• the 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 on an individual basis (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 connected with an increased risk of bleeding, and this bleeding is more likely clinically significant
  • the intracerebral bleeding can be triggered by a number of reasons  → see here
  • screening for occult bleeding 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 anticoagulant drug (e.g. regarding weight and/ 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
    • dose of dabigatran should be reduced at age ≥ 75-80 years (see specifics of each DOAC)
  • race – higher risk in Asians, Hispanics, and blacks

Recent ischemic stroke

  • in the first days-weeks after 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 transient
  • → 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 it is indicated in some circumstances
    • after coronary interventions (dabigatran + clopidogrel)
    • in ischemic stroke, the benefit of low dose rivaroxaban 2×2.5 mg + ASA 100mg over ASA alone has been demonstrated (COMPASS trial)
  • do not combine with NSAIDs

Other specific risk factors

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Bleeding risk scales

HAS-BLED
  • a tool to guide the decision to start anticoagulation in AF patients
  • always compare the risk for major bleeding (calculated by the HAS-BLED score) to the risk for thromboembolic events (calculated by the CHA2DS2-VASc score) ⇒  does the benefit of anticoagulation outweighs 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
Hypertension
uncontrolled BP, >160 mmHg SBP
1
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
1
1
Stroke previous stroke
1
Bleeding
prior major bleeding or predisposition to bleeding
1
Labile INR unstable INR, time in therapeutic range <60% 1
Elderly age ≥ 65 let 1
Drugs / alcohol
medication usage predisposing to bleeding –  aspirin, clopidogrel, NSAIDs
heavy alcohol use
1
1
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 %
There is not enough data for higher scores, risk is very likely over 10%

A score ≥ 3 is associated with a higher risk of major bleeding. Frequent controls, DOAC usage, or alternatives to anticoagulation are advisable.

ORBIT
  • ORBIT bleeding risk score has a better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores. The ORBIT risk score can provide a simple, easily remembered tool to support 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
HEMORR2HAGES
Hepatic / renal disease
1
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
12
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 %

Bleed risk reduction

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