During the last decade many aspects of haemostasis and coagulation management greatly changed in cardiac surgery. On one side, new anti-platelet agents entered the market and became more and more widely used; on the other one, point-of-care monitoring tools are nowadays available for perioperative use. The present survey is aimed to investigate the perioperative haemostasis and coagulation management in European Cardiac Surgery Institutions.

A questionnaire exploring different aspects of perioperative haemostasis and coagulation management was sent to 320 Cardiac Surgery Institutions in Europe.

82 Institutions replied to the survey. Due to the poor quality of the data collection, 9 Institutions were excluded. A pool of 73 questionnaires coming from 24 different Countries was analyzed. Non-routine coagulation tests (antithrombin activity) are done in 34% of the Institutions before the operation and in 23% after the operation. Point-of-care tests are applied as a preoperative routine in 9.9% of the Institutions (thromboelastography, 5.7%; PFA-100, 1.4%; others, 2.8%) and in selected patients in 50% of the Institutions. Postoperative point-of-care test are applied in 17.9% of the Institutions (thromboelastography, 2.7%; PFA-100, 1.4%; others, 13.8%). Allogeneic blood products use widely differs among Institution: packed red cells are used in 47.5% of the patients (range 8%–90%), fresh frozen plasma in 29% (2%–100%) and platelets in 12.4% (0%–50%).

Perioperative haemostasis and coagulation management is widely different among European Institutions. Point-of-care coagulation and platelet function tests are gaining a significant role. Transfusional policy appears strongly Institution-dependent.

The main aim of this review is to summarize the literature with respect to transfusion and bleeding risks and the therapeutic strategies with respect to optimal management of perioperative bleeding.

This review was generated using peer-reviewed manuscripts pertinent to this topic that were identified using a computer-based Medline search.

Although the pathophysiology of many transfusion-related complications are well-documented, the incidence of these complications is changing. Transfusion Medicine initiatives are being implemented to reduce complications, however, the literature is describing new potential problems related to transfusion in addition to identification of new potential pathogens while blood shortages may limit our ability to adequately manage our anemic and bleeding patients. Excessive bleeding after cardiac surgery can result in increased morbidity and mortality related to transfusion and hypoperfusion related complications as well as injury to critical organ systems. Seven of eight studies have demonstrated that use of point-of-care (POC) tests of hemostatic function can facilitate the optimal management of excessive bleeding and reduce transfusion after cardiac surgery. Two randomized prospective studies have demonstrated that point-of-care tests that assess platelet function can identify patients at risk for acquired, platelet-related bleeding that may be attenuated with pharmacologic agents such as DDAVP. The current literature contains fifty publications with over 400 patients that describe the fairly consistent efficacy of off-label use of recombinant factor VIIa to manage intractable, life-threatening bleeding. Most of these publications involve either case reports or case series that describe the use of this agent and therefore do not adequately address the safety of this agent.

There are substantial risks related to excessive bleeding and transfusion. The literature indicates that use of point-of-care diagnostics with a standardized management algorithm can optimize the management of bleeding and reduce transfusion requirements. Recombinant FVIIa has the potential to reduce transfusion and transfusion-related sequelae and may be life-saving in certain circumstances. However, randomized, controlled trials are warranted to assess both the efficacy and, more importantly, the safety of this intervention (i.e., especially with respect to thrombotic complications) in cardiac surgical patients prior to its use as a first line therapy for bleeding or for bleeding prophylaxis. We must continue to carefully investigate the role of new interventions since the ability to reduce use of blood products, to decrease operative time and/or re-exploration rates has important implications for disease prevention and overall patient safety, blood inventory and associated costs as well as overall health care costs.

The main aim of this review is to summarize the literature with respect to the impact of anticoagulation monitoring strategies and therapeutic strategies to manage heparin resistance and optimize anticoagulation with cardiac surgery.

This review was generated using peer-reviewed manuscripts pertinent to this topic that were identified using a computer-based Medline search.

There are a small number of well-controlled prospective, randomized studies, some of which suggest that bleeding and transfusion can be attenuated by refining heparin monitoring techniques by sustaining better anticoagulation during cardiopulmonary bypass especially when applied to operative cases that involve complex procedures that require long intervals on cardiopulmonary bypass. Recent studies indicate that antithrombin III concentrates can be used to treat heparin resistance and thereby enhance preservation of the hemostatic system during CPB. A few recent retrospective analyses suggest that low ATIII concentration is associated with negative outcomes.

The literature indicates that enhanced anticoagulation via more sophisticated heparin monitoring schemes can reduce bleeding and transfusion and that antithrombin III concentrates can be used to effectively manage heparin resistance during cardiac surgery. Well-controlled, randomized studies are needed to better define the relative importance of AT IIII supplementation with respect to either the management of heparin resistance or with respect to optimization of anticoagulation during CPB and specifically if these interventions are able to decrease the incidence of bleeding and/or thrombotic complications.

Bleeding in cardiac surgery is still one of the major concerns for cardiac surgeons and anaesthesiologists. The present review addresses the main pathophysiological mechanisms underlying bleeding after cardiac operations, and analyzes possible therapeutic strategies.

Overview of different bleeding mechanisms and related diagnostic and therapeutic approaches, with specific respect to disseminated intravascular coagulopathy.

Biological bleeding after cardiac operations depends on the interaction of platelet activity, the procoagulant system, and the fibrinolytic system. A diagnostic and therapeutic approach based on a four-phase model of disseminated intravascular coagulation and haemostasis imbalance is presented. At each step, adequate diagnostic tools (thromboelastography and antithrombin activity) are required to make a diagnosis and guide the appropriate treatment.

