A multicenter randomized controlled trial comparing administration of antithrombin III after liver resection (HiSCO-05 trial).

BACKGROUND: Posthepatectomy liver failure is a poor prognostic factor after hepatectomy. Various preventive treatments have been tried; however, there are no clinical trials that use posthepatectomy liver failure as the primary endpoint, and the clinical effects of posthepatectomy liver failure have not been fully verified. The aim of this study was to investigate whether administration of antithrombin III can prevent posthepatectomy liver failure in patients with coagulopathy after hepatectomy. This study also evaluated the safety of AT-III administration after hepatectomy. METHODS: The current study enrolled 141 patients diagnosed with coagulopathy after hepatectomy between October 2015 and September 2018 at 7 hospitals in Hiroshima, Japan (HiSCO group). Patients were randomized to undergo either administration of antithrombin III (n = 64) or non-administration (n = 77). The primary endpoint was the incidence of posthepatectomy liver failure. This randomized controlled trial was registered with the University Medical Information Network Clinical Trial Registry (UMIN000018852). RESULTS: Treatment for postoperative coagulopathy was performed safely without adverse events. The incidence of posthepatectomy liver failure was similar in both treatment groups (nonadministration of antithrombin III group, 28.5%, versus administration of antithrombin III group, 28.1%; P = .953) The rate of morbidity was higher in the administration group than the non-administrated group (17.2% vs 11.7%, P = .351). Following the multivariate analysis of the whole study group, body mass index ≥25, total bilirubin ≥1.5 mg/dL, and the disseminated intravascular coagulation score ≥5 postoperatively were the independent risk factors for posthepatectomy liver failure. CONCLUSION: This study showed that the administration of antithrombin III resulted in no significant difference in preventing posthepatectomy liver failure, possibly through suppressing coagulopathy.

Low level of postoperative plasma antithrombin III is associated with portal vein thrombosis after liver surgery.

PURPOSE: Although decreased antithrombin-III (AT-III) is a risk factor for portal vein thrombosis (PVT) in patients with liver cirrhosis, the association between postoperative PVT and postoperative AT-III levels is unknown in patients undergoing hepatectomy. METHODS: Patients who underwent hepatectomy between 2015 and 2018 were retrospectively analyzed. Postoperative PVT was assessed on CT at days 6-9 after hepatectomy. One-to-one propensity score (PS) matching was used to match the baseline characteristics. RESULTS: Of the 295 patients included in this analysis, 19 patients (6.4%) were diagnosed with postoperative PVT. The AT-III level on postoperative day (POD) 3 predicted postoperative PVT with a sensitivity/specificity of 74%/59% (AUC, 0.644; cut-off value, 60%; p = 0.032). Multivariate analysis revealed that AT-III levels ≤ 60% on POD3 (OR, 3.01; 95% CI 1.02-8.89; p = 0.046), cirrhosis (OR, 5.88; 95% CI 1.92-18.0; p = 0.002) and right-sided hepatectomy (OR, 4.16; 95% CI 1.45-11.9; p = 0.0079) were significant risk factors for postoperative PVT. After PS matching, 56 patients with and without AT-III supplementation were analyzed. The two groups had a similar incidence of PVT (p = 0.489). CONCLUSIONS: Patients with AT-III levels ≤ 60% on POD3 should be carefully followed up regarding postoperative PVT. Our results did not support the efficacy of routine AT-III supplementation for the prophylaxis of postoperative PVT.

Capped antithrombin III dosing is cost effective in the management of asparaginase-associated thrombosis.

Asparaginase therapy induces a transient antithrombin III (ATIII) deficiency, which contributes to the risk of asparaginase-induced thrombosis. At Cincinnati Children's Hospital Medical Center, management of asparaginase-induced thrombosis includes ATIII supplementation during therapeutic anticoagulation with enoxaparin. Due to the expense associated with ATIII, a capped dosing approach for ATIII was evaluated in this population. Peak ATIII levels were obtained following capped doses to evaluate response. In this pilot evaluation, 11 patients received a total of 138 capped doses for a total cost savings of $803 782. This pilot evaluation represents the first reported analysis of capped ATIII dosing in oncology patients.

