• anticoagulant therapy is associated with an increased risk of clinically significant bleeding
  • antiplatelet therapy, however,  is not a safe and effective substitute   AVERROES trial - comparison of apixaban and aspirin
  • specific scales can assess the risk of bleeding individually (see below)
  • always weigh the benefit of therapy against its risk
  • risk of bleeding (mainly intracranial): DOAC < warfarin

Etiopathogenesis of anticoagulation-related bleeding

  • the anticoagulants are associated with an increased risk of bleeding, and this bleeding is more likely clinically significant
  • several factors can trigger intracerebral bleeding → see here
  • screening for occult bleeding, malformation, or CMBs is not part of routine procedures before starting anticoagulant therapy
  • systemic bleeding most usually occurs in GI or urogenital tract

Risk factors

  • modifiable risk factors

    • blood pressure
    • drug interactions
    • the correct dose of the anticoagulant drug (e.g., regarding weight and/or renal function)
  • mon-modifiable risk factors (cannot be changed)
    • age
    • race
    • comorbidities (renal insufficiency, hepatopathy, etc.)
    • previous ICH  (Schreuder, 2021)

Anticoagulant drug and dose

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Age, race

  • older age is associated with a higher risk of bleeding, but it is not a reason to withhold the therapy
    • dabigatran dose should be reduced at ages ≥ 75-80 (see specifics of each drug)
  • race – higher risk in Asians, Hispanics, and blacks

Recent ischemic stroke

  • in the first days-weeks after a stroke, there is an increased risk of bleeding within the ischemic area (hemorrhagic transformation of ischemia)
  • timing of anticoagulation is guided by the patient’s clinical status (NIHSS), compensation of risk factors (BP, platelets count, coagulation), and CT scan findings (localization and extent of ischemia)

History of bleeding

  • previous bleeding increases the risk of recurrence
  • individual assessment is necessary, but reinstitution of anticoagulant therapy is usually possible and associated with reduced overall mortality  [Witt, 2018]
    • risk of GI bleeding can be assessed by endoscopic findings
    • risk of IC bleeding depends on the etiology and compensation of modifiable risk factors
    • postoperative bleeding is a transient risk factor

→ timing of anticoagulation after IC hemorrhage

Other comorbidities

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Thrombocytopenia and thrombocytopathy

Thrombocytopenia and coagulation disorders
  • thrombocytopenia with ≥ 50 000 platelets/μL of blood is not a contraindication for AC therapy. In lower counts, assess the cause and individual risk-benefit
  • hemophilia – some types are also associated with a higher risk of thrombosis – hematologist consultation is required
Iatrogenic trombocytopathy
  • the combination of anticoagulation and antiplatelet drugs increases the risk of bleeding, but in certain circumstances, it is acceptable
    • after coronary interventions (dual therapy with dabigatran + clopidogrel)
    • the benefit of low-dose rivaroxaban 2×2.5 mg + ASA 100mg over ASA alone has been demonstrated (COMPASS trial)
  • do not combine anticoagulant drugs with NSAIDs

Other specific risk factors

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Bleeding risk scales

  • a tool to guide the decision to initiate anticoagulation in patients with Afib
  • always compare the risk for major bleeding (calculated by the HAS-BLED score) with the risk of thromboembolic events (calculated by the CHA2DS2-VASc score) ⇒  does the benefit of anticoagulation outweigh the risk of bleeding?
  • a study comparing HEMORR2HAGES, ATRIA and HAS-BLED showed superior performance of the HAS-BLED score compared to the other two scores
HAS-BLED score
uncontrolled BP, >160 mmHg SBP
Abnormal liver/renal function
renal disease – dialysis, transplant, Cr >2.26 mg/dL or >200 µmol/L
liver disease – cirrhosis or bilirubin >2x normal or AST/ALT/AP >3x normal
Stroke previous stroke
prior major bleeding or predisposition to bleeding
Labile INR unstable INR, time in therapeutic range <60% 1
Elderly age ≥ 65 years
medication use that predisposes to bleeding –  aspirin, clopidogrel, NSAIDs
heavy alcohol use
HAS-BLED score
Pisters et al.annual ICH risk
Lip et al.annual ICH risk
0 1.1% 0.9%
1 1% 3.4%
2 1.9% 4.1%
3 3.7% 5.8%
4 8.7% 8.9%
5 12.5% 9.1 %
Not enough data for higher scores; risk is most likely > 10%

A score ≥ 3 is associated with an increased risk of major bleeding. Frequent monitoring, DOAC use, or alternatives to anticoagulation are recommended.

  • ORBIT bleeding risk score has a better ability to predict major bleeding in AFib patients when compared to HAS-BLED and ATRIA risk scores. The ORBIT risk score may provide a simple, easy-to-remember tool to aid in clinical decision making [O´Brian,  2015]  [Hilkens, 2017]
Older age ( >75 y) 1
Reduced hemoglobin/Hct/anemia  (men <13 g/dL and Hct < 40%, women < 12 g/dL and Hct < 36% ) 2
Bleeding 2
Insufficient kidney function (GFR < 60 mL/min/1.73 m2) 1
Treatment with antiplatelets 1
Maximum score 7
score 0–2 – low risk ~ 2.4% / y
score 3 –  medium risk ~ 4.7% / y
score ≥ 4 – high risk ~ 8.1% / y
Hepatic / renal disease
Ethanol 1
Malignancy 1
Older age (>75 years) 1
Reduced platelet count or function, including aspirin therapy 1
Re-bleeding risk (history of prior bleed) 2
Hypertension 1
Anemia 1
Genetic factors 1
Excessive fall risk 1
Stroke 1
Maximum points
Bleeding risk / year
Score 0 ~ 1.9 %
Score 1 ~ 2.5 %
Score 2 ~ 5.3 %
Score 3 ~ 8.4 %
Score 4 ~ 10.4 %
Score ≥ 5 ~ 12.3 %

Reduction of bleeding risks

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Risk and prevention of bleeding in anticoagulant therapy
link: https://www.stroke-manual.com/risk-and-prevention-of-bleeding-in-anticoagulant-therapy/