Aetiological factors of Budd-Chiari syndrome in Algeria.

AIM: To study the clinical presentation of Budd-Chiari syndrome (BCS) and identify the aetiologies of this disease in Algeria. METHODS: Patients with BCS, hospitalised in our unit from January 2004 until June 2010 were included and the aetiological factors were assessed. Patients presenting a BCS in the setting of advanced-stage cirrhosis or a liver transplantation were excluded from the study. The diagnosis was established when an obstruction of hepatic venous outflow (thrombosis, stenosis or compression) was demonstrated. We diagnosed myeloproliferative disease (MPD) by bone marrow biopsy and V617F JAK2 mutation. Anti-phospholipid syndrome (APLS) was detected by the presence of anticardiolipin antibodies, anti-ß2 glycoprotein antibodies and Lupus anticoagulant. We also detected paroxysmal nocturnal haemoglobinuria (PNH) by flow cytometry. Celiac disease and Behçet disease were systematically investigated in our patients. Hereditary anticoagulant protein deficiencies were also assessed. We tested our patients for the G20210A mutation at Beaujon Hospital. Imaging procedures were performed to determine a local cause of BCS, such as a hydatid cyst or a liver tumour. RESULTS: One hundred and fifteen patients were included. Mean follow up: 32.12 mo. Mean age: 34.41 years, M/F = 0.64. Chronic presentation was frequent: 63.5%. The revealing symptoms for the BCS were ascites (74.8%) and abdominal pain (42.6%). The most common site of thrombosis was the hepatic veins (72.2%). Involvement of the inferior vena cava alone was observed in 3 patients. According to the radiological investigations, BCS was primary in 94.7% of the cases (n = 109) and secondary in 5.2% (n = 6). An aetiology was identified in 77.4% of the patients (n = 89); it was multifactorial in 27% (n = 31). The predominant aetiology of BCS in our patients was a myeloproliferative disease, observed in 34.6% of cases. APLS was found in 21.7% and celiac disease in 11.4%. Other acquired conditions were: PNH (n = 4), systemic disease (n = 6) and inflammatory bowel disease (n = 5). Anticoagulant protein deficiency was diagnosed in 28% of the patients (n = 18), dominated by protein C deficiency (n = 13). Secondary BCS was caused by a compressing hydatic cyst (n = 5) and hepatocellular carcinoma (n = 1). CONCLUSION: The main aetiologic factor of BCS in Algeria is MPD. The frequency of celiac disease justifies its consideration when BCS is diagnosed in our region.

Plasma transfusion in liver transplantation: a randomized, double-blind, multicenter clinical comparison of three virally secured plasmas.

BACKGROUND: The clinical equivalence of plasma treated to reduce pathogen transmission and untreated plasma has not been extensively studied. A clinical trial was conducted in liver transplant recipients to compare the efficacy of three plasmas. STUDY DESIGN AND METHODS: A randomized, equivalence, blinded trial was performed in four French liver transplantation centers. The three studied (fresh-frozen) plasmas were quarantine (Q-FFP), methylene blue (MB-FFP), and solvent/detergent (S/D-FFP) plasmas. The primary outcome was the volume of plasma transfused during transplantation. Secondary outcomes included intraoperative blood loss, hemostasis variables corrections, and adverse events. RESULTS: One-hundred patients were randomly assigned in the MB-FFP, 96 in the S/D-FFP, and 97 in the Q-FFP groups, respectively. The median volumes of plasma transfused were 2254, 1905, and 1798 mL with MB-FFP, S/D-FFP, and Q-FFP, respectively. The three plasmas were not equivalent. MB-FFP was not equivalent to the two other plasmas, but S/D-FFP and Q-FFP were equivalent. The median numbers of transfused plasma units were 10, 10, and 8 units with MB-FFP, S/D-FFP, and Q-FFP, respectively. Adjustment on bleeding risk factors diminished the difference between groups: the excess plasma volume transfused with MB-FFP compared to Q-FFP was reduced from 24% to 14%. Blood loss and coagulation factors corrections were not significantly different between the three arms. CONCLUSION: Compared to both Q-FFP and S/D-FFP, use of MB-FFP was associated with a moderate increase in volume transfused, partly explained by a difference in unit volume and bleeding risk factors. Q-FFP was associated with fewer units transfused than either S/D-FFP or MB-FFP.

Hepatic veins as a site of clot formation following liver resection.

