Short-term recovery pattern of plasma fibrinogen after cardiac surgery: A prospective observational study.

Low plasma fibrinogen level is common after cardiopulmonary bypass (CPB). Current substitution practice with fibrinogen concentrate generally follows a single measurement and cut-off values from the literature, whereas early postoperative endogenous fibrinogen kinetics is incompletely described and widely disregarded. The aim of this study was to determine the short-term recovery pattern of plasma fibrinogen after CPB weaning. Our hypothesis was that in the absence of surgical bleeding, CPB-induced hypofibrinogenemia would resolve spontaneously and predictably within a few hours. In a prospective, observational study of 26 patients undergoing conventional CPB (cCPB) or minimally invasive extracorporeal circulation (MiECC), Clauss fibrinogen level (C-FIB) was determined at 10 closely spaced time points after protamine administration. Primary endpoint was the time to recovery of post-CPB fibrinogen levels to ≥1.5 g/L. C-FIB reached its nadir after protamine administration corresponding to 62 ± 5% (mean ± SD) of the baseline level after cCPB and 68 ± 7% after MiECC (p = 0.027 vs. cCPB). C-FIB recovered spontaneously at a nearly constant rate of approximately 0.08 g/L per hour. In all patients, C-FIB was ≥1.5 g/L at 4 hours and ≥2.0 g/L at 13 hours after CPB weaning. Following cardiac surgery with CPB and in the absence of surgical bleeding, spontaneous recovery of normal endogenous fibrinogen levels can be expected at a rate of 0.08 g/L per hour. Administration of fibrinogen concentrate triggered solely by a single-point measurement of low plasma fibrinogen some time after CPB is not justified.

Perioperative management of patients receiving new oral anticoagulants: an international survey.

New oral anticoagulants (NOACs) are increasingly replacing standard anticoagulants. These new drugs have been recently introduced in clinical practice, and specific knowledge regarding preoperative interruption, anticoagulation assessment, and reversal therapies is needed. In this article, 3 main areas related to perioperative NOACs management are discussed: (1) physicians' knowledge, (2) current practices, and (3) perspectives to improve management of patients treated with NOACs.

A novel blood-sparing agent in cardiac surgery? First in-patient experience with the synthetic serine protease inhibitor MDCO-2010: a phase II, randomized, double-blind, placebo-controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

BACKGROUND: Antifibrinolytics have been used for 2 decades to reduce bleeding in cardiac surgery. MDCO-2010 is a novel, synthetic, serine protease inhibitor. We describe the first experience with this drug in patients. METHODS: In this phase II, double-blind, placebo-controlled study, 32 patients undergoing isolated primary coronary artery bypass grafting with cardiopulmonary bypass were randomly assigned to 1 of 5 increasing dosage groups of MDCO-2010. The primary aim was to evaluate pharmacokinetics (PK) with assessment of plasmatic concentrations of the drug, short-term safety, and tolerance of MDCO-2010. Secondary end points were influence on coagulation, chest tube drainage, and transfusion requirements. RESULTS: PK analysis showed linear dosage-proportional correlation between MDCO-2010 infusion rate and PK parameters. Blood loss was significantly reduced in the 3 highest dosage groups compared with control (P = 0.002, 0.004 and 0.011, respectively). The incidence of allogeneic blood product transfusions was lower with MDCO-2010 4/24 (17%) vs 4/8 (50%) in the control group. MDCO-2010 exhibited dosage-dependent antifibrinolytic effects through suppression of D-dimer generation and inhibition of tissue plasminogen activator-induced lysis in ROTEM analysis as well as anticoagulant effects demonstrated by prolongation of activated clotting time and activated partial thromboplastin time. No systematic differences in markers of end organ function were observed among treatment groups. Three patients in the MDCO-2010 groups experienced serious adverse events. One patient experienced intraoperative thrombosis of venous grafts considered possibly related to the study drug. No reexploration for mediastinal bleeding was required, and there were no deaths. CONCLUSIONS: This first-in-patient study demonstrated dosage-proportional PK for MDCO-2010 and reduction of chest tube drainage and transfusions in patients undergoing primary coronary artery bypass grafting. Antifibrinolytic and anticoagulant effects were demonstrated using various markers of coagulation. MDCO-2010 was well tolerated and showed an acceptable initial safety profile. Larger multi-institutional studies are warranted to further investigate the safety and efficacy of this compound.

