The role of infections in the pathogenesis of bleeding among patients with haemophilia-A: A primer for haemophilia caregivers in the tropics

Abstract

Haemophiliacs are often transfusion-dependent, and are at risk of HIV and non-HIV immunosuppression, making them vulnerable to transfusion-transmissible infections (TTIs) and non-TTIs, many of which can cause infection-associated bleeding (IAB) even in non-haemophilic individuals. Haemophiliacs are particularly susceptible to IAB due to vicious interaction between pre-existing ‘inherited’ FVIII deficiency and infection-induced ‘acquired’ pro-haemorrhagic abnormalities. IAB in haemophiliacs manifests as undue musculoskeletal and/or mucocutaneous haemorrhages. It is thus important for haemophilia caregivers in general (and in the tropics in particular) to have thorough understanding of IAB. Clinico-pathological perspectives of IAB in haemophilia are fragmented, and not comprehensively appraised in previous literature. This review presents updated, comprehensive but concise overview of pathogenesis, trigger mechanisms, clinical implications, therapy and prevention of IAB in haemophiliacs as accrued from literature.

Methodology: Online databases such as PubMed, Medline, Google Scholar and others were interrogated using the search terms; ‘haemophilia-A’, ‘viral, bacterial and parasitic infections’, ‘bleeding’, ‘mucocutaneous’, ‘thrombocytopenia’, ‘ecchymosis’, ‘purpura’, ‘haematuria’, ‘melena’, ‘haematemesis’, and ‘haemoptysis’ in various combinations.

Results: Pathogenesis of IAB in haemophilia include mucosal ulcerations, acquired coagulopathy, and/or portal hypertension. As long as the causative infections are untreated, IAB is often persistent or recurrent, predisposing patients to absenteeism from school/work, iron deficiency, excessive exposure to blood products, high risk of acquiring additional TTIs and increased risk of developing inhibitors to FVIII. Haemophilia caregivers should investigate stool, urine, sputum, blood and/or radiographs of all cases of persistent or recurrent bleeding, especially if bleeding is unabated by blood products transfusion alone, and more-so in patients presenting with constitutional and/or systemic indicators of infections such as pyrexia, asthenia, dysuria, cough, diarrhoea, jaundice, or history of passage of worms in the stool. Transfusion of blood products alone would not suffice for IAB, and transfusions of FVIII containing products without concurrent anti-infection chemotherapy may even promote the development of inhibitors since active infections and inflammations are important risk factors for inhibitor development in haemophiliacs.

Conclusion: It is therapeutically essential to combine transfusion therapy with anti-infective chemotherapy in order to achieve prompt and sustained stoppage of IAB. Haemophilia caregivers should also counsel patients on hygiene, barrier protection against vectors, and vaccination protocols.