Pulmonary embolism occurs more frequently after hepatectomy than previously thought but is infrequently associated with peripheral deep vein thrombosis. In this paper, we report 2 cases of postoperative hepatic vein thrombosis after liver resection. Both patients had undergone major hepatectomy of a non-cirrhotic liver largely exposing the middle hepatic vein. Clots were incidentally found in the middle hepatic vein 4 and 17 d after surgery despite routine systemic thrombo-prophylaxis with low molecular weight heparin. Coagulation of the transition plan in a context of mutation of the prothrombin gene and inflammation induced biloma were the likely predisposing conditions. Clots disappeared following curative anticoagulation. We conclude that thrombosis of hepatic veins may occur after liver resection and is a potential source of pulmonary embolism.

Bleeding in patients with Budd-Chiari syndrome.

BACKGROUND & AIMS: Anticoagulation therapy is recommended for patients with Budd-Chiari syndrome (BCS). This study aimed to assess the incidence, severity, and risk factors of major bleeding in patients with Budd-Chiari syndrome (BCS) receiving anticoagulation therapy. METHODS: We evaluated 94 consecutive BCS patients. Major bleeding required hospitalization, and/or transfusion of ≥ 2 red blood cell units, and/or was located intracranially, and/or retroperitoneally, and/or was fatal. RESULTS: After a median follow-up of 43 months, 47 patients had 92 major bleeding episodes (22.8 per 100 patient-years). Forty episodes were related to invasive therapy for BCS. The origin of the 52 other episodes was gastrointestinal in 26 (including 15 related to portal hypertension) and genital in 10; 26 were spontaneous and 26 provoked. Excess anticoagulation was identified in 13 (27%) out of 49 documented episodes. Bleeding was managed by interrupting or reducing anticoagulation in 34 episodes, surgery in 18, endoscopy in 12, and radiological intervention in 8. The presence of esophageal varices was an independent predictor of bleeding unrelated to invasive therapy for BCS. Bleeding contributed to death in five patients and caused neurological complications in two. These poor outcomes were associated with more severe liver disease at baseline. CONCLUSIONS: Major bleeding is common in BCS patients receiving anticoagulation therapy. Invasive procedures and portal hypertension are major factors, while excess anticoagulation plays a secondary role. Baseline BCS severity is the main determinant of prognosis at bleeding. Reducing anticoagulation intensity during invasive therapy and reinforced prophylaxis for portal hypertension could improve the benefit-risk ratio of anticoagulation.

Obliterative portal venopathy: portal hypertension is not always present at diagnosis.

BACKGROUND & AIMS: Previous studies on obliterative portal venopathy (OPV) have been biased due to the selection of patients with non-cirrhotic portal hypertension. The aim of this study was to clarify the characteristics of OVP diagnosed by liver biopsy. METHODS: Fifty-nine consecutive patients with OPV were retrospectively selected on strict histological criteria. Clinical, laboratory, portal vein patency, and associated disorders potentially involving vascular alterations were analyzed. The occurrence of complications was recorded during follow-up. RESULTS: Mean age at diagnosis was 38.5±15 years old. Initial presentation was portal hypertension (64% of patients) and/or extrahepatic portal vein thrombosis (EHPVT) (22%) or isolated abnormal laboratory tests (20%). Associated diseases found at diagnosis were: prothrombotic disorders (30% of patients) and immune-mediated disorders (17%); 53% of patients had no causal factor (idiopathic OPV). During follow-up (median 8.6 years, range 1-23 years), features of portal hypertension worsened in 46% of patients; EHPVT and portal hypertension were finally found in 44% and 88% of patients. Anti-coagulation and beta-blockers were administered in 47% and 59% of patients, respectively. Severe complications (liver transplantation and/or death) occurred in 11 (19%) patients, 8 had idiopathic OPV. Patients with prothrombotic disorders received earlier anticoagulation therapy; all survived without transplantation. CONCLUSIONS: A confident diagnosis of OPV can be done by biopsy and is conceivable in patients under 40 years without clinically significant portal hypertension. Poor outcome was noted in 19% of patients, most of them affected with idiopathic OPV. Patients with prothrombotic disorders received early anticoagulation and appeared to have a better outcome despite a high proportion of EHPVT.

Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study.