Universal definition of perioperative bleeding in adult cardiac surgery.

OBJECTIVES: Perioperative bleeding is common among patients undergoing cardiac surgery; however, the definition of perioperative bleeding is variable and lacks standardization. We propose a universal definition for perioperative bleeding (UDPB) in adult cardiac surgery in an attempt to precisely describe and quantify bleeding and to facilitate future investigation into this difficult clinical problem. METHODS: The multidisciplinary International Initiative on Haemostasis Management in Cardiac Surgery identified a common definition of perioperative bleeding as an unmet need. The functionality and usefulness of the UDPB for clinical research was then tested using a large single-center, nonselected, cardiac surgical database. RESULTS: A multistaged definition for perioperative bleeding was created based on easily measured clinical end points, including total blood loss from chest tubes within 12 hours, allogeneic blood products transfused, surgical reexploration including cardiac tamponade, delayed sternal closure, and the need for salvage treatment. Depending on these components, bleeding is graded as insignificant, mild, moderate, severe, or massive. When applied to an established cardiac surgery dataset, the UDPB provided insight into the incidence and outcome of bleeding after cardiac surgery. CONCLUSIONS: The proposed UDPB in adult cardiac surgery provides a precise classification of bleeding that is useful in everyday practice as well as in clinical research. Once fully validated, the UDPB may be useful as an institutional quality measure and serve as an important end point in future cardiac surgical research.

The influence of antithrombin substitution on heparin sensitivity and activation of hemostasis during coronary artery bypass graft surgery: a dose-finding study.

BACKGROUND: Cardiopulmonary bypass is associated with a high degree of hemostatic system activation. Supplementation of antithrombin (AT) may attenuate this activation and increase a patient's susceptibility to heparin. However, the appropriate dosage of AT has not been defined. We sought to determine the dosage of AT concentrate necessary to achieve >100% AT activity at the end of cardiac surgery and the influence of AT on heparin sensitivity. METHODS: Forty-one patients were included. Thirty consecutive patients undergoing primary coronary artery bypass graft surgery with cardiopulmonary bypass were assigned to 3 groups of increasing dosages of AT concentrate. Eleven additional patients served as controls. AT activity and molecular markers of thrombin generation were determined, and heparin sensitivity was calculated. RESULTS: A median amount of 36.5 U (19.0; 42.8), 47.0 U (41.3; 61.6), and 50.0 U (47.4; 66.6) AT concentrate/kilogram body weight in the low, medium, and high AT group, respectively, was administered. At the end of surgery, AT activity with substitution was 84% (77; 111), 110% (92; 120), and 104% (97; 120) (median [25th; 75th percentile]), respectively, compared with 63% (49; 79) in controls (P < 0.05 all substitution groups versus control). Heparin sensitivity increased from 1.29 (1.17; 1.66) s/U heparin/kg in the control group to 2.02 (1.43; 3.65), 2.56 (1.52; 3.64), 1.72 (1.24; 2.66) s/U heparin/kg in the groups with substitution (P < 0.05 all substitution groups versus control). Compared with preoperative values, AT activity decreased during the postoperative period in all patients with a nadir on postoperative day 3 (P < 0.05 compared with baseline except for the medium AT group). Corresponding to this decrease, an increase in prothrombin fragment 1+2 and d-dimer could be observed postoperatively. DISCUSSION: High dosages of AT were required to preserve physiologic AT activity during coronary artery bypass graft surgery and to significantly enhance heparin sensitivity, respectively. However, a significant decrease in AT activity, accompanied by high levels of thrombin generation, was encountered up to 5 days postoperatively.