Antithrombin Insufficiency Promotes Susceptibility to Liver Tumorigenesis.

BACKGROUND: Antithrombin (AT) is not only a major regulator of hemostasis, but it shows anti-inflammatory properties as well. We aimed to investigate whether AT-insufficient mice increase susceptibility to liver tumorigenesis. METHODS: We induced the development of liver tumor in AT-insufficient (AT+/-) mice and wild-type (AT+/+) mice by treating them with diethylnitrosamine (DEN) and CCl4. The development of liver tumors and liver inflammation were compared between these mouse groups. Following this, AT was administered to the AT-insufficient mice treated with DEN and CCl4. RESULTS: Tumor size and the number of DEN and CCl4-induced liver tumors significantly increased in AT-insufficient mice compared with the wild-type mice. Serum transaminase levels, cell death, and the expression of cleaved caspase-3 in liver were increased in AT+/-. Furthermore, hepatic neutrophil infiltrations and serum interleukin 6 and tumor necrosis factor-α levels were significantly elevated in AT-insufficient mice. The levels of 8-OHdG, oxidative DNA damage marker, in liver were significantly increased in AT-insufficient mice. Administration of AT led to a significant decrease in DEN- and CCl4-induced liver injury and inflammation in AT-insufficient mice, compared with the wild-type group. CONCLUSIONS: AT insufficiency led to increased susceptibility to liver tumorigenesis by increasing hepatic inflammation.

Strategy for Cardiovascular Surgery in Patients with Antithrombin III Deficiency.

Antithrombin III (ATIII) deficiency is a rare disorder in which thrombosis can be induced by stimuli that do not usually lead to thrombus formation, including minor injuries and surgery. Therefore, patients with ATIII deficiency undergoing cardiovascular surgery that involves heparinization require careful perioperative management. We experienced five patients with ATIII deficiency who underwent cardiovascular surgery and were managed with ATIII replacement. By administration of ATIII concentrate, preoperative ATIII activity was maintained at ≥120% and postoperative ATIII activity at ≥80%. All five patients were treated successfully without postoperative complications such as hemorrhage or thrombosis. In patients with ATIII deficiency undergoing cardiac surgery, it is important to perform ATIII replacement to achieve preoperative ATIII activity ≥120% and postoperative ATIII activity ≥80%, while the activated clotting time (ACT) is maintained at >400 seconds during cardiopulmonary bypass. In addition, long-term postoperative anticoagulant therapy is necessary in hereditary ATIII deficiency patients with a history of thrombosis.

Identification of Cost-Saving Opportunities for the Use of Antithrombin III in Adult and Pediatric Patients.

Thrombate III is a human plasma-derived antithrombin III (AT-III) often utilized in patients on extracorporeal membrane oxygenation (ECMO) with suspected AT-III-mediated heparin resistance. It is supplied as 500-U and 1000-U vials, costing US$4.66 per unit. Literature is limited in describing the clinical value of AT-III in relation to its high cost. The primary objective was to determine conditions of use and associated cost of potentially unnecessary utilization of AT-III at The Johns Hopkins Hospital. Secondary objectives included evaluating the effect of AT-III on anticoagulation parameters and the overall cost utilized and wasted on AT-III. A retrospective cohort study was performed. The primary end point was the total cost associated with potentially unnecessary utilization of AT-III. There were 326 doses of AT-III administered to 65 patients in 2014. There were 177 (54%) potentially unnecessary doses associated with a cost of US$541 634. Antithrombin III repletion significantly increased median AT-III levels in non-ECMO and ECMO patients compared to baseline (non-ECMO: 62% vs 81%, P < .01; ECMO: 63% vs 81%, P < .01); however, 37.3% of ECMO and 49% of non-ECMO patients had therapeutic anticoagulation monitoring parameters prior to administration. A total cost of US$688 478 was spent on administered AT-III and US$417 194 (38%) was wasted. Utilizing restriction criteria and a new dosing strategy potentially results in estimated annual savings of US$556 000. Utilizing restriction criteria and alternative dosing strategies to mitigate waste and unnecessary use has the potential to result in significant cost savings.

