Dabigatran affects thrombin-dependent platelet aggregation after a week-long therapy

Figures & data

Table 1. Clinical baseline characteristics of the patients.

Characteristics	Number of patients or value
Mean age, years ± SD (range)	72 ± 9 (51–88)
≤65 years	9
>65 years	23
Sex
Male	18
Female	14
Duration of dabigatran treatment
Mean (range) ± SD	616 ± 706 (0–2612) days
≤7 days	8
>7 days	24
Indication
Non-valvular atrial fibrillation	32
Paroxysmal	19
Persistent	7
Permanent	6
Dose
2 × 110 mg	19
2 × 150 mg	13
Risk factors
Diabetes mellitus	12
Arterial hypertension	32
Renal disease	6
Dialysis, transplant, creatinine >2.26 mg/dL	0
Glomerular filtration rate	56 ± 13 (28–78)
Liver disease	5
Cerebral stroke/transient ischemic attack history	7
Coronary artery disease
One vessel	4
Two vessels	3
History of pulmonary embolism	0
Myocardial infraction history	5
BMI (kg/m^2)
Normal weight (18.5–24.9)	11
Overweight (25.0–29.9)	13
Obese (30.0–39.9)	8
Ischemic heart disease – Classification according to New York Heart Association
I	3
II	25
III	4
CHA2DS2VASc∗ ± SD	3 ± 1
HAS-BLED^ score	2 ± 1
Platelets × 10^9/L (range × 10^9/L)	190 (135–314)
Creatinine (μmol/L ± SD)	105 ± 18
Male
Normal (55 – 100)	7
Pathological (>100)	11
Female
Normal (44 – 95)	8
Pathological (>95)	6
ALT (μkat/L ± SD) (ALT)	0.4 ± 0.2
Normal (0.1 – 0.6)	26
Pathological (>0.6)	6
AST (μkat/L ± SD) (AST)	0.4 ± 0.2
Normal (0.1 – 0.6)	28
Pathological (>0.6)	4
GMT (μkat/L ± SD)	1 ± 1
Normal (0.07 – 0.63)	14
Pathological (>0.63)	18
Drugs
Beta blockers	22
Calcium channel blockers	14
Angiotensin converting enzyme blockers	6
Angiotensin II receptor antagonists	7
Antiplatelet drugs	0
Proton-pump inhibitor	8
Statins	7

∗CHADS2-VASC score is presented as points on a scale of 1–9 (±SD)

^{^}HAS/BLED score is presented as points on scale of 0–9 (±SD)

ALT: alanine transaminase; AST: aspartate transaminase; GMT: gamma glutamyltransferase; SD: standard deviation.

Figure 1. Results of thrombin induced platelet aggregation between groups.

Figure 2. The dose-response curve for the plasma-diluted thrombin time assay with dabigatran. Line represent the best-fit regressions for dabigatran.

Table 2. Subgroup analysis

Subgroup analysis	Thrombin induced platelet aggregation∗	p value
≤65 years old vs. >65 years old	baseline: 36% ± 28% vs. 27% ± 17%	p = .23
	after 2 hours: 7% ± 4% vs. 10% ± 6%	p = .27
Treatment duration: ≤7 days vs. >7 days	baseline: 73% ± 24% vs. 28% ± 20%	p = .02
	after 2 hours: 25% ± 7% vs. 8% ± 5%	p = .03
Diabetes mellitus vs. without diabetes mellitus	baseline: 26% ± 10% vs. 32% ± 25%	p = .43
	after 2 hours: 8% ± 6% vs. 9% ± 5%	p = .69
With a history of renal disease vs without a history of renal disease	baseline: 18% ± 8% vs. 32% ± 22%	p = .12
	after 2 hours: 7% ± 4% vs. 10% ± 5%	p = .09
With a history of liver disease vs without a history of liver disease	baseline: 22% ± 10% vs. 31% ± 22%	p = .37
	after 2 hours: 8% ± 4% vs. 9% ± 6%	p = .72
Dose: 2×110 mg vs. 2×150 mg	baseline: 31% ± 22% vs. 28% ± 19%	p = .67
	after 2 hours: 10% ± 5% vs. 8% ± 6%	p = .27
Normal weight vs. overweight and obese	baseline: 29% ± 23% vs. 30% ± 20%	p = .9
	after 2 hours: 9% ± 7% vs. 9% ± 5%	p = .91
Normal creatinine level vs. pathological creatinine level	baseline: 31% ± 18% vs. 28% ± 23%	p = .66
	after 2 hours: 9% ± 5% vs. 9% ± 6%	p = .72
Normal AST level vs. pathological AST level	baseline: 30% ± 22% vs. 23% ± 7%	p = .48
	after 2 hours: 9% ± 6% vs. 10% ± 2%	p = .59
Normal ALT level vs. pathological ALT level	baseline: 31% ± 22% vs. 22% ± 5%	p = .33
	after 2 hours: 9% ± 6% vs. 11% ± 6%	p = .42
Normal GMT level vs. pathological GMT level	baseline: 34% ± 23% vs. 26% ± 18%	p = .24
	after 2 hours: 9% ± 5% vs. 9% ± 6%	p = .79
Beta blockers vs. no beta blockers	baseline: 29% ± 20% vs. 30% ± 23%	p = .98
	after 2 hours: 9% ± 5% vs. 9% ± 8%	p = .71
Calcium channel blockers vs. no calcium channel blockers	baseline: 26% ± 9% vs. 32% ± 26%	p = .48
	after 2 hours: 9% ± 5% vs. 8 ± 6%	p = .65
Angiotensin converting enzyme blockers vs. no angiotensin converting enzyme blockers	baseline: 32% ± 30% vs. 29% ± 19%	p = .7
	after 2 hours: 8% ± 5% vs. 9% ± 6%	p = .68
Angiotensin II receptor antagonists vs. no angiotensin II receptor antagonists	baseline: 37% ± 29% vs. 25% ± 16%	p = .08
	after 2 hours: 7% ± 4% vs. 9% ± 6%	p = .45
Proton-pump inhibitor vs. no proton-pump inhibitor	baseline: 21% ± 9% vs. 32% ± 23%	p = .18
	after 2 hours: 8% ± 5% vs. 9% ± 6%	p = .73
Statins vs. no statins	baseline: 30% ± 23% vs. 29% ± 20%	p = .9
	after 2 hours: 7% ± 7% vs. 9% ± 5%	p = .32

∗values are mean (± SD) for continuous variables.

ALT: alanine transaminase; AST: aspartate transaminase; GMT: gamma glutamyltransferase; SD: standard deviation.