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Velmahos GC, Kern J, Chan L, et al. Prevention of Venous Thromboembolism After Injury. Rockville (MD): Agency for Healthcare Research and Quality (US); 2000 Nov. (Evidence Reports/Technology Assessments, No. 22.)

**This publication is provided for historical reference only and the information may be out of date.**

## Analysis of Complications of Methods of VT Prevention

Bleeding and thrombocytopenia are two complications frequently reported in the literature as being associated with the administration of heparin (LDH or LMWH) for VT prophylaxis. There were not enough data to perform meta-analysis on these two outcomes. Our calculation of the incidence of these variables is confounded by the different drugs and doses used, the lack of standard definitions of the outcomes, and the differences in study designs.

Tables 52 and 53 show the available studies that reported bleeding and thrombocytopenia. The cumulative incidence (random-effects estimate) of bleeding was 3.6 percent (95 percent CI: 0.010, 0.061) after administration of LDH in 28 of 662 patients and 3.1 percent (95 percent CI: 0.017, 0.045) after administration of LMWH in 19 of 585 patients. The cumulative incidence of thrombocytopenia was 1.9 percent (95 percent CI: 0.004, 0.035) for LDH and 0.4 percent (95 percent CI: -0.003, 0.011) for LMWH. Overall, for all trauma patients in studies reporting on these rates, the incidence of bleeding following VT prophylaxis was 2.8 percent (95 percent CI: 0.016, 0.040) and the incidence of thrombocytopenia was 1 percent (95 percent CI: 0.000, 0.020). The 15 studies reporting on bleeding and the 5 reporting on thrombocytopenia were homogeneous according to the chi-squared test of heterogeneity (Q-statistic: 20.97, p value: 0.102 for bleeding, and Q-statistic: 8.31, p value: 0.081 for thrombocytopenia). These rates represent the existing uncontrolled literature data and should be viewed as hypothesis-generating rather than hypothesis-proving. The relevance of these rates to individual patients or practices is unknown.

### Incidence of Fatal PE

The incidence of fatal PE cannot be accurately assessed by the existing literature on trauma. PEs are frequently missed in critically ill patients. These patients usually have multiple complications and organ failures, and even if a PE is found, its role as the cause of death is unclear. In 19 studies describing the incidence of fatal PE, none provided an accurate incidence of fatal PE because no study required autopsies to be performed on all patients who died.

In these 19 studies, 73 of 4,223 patients developed a fatal PE. Sixteen of these studies reported the incidences of both PE and fatal PE. These 16 studies included a total of 3,124 patients, of whom 78 had PE and 37 fatal PE. The incidence (random-effects estimate) of PE was 2 percent (95 percent CI: 0.011, 0.028) and fatal PE 0.6 percent (95 percent CI: 0.002, 0.009). According to these results, approximately one-third of trauma patients who develop PE die from it. As explained above, these figures should be viewed with caution given the nature of the studies, which are very heterogeneous (according to the chi-squared heterogeneity test [Q-statistic: 45.22, p value <0.001]).

### Length of Hospital Stay

It is not clear whether length of stay (LOS) is a risk factor for, or a consequence of, DVT; therefore, it is not reported as a risk factor. A meta-analysis of five studies reporting on the hospital LOS between patients with and without DVT showed that this parameter was statistically different in the two populations (Figure 19). Patients with DVT stayed14.6±2.1 days longer (95 percent CI: 10.4, 18.8) in the hospital than patients without DVT.

## Cost-Effectiveness Analysis

Figures 20 to 22 show the cost-effectiveness models created for the three most common methods of prophylaxis (LDH, LMWH, mechanical).

The meta-analysis found no statistically significant reduction in the risk of DVT for patients who received any of the methods of VT prophylaxis examined in this evidence report. Therefore, if true, prophylaxis cannot be cost effective because the additional costs of both adverse drug reactions and the prophylaxis itself are not offset by improved patient outcomes. Row 1 of Table 54 illustrates this point. Increasing the cost (numerator) without any added benefit in terms of life saved (0 denominator) results in an infinite cost-per-life-saved. However, the 95% confidence interval on our estimates of efficacy are wide; we cannot exclude a clinically important beneficial effect of prophylaxis. Table 54 shows the costs associated with different methods of prophylaxis per death avoided according to different probabilities of DVT. Synthesis of data from the existing literatures shows that the rate of DVT with or without prophylaxis is 0.12 (range: 0.10 to 0.13). The third row of Table 54 shows the costs of the different methods of prophylaxis when DVT is reduced to the lower bound probability of the 95 percent confidence interval, as found in our analysis.

Cost-effectiveness analysis generally employs a
cost-per-*life-year-*saved metric rather than the
cost-per-*life-*saved metric, which is what we report in
Table
54. To find the cost per life-year saved, the cost
per life saved must be divided by an estimate of the years of life gained. The
cost per life-year saved depends on the age of the patient because life
expectancy varies inversely with age. However, future years of life must also be
discounted since 1 additional year of life saved today is worth more than 1 year
of life saved in the future. If the future stream of years of life saved is not
discounted to present value, the cost-effectiveness ratio will be biased
downward (i.e., more cost-effective) as a result of inflated benefits. The
discount rate commonly used in this type of analysis ranges anywhere from 0
percent to 7 percent (Gold, Siegel, Russell,
et al., 1996). In this analysis, we used 3 percent as the discount
rate to derive the discounted years of life (Gold, Siegel, Russell, et al., 1996). Table 55
illustrates the life-expectancy values and discounted years of life for various
cohorts.

The following examples illustrate how to combine the data in Tables 54 and 55. Prophylaxis with LDH resulting in a 10 percent rate of DVT has a cost per life saved of $103,175 (line 3, Table 54). For a 20-year-old patient, the $103,175 cost per life saved would be divided by 28.0 discounted years of life, resulting in a cost of $3,685 per life-year saved when LDH is used as prophylaxis. For the same patient, the cost would be $71,712 per life-year saved when LMWH is used as prophylaxis. A range of $40,000 to $50,000 per life-year saved is usually accepted as a criterion to determine cost-effectiveness (Gold, Siegel, Russell et al., 1996). Therefore, prophylaxis of 20-year-old trauma patients with LDH is highly cost-effective. However, LMWH is not cost-effective because its cost-effectiveness ratio ($71,712) is greater than the standard range and a more cost-effective alternative is available (LDH).

If the trauma patient receiving prophylaxis with LDH were 60 years old, the cost per life saved ($103,175) would be divided by 15.9, resulting in an estimated cost per life-year of $6,489. Again, prophylaxis with LDH would be cost-effective in a 60-year-old trauma patient. Obviously, prophylaxis of trauma patients becomes less cost-effective with older age because of reduced life expectancy.

- Supplemental Analysis - Prevention of Venous Thromboembolism After InjurySupplemental Analysis - Prevention of Venous Thromboembolism After Injury

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