Review article: unexpected bleeding in the operating room: the role of acquired von Willebrand disease.

Acquired von Willebrand disease (AvWD) is a rare bleeding disorder that occurs in association with a variety of underlying disorders and can lead to unforeseen bleeding in surgical patients. Cardiovascular as well as malignant and immunological diseases may be associated with AvWD, and several pathophysiological mechanisms have been proposed. von Willebrand factor (vWF) is a plasma glycoprotein that mediates platelet adhesion to subendothelial collagen and causes platelet aggregation under high shear stress. Additionally, vWF acts as a specific carrier for coagulation factor VIII (FVIII) in the plasma. AvWD results from a reduced rate of vWF synthesis, an increased rate of vWF removal, or a final generation of lower-molecular-weight, less active subunits or multimers. In contrast to inherited von Willebrand disease patients, who are characterized by lifelong bleeding episodes, AvWD patients present with a sudden onset of bleeding symptoms, which can induce acute bleeding episodes during critical surgical procedures. Typically, no family history of bleeding is found. The clinical visualization of AvWD is similar to that of the hereditary form with mucocutaneous bleeding and increased perioperative bleeding, ranging from mild to severe bleeding. Laboratory evaluation of AvWD is mainly based on the measurement of vWF activity and antigens as well as on the multimeric analysis of vWF. A variety of therapeutic approaches have been used depending on the underlying disease and pathophysiological mechanisms. Treatment options to control acute hemorrhages or to prevent bleeding complications during surgery include desmopressin, FVIII/vWF concentrates, high-dose IV immunoglobulins, and plasma exchange. Because the half-life of vWF is reduced in AvWD, high doses of FVIII/vWF concentrates administered at frequent intervals may be necessary during bleeding episodes. In cases of unresponsiveness to standard therapy, recombinant activated factor VIIa may be an alternative option. However, the most effective therapy is the resolution of the underlying disease. In the present review, we focus on the current understanding of AvWD, outlining the associated disorders, underlying pathophysiological mechanisms, and possible treatment options.

Tumor necrosis factor-α -863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery.

OBJECTIVE: Cardiac surgery using cardiopulmonary bypass (CPB) initiates an inflammatory response that shows a wide inter-individual range and determines postoperative morbidity. Previous research suggests that genetic diversity contributes to individual susceptibility to perioperative trauma and stress. Nevertheless, the genetic triggering of the tumor necrosis factor-alpha (TNF-α) release remains unclear. We tested two genetic single-nucleotide polymorphisms (SNPs) from the promoter region of the TNF-α gene for associations with perioperative TNF-α level after CPB. METHODS: We prospectively included 122 patients, who underwent elective coronary artery bypass grafting (CABG). Patients were genotyped for TNF-α -863 C/A (rs1800630) and TNF-α -308 G/A (rs1800629). Plasma level of TNF-α was obtained preoperatively, at the end of CPB, 6h postoperatively, and on the first postoperative day (POD). RESULTS: Demographic characteristics and operative data revealed no significant differences between the different genotypes. Multiple linear regression analyses revealed significant associations for the TNF-α 863 C/A polymorphism: the major -863 CC variant was associated with higher TNF-α level preoperatively (p = 0.003), after CPB (p = 0.005), and 6h postoperatively (p = 0.010), independently from CPB time, left ventricle (LV) function and age. Contrarily, the AA allele had lower TNF-α level preoperatively (p = 0.008), after surgery (p = 0.024) and 6h postoperatively (p = 0.001). For the TNF-α 308 G/A polymorphism, only few significant associations could be observed: -308 GG carriers were associated with lower TNF-α level immediately after CPB (p = 0.020), whereas 308 AA carriers were significantly associated with elevated TNF-α level preoperatively (p = 0.032) and immediately after CPB (p = 0.05). No heterozygote variant of both SNPs revealed any significant associations with perioperative TNF-α level. CONCLUSIONS: The current study suggests that the major -863 CC variant determines elevated TNF-α level preoperatively and throughout the postoperative course after CPB.