UNLABELLED: Current recommendations for early anticoagulation in acute portal vein thrombosis unrelated to cirrhosis or malignancy are based on limited evidence. The aim of this study was to prospectively assess the risk factors, outcome, and prognosis in patients managed according to these recommendations. We enrolled 102 patients with acute thrombosis of the portal vein, or its left or right branch. Laboratory investigations for prothrombotic factors were centralized. Thrombus extension and recanalization were assessed by expert radiologists. A local risk factor was identified in 21% of patients, and one or several general prothrombotic conditions in 52%. Anticoagulation was given to 95 patients. After a median of 234 days, the portal vein and its left or right branch were patent in 39% of anticoagulated patients (versus 13% initially), the splenic vein in 80% (versus 57% initially), and the superior mesenteric vein in 73% (versus 42% initially). Failure to recanalize the portal vein was independently related to the presence of ascites (hazard ratio 3.8, 95% confidence interval 1.3-11.1) and an occluded splenic vein (hazard ratio 3.5, 95% confidence interval 1.4-8.9). Gastrointestinal bleeding and intestinal infarction occurred in nine and two patients, respectively. Two patients died from causes unrelated to thrombosis or anticoagulation therapy. CONCLUSION: Recanalization occurs in one-third of patients receiving early anticoagulation for acute portal vein thrombosis, whereas thrombus extension, intestinal infarction, severe bleeding, and death are rare. Alternative therapy should be considered when ascites and splenic vein obstruction are present.

Pregnancy in women with known and treated Budd-Chiari syndrome: maternal and fetal outcomes.

BACKGROUND/AIMS: Budd-Chiari syndrome (BCS) mainly affects women of childbearing age. We aimed to clarify whether pregnancy, a thrombotic risk factor, should be contraindicated in patients with known and treated BCS. METHODS: A retrospective study of pregnancy in women with known and treated BCS. RESULTS: Sixteen women had 24 pregnancies. Nine women had undergone surgical or radiological treatment. Anticoagulation was administered during 17 pregnancies. Seven fetuses were lost before gestation week 20. Deliveries occurred between week 20 and 31 in two patients, week 32 and 36 in eleven and after week 37 in four. There was one stillbirth, but 16 infants did well. Factor II gene mutation was a factor for a poor outcome of pregnancies. In two patients, symptomatic thrombosis recurred during pregnancy or postpartum. All patients were alive after a median follow-up of 34 months after the last delivery. Bleeding at delivery, although non-lethal, occurred only on anticoagulation therapy. CONCLUSIONS: When known and treated BCS is well controlled, pregnancy should not be contraindicated as maternal outcome, and fetal outcome beyond gestation week 20, are good. The risk-benefit ratio of anticoagulant therapy needs to be further clarified. Patients should be fully informed of the persistent risks of such pregnancies.

Prognostic indices for Budd-Chiari syndrome: valid for clinical studies but insufficient for individual management.

OBJECTIVES: Several prognostic indices (PIs) have been proposed for Budd-Chiari syndrome (BCS). However, patient characteristics, causal factors, and treatment outcomes have changed since these indices have been elaborated. Validation in a recent patient population and comparison of predictive accuracy between these PIs are needed. METHODS: A database of 96 BCS patients diagnosed between 1995 and 2005 was analyzed. Cox survival models were fitted with time to liver transplantation or death, and time to invasive therapy or death, as end points. The prognostic values of known indices (Child-Pugh score, model for end-stage liver disease (MELD), Clichy, Rotterdam BCS index, New Clichy, and BCS-TIPS (transjugular intrahepatic portosystemic shunt)) at diagnosis were assessed in Cox models using the chi-square test, the Kent and O'Quigley measure of dependence, and unrestricted bootstrapping analysis. Areas under receiver operating characteristic curves (AUROCs) were built for both end points and compared. RESULTS: All prognostic indices, except BCS-TIPS, were significant predictors of transplant-free and invasive therapy-free survival. However, only 31 and 37% of the variance in transplant-free and invasive therapy-free survival, respectively, were explained by the best performing indices. For transplant-free survival, AUROCs were < 0.70. For invasive therapy-free survival, AUROCs were < 0.80. For both end points, BCS-TIPS PI AUROCs were significantly lower than others. CONCLUSIONS: Most PIs are valid for transplant-free survival and invasive therapy-free survival in a population of current BCS patients, and thus can be used for stratification in clinical studies. However, predictive accuracy is insufficient to be used for individual patients.

Hypercoagulability after partial liver resection.