Outcomes of Geriatric Trauma Patients on Preinjury Anticoagulation: A Multicenter Study.

Outpatient anticoagulation in the geriatric trauma patient is a challenging clinical problem. The aim of this study is to determine clinical outcomes associated with class of preinjury anticoagulants (PA) used by this population. This is a multicenter retrospective cohort study among four Level II trauma centers. A total of 1642 patients were evaluated; 684 patients were on anticoagulation and 958 patients were not. Patients on PA were compared with those who were not. Drug classes were divided into thromboxane A2 inhibitors, vitamin K factor-dependent inhibitors, antithrombin III activation, platelet P2Y12 inhibitors, and thrombin inhibitors. Multivariate regression was used to adjust for age, gender, race, mechanism of injury, and Injury Severity Score. No single or combination of anticoagulation agents had a significant association with mortality; however, there were positive trends toward increased mortality were noted for all antiplatelet groups involving thromboxane A2 inhibitors and platelet P2Y12 inhibitors classes. The likelihood of complications was significantly higher with platelet P2Y12 inhibitors adjusted odds ratio (aOR) 2.39 [95% confidence interval (CI) 1.32, 4.3]. The likelihood of blood transfusion was increased with vitamin K inhibitors aOR 2.89 (95% CI 1.3, 6.5), P2Y12 inhibitors aOR 2.76 (95% CI 1.12, 6.76), and combined thromboxane A2 and P2Y12 inhibitors aOR 2.89 (95% CI 1.13, 7.46). P2Y12 inhibitors were also more likely associated with traumatic brain injury aOR 2.16 (95% CI 1.01, 4.6). All classes of PA were associated with solid organ injury. There were no significant differences in the use of antiplatelet agents between patients with major indications for PA and those without major indications. Geriatric trauma patients on outpatient anticoagulants have a higher likelihood of developing complications, packed red blood cell transfusions, traumatic brain injury, and solid organ injury. Attention should be paid to patients on platelet P2Y12 inhibitors, vitamin K inhibitors, and thromboxane A2 inhibitor agents combined with platelet P2Y12 inhibitors. Opportunities exist to address the use of antiplatelet agents among patients without major indications to improve patient outcomes.

Antithrombin III Protects Against Contrast-Induced Nephropathy.

We previously reported that insufficiency of antithrombin III (ATIII), the major anti-coagulation molecule in vivo, exacerbated renal ischemia-reperfusion injury in animal models and possibly humans. In the present study, we investigated the relationship between ATIII level and contrast induced nephropathy (CIN) in patients and examined therapeutic effect of ATIII on CIN in Sprague-Dawley rats. Patients with low ATIII activity presented a higher incidence of acute kidney injury (AKI) following coronary angiography. ATIII (500µg/kg) was intravenously injected before or after the induction of AKI in rats. Our data demonstrated ATIII significantly attenuated the elevation of serum creatinine, blood urea nitrogen, and renal histological injury. The beneficial effects of ATIII were accompanied by diminished renal inflammatory response, oxidative stress, cell apoptosis and improved renal blood flow in rats. In conclusion, ATIII appears to attenuate CIN through inhibiting inflammation, oxidative stress, apoptosis and improving renal blood flow. ATIII administration may represent a promising strategy for the prevention and treatment of contrast-induced AKI.

[Atrial Septal Defect with Hereditary Deficiency of Antithrombin III].

