ALBERT

Description: Background: Many hospitalized patients with PE die. A large registry study described a mortality rate of 17.4% in patients with PE and suggested 45% of these deaths were due to the PE. Data on death and PE is usually derived retrospectively from hospital databases without chart confirmation and to our knowledge no study has attempted to determine the accuracy of coding for PE deaths. Furthermore, it is unclear how often deaths caused by PE could have been prevented. Methods: A retrospective chart review of PE cases hospitalized at a tertiary care center. Charts over an 8 year period ending in 2004 were reviewed if the hospital database record identified PE as a diagnosis by the ICD-10 coding system. Charts of those who died were independently reviewed by two thrombosis experts with discrepancies resolved by consensus or a third reviewer. Prior to chart review definitions were agreed upon. The coding as PE was considered correct (confirmed PE) if there was supportive imaging, an autopsy, or in the case of death without imaging or autopsy, the clinical scenario was such that PE could have occurred. The degree of certainty that PE contributed to the death was classified as certain (unexplained hypotension, hypoxia, cardiac arrest with no other explanation other than PE and autopsy confirmation or radiographic confirmation), highly probable (same as certain but no autopsy confirmation), probable (criteria for highly probable but another disease could have caused the death). We considered these cases to be death due to PE. Deaths were also classified as possible (other cause suspected based on clinical evidence but 100% certainty not available), or unlikely due to PE (all other cases). In cases defined as death due to PE we determined whether any further intervention could have prevented death. Results: 612 cases were identified of whom 68 had radiographic or autopsy data that ruled out the diagnosis and in 46 the coding was clearly an error. 498 cases of PE were identified, 111 of whom died during hospitalization; the mortality rate in those the hospital coded as PE was 18% vs 22% of those with confirmed PE. Death due to PE was diagnosed in 70 patients (14% of patients with confirmed PE and 11% of all patients coded as PE). In the remaining 41 deaths, PE was possible in 24 and unlikely in 17. Disagreement was uncommon. There was no difference between the likelihood of death from PE in the group diagnosed by imaging and autopsy compared with the group where PE death was confirmed by an appropriate clinical scenario. 38 deaths due to PE may have been prevented with an additional intervention: prophylaxis (55%), earlier diagnosis (45%), inferior vena cava filter (IVCF) (32%), anticoagulation (18%), embolectomy 5%, thrombolytics (3%). The remaining deaths due to PE were not preventable since 15 patients were palliative and did not receive active treatment, 9 died before a diagnosis was made and in 8 another disease prevented treatment. Conclusions: Using hospital database records is a reasonable means to evaluate PE mortality and our death due to PE rates are similar to those in registry publications. Surprisingly imaging and autopsy results do not increase the probability of reaching the conclusion that death is due to PE. Over half of preventable PE deaths may have been prevented by prophylaxis and one third with an IVCF.

Description: Introduction: Upper extremity deep vein thrombosis (UEDVT) is a frequent complication of central venous catheters in cancer patients. Anticoagulation with low molecular weight heparin (LMWH) for a minimum of 3 months is the currently recommended treatment for catheter-related UEDVT in cancer patients. Following catheter removal and a minimum of three months of anticoagulant therapy, the risk of recurrence of VTE is likely to be low and it might be reasonable to discontinue anticoagulant therapy. However, there are no data available to support these hypotheses. Therefore, we sought to assess the efficacy and safety of LMWH for the treatment of catheter-related UEDVT in cancer patients and determine the risk of recurrence of VTE after discontinuation of anticoagulation. Material and methods: A retrospective single center cohort study including consecutive cancer outpatients assessed between July 2008 and December 2012 for the management of symptomatic central venous catheter associated proximal UEDVT was conducted. Results: A total of 99 patients were included. Among them, 89 were treated with one month of full therapeutic weight-adjusted dose of LMWH followed by an intermediate dose. A prophylactic dose of LMWH was given after 3 (n=8), 6 (n=4), or 12 (n=1) months of intermediate dosing of LMWH. The remainder patients continued with intermediate dose of LMWH until discontinuation or last follow up. Median duration of anticoagulation was 124 days (range 40 to 1849). No recurrent VTE and two major bleeding episodes occurred during the first 3 months of treatment. Among the 13 patients who were receiving prophylactic doses of LMWH after completion of 3, 6 or 12 months at full and intermediate doses, 2 (15.4%) had a recurrent VTE event. Others did not recurred while on treatment. Eighty-three patients discontinued anticoagulation and 80 could be followed-up after anticoagulation discontinuation for a median of 632 days (range 6 to 2495). Central venous line was pulled out in 77 patients (96.2%). Five recurrences were observed during follow up. The cumulative probability of recurrent VTE was higher in patients whose cancer was active at the time of anticoagulation discontinuation as compared with those in remission (22.2% (95% CI: 0 to 40.6) vs. 2.3% (95% CI: 0 to 6.7)) (Figure 1). Conclusion: LMWH can safely be used to treat catheter associated proximal UEDVT in the setting of cancer. In patients whose central venous line has been pulled and cancer is in remission, anticoagulation therapy can be safely discontinued. Figure 1: cumulative probability of recurrence according to cancer status at the time of anticoagulation discontinuation Disclosures No relevant conflicts of interest to declare.

