Incidence, clinical impact and risk of bleeding during oral anticoagulation therapy

Table 1 Different definitions of major bleeding in various studies

Ref.	Clinical setting	Definition
Landefeld et al[53]	Various	Fatal, life-threatening, potentially life-threatening, causing severe blood loss, leading to surgical treatment or moderate acute/subacute blood loss not explained by surgery/trauma
Palareti et al[32]	Various	Fatal intracranial (documented by imaging); ocular (with blindness); articular; retroperitoneal; requiring surgery/angiographic intervention; associated to Hb decrease ≥ 2 g/dL or need for ≥ 2 blood units transfusion
Beyth et al[54]	Various	Overt bleeding leading to ≥ 2 blood units loss in ≤ 7 d, or life-threatening
Gage et al[55]	AF	ICD-9CM codes for bleed in any location
Shireman et al[56]	AF	Hospitalization for “major acute bleeding” (including gastrointestinal or intracranial hemorrhage)

AF: Atrial fibrillation; Hb: Hemoglobin.

Table 2 Factors associated with an increased risk of bleeding

Author
Age > 65-70 yr
Female gender
CYP2C9 and/or VKORC1 gene polymorphism
Higher intensity of anticoagulation (i.e., INR > 4.5)
Labile INR (i.e., TTR < 60%)
Early 90 d of anticoagulation
History of bleeding
Comorbidities (i.e., hypertension, malignancy, liver and/or renal and/or cardiac failure)
Comedications (i.e., antiplatelet agents, non-steroidal anti-inflammatory drugs)

INR: International normalized ratio; TTR: Time within the therapeutic range.

Table 3 Most popular bleeding risk prediction scores

Author	Ref.	Calculation	Risk classification
mOBRI	[54]	Age ≥ 65 yr, previous stroke, GI bleed in the last 2 wk, ≥ 1 of the following: recent MI, hematocrit < 30%, creatinine > 1.5 mg/dL, diabetes)	Low: 0 points
			Intermediate: 1-2 points
		1 point each	High: ≥ 3 points
HEMORR2HAGES	[55]	Hepatic or renal disease, ethanol abuse, malignancy, older, reduced platelet count/function, re-bleeding, uncontrolled hypertension, anemia, genetic factors, excessive fall risk, and stroke	Low: 0-1 points
			Intermediate: 2-3 points
		1 point each and 2 points for previous bleed	High: ≥ 4 points
Shireman et al	[56]	(0.49 × age ≥ 70 yr) + (0.32 × female gender) + (0.58 × remote bleed) + (0.62 × recent bleed) + (0.71 × alcohol/drug abuse) + (0.27 × diabetes) + (0.86 × anemia) + (0.32 × antiplatelet therapy)	Low: ≤ 1.07 points
			Intermediate: < 1.07 to < 2.19 points
		1 point each	High: ≥ 2.19 points
HAS-BLED	[57]	Hypertension (SBP > 160 mmHg), abnormal renal/liver function, stroke, history of bleeding, labile INR, elderly age (> 65 yr), drugs (antiplatelets/NSAIDs/alcohol)	Low: 0-1 points
			Intermediate: 1-2 points
		1 point each	High: ≥ 3 points

GI: Gastrointestinal; MI: Myocardial infarction; SBP: Systolic blood pressure; NSAIDs: Non-steroidal antiinflammatory drugs.