Table 2.
—[Section 2.3, 3] Risk Factors for Bleeding With Anticoagulant Therapy and Estimated Risk of Major Bleeding in Low-, Moderate-, and High-Risk Categories
| Risk Factorsa | |||
| Age > 65 y17-25 | |||
| Age > 75 y17-21,23,25-34 | |||
| Previous
bleeding18,24,25,30,33-36 | |||
| Cancer20,24,30,37 | |||
| Metastatic cancer36.38, | |||
| Renal failure18,24,25,28,30,33 | |||
| Liver failure19,21,27,28 | |||
| Thrombocytopenia27,36 | |||
| Previous stroke18,25,27,39 | |||
| Diabetes18,19,28,32,34 | |||
| Anemia18,21,27,30,34 | |||
| Antiplatelet
therapy19,27,28,34,40 | |||
| Poor anticoagulant
control22,28,35 | |||
| Comorbidity and reduced functional
capacity24,28,36 | |||
| Recent surgery21,41,b | |||
| Frequent falls27 | |||
| Alcohol abuse24,25,27,34 | |||
| Estimated Absolute Risk of Major
Bleeding, % | |||
| Categorization of Risk of Bleedingc |
Low Riskd (0 Risk Factors) |
Moderate Riskd (1 Risk Factor) |
High Riskd (≥ 2 Risk
Factors) |
| Anticoagulation 0-3 moe | |||
| Baseline risk (%) |
0.6 |
1.2 |
4.8 |
| Increased risk (%) |
1.0 |
2.0 |
8.0 |
| Total risk (%) |
1.6e |
3.2 |
12.8f |
| Anticoagulation after first 3 mog | |||
| Baseline risk (%/y) |
0.3h |
0.6 |
≥ 2.5 |
| Increased risk (%/y) |
0.5 |
1.0 |
≥ 4.0 |
| Total risk (%/y) | 0.8i | 1.6i | ≥ 6.5 |
See Table 1 legend for expansion of abbreviations.
The increase in bleeding associated with a risk factor will vary with (1) severity of the risk factor (eg, location and extent of metastatic disease, platelet count), (2) temporal relationships (eg, interval from surgery or a previous bleeding episode),29 and (3) how effectively a previous cause of bleeding was corrected (eg, upper-GI bleeding).
Important for parenteral anticoagulation (eg, first 10 d) but less important for long-term or extended anticoagulation.
Although there is evidence that risk of bleeding increases with the prevalence of risk factors,20,21,25,27,30,33,34,36,42,43 this categorization scheme has not been validated. Furthermore, a single risk factor, when severe, will result in a high risk of bleeding (eg, major surgery within the past 2 d, severe thrombocytopenia).
Compared with low-risk patients, moderate-risk patients are assumed to have a twofold risk and high-risk patients an eightfold risk of major bleeding.18,20,21,27,28,30,36,44
The 1.6% corresponds to the average of major bleeding with initial UFH or LMWH therapy followed by VKA therapy (Table S6 Evidence Profile: LMWH vs IV UFH for initial anticoagulation of acute VTE). We estimated baseline risk by assuming a 2.6 relative risk of major bleeding with anticoagulation (footnote g in this table).
Consistent with frequency of major bleeding observed by Hull et al41 in high-risk patients.
We estimate that anticoagulation is associated with a 2.6-fold increase in major bleeding based on comparison of extended anticoagulation with no extended anticoagulation (Table S27 Evidence Profile: extended anticoagulation vs no extended anticoagulation for different groups of patients with VTE and without cancer). The relative risk of major bleeding during the first 3 mo of therapy may be greater that during extended VKA therapy because (1) the intensity of anticoagulation with initial parenteral therapy may be greater than with VKA therapy; (2) anticoagulant control will be less stable during the first 3 mo; and (3) predispositions to anticoagulant-induced bleeding may be uncovered during the first 3 mo of therapy.22,30,35 However, studies of patients with acute coronary syndromes do not suggest a ≥ 2.6 relative risk of major bleeding with parenteral anticoagulation (eg, UFH or LMWH) compared with control.45,46
Our estimated baseline risk of major bleeding for low-risk patients (and adjusted up for moderate- and high-risk groups as per footnote d in this table).