부산대학교 도서관

Venous thromboembolism (VTE) has a background incidence of between 0.7 and 2.69 per 1000 per year (L. N. Roberts et al., 2013). Risk factors are either permanent or transient. Permanent risk factors include thrombophilia (80 x increase risk if homozygous for factor V Leiden), cancer (58 x increase risk if metastatic cancer or diagnosis within last 3 months), increasing age (risk doubles for each decade over age 40 years), family or personal history of deep vein thrombosis (2-3 x increase risk) and increasing body mass index (2 x increase for BMI > 35 kg/m2 in comparison with BMI < 20 kgm2) (Y.-H. Kim & Kim, 2007) (Blom, Doggen, Osanto, & Rosendaal, 2005) (Anderson & Spencer, 2003) (Decramer, Lowyck, & Demuynck, 2008) (Holst, Jensen, & Prescott, 2010). Transient risk factors include surgery (165 x risk in first 6 weeks after total hip or knee replacement, equating to 2% symptomatic VTE rate) (Sweetland et al., 2009). Foot and ankle procedures including ankle fracture fixation, hindfoot fusion and 1st metatarsal osteotomy are associated with 18x, 8x and 2x increase VTE risk respectively (Jameson et al., 2011). Other transient risk factors include postpartum state (21-84 x increase in first 6 weeks), use of oral contraceptive pill or hormone replacement therapy (at least 2 x risk) and lower limb cast immobilization (Jackson, Curtis, & Gaffield, 2011) (Grodstein et al., 1996). Within 90 days of lower limb cast treatment, asymptomatic DVT affects between 4 and 40% of patients, symptomatic DVT affects 1 in 250, symptomatic pulmonary embolism affects 1 in 500, with fatal pulmonary embolism affecting 1 in 15,000 (Jameson et al., 2014). It is apparent that patients will therefore have a differing risks depending on their permanent and transient risks. The types of VTE include asymptomatic events, for which the relevance is not fully understood (often used in studies as a surrogate for symptomatic events). Symptomatic below knee DVT (approximately 20% propagate to become above knee) (Philbrick & Becker, 1988). Symptomatic above knee DVT (affecting popliteal vein or more proximal), which are 4 times more likely to occur (Baglin et al., 2010). Pulmonary embolism can also occur. The clinical relevance of DVT is that 6% of patients will have severe post thrombotic syndrome (venous ulceration, swelling, itching) at 10 years after the event, with 66% of patients displaying some signs (Schulman et al., 2006). Uncomplicated DVT does not appear to impact on quality of life, however if DVT is complicated by post thrombotic syndrome, patients will have significantly reduced quality of life, mental and physical health. Simple non fatal PE reduces physical health and if it is complicated by pulmonary hypertension (affecting approximately 2%) it results in significantly reduced quality of life, mental and physical health (Ghanima, Wik, Tavoly, Enden, & Jelsness-Jørgensen, 2017) (Lubberts, Paulino Pereira, Kabrhel, Kuter, & DiGiovanni, 2016). In view that VTE has significant effects on patients quality of life, it is important to try and prevent it. In order to develop strategies for preventing DVT in patients with lower limb injury treated with leg cast, it is important to investigate the relative contributions of injury, stasis and immobility to thrombogenesis. I start by performing systematic review of the literature to determine whether thromboprophylaxis reduces symptomatic venous thromboembolism in patients with below knee cast treatment for foot and ankle trauma. A systematic review of randomised controlled trials of thromboprophylaxis in patients with foot and ankle injuries treated with cast immobilization was performed, searching MEDLINE and EMBASE from inception to June 2015 (B. A. Hickey, Watson, et al., 2016b). Outcomes of interest were VTE (asymptomatic and symptomatic DVT and PE) and bleeding. 3 reviewers used a data extraction form and assessed the literature according to the Cochrane risk of bias tool. Statistical analysis was performed using RevMan. 7 studies of chemical thromboprophylaxis were included, all except one used venography to assess for DVT, with one study using venous ultrasound. 