Page 197 - Haematologica-April 2018

Major bleeding associated with oral anticoagulants
Cambridge South Research Ethics Committee, reference: 12/EE/0431). Data on major bleeding events were submitted by multiple hospitals across England, Scotland, Wales and Northern Ireland between October 1, 2013 and August 31, 2016. Patients underwent the normal course of treatment as directed by their clinicians and hospital protocols; at no point was their care altered for the purpose of this study.
Definition of major bleeding
The definition of major bleeding adopted was an augmented version of the International Society on Thrombosis and Haemostasis criteria.16 It was defined as bleeding requiring hospi- talization and at least one of the following: (i) resulting in death; (ii) transfusion of ≥2 units of red blood cells or a drop in hemoglo- bin of ≥20 g/L; (iii) symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intra-ocular, retroperi- toneal, intra-articular or pericardial, or intramuscular with com- partment syndrome; (iv) transfusion of fresh-frozen plasma; (v) administration of prothrombin complex concentrate, recombinant activated factor VII, factor VIII inhibitor bypassing activity or fib- rinogen concentrate. The rationale for appending (iv) and (v) was to ensure that the routes for case identification were as compre- hensive as possible.
Data collection
Any patient of 18 years or over on OAC therapy at the time when they developed major bleeding was eligible for the study.
Cases were reported consecutively and identified by clinical and research staff in participating hospitals from the emergency department, transfusion laboratory, pharmacy (if they stored hemostatic agents) and hematology doctors who were called to give medical advice on the management of these patients.
The study collected information on patients’ baseline character- istics; type of OAC and indication(s), as well as co-morbidities and clinical outcomes at 30 days, death, or discharge, whichever occurred first. Further information on details of data collection/verification, and justification for sample size are given in the Online Supplementary Material.
Statistical analysis
The first bleeding episode of each individual patient was ana- lyzed, with all DOAC grouped together for comparisons. Associations between categorical variables were examined with a chi-squared or Fisher exact test and Mann-Whitney U tests were used for continuous variables (all two-sided at a 5% level of signif- icance). Multinomial logit models were used to estimate the con- ditional odds ratios for DOAC versus warfarin on the site of bleed- ing (versus a reference site), adjusting for age and bleeding provo- cation. Risk factors for in-hospital 30-day mortality were investi- gated using mixed-effects multivariable logistic regression to take into account intra-hospital correlation, controlling for age, co-mor- bidities, bleeding provocation and indications for OAC therapy. All analyses were performed using STATA version 14 (StataCorp LP, USA).
Table 3. Comparison of warfarin and direct oral anticoagulants, for patients with atrial fibrillation and/or venous thromboembolism (n=1958).
Total patients
Age, years
Number of co-morbiditiesd None
1-2
3-4
5+
CHA2DS2-VASc score HAS-BLED scoree
Sites of bleed
Lower gastrointestinal Upper gastrointestinal Subdural Subarachnoid Intracerebral
Other
Patients followed-up
In-hospital deaths within 30 days
Days in hospital before death
Days in hospital for discharged patients
Number of complications in hospital
None 1
2
3+
Warfarin
1,557
80 [72-85]
227 (15) 868 (56) 398 (26) 64 (4)
3 [2-4] 2 [1-3]
166 (11)
293 (19)
313 (20)
74 (5)
342 (22)
369 (24)
1512
322 (21) 3 [1-8] 7 [3-13]
1,184 (76) 229 (15)
All DOAC
number (%) or median[IQR]
401
82 [75-88]
57 (14) 216 (54) 107 (27) 21 (5)
3 [2-5] 2 [2-3]
75 (19)
101 (25)
42 (10)
17 (4)
92 (23)
74(18)
393
84 (21) 3 [1-10] 6 [3-11]
308 (77) 60
P
<0.001a
0.724b
0.1a 0.1a
<0.001b
0.973b 0.948a 0.303a
0.977c
62(4) 17(4)
37(2) 8(2)
DOAC:directoralanticoagulants.aMannWhitneytest;bchi-squaredtest;cFisherexacttest;dco-morbiditiesasdescribedinTable1e scoredoesnotincludethelabileInternational Normalized Ratio.
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