Description: Abstract 3125 Poster Board III-62 VTE is the most frequent complication of OS and it can be prevented through anticoagulant prophylaxis. Numerous studies have evaluated different agents for this purpose and there are new agents currently under development or recently approved for this indication. We conducted a systematic review of randomized controlled trials (RCT) evaluating administration of anticoagulants for VTE prophylaxis in OS and performed a MA of proportions to estimate the overall incidence of major VTE (proximal VTE, pulmonary embolism (PE), or death from PE), total VTE (proximal and distal VTE, PE or death from PE), symptomatic VTE and major bleeding episodes (as defined by the International Society on Thrombosis and Hemostasis). We included RCT comparing currently approved anticoagulants (head-to-head or placebo-controlled) for VTE prophylaxis in OS (hip and knee arthroplasty and hip fracture surgery) using systematic evaluation of VTE (ultrasound or venography, pulmonary angiography, CT pulmonary angiography, or ventilation perfusion scan). Heterogeneity of proportions was evaluated using a chi2 test and pooled estimates of proportions were obtained using either a fixed or a random effects model in which the weights were estimated as proposed by Laird and Mosteller. We retrieved 74 studies including180 research arms and enrolling 71,012 patients. The total number of events and evaluable patients, percentage of events and 95% CI, and number of study arms included are shown in the table. We found differences in the percentage of VTE and bleeding events associated with the use of different anticoagulants for VTE prophylaxis after OS. Due to the nature of the analysis no effect measure can be estimated. These estimates might help to design future studies. Major VTE Total VTE Symptomatic VTE Major Bleeding Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) All patients LMWH 993/23692 5.96 (5.81, 6.11) 72 4068/22610 20.29 (20.04, 20.55) 80 193/19431 1.32 (1.27, 1.37) 35 476/28725 1.98 (1.93, 2.02) 70 UFH 234/2407 13.39 (12.86, 13.93) 14 596/2537 22.54 (22, 23.08) 17 11/339 3.24 (3.06, 3.43) 4 70/2849 2.75 (2.61, 2.89) 16 Warfarin 269/5677 6.28 (6.09, 6.46) 12 1317/4203 31.05 (30.44, 31.66) 12 71/4146 1.95 (1.83, 2.08) 6 96/6751 1.78 (1.69, 1.87) 12 Fonda 96/3673 3.81 (3.53, 4.09) 7 223/3477 6.82 (6.57, 7.07) 6 69/6398 1.06 (1.01, 1.1) 8 121/6576 1.63 (1.55, 1.71) 9 Riva 50/5025 2.02 (1.86, 2.19) 8 242/4595 13.05 (12.16, 13.94) 8 29/6252 0.46 (0.45, 0.48) 6 31/6643 