Thrombosis risk with haemoglobin C trait and haemoglobin C disease: A systematic review

The thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild-type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty-two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9-5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9-16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.