A 41-year-old female with hereditary deficiency of antithrombin III (ATIII) was diagnosed with atrial septal defect( ASD) and scheduled for the closure of ASD. She had been taking warfarin since she suffered from deep vein thrombosis 10 years ago. Preoperative management of anticoagulation included discontinuation of warfarin, and supplementation of antithrombin with heparin infusion. On the day of operation, antithrombin activity was maintained above 80% by administering antithrombin, and closure of ASD was carried out under standard cardiopulmonary bypass support using heparin. Heparin infusion was continued with antithrombin supplementation until prothrombin time-international normalized ratio(PT-INR) recovered to around 2.5 with warfarin. Her intra-and postoperative courses did not show any thromboembolic events, and she was discharged 20 days after the surgery.

[Experience in treating portal thromboses in patients with chronic myeloproliferative diseases].

Patients with myeloproliferative diseases (MPD) are noted to be at high risk for portal thromboses. This problem gives rise to disability if it is untimely treated or resistant to therapy. The paper gives the experience of the Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation, in using antithrombin III in MPD patients (3 patients with primary myelofibrosis, 3 with essential thrombocythemia) and acute and subacute portal vein thromboses resistant to therapy with direct anticoagulants. In all 5 cases, the use of antithrombin III in combination with low-molecular-weight heparin showed a positive clinical effect as rapid relief of pain syndrome and comparatively early (3-week to 1.5-2-month) recanalization of thrombosed vessels. Three clinical cases are described in detail.

Protective effects of antithrombin on free groin flaps after secondary venous stasis in the rat model.

BACKGROUND: The anticoagulant activity of heparin is well established and led to its widespread clinical use for the prophylaxis and treatment of venous thrombosis in microsurgery. Heparin accelerates antithrombin (AT)-mediated inhibition of clotting and fibrinolytic proteinases. AIM: The aim of the study is to determine whether the focussed delivery of AT by rinsing of free adipocutaneous groin flaps shows protective effects on flap survival, following a fatal secondary venous stasis in the rat model. Further, intravital video microscopy (IVM) is used to detect substance-specific alterations in microvascular perfusion with special focus on regional differences between central and peripheral flap regions. METHODS: Free microvascular groin flaps (n = 22) were transplanted to the neck in adult Sprague-Dawley rats. The flap pedicle was re-explored and the distal stump of the flap artery was catheterised 20 h later. Animals in group I (n = 11) were treated with 1 ml of Ringer's solution administered over 10 min via intraarterial infusion. Those in group II (n = 11) received 1 ml of AT (50 IU/kg). Afterwards, the flap vein was clamped for 35 min. The skin of the flaps and the native contralateral groin was examined by IVM using the plasma-marker fluorescein isothiocyanate (FITC)-dextran and carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labelled thrombocytes. After 14 days, the viability of the flaps was evaluated. RESULTS: The treatment with AT significantly increased the functional capillary density (FCD) of the flaps. After 14 days, flap necrosis occurred in nine animals of group I and three animals of group II, respectively. No partial flap loss was detected. CONCLUSIONS: The focussed delivery of AT resulted in significantly improved flap salvage. The results may reinforce the clinical custom of AT substitution in the setting of major surgical procedures such as elaborate microsurgical reconstructions, at least in cases with diminished AT levels.

Retrospective evaluation of antithrombin III supplementation in neonates and infants receiving enoxaparin for treatment of thrombosis.