0.63 (0.59, 0.68) 8 Dabi 149/4091 3.64 (3.59, 3.69) 6 834/4051 22.96 (21.91, 24.01) 6 26/3664 0.71 (0.67, 0.75) 4 67/5419 1.21 (1.17, 1.26) 6 Placebo 193/710 24.26 (23.17, 25.34) 10 379/816 49.35 (48.08, 50.62) 11 19/198 12.02 (10.32, 13.72) 3 12/753 1.59 (1.5, 1.68) 7 Total 1984/45275 129 7659/42289 140 418/40428 66 873/57716 128 Total Hip Arthroplasty LMWH 653/15978 6 (5.85, 6.16) 50 1817/14480 15.58 (15.35, 15.82) 55 81/11552 0.7 (0.69, 0.72) 19 306/18010 1.97 (1.92, 2.02) 45 UFH 187/1739 14.3 (13.64, 14.96) 11 354/1836 20.13 (19.46, 20.8) 13 11/246 4.47 (4.21, 4.73) 3 52/1451 3.2 (3.01, 3.39) 11 Warfarin 77/2758 4.28 (4.08, 4.48) 6 265/1273 20.82 (20.59, 21.04) 6 32/1833 1.75 (1.69, 1.81) 2 47/2856 2.23 (2.09, 2.37) 5 Fonda 28/1799 2.96 (2.58, 3.33) 3 85/1695 5.01 (4.91, 5.12) 2 15/2255 0.67 (0.63, 0.7) 2 69/2349 2.94 (2.87, 3.01) 3 Riva 25/2938 2.21 (1.95, 2.46) 5 73/2749 9.72 (8.92, 10.53) 5 10/3468 0.29 (0.27, 0.31) 3 14/3795 0.49 (0.44, 0.54) 5 Dabi 72/1803 3.99 (3.88, 4.11) 2 124/1766 7.02 (6.77, 7.27) 2 21/2293 0.92 (0.91, 0.93) 2 38/2309 1.65 (1.58, 1.72) 2 Placebo 105/414 26.01 (24.76, 27.27) 7 174/418 45.43 (43.74, 47.13) 7 4/147 2.72 (2.46, 2.98) 2 3/388 0.77 (0.69, 0.86) 5 Total 1147/27429 84 2892/24217 90 174/21794 33 529/31158 76 Total Knee Arthroplasty LMWH 277/6916 4.45 (4.34, 4.55) 25 2062/7326 30.72 (30.37, 31.07) 32 83/4902 1.69 (1.66, 1.73) 11 89/7808 1.14 (1.12, 1.16) 26 UFH 42/638 6.58 (6.39, 6.78) 3 226/638 35.42 (35.05, 35.79) 3 0/93 NE 1 3/318 0.94 (0.84, 1.05) 2 Warfarin 192/2919 8.1 (7.88, 8.32) 9 1052/2930 39.36 (38.69, 40.02) 9 39/2056 1.9 (1.84, 1.96) 3 28/3407 0.82 (0.79, 0.85) 8 Fonda 23/452 9.3 (7.93, 10.67) 2 45/361 12.47 (12.12, 12.81) 1 3/517 0.58 (0.51, 0.65) 1 12/601 2 (1.88, 2.11) 2 Riva 25/2087 1.2 (1.15, 1.24) 3 169/1846 18.55 (16.47, 20.63) 3 19/2784 0.68 (0.65, 0.71) 3 17/2848 0.6 (0.57, 0.63) 3 Dabi 77/2288 3.37 (3.32, 3.41) 4 710/2285 30.98 (30.42, 31.55) 4 5/1371 0.36 (0.32, 0.41) 2 29/3110 0.93 (0.89, 0.98) 4 Placebo 88/296 27.12 (24.54, 29.7) 4 205/398 55.19 (53.53, 56.84) 5 15/51 29.41 (28.16, 30.66) 1 9/365 2.47 (2.31, 2.62) 4 Total 724/15596 50 4469/15784 57 164/11774 22 187/18457 49 LMWH Low molecular weight heparin, UFH unfractionated heparin, Riva Rivaroxaban, Dabi Dabigatran etexilate Disclosures Lazo-Langner: Boehringer Ingelheim: Honoraria. Rodger:Bayer: Research Funding; Leo Pharma: Research Funding; Pfizer: Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Biomerieux: Research Funding; GTC Therapeutics: Research Funding.