One concern of living donor liver transplantation remains the risk of morbidity and/or mortality for the donors, including the risk of postoperative thrombosis. We studied the coagulation changes after partial liver resection in l2 living donors and eight patients with non-malignant hepatic tumors (controls) and searched for potential predictive markers of thrombotic complications. Thrombosis (pulmonary embolism and portal vein thrombosis) developed in two donors and two controls. In donors and controls, we observed an early postoperative decrease in coagulation inhibitors protein C and antithrombin together with an increase in factor VIII and von Willebrand factor, which both persisted when prothrombin time had returned to normal. Dysregulation in the haemostatic system was confirmed by increased prothrombotic markers, with a 10- to 30-fold increase in thrombin-antithrombin complexes and moderate increase(1.5- to 2.0-fold) in sP-Selectin. No difference between donors and controls was observed and the data were pooled for comparison of patients with (n = 4) versus without (n = 16) thrombosis. Thrombin-antithrombin complexes were significantly higher in the thrombosis group, on day 1 (28.8 vs. 13.5 microg/l, p = 0.027) and day 2 (52.3 vs. 9.3 microg/l, p = 0.013). sP-selectin was also significantly higher in the thrombosis group on day 2 (103 vs. 53 ng/ml, p = 0.044) and day 4 (116 vs. 58 ng/ml, p = 0.026) after surgery. Our study indicates that improvement of thromboprophylaxis in partial liver resection is needed. It also suggests that thrombin-antithrombin complexes and sP-selectin could serve as early biological predictors of thrombotic complications in the post-operative period.

Characterization of seven novel mutations causing factor XI deficiency.

BACKGROUND AND OBJECTIVES: Factor XI (FXI) deficiency is a rare autosomal recessive disorder, the main manifestation of which is injury-related bleeding. The disorder is rare in most populations, but common among Jews in whom two mutations, E117X and F283L, account for 98% of cases. Other mutations, C38R and C128X, are prevalent in French Basques and Britons, respectively. Additional sporadic mutations have been described in most parts of the world. The objective of this study was to identify the mutations in 15 unrelated FXI-deficient patients and characterize missense mutations by expression in baby hamster kidney (BHK) cells. DESIGN AND METHODS: Clinical and laboratory information and DNA samples were obtained from the patients and mutations were identified by sequencing. Missense mutations were expressed in BHK cells and their effect on FXI secretion and dimerization was assessed using enzyme-linked immunosorbent assay and immunoblotting. RESULTS: Of 16 mutations detected, seven are novel including two deletions, one splice site and four missense mutations. Expression of the four novel missense mutations (C58Y, Y427C, C527Y and V20A) in cells revealed no secretion of FXI-C58Y, Y427C and C527Y and secretion of only 22% of normal in the medium for FXI-V20A. Secretion of FXI from BHK cells harboring a previously reported E297K substitution cells was also impaired (4.5% of wild-type). Homodimerization was normal for all five mutants. INTERPRETATION AND CONCLUSIONS: Defective homodimerization of FXI was previously recognized as a major mechanism for defective secretion of FXI from producing cells. In this study, five FXI missense mutations (four novel) were associated with impaired secretion albeit normal dimerization, underscoring the existence of other mechanisms for defective secretion.

Aiming at minimal invasiveness as a therapeutic strategy for Budd-Chiari syndrome.

The 1-year spontaneous mortality rate in patients with Budd-Chiari syndrome (BCS) approaches 70%. No prospective assessment of indications and impact on survival of current therapeutic procedures has been performed. We evaluated a therapeutic strategy uniformly applied during the last 8 years in a single referral center. Fifty-one consecutive patients first received anticoagulation and were treated for associated diseases. Symptomatic patients were considered for hepatic vein recanalization; then for transjugular intrahepatic portosystemic shunt (TIPS), and finally for liver transplantation. The absence of a complete response led to the next procedure. Assessment was according to the strategy, whether procedures were technically applicable and successful. At entry, median (range) Child-Pugh score and Clichy prognostic index were 8 (5-12), and 5.4 (3.1-7.7), respectively. A complete response was achieved on medical therapy alone in 9 patients; after recanalization in 6, TIPS in 20, liver transplantation in 9, and retransplantation in 1. Of the 41 patients considered for recanalization, the procedure was not feasible in 27 and technically unsuccessful in 3. Of the 34 patients considered for TIPS, the procedure was considered not feasible in 9 and technically unsuccessful in 4. At 1 year of follow-up, a complete response to TIPS was achieved in 84%. One- and 5-year survival from starting anticoagulation were 96% (95% CI, 90-100) and 89% (95% CI, 79-100), respectively. In conclusion, excellent survival can be achieved in BCS patients when therapeutic procedures are introduced by order of increasing invasiveness, based on the response to previous therapy rather than on the severity of the patient's condition.

