Incidence and prevention of post-immunisation bleeding complications in people with haemophilia at a treatment centre in India

Data analysis was undertaken using R software and Microsoft Excel. Descriptive statistics using frequency tables and percentages were used to describe the demographic characteristics of the study participants. The statistical analysis was implemented using R software.

Among the 65 PwH to participated in the study, 22 (33.8%) were under 10 years old and 22 (33.8%) were between 11 and 20 years old. The majority (46; 70.7%), were diagnosed before the age of two, whereas 8 (12.3%) were diagnosed between ages 3 to 5, and 11 (16.9%) were diagnosed after the age of 5. Haemophilia A was the predominant type, affecting 55 participants (84.6%), while 10 (15.3%) had haemophilia B. The severity distribution indicated that 47 participants (72.3%) had severe haemophilia (Table 2).

Among the 79 participants surveyed, 65 (82.2%) had received immunizations (Table 2). Of these, 50 (76.9%) did not experience any post-vaccination bleeding complications. However, 15 (23.1%) reported issues including haematoma, swelling, and pain at the injection site, primarily occurring between 16 to 24 months (Figure 1).

Figure 1.

Distribution of site of bleeding complications (%)

A notable trend in immunisation practices was observed, with an increasing preference for subcutaneous vaccine administration. Initially, 83.1% of participants received their first vaccination subcutaneously (Figure 2). Following diagnosis, 100% of participants were exclusively vaccinated via the subcutaneous route, aligning with WFH recommendations ^[2] that emphasise this method to reduce bleeding risk.

Figure 2.

Shift in route of vaccination (%)

Regarding injection sites, the thigh was the most common site for both primary series and booster vaccinations in children under 24 months. Among the 15 participants who experienced bleeding complications, 10 (15.3%) reported bleeding at the thigh injection site, while five (7.7%) reported bleeding in the upper arm.

A summary of prophylactic measures to prevent bleeding complications after vaccination is shown in Table 3. Of the 65 participants, 37 (56.9%) received clotting factor replacement therapy before their first vaccination, highlighting the high standard of preventive care in managing haemophilia. Among those who experienced post-vaccination bleeding, 9/15 (60%; 13.84% of total cohort) required clotting factor infusion to control the bleeding. One had moderate haemophilia, and the remaining eight had severe haemophilia. The other six participants who experienced post-vaccination bleeding (40%; 9.23% of total cohort) managed their symptoms with ice packs and compression therapy; of these, three had mild haemophilia and three had moderate haemophilia.

These findings reinforce the effectiveness of pre-vaccination clotting factor replacement in preventing severe complications. The results suggest that careful selection of vaccination routes and prophylactic measures can effectively mitigate bleeding complications in people with haemophilia. The widespread adoption of subcutaneous immunisation and pre-vaccination clotting factor administration in this study reflects adherence to best practices in haemophilia management.

In this study, a small proportion of PwH (14 out of 79) had not received the vaccination. The reasons for this are outlined in Figure 3. Primary factors for non-vaccination included fear of bleeding, safety concerns, and existing illness in the child. Similarly, a study by Azarpanah et al. (2021), emphasizes that vaccine hesitancy is often influenced by concerns about vaccine safety and potential adverse events ^[11].

Figure 3.

Reasons for not taking vaccination (n=14)*

*It is to be noted that this table the participants may have more than one reason for not taking vaccination. The data includes all the options mentioned by the participants.

In our study, 15 participants (23.1%) experienced bleeding complications after intramuscular vaccination, consistent with existing research that highlights the heightened bleeding risk in PwH due to coagulation deficiencies ^[13]. These complications ranged from minor bruising to more significant bleeding, primarily occurring at common intramuscular injection sites such as the upper arm and thigh. Notably, 76.9% of participants in our study did not experience bleeding complications, indicating that prophylactic measures and careful management protocols are effective. Similarly, a study by Carpenter et al. found that among 114 children who received intramuscular vaccinations, 23 (20.2%) developed a total of 38 intramuscular haematomas; however, the difference in haematoma occurrence between vaccination routes was not statistically significant (P=0.07). Due to data limitations, it was unclear whether haematoma formation was directly attributable to vaccine administration ^[14].

The study revealed that nine participants (13.84%) received factor replacement therapy, while six (9.23%) used ice packs and compression as a preventive measure to minimise post-vaccination complications. According to the WFH Guidelines ^[2], if an intramuscular injection is necessary, it should be administered after coagulation factor replacement therapy. Additionally, it is recommended to apply an ice pack to the injection site for five minutes beforehand, use a small-gauge needle (23G), and to apply firm pressure to the site for five minutes post-vaccination ^[15]. Dochart et al. examined the risk of bleeding associated with intramuscular vaccination in individuals with haemophilia and concluded that, with appropriate management, it can be safely administered without significant bleeding complications ^[16].

In the current study, we found that 83.1% of participants received their first vaccination via the subcutaneous route, aligning with WFH recommendations ^[2]. This shift towards subcutaneous administration minimises the risk of bleeding compared to intramuscular injections. The fact that 100% of participants received subsequent vaccinations subcutaneously after diagnosis further supports the effectiveness of this approach. Although most vaccines can be administered subcutaneously, some require intramuscular administration. However, PwH should preferably receive vaccines subcutaneously rather than intramuscularly as this is a safer method and does not require infusion of clotting factor as a preventive measure.

It was noted in this study that prior to vaccination, 56.9% of participants received clotting factor replacement, which is a critical prophylactic measure to reduce bleeding risks ^[10]. The use of factor injections for managing bleeding complications was reported by 13.8% of participants, indicating that factor replacement is a standard practice in addressing post-vaccination bleeding issues. A survey in HTCs in Germany showed the need for standardised vaccination protocols, improved training for healthcare providers, and better patient education to ensure effective and safe vaccination practices for PwH ^[1]. Our study aligns with existing studies emphasising the safety of subcutaneous vaccination routes in haemophilia people ^[5]. The low incidence of significant bleeding complications among those who received factor replacement shows the importance of this practice reducing risks associated with immunisation.

Our study indicates the effectiveness of subcutaneous vaccination routes and the role of prophylactic measures in reducing the incidence of bleeding complications. Healthcare professionals should continue to emphasise these practices to enhance safety. Additionally, the findings advocate for continued education and training for healthcare professionals on the importance of appropriate vaccination routes and timely prophylactic measures.

The study findings reflect the successful implementation of recommended practices and highlight the importance of ongoing vigilance and adaptation of clinical protocols to ensure the safety and well-being of PwH. Parental attitudes and knowledge towards vaccination is likely to increase the uptake of childhood vaccination. Vaccine information for the parents should focus on vaccine safety and engage communities to increase and sustain the uptake of childhood vaccines.

This study has several limitations, primarily its retrospective design, which may affect the accuracy and completeness of the data. This is especially relevant for vaccination, as it is often administered by a child’s primary care provider. Additionally, information on the frequency of factor product administration before intramuscular vaccination, specifically to prevent haematoma formation, was not available. The small sample size further limits the generalisability of the findings.