2 studies reported on mechanical thromboprophylaxis, neither reported symptomatic DVT events. Neither study of mechanical thromboprophylaxis found a reduction in asymptomatic DVT in the intervention group. Funnel plot of studies of chemical thromboprophylaxis suggested no publication bias. Pooled symptomatic DVT occurred in 1.58% of patients in the control group, with 0.43% sustaining symptomatic PE. At meta analysis, symptomatic DVT was reduced in the low molecular weight heparin chemical thromboprophylaxis group (OR 0.29, CI 0.09-0.95). Chemical thromboprophylaxis did not influence PE. There was one non-fatal retroperitoneal haemorrhage (major bleed), which equated to 0.11% (1 in 886). Based on these findings, 11 symptomatic VTE events would be prevented for every 1 major bleed. These findings are comparable with the recent Cochrane review, which included 2 additional studies and a total of 2924 participants. Meta analysis found reported a reduction of VTE in the LMWH chemical thromboprophylaxis group (OR 0.40, 95% CI 0.21-0.76) (Zee, van Lieshout, van der Heide, Janssen, & Janzing, 2017). In order to develop strategies for prediction and prevention of VTE in patients with foot and ankle injury treated with cast immobilization, it is necessary to consider why venous thrombosis occurs in these patients. As previously discussed, patients may have permanent risk factors, which may influence hypercoagulability. The transient risk factors of injury and cast treatment may also influence risk by causing endothelial dysfunction and venous stasis (Virchow, 1856). Several important mechanisms for prevention of venous stasis have previously been found. Weight bearing is important; with Gardner et al (1990) reporting that 30ml of venous contrast was pumped out of the foot during weight bearing (Gardner & Fox, 1983). This is not always possible for a patient with foot and ankle injury treated with a cast, because they may be non-weight bearing. For patients who are non-weight bearing, it is still possible to influence venous flow. For example, Elsner et al (2007) previously found that movement of the 1st metatarsophalangeal joint increased popliteal vein flow from 13 to 39 cm/s (Elsner, Schiffer, Jubel, Koebke, & Andermahr, 2007). In patients without leg casts, intermittent pneumatic compression of the leg or thigh to prevent venous stasis was found to be effective in reducing DVT and PE in a meta analysis of over 16, 000 patients (RR 0.43, 95% CI 0.36-0.52) (Ho & Tan, 2013). It therefore seems that this is a viable mechanism. Furthermore, Whitelaw et al (2001) found that none of the IPC devices studied resulted in significantly better calf pump function when compared with simple passive or active ankle movements (Whitelaw et al., 2001). To assess the influence of toe and ankle movement on venous stasis, I examine the effect of these movements on venous velocities measured at the popliteal vein with ultrasound. To determine whether this is a viable strategy for prevention of DVT, I then assess the impact of application of below knee cast on venous velocities. In this proof of principle study, 20 healthy volunteers were recruited (B. A. Hickey, Morgan, Pugh, & Perera, 2014). All had measurement of calf pump function in the un-casted leg whilst seated, using ultrasound at the popliteal vein. Baseline and peak velocities were measured during active toe movement (dorsiflexion and plantarflexion) and during ankle movement (dorsiflexion and plantarflexion). A below knee cast was then applied and measurements were repeated. Mean resting baseline venous velocity was 10 cm/s, which remained unchanged when the below knee cast was applied. There was approximately 5-fold increase in venous velocities with active toe movement (mean 54 cm/s for toe dorsiflexion, mean 50 cm/s for toe plantarflexion), and 10 fold increase from baseline with ankle movements (mean 115 cm/s ankle dorsiflexion, mean 87 cm/s ankle plantarflexion). All were statistically significant. When the below knee cast was applied, there was no statistically significant decrease in the peak velocities achieved during movement excepting for ankle dorsiflexion (isometric), however this was still increased approximately 8 times compared with baseline (88 cm/s).
It was therefore apparent that venous stasis did not occur when a below knee cast was applied to healthy volunteers and that active toe movement may have a role in preventing stasis in patients with injury, with subsequent reduction in DVT.