuals receiving preventive treatment was significantly higher in children than in adults. Nevertheless, no difference was found in the proportion of patients infected with SARS-CoV-2 between children and adults. In addition, the amount of coagulation factors used did not significantly differ between adults and children during the COVID-19 pandemic.
The initial treatment of patients with haemophilia involved blood-derived coagulation factors, such as purified factors (cryoprecipitate) [11]. This was followed by the development of recombinant coagulation factors, long-acting coagulation factors, and nonfactor preparations. Genetic therapy has been researched and has shown impressive results in reducing arthropathy and mortality rates in patients with haemophilia [9, 11, 12]. However, the evolution of treatments has been accompanied by the induction of inhibitors, which occurs more in patients with haemophilia A than in those with haemophilia B. Nonfactor treatments, such as ITI treatment [13, 14], bypass drug (recombinant activated coagulation factor VII and prothrombin complex) therapy [15], and emicizumab, are treatments for patients positive for inhibitors [16–18]. In addition, genetic therapies being studied in ongoing clinical trials are also very promising [19]. In this study, all 17 inhibitor-positive patients had haemophilia A [20, 21]. Currently, one patient is receiving ITI treatment in our center.
The lockdowns around the world during the COVID-19 pandemic inevitably impact patients with haemophilia. Most data show that lockdowns had little impact on haemophilia symptoms, medication adherence, and mental health of patients. Only one multicenter cross-sectional study performed in Germany investigated the mental health of patients with hereditary bleeding disorders and reported significant differences in the particular thoughts and concerns about COVID-19 in patients and their caregivers [22]. Thus far, no research has explored the impact of COVID-19 on the aspects of infection, bleeding symptoms, and medication adherence in patients with haemophilia. Our findings suggested that having COVID-19 did not significantly influence the symptoms and treatments in patients with haemophilia. Compared with adults, the pediatric patients had significantly fewer bleeding events.
In this study, about half of the patients lived in rural areas, which had poorer economic levels, medical levels, and transportation facilities than urban areas. During the COVID-19 pandemic, our center more actively used remote communication methods like WeChat, telephone, and online teleconferencing to maintain regular contact with patients, particularly those who need more attention and regular follow-ups. In addition, the three-level graded diagnosis and treatment that the Chinese government has been committed to has elevated the treatment level and supported drug allocation in village health centers. Consequently, the findings of this study showed no significant difference in bleeding events, bleeding frequency, and amounts of coagulation factors used between patients in rural and urban areas. In addition, 87.9% of patients in urban areas and 83.2% of patients in rural areas reported that they were capable of purchasing drugs without difficulties in accessibility of drugs. The only difference between patients in rural and urban areas was that the proportion of patients with SARS-CoV-2 infection was significantly lower in rural areas than in urban areas.
In this study, 171 patients (64.5%) contracted the SARS-CoV-2 infection. Similar to regular patients with SARS-CoV-2 infection, patients with haemophilia who contracted the SARS-CoV-2 infection also had symptoms of fever, cough, fatigue, sore throat, muscular or body aches, and headache [23, 24]. The presence of this infection did not significantly increase the bleeding volume in patients with haemophilia. However, the number of bleeding events was significantly higher in patients without the SARS-CoV-2 infection than in patients with it. Whether this finding can be attributed to the hypercoagulable state of the body after infection with COVID-19 [25, 26] needs further verification using big data results. Six patients were hospitalized for pneumonia, including four unvaccinated and two vaccinated patients, with the former having had a significantly longer hospital stay. The average duration of symptoms after SARS-CoV-2 infection was approximately 6.1 days. However, this duration was not significantly associated with bleeding, type and classification of haemophilia, inhibitors, comorbidities, and vaccination status. These findings showed that SARS-CoV-2 infection did not significantly affect the symptoms and treatment of patients with haemophilia.
This study has some limitations. We only collected data from one haemophilia center, and COVID-19 is still mutating. In the future, we will further analyze the impact of COVID-19 infection on haemophilia patients by increasing the inclusion of data from multiple centers and incorporating detailed viral subtypes. Therefore, during the pandemic, patients with haemophilia should reduce social activities and take regular prophylaxis. Haemophilia diagnosis and treatment centers can help patients with haemophilia receive better support during disease epidemics using better communication measurements for management and preparation.