Multiple electrode whole blood aggregometry, PFA-100, and in vivo bleeding time for the point-of-care assessment of aspirin-induced platelet dysfunction in the preoperative setting.

BACKGROUND: Acquired platelet dysfunction due to aspirin ingestion may increase bleeding tendency during surgery. Thus, we examined the diagnostic accuracy of in vivo bleeding time (BT) and 2 platelet function assays for the preoperative assessment of a residual antiplatelet effect in patients treated with aspirin. METHODS: Consecutive patients scheduled for surgery were prospectively enrolled in this study. The patients' last aspirin ingestion had occurred within the previous 48 hours before blood sampling in the "full aspirin effect" group, between 48 and 96 hours before in the "variable aspirin effect" group, and >96 hours before in the "recovered aspirin effect" group. The control group had not taken any aspirin. Multiple electrode aggregometry, platelet function analyzer (PFA)-100, and in vivo BT were performed to assess the effects of aspirin. One-way analysis of variance on ranks with a post hoc multiple-comparison procedure (Dunn) was used to detect differences among the groups. Categorical data were compared using the z test. Receiver operating characteristic (ROC) curves were created to determine the diagnostic accuracy of the platelet function assays investigated. The area under the ROC curve (AUC), sensitivity, and specificity of the assays were calculated. The level of statistical significance was set at P < 0.05. RESULTS: Three hundred ninety-four patients were included in the analysis (133 control and 261 aspirin-treated patients). All 3 methods were able to detect the antiplatelet effect of aspirin in the full aspirin effect group. Furthermore, no difference in the measurement values between the recovered aspirin effect and control group was found, irrespective of the assay performed. Measurement values in the variable aspirin effect group were different from those of the control group in the ASPItest using multiple electrode aggregometry and COL-EPI using PFA-100 but not in BT. ROC analysis showed the highest diagnostic accuracy in excluding the residual aspirin effect in the ASPItest (AUC 0.81, P < 0.001), followed by COL-EPI (AUC 0.78, P < 0.001) and BT (AUC 0.56, P = 0.05). The cutoff value of 53 U in the ASPItest excluded the effect of aspirin with a sensitivity of 88% and specificity of 71%. CONCLUSIONS: The full therapeutic antiplatelet effects of aspirin can be expected within 48 hours of the patient's last aspirin ingestion. Platelet function recovered in our study if aspirin cessation occurred >96 hours (4 days) before; thus, in these patients, preoperative platelet function testing is not useful. To quantify any residual aspirin effect in patients who ceased their intake of aspirin between 48 and 96 hours before surgery, the ASPItest might have the highest diagnostic accuracy.

Hemophilia A in cardiac operations: a model of reduced thrombin generation.

Patients with hemophilia A have a congenital defect in thrombin generation. Only limited data are available on the substitution regimens in hemophilia A patients during and after cardiac operations. There are no data on heparinization of these patients during cardiopulmonary bypass. Whereas most case reports suggest factor VIII replacement in combination with standard heparinization to achieve near-normal physiologic factor VIII activity, we describe the successful management of a hemophilic A patient using a low-level factor VIII replacement combined with a reduced heparin dosage during cardiopulmonary bypass. This approach facilitated adequate anticoagulation and minimized the amount of factor VIII treatment necessary without compromising bleeding control.

Enhanced thrombin generation after cardiopulmonary bypass surgery.