BACKGROUND: Thromboembolic events are occurring at increasing rates in neonates and infants. At Children's Mercy Hospitals and Clinics, antithrombin III (AT3) concentrates are often used in combination with enoxaparin to supplement physiologically low AT3 levels. Theoretically, AT3 enhances the anticoagulant activity of enoxaparin and results in decreased time to therapeutic anti-Xa levels. No data exist on use of AT3 for this indication. PROCEDURE: This retrospective study compared time to therapeutic anti-Xa levels in patients <1 year of age receiving enoxaparin with AT3 (Group 1) and without AT3 (Group 2) for treatment of thrombosis. Primary objective was to compare time to therapeutic anti-Xa levels (0.5-1 U/ml) between groups. Secondary objectives included comparison of the initial and therapeutic dose of enoxaparin, enoxaparin dose changes, AT3 supplementation, and level monitoring. Bleeding events and cost were also evaluated. Statistical tests included Schuirmann's two one-sided tests for equivalence and general linear models/logistic regression for independent effects of age, critical illness, and timing of AT3. RESULTS: Mean time to therapeutic anti-Xa levels were not equivalent between Groups 1 and 2 (80.7 vs. 65.2 hours; P = 0.28). Initial enoxaparin dose and number of dose changes were equivalent. Group 1 required higher doses of enoxaparin to achieve therapeutic anti-Xa levels. Age, critical illness, and timing of AT3 had no effect on time to therapeutic anti-Xa levels. Bleeding events were not equivalent between Groups 1 and 2 (14.3% vs. 3.9%; P = 0.55). CONCLUSION: Supplementation with AT3 did not decrease time to therapeutic anti-Xa levels, added significant cost, and was associated with increased bleeding events.

[Annuloaortic ectasia associated with antithrombin III deficiency; report of a case].

A 33-year-old male with hereditary deficiency of antithrombin III (AT III) was diagnosed with annuloaortic ectasia and scheduled for the aortic root replacement. As perioperative anticoagulation, AT III was administered to have its activity≥70% in addition to heparin. During the operation with cardiopulmonary bypass, 3,000 IU of AT III concentrate was infused, and there was no hemorrhagic complication. After the operation low-molecular-weight heparin was used instead of unfractionated heparin to avoid bleeding. However, renal infarction occurred on postoperative day 11. Heparin was continuously given in combination with 1,500 IU/day of AT III concentrate until oral warfarin reached within therapeutic range. The patient recovered without further sequelae. Cardiac surgery might be safely performed in patients with AT III deficiency by replenishing AT III concentrate to keep its activity higher than 80%.

Surgical treatment of atrial septal defect in a patient with familial antithrombin-III deficiency.

PURPOSE: A 41-year-old woman with familial antithrombin-III deficiency was admitted to our hospital for patch closure of an atrial septal defect. Antithrombin-III activity was 43% and its antigen level was 12.2 mg/dl, was diagnosed so type I antithrombin-III deficiency was diagnosed. METHODS: A dose of 2500 U of antithrombin-III concentrate was administered at 1 day before surgery, 1 hour before surgery, and 1 day after surgery. Heparinazation was performed at 200 IU/kg and the activated clotting time increased from a baseline of 140s to 622s. After establishing cardiopulmonary bypass and cardioplegic arrest, closure of the septal defect was done with a pericardial patch. RESULTS: The activated clotting time was maintained at more than 400s during cardiopulmonary bypass. There were no intraoperative complications and the postoperative course was uneventful. CONCLUSION: In patients with familial antithrombin-III deficiency, administration of antithrombin-III concentrate is effective when cardiopulmonary bypass is required.

Antithrombin III injection via the portal vein suppresses liver damage.

AIM: To investigate the effects of antithrombin III (AT III) injection via the portal vein in acute liver failure. METHODS: Thirty rats were intraperitoneally challenged with lipopolysaccharide (LPS) and D-galactosamine (GalN) and divided into three groups: a control group; a group injected with AT III via the tail vein; and a group injected with AT III via the portal vein. AT III (50 U/kg body weight) was administrated 1 h after challenge with LPS and GalN. Serum levels of inflammatory cytokines and fibrin degradation products, hepatic fibrin deposition, and hepatic mRNA expression of hypoxia-related genes were analyzed. RESULTS: Serum levels of alanine aminotransferase, tumor necrosis factor-α and interleukin-6 decreased significantly following portal vein AT III injection compared with tail vein injection, and control rats. Portal vein AT III injection reduced liver cell destruction and decreased hepatic fibrin deposition. This treatment also significantly reduced hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1. CONCLUSION: A clinically acceptable dose of AT III injection into the portal vein suppressed liver damage, probably through its enhanced anticoagulant and anti-inflammatory activities.

