Cardiac surgery greatly changed during the last 20 years. The patient's profile is becoming more and more complex, with an increased amount of elderly patients and the presence of an higher rate of comorbidities. Moreover, the operations themselves are more complex: basically, there are few simple coronary operations, and more redo and complex procedures. Finally, the patients often reach the operating theater with complex, combined therapies acting on both the coagulation factors and the platelet function.
Using a very schematic approach, we can say that at the beginning of the nineties a cardiac surgery patient was usually treated before the operation with few anticoagulant/antiaggregants drugs: basically, salicylates and warfarin. Perioperative coagulation monitoring was based on standard coagulation tests, platelet count, and celite or kaolin activated clotting time (ACT). Intraoperative anticoagulation was achieved with heparin and heparin was reversed by protamine. Drugs available to limit postoperative bleeding and contain transfusional needs were synthetic antifibrinolytics (tranexamic and epsilon-aminocaproic acid), aprotinin and desmopressin.
Nowadays, a cardiac surgery patient may receive different kinds of new drugs before the operation: GPIIb/IIIa inhibitors, clopidogrel, ticlopidine, salicylates and warfarin, and sometimes huge combinations of these drugs. Only one new drug is available to limit postoperative bleeding (recombinant activated factor VII, [rFVIIa]). However, other approaches have been recently suggested to modulate the coagulation system during the operation, and namely the use of purified antithrombin (AT) for treating heparin resistance and limiting the postoperative thromboembolic events represents a open debate [1-18]. The intraoperative coagulation management is no more simply based on standard ACT, and new methods for assessing heparin sensitivity and the adequate dose of heparin are available [19-23]. Finally, point-of-care monitoring tools (thromboelastography [TEG]; platelet function analyzers) for assessing coagulation and platelet function are available [24-28].
Given this deeply changed clinical scenario, we decided to settle the present state-of-the--art of perioperative haemostasis and coagulation management in the European Cardiac Institutions in the year 2006.
A questionnaire (see Appendix) was prepared and delivered via e-mail to 320 Cardiac Surgery Institutions in Europe, as a survey endorsed by the European Association of Cardiothoracic Anaesthesiologists (EACTA). The questionnaire contained various questions addressing haemostasis/coagulation monitoring, use of specific drugs and blood derivates before, during and after a cardiac operation with cardiopulmonary bypass (CPB). Altough Institutions doing paediatric cases were admitted to the study, only data regarding adult patients were requested. Data collection covered 2 months (March-April 2006). The questionnaire could be either electronically filled and sent back via e-mail, or manually filled and sent back by regular mail.
Data analysis included a descriptive statistical analysis. No inferential analyses were performed on the data.
82 Institutions (25.6%) replied to this survey. 9 questionnaires were discharged due to a poor quality/incomplete submission of the data. A final pool of 73 questionnaires remained available for the descriptive statistical analysis.
Twenty-four countries replied to this survey. The distribution of Institutions per each country is reported in Table 1.
The number of adult patients operated per year ranged from 191 to 3,360 (see Fig. 1).
Haemostasis and coagulation management before CPB
In all the Institutions the pre-CPB profile is assessed with standard laboratory tests (prothrombin time and activity, International Normalized Ratio, activated partial thromboplastin time, fibrinogen levels, platelet count). Other laboratory and point-of-care coagulation tests (AT activity, TEG, PFA-100, other platelet function tests) are used at variables rates, as a routine or in a selected patient population (Fig. 2). AT activity is measured as a routine in 34% of the Institutions, and in selected patients in 15.7%. Within the Institutions measuring AT activity before the operation, subnormal values are corrected with purified AT concentrates in 42% of the Institutions, with a mean cut-off value for correction settled at an AT activity of 62%. The total rate of patients receiving purified AT concentrates before going on CPB is 2.4%.
Pre-CPB antifibrinolytic agents used are tranexamic acid in 46.6% of the Institutions, aprotinin in 41.1%, and others in 1.4%. Heparin is used at a mean loading dose of 336 ± 48 IU/kg (range 200-400 IU/kg), and the target ACT to establish and maintain CPB is 450 ± 35 seconds (range 400-500 seconds). 61% of the Institutions use kaolin-ACT to verify adequate anticoagulation during CPB, 26% celite-ACT, and 13% are using heparin monitoring systems.