Description: AC proph after OS results in a decrease in the incidence of VTE with an associated increase in the risk of major bleeding (MB). Several AC agents and schedules are used; however the optimal timing of initiation has not been determined. It is likely that the proximity to the time of surgery might influence both the efficacy and safety of the AC thus altering their risk-benefit profile. Using a clinical cost-effectiveness approach we compared different AC and timings of VTE proph in patients undergoing OS. A meta-analysis of 55 randomized trials was done to estimate the risk (MB) and benefit (averted VTE) of proph in OS using placebo (plac) or different AC (ximelagatranxim, low molecular weight heparin-LMWH, unfractionated heparin-UFH, warfarin-warf and fondaparinux-fonda) and timings of initiation (defined as preoperative (preop) if the first dose of the AC was administered 〉2 hrs before surgery, perioperative (periop)if between 2 hrs before or up to 12 hrs after the surgery and postoperative (postop) if starting 12 hrs or more after surgery). Means and variances of the MB and VTE estimates were used to parameterize Monte Carlo simulations for a beta distribution using 1,000 replications. Incremental risk, benefit and risk-benefit ratios (compared to placebo) were calculated from the replications. All AC/timing combinations were compared across a range of benefit-risk tradeoff values (risk acceptance) by calculating the percentage of replications with the highest net clinical benefit (NCB; e.g. incremental benefit - incremental risk · tradeoff) for each AC/timing combination. A higher NCB represents a better risk-benefit profile. In addition all anticoagulants were pooled together according to the initial timing of administration and NCB was calculated using random re-sampling of the replications. Analyses were done separately for major VTE (mVTE; proximal deep vein thrombosis (DVT) + pulmonary embolism), and total VTE (tVTE; mVTE + distal DVT) and a sensitivity analysis was done after excluding xim. The reference tradeoff was estimated from the case-fatality rate-ratios of VTE to MB (mVTE/MB=0.39; tVTE/MB=0.10). At the reference tradeoff value, the AC/timing combination with the highest probability of having the best risk-benefit profile was postop xim analyzed by both mVTE and tVTE (99 and 58%, respectively). After excluding xim the AC/timing combination of choice was postop LMWH if analyzed by mVTE (60%) or preop LMWH if analyzed by tVTE (59%). When all AC were pooled those administered postop had the highest probability of having the best risk-benefit profile analyzed by mVTE (48%) and the choice was indifferent between preop (45%) and postop (40%) if analyzed by tVTE. After excluding xim from the pooled analysis the choice was indifferent between preop (40%) and postop (35%) if analyzed by mVTE and if analyzed by tVTE the choice was preop (55%) followed by postop (27%). Our results suggest that: postop administration of AC proph has the best risk-benefit profile; the results are influenced by the event defining benefit (mVTE or tVTE); in some analyses preop administration was best, and; periop administration always had the worst risk-benefit profile. We conclude that periop AC proph after OS should not be used.

Description: Background: 5% of the population over 65 is on oral anticoagulant therapy. The indications for anticoagulation therapy are wide, not limited to but including treatment of arterial and venous thrombosis, and primary stroke prophylaxis is patients with atrial fibrillation and mechanical cardiac valves. While new oral anticoagulants not requiring monitoring are being more widely prescribed, vitamin K antagonists (VKA) are still being used for many patients in whom the novel agents are contra-indicated (renal failure), not available (funding), or patient/physician preference. Most patients on VKA have their family physicians manage their oral anticoagulants. On average, the time in therapeutic range achieved by family physicians is low (50-55%). There is also a number of patients who have no family physician and are either taking VKA without monitoring, or are having their anticoagulants monitored routinely though emergency room physicians/visits. The Ottawa Hospital (TOH) anticoagulation management service is an e-health solution that offers patients world beating time in therapeutic range (TIR). TOH uses a pharmacy managed DAWN software package (computer-assisted warfarin dosing program). Maintaining patients in therapeutic range for