BACKGROUND: Thrombin generation has a key role in the pathophysiology of hemostasis. Research has focused on the intraoperative course of hemostasis, while little is known about postoperative hemostatic activation. Thrombin generation assays quantify the potential for thrombin generation ex vivo and may be useful for determining hypercoagulability. The thrombin dynamics test (TDT) assesses the initial kinetics of thrombin formation. We hypothesized that there would be an increase in thrombin generation as well as thrombin capacity after cardiac surgery. METHODS: Two hundred twenty patients undergoing primary coronary artery bypass grafting or aortic valve replacement (AVR) surgery were prospectively enrolled. Patients undergoing AVR received warfarin beginning on the second postoperative day. In addition to prothrombin fragment (F(1+2)), TDT, d-dimer, and troponin T were assessed. Blood samples were obtained preoperatively, at the end of the operation, 4 hours postoperatively, and the morning of postoperative days (PODs) 1, 3, and 5. The primary end point was the change of thrombin dynamics on POD 1. RESULTS: In all patients, F(1+2) peaked at the end of the operation and remained significantly elevated until POD 5. Compared with baseline and after an initial decrease, TDT was found to be significantly elevated on POD 1. After coronary artery bypass graft, TDT remained significantly elevated, whereas in AVR patients with warfarin treatment, TDT was significantly reduced on PODs 3 and 5. CONCLUSIONS: After cardiac surgery, thrombin generation continues, accompanied by a high thrombin-generating capacity and elevated fibrinogen levels. This constellation suggests a marked procoagulopathic state in the postoperative period with the potential to aggravate the risk of thromboembolic complications. Warfarin treatment after AVR significantly reduced thrombin-generating capacity.

A point-of-care assessment of the effects of desmopressin on impaired platelet function using multiple electrode whole-blood aggregometry in patients after cardiac surgery.

BACKGROUND: Blood loss after cardiac surgery can be caused by acquired platelet dysfunction after cardiopulmonary bypass. Monitoring of platelet function is clinically important for the identification of patients experiencing such platelet dysfunction. 1-Deamino-8-D-arginine vasopressin (desmopressin acetate, DDAVP) has been shown to augment platelet function and to reduce blood loss in patients with platelet dysfunction. In this study, we examined the feasibility of whole blood multiple electrode aggregometry (MEA) for the detection of cardiopulmonary bypass-induced platelet dysfunction and investigated its ability to monitor DDAVP treatment. METHODS: Fifty-eight consecutive patients with blood loss exceeding 150 mL/h in the first 2 consecutive hours after cardiac surgery were screened for suspected isolated platelet dysfunction. Twenty-two patients had suspected isolated platelet dysfunction and were enrolled in the study. Platelet dysfunction was assumed if conventional coagulation analyses (platelet count, activated partial thromboplastin time, international normalized ratio, and fibrinogen) did not show abnormal values as defined for transfusion of allogenic blood products, and no surgical cause of bleeding was suspected. Eleven patients received 0.3 microg/kg DDAVP, and 11 patients received no therapy in a nonrandomized manner. MEA was performed after stimulation with thrombin receptor-activating peptide (TRAPtest, 32 microM), adenosine diphosphate (ADPtest, 6.4 microM), and arachidonic acid (ASPItest, 0.5 mM) before and 2 hours after intervention. Conventional laboratory variables were recorded. The Mann-Whitney test was used to detect differences between the groups, and the Wilcoxon test was used to detect differences before and after intervention. RESULTS: All enrolled patients showed platelet dysfunction that manifested as impaired platelet aggregation in MEA before intervention. After the intervention, platelet function improved in the DDAVP group (49 U [30/72 U], median [25th/75th percentile] postintervention vs 15 U [8/21 U] preintervention for the ASPItest [P < 0.001]; 35 U [24/54 U] vs 14 U [7/28 U] for the ADPtest [P = 0.002]; and 85 U [66/115 U] vs 64 U [26/88 U] for the TRAPtest [P = 0.007]). In contrast, MEA remained unchanged in the control group (22 U [10/50 U] postintervention vs 33 U [14/57 U] preintervention for the ASPItest [P = 0.175]; 17 U [12/20 U] vs 14 U [10/28 U] for the ADPtest [P = 0.147]; and 65 U [41/89 U] vs 57 U [30/91 U] for the TRAPtest [P = 0.123]). CONCLUSIONS: Impaired platelet function after cardiac surgery can be assessed at the bedside using MEA. The effect of DDAVP on impaired platelet function can also be detected as significant improvement in platelet aggregation to all activators. This device might be helpful for the identification of patients who may benefit from DDAVP therapy.

