Associations of anaemia with bleeding and thrombotic complications in patients with atrial fibrillation treated with warfarin: a registry-based nested case–control study

OBJECTIVES: We studied association of laboratory testing beyond the international normalised ratio (INR) with bleeding and stroke/transient ischaemic attack (TIA) outcomes in patients with atrial fibrillation treated with warfarin. DESIGN: This was a retrospective nested case–control study from the Finnish Warfarin in Atrial Fibrillation (FinWAF) registry (n=54 568), reporting the management and outcome in warfarin-anticoagulated patients. Associations of blood count test frequency and results were assessed together with risk of bleeding or stroke/TIA during 5-year follow-up. SETTING: National FinWAF registry, with data from all six hospital districts. Follow-up period for complications was 1 January 2007–31 December 2011. PARTICIPANTS: A total of 54 568 warfarin-anticoagulated patients. RESULTS: The number of patients with bleeding was 4681 (9%) and stroke/TIA episodes, 4692 (9%). In patients with bleeds, lower haemoglobin (within 3 months) preceded the event compared with the controls (median 126 vs 135 g/L; IQR 111–141 g/L vs 123–147 g/L, p<0.001), while patients with stroke/TIA had only modestly lower INR (median 2.2 vs 2.3; 1.8–2.6 vs 2.1–2.7, p<0.001). When the last measured haemoglobin was below the reference value (130 g/L for men, 120 g/L for women), the OR for a bleeding complication was 2.9 and stroke/TIA, 1.5. If the haemoglobin level was below 100 g/L, the complication risk increased further by 10-fold. If haemoglobin values were repeatedly (more than five times) low during the preceding 3 months, future OR was for bleeds 2.3 and for stroke/TIA 2.4. CONCLUSIONS: The deeper the anaemia, the higher the risk of bleeding and stroke/TIA. However, INR remained mainly at its target and only occasionally deviated, failing to detect the complication risk. Repeated low haemoglobin results, compatible with persistent anaemia, refer to suboptimal management and increased the complication risk in anticoagulated patients.