a high percentage of time (greater than 70%) can reduce the risk or recurrent thrombosis (venous or arterial) from under-anticoagulation and the risk of bleeding complications from over-anticoagulation. Well managed VKA therapy has also been suggested to be as safe as therapy with novel oral anticoagulants in some subgroup analysis of studies investigating the novel oral anticoagulants. Objectives/Methods: The purpose of this study was to bring the benefits of the TOH experience to provide a Regional Anticoagulation Management Service across a wide region of eastern Ontario, Canada. This service includes remote blood testing (at a lab near the patient’s home), integrated LIS link to a computerized dosing system (possible through a commercial lab partnership), and communication of dosing and testing instructions via interactive voice recognition (IVRS), email, or live (pharmacist/pharmacist assistant). We administered a patient satisfaction survey to a sample of 111 patients enrolled in the service as well as reported TIR for patients enrolled in our service during the study period (2009-2011). Results: At the beginning of the study, 1400 patients were enrolled in the program. After 2 years, the number has increased to by 66% to 2325. The average TIR for patients in the program as of October 2011 was 76.3% (overall), 77.8% (IVRS), 76.8% (email), and 73.3% (live). The patient satisfaction survey demonstrated that 94% patients prefer VKA anticoagulation monitoring through TOH service compared to their previous experience. 84% patients either satisfied or very satisfied with VKA anticoagulation care through TOH service (compared to 53% satisfaction with anticoagulant care prior to enrolling in our program). Conclusions: The TOH model of anticoagulation management service results in excellent VKA monitoring (high TIR) for a large number of patients across a wide geographical area, as well as a high level of patient satisfaction. This service allows for the safe and efficient management of VKAs in patients in whom VKA therapy is indicated. Disclosures No relevant conflicts of interest to declare.

Description: Controversy over whether the factor XIII Val34Leu polymorphism confers protection against venous thromboembolism (VTE) is a persistent debate in the current thrombosis literature. If an accurate estimate of the protective effect were established, routine screening for this mutation in patients with VTE could provide more precise individual risk-profiling, but presently, it remains undetermined whether it is worthwhile to screen for this polymorphism. We performed a meta-analysis to determine whether the 34Leu allele of the factor XIII gene is associated with a decreased risk of VTE. Studies were identified by searching MEDLINE (1966 through to June Week 2 2004) followed by a manual search of reference lists from previously retrieved articles, symposia proceedings, and abstracts from major thrombosis conferences. Studies were selected for review if they involved unselected objectively diagnosed VTE patients with factor XIII Val34Leu genotypes reported and were a case-controlled study. Inclusion decisions, quality assessment and data extraction were conducted by two reviewers and consensus was achieved by discussion or by a third independent reviewer. Hardy-Weinberg equilibrium of the study control populations were verified. Four of the studies did not report whether they had verified Hardy-Weinberg equilibrium (Balogh, Catto, Margaglione, and Zidane). Authors were contacted for missing data. Forty-five studies were reviewed for eligibility and ten studies met the inclusion criteria. Pooled Odds Ratios and their 95% confidence intervals (CI) were determined using the method of DerSimonian-Laird. Prior to pooling, heterogeneity testing was performed using the Breslow-Day statistic and was insignificant (p = 0.06) which validated testing our FXIII 34Leu recessive model using the random effects model. Funnel plots ruled out the possibility of publication bias. The random effects model gave a combined odds ratio of 0.75 (95% CI= 0.55 to 1.01). Testing our dominant model using a random effects model gave a combined odds ratio of 0.86 (95% CI=0.76 to 0.98). Heterogeneity testing was insignificant (p=0.16). Our meta-analysis found significantly lower odds of VTE with the presence of FXIII 34Leu allele using a dominant model (i.e. the presence of at least one Leu allele). This polymorphism should be given consideration as part of routine risk profiling in patients at risk for VTE.