Whole blood multiple electrode aggregometry is a reliable point-of-care test of aspirin-induced platelet dysfunction.

BACKGROUND: Aspirin is one of the most commonly ingested over-the-counter drugs. In addition to its analgesic and antiinflammatory actions, it also potently inhibits platelet aggregation. Evaluation of aspirin-induced platelet dysfunction is relevant in various clinical situations, including during complex surgeries with high bleeding risk in individuals who have ingested aspirin. In this study, we examined the suitability of multiple electrode aggregometry (MEA) for time course assessment of the antiplatelet effects of a single oral dose of 500 mg aspirin. We also determined the applicability of this method in the point-of-care (POC) setting by comparing the results of the test after different time intervals after blood sampling. METHOD: Twenty-four adult volunteers were enrolled in the study. After blood drawing at baseline, 500 mg aspirin was administered to all volunteers. Blood samples were taken at 4, 24, 56, 80, and 124 h after aspirin ingestion. At each time point, measurements were performed immediately and 30 and 60 min after drawing blood. Whole blood MEA was performed after stimulation with thrombin receptor activating peptide (TRAPtest, 32 microM) and arachidonic acid (ASPItest, 0.5 mM). Repeated measurement analysis of variance with a Bonferroni correction for multiple comparisons was performed to detect differences between time points. Assay imprecision was determined by calculating the coefficient of variation. The level of statistical significance was set to P < 0.05. RESULTS: Platelet aggregation by ASPItest was markedly decreased 4 h after aspirin intake. From the second day after aspirin intake, ASPItest values recovered with high interindividual variability, and 5 days after aspirin intake, ASPItest values did not differ significantly from baseline. TRAP-induced platelet aggregation (TRAPtest) showed no systematic changes during the study period. The resting time of the sample did not affect TRAPtest or ASPItest values. The coefficients of variation were 10% for the ASPItest and 7% for the TRAPtest. CONCLUSIONS: MEA reliably detected the effects of aspirin. Notably, 500 mg aspirin caused complete inhibition of arachidonic acid-induced platelet aggregation for 2 days in all volunteers. Aggregation returned to baseline values with a wide interindividual variation in time course by day 5. No resting time for the blood sample was required for ASPItest or TRAPtest. These assays can be implemented as real POC tests. The reproducibility of the assays studied here is within the range of modern POC analyzers.

Aprotinin: 1 year on.

PURPOSE OF REVIEW: The nonspecific protease inhibitor aprotinin has been used successfully to reduce bleeding in cardiac surgery. Recent investigations have questioned its safety, and aprotinin has finally been withdrawn from marketing after a large prospective study demonstrated a trend toward higher mortality. RECENT FINDINGS: The initial studies of Karkouti and Mangano provoked a considerable number of large-scale investigations focusing on the safety issues of aprotinin. These studies were of retrospective nature and used sophisticated statistical methods to overcome a possible selection bias. Recently, aprotinin was predominantly used in patients with a higher risk of bleeding, which hampers a retrospective comparison with patients without the drug. This review summarizes the diverging results of these studies. SUMMARY: It remains a matter of speculation whether the quality and results of published data justify the withdrawal of aprotinin; however, one has to accept that this drug is no longer available. It is clear from the aprotinin story that there are no effective instruments to control the safety and clinical efficacy of a drug after its regulatory approval. This highlights the urgent need for independent clinical safety studies after the formal registration of a drug.

CU-2010--a novel small molecule protease inhibitor with antifibrinolytic and anticoagulant properties.

