Page 198 - Haematologica-April 2018

L. Green et al.
Table 4. Univariable and multivariable analysis of risk factors for mortality (n=2,132).
Univariable analysis Adjusted OR [95%CI] P ORa [95%CI]
Age (years)
<65 1 1
Multivariable analysis
P
0.12 <0.001 <0.001
0.77
0.005 0.44 <0.001 <0.001 <0.001
0.005 0.12 0.001 0.001 0.04
65-74 75-84 85+
Type of oral anticoagulant Warfarin
Direct oral anticoagulantb
Site of bleed
Other
Lower gastrointestinal Upper gastrointestinal Subdural/epidural Subarachnoid Intracerebral
Provocationc
Spontaneous Trauma Surgery/procedure Fall
Liver failure
Cancer
1.84 [1.12,3.01] 3.07 [1.97,4.80] 3.59 [2.28,5.65]
1
0.99 [0.76, 1.31]
1
0.65 [0.38, 1.12] 1.67 [1.14, 2.46] 2.43 [1.66, 3.55] 2.72 [1.58, 4.68] 6.34 [4.51, 8.91]
1
0.82 [0.55,1.21] 0.23 [0.10,0.52] 0.97 [0.74,1.28] 2.08 [1.02,4.26] 1.29 [0.97,1.70]
0.016 <0.001 <0.001
0.98
0.12
0.01 <0.001 <0.001 <0.001
0.31 0.001 0.84 0.04 0.08
1.50 [0.89,2.53] 2.77 [1.73,4.44] 3.78 [2.33,6.14]
1
0.96 [0.71,1.28]
1
0.45 [0.25, 0.79] 1.17 [0.78, 1.75] 2.55 [1.69, 3.84] 3.23 [1.82, 5.71] 5.75 [4.01, 8.23]
1
0.54 [0.35, 0.83] 0.50 [0.21, 1.19] 0.53 [0.38, 0.73] 3.86 [1.79, 8.36] 1.37 [1.01, 1.84]
742
OR: odds ratio; aOdds ratios adjusted for all other variables in model; bIncludes dabigatran, rivaroxaban, apixaban and edoxaban; cunclassified provocations not displayed (n=21).
Results
Cases were identified and reported by 32 hospitals across the UK, with the median number (inter-quartile range, IQR) of cases reported per hospital being 44 (25 – 88), and the median (IQR) duration for completing a case report (measured from the date of bleeding) being 38 (13- 87) days. Table 1 shows the demographics, OAC therapy specifications and co-morbidities of 2,192 individual patients reported with major bleeding between October 2013 and August 2016; 34 (1.6%) had more than one episode during the study period (data not shown). All patients fulfilled the International Society of Thrombosis and Haemostasis criteria for major bleeding: 20% had a fatal bleed; 62% were transfused with ≥2 units of red blood cells or had a drop of ≥20g/L hemoglobin; and 86% had symptomatic bleeding in a critical organ (overall, 67% of patients met more than one criteria). At the time of the bleed, the majority of patients were on warfarin (81%) with the remainder being on a DOAC. Patients taking an OAC for atrial fibrillation and venous thromboembolism made up 72% and 21% of the cohort respectively; approximately 10% had multiple indications.
Bleeding presentations and outcomes are shown in Table 2. All intracranial hemorrhages (subdural, subarach- noid and intracerebral bleeds combined), gastrointestinal bleeds (upper and lower) and other bleeds made up 44%, 32% and 24% of the total, respectively. Two-thirds of the bleeds were reported as spontaneous and one-fifth as resulting from a fall. Outcomes up to 30 days were report- ed for 2,132 (97%) patients. The overall in-hospital mor- tality rate was 20.9% (95% CI: 19.2% - 22.7%) but was 32.7% (95% CI: 29.7-35.9%) among patients with an
intracranial hemorrhage. Bleeding was mentioned as the cause of death in 70% of cases, while in 22% it was not, and in 8% the cause of death was unknown/ or referred to the coroner. Patients discharged within 30 days of bleed- ing stayed a median of 7 days in hospital. In-hospital com- plications included admission to an Intensive Care Unit (10%), ventilation or acute respiratory distress syndrome (5%), hemorrhagic stroke (3%), cardiac arrest (2%), sepsis or pneumonia (2%), thrombotic events (2%), and re- bleeding (2%).
For the management of bleeding, patients on warfarin were given any blood transfusion (31%), prothrombin complex concentrate (78%) and vitamin K (74%); patients on DOAC were given any blood transfusion (43%), pro- thrombin complex concentrate (39%) and tranexamic acid (28%). OAC therapy was resumed in 43% of survivors while they were in hospital. The proportions of patients (among survivors) who restarted OAC after a bleed varied by site of bleed: intracranial hemorrhage (24%), gastroin- testinal (46%), other (65%), as well as indication: atrial fibrillation (36%), mechanical heart valves (86%), venous thromboembolism (50%), other (42%). One–third of patients on a DOAC were restarted on a different OAC, as were approximately one-fifth of patients with intracra- nial hemorrhage or venous thromboembolism. Out of 111 DOAC patients, 29 (26%) were switched to vitamin K antagonists and out of 610 patients on warfarin, 42 (7%) were switched to a DOAC.
Comparison of the 1,958 (89%) patients who were on OAC for atrial fibrillation and/or venous thromboem- bolism (Table 3) showed that those admitted on DOAC were significantly older than those on warfarin (P<0.001), but there was no significant difference in the number of
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