Prophylactic anticoagulation to prevent venous thromboembolism in traumatic intracranial hemorrhage: a decision analysis

Abstract

Introduction: Patients with intracranial hemorrhage due to traumatic brain injury are at high risk of developing venous thromboembolism including deep vein thrombosis (DVT) and pulmonary embolism (PE). Thus, there is a trade-off between the risks of progression of intracranial hemorrhage (ICH) versus reduction of DVT/PE with the use of prophylactic anticoagulation. Using decision analysis modeling techniques, we developed a model for examining this trade-off for trauma patients with documented ICH.

Methods: The decision node involved the choice to administer or to withhold low molecular weight heparin (LMWH) anticoagulation prophylaxis at 24 hours. Advantages of withholding therapy were decreased risk of ICH progression (death, disabling neurologic deficit, non-disabling neurologic deficit), and decreased risk of systemic bleeding complications (death, massive bleed). The associated disadvantage was greater risk of developing DVT/PE or death. Probabilities for each outcome were derived from natural history studies and randomized controlled trials when available. Utilities were obtained from accepted databases and previous studies.

Results: The expected value associated with withholding anticoagulation prophylaxis was similar (0.90) to that associated with the LMWH strategy (0.89). Only two threshold values were encountered in one-way sensitivity analyses. If the effectiveness of LMWH at preventing DVT exceeded 80% (range from literature 33% to 82%) our model favoured this therapy. Similarly, our model favoured use of LMWH if this therapy increased the risk of ICH progression by no more than 5% above the baseline risk.

Conclusions: Our model showed no clear advantage to providing or withholding anticoagulant prophylaxis for DVT/PE prevention at 24 hours after traumatic brain injury associated with ICH. Therefore randomized controlled trials are justifiable and needed to guide clinicians.

Figure 1

Decision node and anticoagulation subtree. Decision analysis tree demonstrating two strategies: providing anticoagulant prophylaxis at 24 hours to an adult patient following head injury with intracranial hemorrhage (ICH), or withholding anticoagulant prophylaxis. A linkage term representing the complement of the effectiveness of anticoagulant prophylaxis for reducing the risk of DVT was used to link the main subtrees. This effectiveness term was calculated as follows: effectiveness of anticoagulant prophylaxis = ((probability of DVT without LMWH) - (probability of DVT with LMWH))/(probability of DVT without LMWH). The square node at the extreme left represents the decision node, the circles represent chance nodes, and the plus signs at the far right indicate the presence of additional branches. Numerical values under each branch are the baseline probabilities used at each chance node. CNS Bleed: progression of intracranial hemorrhage; DVT: deep vein thrombosis; PE: pulmonary embolism.

Figure 2

Deep vein thrombosis subtree with systemic bleeding subtrees. Deep vein thrombosis (DVT) subtree showing possible outcomes following development of DVT (tree shown is for strategy of anticoagulant prophylaxis). A linkage term representing the complement of the effectiveness of withholding anticoagulant prophylaxis for reducing the risk of systemic bleeding was used to link the distal subtrees. This effectiveness term was calculated as follows: effectiveness of withholding anticoagulant prophylaxis = ((probability of systemic bleeding with LMWH) - (probability of systemic bleeding without LMWH))/(probability of systemic bleeding with LMWH). The circles represent chance nodes, and the triangles on the far right represent the outcome measure, expected utility. Numerical values under each branch are the baseline probabilities used at each chance node for the baseline case with administration of anticoagulant prophylaxis. Values to the right of each triangle are the final expected values (utility) for each state. Alive PE: survival after a pulmonary embolism; Alive w Systemic Bleed: survival after a systemic bleeding complication; CNS Bleed: progression of intracranial hemorrhage; Disabling: disabling neurological deficit; DVT: deep vein thrombosis; Non Disabling: non-disabling neurological deficit; No Sys Bleed: no systemic bleeding complication; PE: pulmonary embolism; Systemic Bleed: hemorrhagic complication not involving central nervous system.

Figure 3

No deep vein thrombosis (DVT) subtree showing possible outcomes without development of DVT. The tree shown is for strategy of anticoagulant prophylaxis. A linkage term representing the complement of the effectiveness of withholding anticoagulant prophylaxis for reducing the risk of progression of ICH progression was used to link the main subtrees. This effectiveness term was calculated as follows: effectiveness of withholding anticoagulant prophylaxis = ((probability of ICH progression with LMWH) - (probability of ICH progression without LMWH))/(probability of ICH progression with LMWH). The circles represent chance nodes, and the triangles on the far right represent the outcome measure, expected utility. Numerical values under each branch are the baseline probabilities used at each chance node for the baseline case and with administration of anticoagulant prophylaxis. Values to the right of each triangle are the final expected values (utility) for each state. Alive w Systemic Bleed: survival after a systemic bleeding complication; CNS Bleed: progression of intracranial hemorrhage; Disabling: disabling neurological deficit; DVT: deep vein thrombosis; Live CNS Bleed: survival after progression of intracranial hemorrhage; Non Disabling: non-disabling neurological deficit; No Sys Bleed: no systemic bleeding complication; Systemic Bleed: gastrointestinal bleeding.

Figure 4

Results of decision analysis. The square node at the extreme left represents the decision node and the circles represent chance nodes. Numbers in boxes are the final calculated expected value at each chance node. The overall expected value associated with withholding anticoagulation prophylaxis (0.8961) is similar to that associated with the anticoagulant prophylaxis strategy (0.8862), indicating the choice is a toss-up. CNS Bleed: progression of intracranial hemorrhage; DVT: deep vein thrombosis; ICH: intracranial hemorrhage; PE: pulmonary embolism.

Figure 5

Sensitivity analysis on effectiveness of low molecular weight heparin at preventing deep venous thrombosis. One-way sensitivity analysis in which the relative effectiveness of low molecular weight heparin (LMWH) at preventing deep vein thrombosis (DVT) is varied (small green diamonds). The two strategies (LMWH versus no prophylaxis) are seen to have equivalent expected values (utilities) at the point (threshold value) where the two lines intersect. This analysis suggests that providing LMWH at 24 hours after traumatic brain injury with intracranial hemorrhage would become the preferred strategy only if it was more than 80% effective at preventing DVT.

Figure 6

Sensitivity analysis on effectiveness of no anticoagulant prophylaxis at preventing progression of intracranial hemorrhage. One-way sensitivity analysis in which the relative effectiveness of withholding low molecular weight heparin (LMWH) to prevent progression of intracranial hemorrhage (CNS bleed) is varied (large blue diamonds). The two strategies (LMWH versus no prophylaxis) are seen to have equivalent expected values (utilities) at the point (threshold value) where the two lines intersect. This analysis suggests that LMWH would become the preferred strategy only if it increased the risk of intracranial hemorrhagic progression by no more than 5% above the baseline risk.