Description: Background: Heparin induced thrombocytopenia (HIT) is a syndrome characterized by thrombocytopenia and an elevated risk of thrombosis. In the evaluation of patients with suspected HIT, laboratory testing is used to help differentiate between those patients who have HIT and those who do not and therefore do not require non-heparin anticoagulation. Laboratory tests include activation (serotonin release, heparin-induced platelet aggregation, ATP luminescence) and antigen (enzyme-linked immunoabsorbant assay (ELISA)) assays directed against the platelet factor 4-heparin or PF4/PVS complex. A pre-test scoring system (Warkentin 4T’s) has been derived to assess the probability of HIT which can be used in conjunction with laboratory testing in the evaluation for HIT. Objectives: To compare the activation assay used at The Ottawa Hospital (ATP luminescence) with the PF4 enhanced® ELISA and correlate results with clinical data. Methods: Patients undergoing HIT testing were identified. ELISA and activation assays were performed. Charts were reviewed in order to derive a 4T’s score and to assess response to therapeutic non-heparin anticoagulation (when administered). Correlation between ELISA, activation assay, 4T’s score and platelet response to alternative anticoagulation was determined. Sensitivity, specificity, PPV and NPV of laboratory tests or 4T’s scores were calculated depending on the measure chosen as the reference standard to diagnose HIT. Results: 111 patients undergoing HIT testing were evaluated. 41 and 43 were positive by ELISA (OD 〉 0.4) or activation assay respectively. 12 were positive only by ELISA (mean optical density (OD): 1.27) and 10 were positive by both activation assay and ELISA (mean OD: 2.28). Clinical information was available for 70 patients. 26 of these received therapeutic non-heparin anticoagulation as treatment for suspected HIT. Reference standard= activation assay: ELISA: Sens 95% (95% CI 73–99%), Spec 80% (66–89%), PPV 66% (46–81%), NPV 98% (86–100%). 4T’s (low vs. high score): Sens 85% (54–97%), Spec 95% (83–99%), PPV 85% (54–97%), NPV 95% (83–99%). ELISA OD 〉 1.5 + high 4T’s score: Sens 61% (36–82%), Spec 100% (56–100%), PPV 100% (68–100%), NPV 50% (24–76%). Reference standard= 4T’s score (high and low score only, excludes intermediate category): ELISA: Sens 85% (53–97%), Spec 77% (61–88%), PPV 52% (30–74%), NPV 94% (79–99%). Activation: Sens 85% (54–97%), Spec 95% (83–99%), PPV 85% (54–97%), NPV 95% (83–99%). Reference standard= “clear response to non-heparin anticoagulation” defined as significant platelet increase within 48 hours of start of therapy and no other explanation for platelet recovery: ELISA: Sens 100% (72–100%), Spec 54% (26–80%), PPV 68% (43–86%), NPV 100% (56–100%). Activation: Sens 85% (54–97%), Spec 69% (39–90%), PPV 73% (45–91%), NPV 82% (48–97%). 4T’s (low vs. high score): Sens 90% (54–99%), Spec 100% (60–100%), PPV 100% (63–100%), NPV 89% (51–99%). ELISA OD 〉 1.5 + 4T’s (low vs. high score): Sens 89% (51–99%), Spec 100% (56–100%), PPV 100% (60–100%), NPV 88% (47–99%). Conclusions: A high 4T’s score best predicts a clinical response to non-heparin therapeutic anticoagulation when HIT is suspected. ELISA OD 〉 1.5 does not add additional information in this respect. A negative ELISA and a low 4T’s score have comparable NPVs when an activation assay is the reference standard. Future trials should employ a clinical reference standard such as “clear response to non-heparin anticoagulation” when evaluating the operator characteristics of HIT assays.

Description: Major VTE is the most frequent complication of OS. Current recommendations are to administer prophylaxis with an anticoagulant agent for at least 7–10 days. Numerous studies have evaluated different agents for this purpose. Although the most recent studies are usually methodologically sound, several studies have been hampered by inappropriate designs and insufficient sample sizes. In order to help with the design of future trials we conducted a systematic review of randomized trials evaluating short-term (〈 15 days) administration of anticoagulants for VTE prophylaxis in OS and performed a MA of simple proportions to estimate the overall incidence of major VTE (proximal VTE, pulmonary embolism (PE), or death from PE), total VTE (proximal and distal VTE, PE or death from PE), and major bleeding episodes (as defined by the authors and defined using a definition similar to the one proposed by the International Society on Thrombosis and Haemostasis-ISTH). We included randomized trials comparing different drugs for VTE prophylaxis in OS (hip and knee arthroplasty and hip fracture surgery) using systematic evaluation of VTE (ultrasound or venography, pulmonary angiography, tomographic angiography, or ventilation perfusion lung scan). Heterogeneity of proportions was evaluated using a chi ² test and pooled estimates of proportions were obtained using a fixed or a random effects model as appropriate. In the latter the weights were estimated as proposed by Laird and Mosteller. We retrieved 55 studies (135 research arms) which enrolled 42,131 patients. The percentage and variance of major and total VTE and major bleeding are shown in table 1. The total number of events and the number of evaluable patients are shown in table 2. We found differences in the percentage of clinical outcomes associated with the use of different agents for VTE prophylaxis after OS, however, because of the analytical strategy used no estimation of odds or risk reduction can be derived from this data. We believe that these estimates will be of help for the design of future studies.