Peroperative effects of fresh frozen plasma and antithrombin III on heparin sensitivity and coagulation during nitroglycerine infusion in coronary artery bypass surgery.

Nitroglycerin (NTG) reduces the anticoagulant effects of heparin and may lead to heparin resistance. Fresh frozen plasma (FFP) and antithrombin III (ATIII) may be used for the treatment of heparin resistance. We aimed to compare the effects of FFP and ATIII on heparin requirement, coagulation parameters, and bleeding in patients undergoing coronary artery bypass graft surgery (CABGS) with moderate dose of intraoperative NTG infusion. Forty-eight patients undergoing CABGS with NTG infusion were randomly allocated to three groups. Group C served as control, whereas the patients in group P received FFP and those in group A received ATIII after anesthesia induction. ATIII activity and coagulation parameters were measured at five different times intraoperatively. Total heparin requirement, heparin consumption, and heparin sensitivity were calculated. ATIII activity and ACT were significantly higher and activated partial thromboplastin time and fibrinogen level were significantly lower during cardiopulmonary bypass in group A than in groups P and C. Heparin sensitivity was significantly higher and total heparin requirement and consumption were significantly lower in ATIII group than in other groups. ATIII administration increases heparin sensitivity and decreases heparin requirements compared with FFP in patients undergoing CABGS with peroperative NTG infusion. ATIII may be preferred to FFP in patients with heparin resistance due to NTG infusion undergoing CABGS.

Our failures and ways to decrease hospital mortality in surgical management of thoracoabdominal aortic aneurysms.

The present study was undertaken to investigate the structure of hospital mortality associated with surgical treatment of 166 patients presenting with thoracoabdominal aortic aneurysms. According to the findings obtained, haemorrhagic, renal, and pulmonary complications turned out to predominate in the structure of an unfavourable postoperative outcome, accounting for 54%, 25% and 17%, respectively. Also determined and outlined herein are promising trends aimed at decreasing the hospital lethality rate related to the pathology involved. These include but are not limited to the following measures to be taken: making an early and accurate diagnosis of the nosological entity concerned, maximally diminishing the operative wound and reducing blood loss to a minimum, as well as using the state-of-the-art "sparing" methods of protecting the patient.

Impact of antithrombin III concentrates on portal vein thrombosis after splenectomy in patients with liver cirrhosis and hypersplenism.

OBJECTIVE: The aim of this study was to determine the role of antithrombin III (AT-III) in portal vein thrombosis (PVT) after splenectomy in cirrhotic patients. SUMMARY BACKGROUND DATA: There is no standard treatment for PVT after splenectomy in liver cirrhosis. METHODS: A total of 50 consecutive cirrhotic patients who underwent laparoscopic splenectomy for hypersplenism were enrolled into this study. From January 2005 to December 2005, 25 cirrhotic patients received no prophylactic anticoagulation therapy after the operation (AT-III [-] group). From January 2006 to July 2006, 25 cirrhotic patients received prophylactic administration of AT-III concentrates (1500 U/d) on postoperative day (POD) 1, 2, and 3 (AT-III [+] group). RESULTS: In AT-III (-) group, 9 (36.0%) patients developed PVT up to POD 7, and risk factors for PVT were identified as: low platelet counts, low AT-III activity, and increased spleen weight. Although there were no significant differences in the clinical characteristics, including the above risk factors, between the 2 groups, only 1 (4.0%) patient developed PVT on POD 30 in AT-III (+) group, and the incidence of PVT was significantly lower than in AT-III (-) group (P = 0.01). In AT-III (-) group, AT-III activity was significantly decreased from POD 1 to POD 7, as compared with the preoperative level, whereas AT-III concentrates prevented the postoperative decrease in AT-III activity. CONCLUSIONS: These results demonstrate that low AT-III activity and further decreases in this activity are associated with PVT after splenectomy in cirrhotic patients, and that treatment with AT-III concentrates is likely to prevent the development of PVT in these patients.