Respiratory complications: a major concern after right hepatectomy in living liver donors.

BACKGROUND: One of the main concerns after living donor liver transplantation is the risk of morbidity and/or mortality that it imposes on the donors. Respiratory postoperative complications in living liver donors have already been reported but their frequency seems to be underestimated. We designed a prospective study to evaluate the rate and the nature of postoperative pulmonary complications in 112 consecutive donors. METHODS: The medical records of the 112 living liver donors operated on at our center from 1998 to 2003 were reviewed and all the cases of respiratory complications were retrieved. Moreover, since 2000, all patients had a computed tomography angiography of the thorax at day 7 on a prospective basis. RESULTS: In all, 112 hepatectomies (44 right and 68 left) for adult-to-adult or adult-to-child liver donation were performed in our center. No postoperative mortality was recorded. Fourteen major respiratory complications developed in of 11 of 112 donors (9.8%), in all cases after right hepatectomy, and included nonsevere pulmonary embolism (n=7), right pleural empyema (n=3), and bacterial pneumonia (n=3). Minor respiratory complications (7.1% of the donors) included iatrogenic pneumothorax (n=3) and pleural effusion requiring thoracocentesis (n=5). Abdominal complications (mainly biliary leak) developed in 10 donors (8.9%), who in the vast majority remained free of pulmonary complications. CONCLUSIONS: In our series, pulmonary complications are frequent in living liver donors. These complications are mainly observed after right hepatectomy. The particular prevalence of pulmonary embolism should lead to focus on its early diagnosis and prevention.

Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis.

Myeloproliferative disorders (MPD) are reported in 25-65% of patients with splanchnic vein thrombosis (SVT). Diagnostic criteria for MPD have not been fully established in this context. Using clusters of abnormal megakaryocytes in bone marrow (BM) biopsy as a reference standard for Philadelphia negative MPD, we assessed the relevance of other criteria currently recommended for the diagnosis of MPD in SVT (128 consecutive SVT patients). First, usual criteria were compared with BM results: endogenous erythroid colony formation (EEC) was strongly correlated with BM results; splenomegaly, blood cell count, total red cell volume, erythropoietin level and cytogenetic were much less accurate. Then, patients were assigned to three groups according to the combination of BM and EEC findings (group I: both present; group II: both absent; group III: other patients); clinical presentation and outcome were compared in each group. At a mean follow-up of 6.09 +/- 6.6 years, progression to a severe form of MPD occurred in 7 of 31 group I patients (23%), in 1 of 34 group III patients (3%) and 0 of 63 group II patients. The combination of marked splenomegaly and platelet count >200 x 10(9)/l was restricted to groups I and III. In conclusion, in patients with SVT, BM findings and EEC allowed the diagnosis of MPD at risk of aggravation. Marked splenomegaly in association with platelet counts >200 x 10(9)/l constitute a simple index with high specificity but low sensitivity.

Arterial and portal circulation and parenchymal changes in Budd-Chiari syndrome: a study in 17 explanted livers.

Hepatic parenchymal changes associated with Budd-Chiari syndrome (BCS) have been tentatively explained by combined arterial and portal perfusion disturbances in addition to the complete occlusion of hepatic veins. The aim of this study was to correlate pretransplant course and vascular imaging with pathologic findings in livers explanted for BCS. Seventeen consecutive white patients who underwent transplantation for severe classic BCS were retrospectively analyzed. Pretransplant course was 1 year or less in 8 patients and more than 1 year in 9 patients. Thrombophilia was found in 16 patients (94%). Imaging showed decreased portal perfusion in 16 patients (94%) and increased arterial perfusion in 9 patients. Histology showed obstructive portal venopathy and nodular regenerative hyperplasia (NRH) aspects in all cases, large regenerative nodules resembling focal nodular hyperplasia (FNH) in 9 cases, and cirrhosis in 2 cases. Patients with increased arterial inflow had large regenerative nodules and a protracted pretransplant course. Patients with acute thrombi in portal veins had parenchymal infarcts (2 cases) and a short pretransplant course. In conclusion, patients with severe BCS have a constant impaired perfusion inflow unrelated to progression of cirrhosis but related to the outcome. An early decrease in portal perfusion is observed in the short term and is responsible for NRH or infarcts if complicated with large thrombi. An increase in arterial perfusion compensates impaired portal flow in chronic BCS. Arterial hyperemia contributes to the development of large regenerative nodules that are FNH-like. This pathologic situation offers an interesting vascular model to further understand the parenchymal response to changes in hepatic blood flow.