BACKGROUND: In cardiac surgery, the contact of blood with the artificial surfaces of the cardiopulmonary bypass results in activation of coagulation, fibrinolysis, and platelets, which is recognized as reason for increased bleeding tendency. Antifibrinolytics like tranexamic acid or the broad-spectrum protease inhibitor aprotinin attenuate this response. The marketing of aprotinin has been suspended after a recent clinical trial suggested increased risks associated with aprotinin. Moreover, aprotinin is a protein of animal origin and has antigenic properties. As a result, alternative antifibrinolytic compounds are desirable. METHODS: This in vitro study compared the antifibrinolytic efficacy of the synthetic small molecule CU-2010 with aprotinin and tranexamic acid. Antifibrinolytic activity in plasma and whole blood of ten healthy volunteers was examined with a turbidometric method and with tissue factor-activated thromboelastometry (ROTEM; Pentapharm, Munich, Germany). In addition, anticoagulant effects were assessed through measurement of plasma and whole blood clotting times and thrombin generation. RESULTS: With its high affinity for plasmin (Ki, 2 nM), CU-2010 inhibited fibrinolysis comparable to aprotinin (Ki, 4 nM) and was ten times more potent than tranexamic acid. CU-2010 also inhibited plasma kallikrein (Ki < 1 nM) and factors Xa (Ki, 45 nM) and XIa (Ki, 18nM), which was reflected in prolongation of coagulation times and an attenuation of thrombin generation. CONCLUSION: These findings suggest that CU-2010 has similar antifibrinolytic potency compared to aprotinin, is more potent than tranexamic acid, and possesses some anticoagulant effects.

Thrombophilia in cardiac surgery-patients with symptomatic factor V Leiden.

BACKGROUND AND AIM OF THE STUDY: Thrombophilia may cause severe complications in cardiac surgical patients. We analyzed our experience with symptomatic factor V Leiden patients. METHODS: Over an eight-year period, 14 symptomatic patients previously diagnosed with activated protein C resistance,caused by factor V Leiden, underwent a cardiac surgical procedure. We retrospectively reviewed the clinical data, operative and postoperative courses, and the intermediate-term results of these patients. RESULTS: Procedures performed were coronary artery bypass grafting (CABG, 10 patients), aortic valve replacement+ CABG, pulmonary thromboendarterectomy, left ventricular thrombus removal, and aortic valve reconstruction(one patient each). Eleven patients survived; three patients died perioperatively, one from sepsis (25 days after surgery), one from recurrent stroke (28 days after surgery), and one from multiorgan failure following perioperative stroke (31 days after surgery). In one patient, all bypass grafts occluded intraoperatively.Three patients underwent cardiac surgery under continuous anticoagulation with phenprocoumon. In these three patients, no perioperative thromboembolic events occurred. At a mean follow-up of 32 months,three patients had suffered from cerebral stroke, two from graft occlusion, of which one was recurrent. Two more patients had died (one after cerebral stroke and one from cerebral metastases of a renal cell carcinoma). CONCLUSION: In 14 patients with symptomatic factor V Leiden who underwent cardiac surgery, we observed a considerable number of fatal and nonfatal thromboembolic events in the perioperative period and during a 32 months' follow-up. As conducted in three patients, continued anticoagulation with coumarin was safe and prevented perioperative thromboembolic events.

Perioperative hemostatic management of patients treated with vitamin K antagonists.

Clinicians, including anesthesiologists, surgeons, and intensivists, are frequently called on to correct coagulopathy in patients receiving oral anticoagulation therapy. Before elective surgery, anticoagulation reversal may be undertaken over several days by discontinuing warfarin or vitamin K treatment, but rapid correction is required in an emergency. European and American guidelines recommend prothrombin complex concentrates (PCCs) for anticoagulation reversal in patients with life-threatening bleeding and an increased international normalized ratio. Compared with human fresh frozen plasma, PCCs provide quicker correction of the international normalized ratio and improved bleeding control. Although there are historic concerns regarding potential infectious and thrombotic risks with PCCs, current PCC formulations are much improved. Recombinant activated factor VII is a potential alternative to PCCs, but preclinical comparisons suggest that PCCs are more effective in correcting coagulopathy. Although many patients who require rapid reversal of warfarin are currently treated with fresh frozen plasma, PCCs should be considered as an alternative therapy.