Bleeding is not a fatality. Quite the contrary, it must be treated through a multi-system approach, and as early as possible, preferably at a biological phase before clinical bleeding. In addition, early monitoring and treatment adapted to each patient makes it possible to better follow a patient’s evolution and helps reduce the occurrence of later thromboembolic events.

Antithrombin levels during cardiac surgery critically decrease, due to both hemodilution and consumption. This factor prompted the question of whether improved attenuation of hemostatic activation can be achieved by high dose treatment with antithrombin. The aim of this review is to present the currently available pre-clinical and clinical data on the use of antithrombin in cardiac surgery.

Review of the available literature searched using the terms ‘AT’ or ‘Antithrombin’ and ‘Cardiac surgery’ or ‘CPB’ or ‘Cardiopulmonary bypass’.

Antithrombin has been proposed in cardiac operations both as purified concentrates and as recombinant human preparations. The main clinical field where antithrombin supplementation is proposed is in case of heparine resistance (failure to achieve adequate anticoagulation following a standard heparin dose). However, other clinical scenarios have been investigated (modulation of inflammatory reaction; pulmonary vasodilation; prevention of thromboembolic complications).

Many studies suggest that antithrombin supplementation during and after cardiac surgery may be beneficial to correct abnormally low values. One article found an association between low values of antithrombin activity at the end of the operation and adverse postoperative outcomes. However, a large prospective, randomized trial is still needed to finally set the role of antithrombin supplementation in cardiac surgery.

Purified antithrombin concentrates or human recombinant antithrombin have been proposed for treating heparin resistance in cardiac operations with cardiopulmonary bypass, and exert a beneficial effect in terms of haemostatic system activation control. However, little information is available with respect to antithrombin supplementation and clinical outcome in selected categories of patients. The aim of this study is to evaluate clinical outcome data in patients intraoperatively treated with purified antithrombin compared to a control population.

89 patients forming the AT-treated group received purified antithrombin to correct preoperatively low values of antithrombin activity or to treat heparin resistance. The Control group was retrospectively created with a propensity score analysis. After verifying the homogeneity of the two groups, various outcome variables were compared between groups.

Patients in the AT-treated group had a shorter Intensive Care Unit (2.6 ± 3 vs. 3 ± 2.7 days) and Hospital (7.5 ± 3.5 vs. 8.6 ± 4.5 days) stay, and a lower rate (relative risk 0.1, 95% confidence interval 0.01–0.81) of severe postoperative morbid events. Conversely, they demonstrated a significant, albeit clinically irrelevant, more pronounced postoperative bleeding tendency.

AT supplementation in patients at risk for inadequate thrombin suppression during the operation reduces postoperative complications and shortens the recovery time. However, a careful monitoring of the heparin requirements is recommended in order to avoid an undesired excessive postoperative bleeding.

Despite the absence of cardiopulmonary bypass, systemic anticoagulation is needed for off-pump coronary artery bypass (OPCAB) surgery. The aim of the current review is to describe the influence of OPCAB surgery on hemostatic activation and to review the literature with regard to perioperative anticoagulation protocols in OPCAB surgery.

Research of the pertinent literature with appropriate terms for anticoagulation in OPCAB surgery.

While during on-pump cardiac surgery a target activated clotting time (ACT) value of 400–480 is generally accepted, to date no standardized target ACT value for OPCAB surgery has been established. However, an ACT value of > 300 seconds is accepted by approximately 80% of US/Canadian surgeons and 60% of European surgeons. Even given the large variation commercially available heparins, the inter-individual variability of the effect of heparins on the ACT, and large differences in coagulation activation and ‘clot detection’ of currently used ACT systems, this target ACT corresponds to a heparin dose of approximately 150–300 IU/kg. New anticoagulant drugs have been proposed, acting through a selective anti-Xa activity (danaparoid) or directly inhibiting thrombin (bivalirudin).

Anticoagulation management is performed without any internationally accepted standard and, due to this and the lack of adequately powered studies, there is scarce information about the effects of OPCAB surgery on hemostatic activation in the immediate perioperative period. Although limited to two modest studies, bivalirudin appears to be an interesting option for the future.

Recombinant activated factor VII (rFVIIa) is a pharmacologic compound approved for the use in patients with congenital or acquired hemophilia and inhibiting antibodies toward factor VIII or IX. In recent years its use has been proposed in surgical patients demonstrating a lifethreatening bleeding, refractory to the standard therapies. The present study is a review of the clinical information available on the use of rFVIIa in cardiac surgery patients.

Current literature was investigated using a Pubmed search with appropriate key words (rFVIIa OR recombinant activated factor VII AND cardiac surgery).

35 articles were found. These are 11 case reports, 12 case series, 5 review articles, 3 retrospective studies, 2 letters to the Editor, and only one prospective, double-blinded, randomized clinical trial (RCT). The majority of the case reports and case series report a beneficial effect of this drug in the treatment of refractory bleeding. Comparative retrospective studies show conflicting results, and the only RCT demonstrate a significant reduction of allogeneic blood products use in patients treated with rFVIIa. No definitive information is available with respect to thromboembolic complications and general safety of this therapy.

rFVIIa is a promising agent for intractable bleeding in surgical patients. However, large prospective randomized trials are needed to define efficacy, dose, and potential side-effects.