Coagulation disorders in patients with cirrhosis and severe sepsis.

BACKGROUND: In patients with cirrhosis, severe sepsis may stimulate the extrinsic coagulation pathway resulting in thrombin generation and fibrin formation. AIMS: To compare 23 patients with severe sepsis to 13 infected patients without severe sepsis and 18 patients without infection. METHODS: Zymogen forms of clotting factors involved in the extrinsic pathway (i.e., factors VII + X, V, prothrombin), and the presence of soluble fibrin were assessed. RESULTS: Zymogen forms of clotting factors were significantly lower, while Child-Pugh score and the proportion of patients with soluble fibrin were higher in the severe-sepsis group than in the other groups. Decreased zymogen levels were independently correlated with an elevated Child-Pugh score and the presence of severe sepsis. In the severe-sepsis group, after adjustment for the severity of cirrhosis, decreased zymogen levels were associated with significant increases in the relative risk ratios of in-hospital death. CONCLUSIONS: Cirrhotic patients with severe sepsis have decreased blood levels of zymogen forms of factors VII+X, V, and prothrombin, which may be due not only to the severity of cirrhosis but also, at least in part, to the consumption of these zymogens by the extrinsic coagulation pathway.

Donor safety in living related liver transplantation: underestimation of the risks for deep vein thrombosis and pulmonary embolism.

Optimal safety for donors is a necessary condition for living related liver transplantation to expand. Although the risks for complications directly related to surgical intervention have been carefully evaluated, the extent and nature of other complications, such as pulmonary embolism, associated with living donation have not been clearly anticipated. We report a case of severe pulmonary embolism followed by ulcer-related upper digestive tract bleeding in an adult donor after right hepatectomy. In this donor, we found an unexpected predisposing coagulation disorder (increased von Willebrand factor activity) postoperatively. This finding led us to include systematic screening for coagulation disorders during evaluation of donors, a policy which led us thereafter to reject definitely or temporarily some candidates for donation. Although the cost-effectiveness of such investigations is not definitely established, we strongly recommend a specific approach to improve donor safety. In addition, we emphasize that the major complications observed in living donors should be systematically reported in an international database.

Antiplatelet agents in the perioperative period: expert recommendations of the French Society of Anesthesiology and Intensive Care (SFAR) 2001--summary statement.

PURPOSE: Antiplatelet agents are administered to an increasing number of patients. Preoperative treatment with these agents represents a major problem for the anesthesiologist. The results of a French expert meeting on their perioperative management are reported. METHODS: Responses to questions formulated by the Organizing Committee were drafted by a group of experts and reviewed by a multidisciplinary. Reading Committee. Recommendations were classified (grade) according to the evidence level of the studies supporting them. PRINCIPAL FINDINGS: First, antiplatelet agents have a variable effect on hemostasis as far as bleeding risk is concerned. Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) increase intra- and postoperative bleeding moderately, but not transfusion requirements. Very few data are available on clopidogrel and ticlopidin. Anti-glycoprotein (GP) IIb/IIIa agents may increase bleeding when surgery is required in proximity with their administration. Second, the common practice of withdrawing antiplatelet agents is now challenged because an increased incidence of myocardial infarction has been reported in patients in whom treatment was interrupted. Third, aspirin should not be withdrawn for most vascular procedures and in several additional settings. When a definite increase in intraoperative bleeding is feared, or when surgical hemostasis is difficult, aspirin, clopidogrel or ticlopidine can be replaced by short-acting NSAIDS, given for a ten-day period and interrupted the day before surgery. Platelet transfusion should only be given when overt bleeding is observed. Postoperatively, antiplatelet treatment should be resumed immediately after surgery (first six hours). CONCLUSION: Anesthesiologists should be aware of the indications, potential complications and means of substitution of these agents.