Pharmacological interventions to decrease blood loss and blood transfusion requirements for liver resection.

BACKGROUND: Blood loss during liver resection is one of the most important factors affecting the peri-operative outcomes of patients undergoing liver resection. OBJECTIVES: To determine the benefits and harms of pharmacological interventions to decrease blood loss and to decrease allogeneic blood transfusion requirements in patients undergoing liver resections. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until November 2008 for identifying the randomised trials. SELECTION CRITERIA: We included all randomised clinical trials comparing various pharmacological interventions aimed at decreasing blood loss and allogeneic blood transfusion requirements in liver resection. Trials were included irrespective of whether they included major or minor liver resections, normal or cirrhotic livers, vascular occlusion was used or not, and irrespective of the reason for liver resection. DATA COLLECTION AND ANALYSIS: Two authors independently identified trials for inclusion and independently extracted data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. For each outcome we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference with 95% confidence intervals (CI) based on intention-to-treat analysis or available case-analysis. For dichotomous outcomes with only one trial included under the outcome, we performed the Fisher's exact test. MAIN RESULTS: Six trials involving 849 patients satisfied the inclusion criteria. Pharmacological interventions included aprotinin, desmopressin, recombinant factor VIIa, antithrombin III, and tranexamic acid. One or two trials could be included under most comparisons. All trials had a high risk of bias. There was no significant difference in the peri-operative mortality, survival at maximal follow-up, liver failure, or other peri-operative morbidity. The risk ratio of requiring allogeneic blood transfusion was significantly lower in the aprotinin and tranexamic acid groups than the respective control groups. Other interventions did not show significant decreases of allogeneic transfusion requirements. AUTHORS' CONCLUSIONS: None of the interventions seem to decrease peri-operative morbidity or offer any long-term survival benefit. Aprotinin and tranexamic acid show promise in the reduction of blood transfusion requirements in liver resection surgery. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the high risk of bias. Further randomised clinical trials with low risk of bias and random errors assessing clinically important outcomes such as peri-operative mortality are necessary to assess any pharmacological interventions aimed at decreasing blood loss and blood transfusion requirements in liver resections. Trials need to be designed to assess the effect of a combination of different interventions in liver resections.

Thromboprophylaxis--key points for the angiologist.

The expertise and the advice of vascular specialists are important in diagnosis and treatment of venous thromboembolism (VTE) and equally important for thromboprophylaxis. Thus, vascular specialists are expected to have significant knowledge of the exposing and disposing risk factors for VTE. They are also expected to be familiar with the risk groups for VTE and the appropriate measures for thromboprophylaxis. Because different pharmacological prophylactic strategies are available, angiologists must be familiar with the properties, the specific labeling and the product information regarding their drugs of choice. Being familiar with the pharmacological profile and the potential risk of impaired renal function due to drug accumulation is essential for angiologists, both for the treatment and prophylaxis of VTE. Appropriate time intervals between application of thromboprophylaxis and spinal or epidural anaesthesia should be observed. This is also important for the recently available oral thrombin- and factor Xa-inhibitors. Presently available data do not support routine pharmacological prophylaxis for patients in the low VTE-risk group. Rather, individual risk benefit assessment is required in these patients. Patients with moderate or high VTE risk should receive pharmacological thromboprophylaxis. There is clear evidence and recommendation for prolonged administration of thromboprophylaxis over a 4-week period in patients following major orthopaedic surgery, such as hip replacement, hip fracture and in cancer surgery patients. Pulmonary embolism (PE) remains the most common preventable cause of death among hospitalized patients. Therefore, angiologists have a central role in ensuring adequate and consistent implementation of thromboprophylaxis, which is the number one strategy to improve patient safety in hospitals.