Description: Background: Hydroxyethyl starch (HES) is a commonly used intravascular volume expander in the peri-operative period. The use of such volume expanders has been demonstrated to cause significant abnormalities of laboratory tests of hemostasis by a number of mechanisms including a reduction of factor VIII activity. In Canada, Pentaspan® is commonly used, and its shorter half life has been reported to cause less coagulation abnormalities than older HES formulations. A recent study has demonstrated that in patients receiving Pentaspan®, a volume of up to 45ml/kg per 24hrs will not cause significant changes to coagulation parameters (Arellano et al. Anaesth Analg2005;100:1846–53). Following is a report of a coagulopathy caused by much lower doses of Pentaspan®. Case report: A 53 year old male was scheduled to undergo elective aortic valve replacement for severe aortic stenosis. He had no previous history of a bleeding disorder and one week pre-operatively he had normal coagulation parameters with an activated partial thromboplastin time (aPTT) of 33 seconds (normal range 24–36 sec). On the day of surgery, after sternotomy was performed, the patient experienced an allergic reaction to morphine and developed transient hypotension necessitating a small dose of phenylephrine and 500cc of Pentaspan®. The patient recovered, but subsequent to this, the activated clotting time (ACT) was 〉300sec in the absence of heparin and the aPTT was 68sec. Other coagulation parameters included a thrombin time of 14sec (upper limit normal (ULN) 16sec), a fibrinogen of 3.7g/L and a heparin anti-Xa level of

Description: Genetic factors involving blood coagulation are thought to contribute to the pathogenesis of myocardial infarction. A common polymorphism of Factor XIII, Factor XIII Val34Leu, may be protective against developing an acute myocardial infarction, but various studies show conflicting results. We performed a meta-analysis to determine whether the Factor XIII Val34Leu polymorphism is associated with a decreased risk of myocardial infarction. 93 articles were reviewed after a MEDLINE search of the literature (1966 through April Week 1 2005) and 12 case-control studies were selected. We included studies involving patients with objectively diagnosed myocardial infarctions (according to the WHO criteria) provided Factor XIII genotyping data were available. Inclusion decisions, quality assessment and data extraction were conducted by two reviewers. Hardy-Weinberg equilibrium was verified in all studies. Hypothesizing that the Leu allele was protective we performed 3 analyses with the Val/Val genotype as the reference group. Pooled odds ratios and their 95% confidence intervals were determined using the method of DerSimonian-Laird. Prior to pooling, heterogenity testing was performed using the I2 statistic. Funnel plots ruled out the possibility of publication bias. These studies included a total of 8743 patients, of which 3663 were MI patients and 5080 were healthy controls. Using the random effects methods, protective effects were seen with the Leu/Val genotype alone (OR for MI 0.79, 95% CI 0.68–0.93) and with Leu/Val and Leu/Leu genotypes (OR 0.79, 95% CI 0.68–0.93). There was also a protective effect with the Leu/Leu genotype alone, but this was not statistically significant (0.83, 95% CI 0.61–1.12) likley due to the low frequency of this genotype. Removing the first published study (Kohler 1998) due to potential publication bias assocaited with the first study evaluating a genotype did not significantly change the results. Our analysis found that the Factor XIII Leu allele confers a small but significant protective effect against myocardial infarction. The polymorphism may be useful in profiling an individual’s susceptibility for arterial thrombosis. It remains to be elucidated whether or not routine testing for the FXIII Val34Leu polymorphism will be clinically relevant.