Heparin resistance (defined as the failure to reach or maintain the target ACT despite a standard dose of heparin) is reported with an incidence of 7.9% (95% confidence interval 5.8-9.9). The reported incidence greatly varies between Institutions (range 0-35%, Fig. 3). In case of heparin resistance, the clinical approach is (a) giving more heparin and fresh frozen plasma (43%), (b) more heparin and purified AT concentrates (42%), (c) only more heparin (13%) and (d) only purified AT concentrates (2%).
Management after CPB
After weaning the patient from CPB, and before transferring him to the ICU, 32% of the Institutions routinely use tranexamic acid, 26% aprotinin, 4.2% desmopressin, and 2.1% other antifibrinolytics.
Haemostasis and coagulation tests performed as a routine or in selected patients are reported in Figure 4. In case of evidence of bleeding, the majority (60%) of the Institutions follow a strategy based on (a) supplemental dose of protamine and (b) if ineffective, fresh frozen plasma and/or platelets. 40% of the Institutions declare to follow the indications of specific tests like TEG and platelet function tests.
Management in the ICU
Haemostasis and coagulation tests performed as a routine in the ICU are reported in Figure 5.
Low values of AT are corrected in 34% of the Institutions. The threshold value for correction with purified AT concentrates is 56% (95% confidence interval 51%-61%). 5.8% of the total amount of patients received purified AT in the ICU.
Transfusions and general observations
The rate of patients being transfused with allogeneic blood products and coagulation factors used during the whole hospital stay is reported in Figure 6.
Allogeneic blood products use greatly varies among Institutions (Figs 7-9), ranging from 8% to 90% for packed red cells, from 2% to 100% for fresh frozen plasma, and from 0% to 50% for platelets.
The Institutions have been investigated about their satisfaction regarding the present status of haemostasis and coagulation management in their clinical environment. 22% declared to be completely satisfied, 48% partially satisfied, 28% not satisfied at all; 2 Institutions did not answer.
This survey suffers from the usual limitations of a study based on voluntary, uncontrolled reply to a questionnaire. However, given these limitations, it offers an overlook on the present status of perioperative haemostasis and coagulation management in cardiac surgical Institutions in Europe, with a large patient population (60,573) studied.
A first comment is that the participating Institutions cover almost all the geographical area of Europe, with almost an equal distribution of Institutions in North, Center, East and South Europe.
The preoperative coagulation profile is still addressed by the majority of the Institutions with standard laboratory tests; however, the measurement of AT activity before the operation is done, as a routine or in selected patients, in about 50% of the Institutions. Interestingly, there is a geographical difference to this respect: in Germany and Italy there is the higher rate of Institutions measuring AT activity, whereas in UK no Institutions is doing this. We can hypothesize that the presence of groups which studied and published articles [4,6,14,17] focused on AT in cardiac surgery in Germany and Italy may be the trigger for the wide diffusion of AT activity measurement in these two Countries.
An interesting point is that the Institutions measuring AT activity are generally doing this in order to apply possible corrections in case of low values. The mean trigger value for correcting a low AT activity is 62%, and under this value 42% of the Institutions are using purified AT concentrates.
The most commonly point-of-care test used before the operation is TEG. Many authors addressed the potential use of TEG in cardiac surgery [24-27] and its role in guiding the management of postoperative bleeding is gaining more and more consensus. Conversely, before the operation, specific platelet function testing is less common, and appears more applied to a selected patients population (probably patients receiving strong anti-platelet therapy).
Heparin resistance is reported at a highly variable rate. This reflects what already demonstrated in the specific literature: depending on the definition applied, the incidence is from 5% to 22% [1-6]. We have proposed a simple, clinical definition of this condition in the questionnaire; therefore, this high variability probably reflects more the clinical judgement of the doctors more than a well established value. However, this data confirm that the phenomenon exists and has a relevant impact (30% of the Institutions declared an incidence ≥ 10%). In presence of heparin resistance, purified AT concentrates are used by many Institutions (45%).
Specific therapies aimed to limit postoperative bleeding are used in the majority (60%) of the Institutions, and the most commonly used drugs are tranexamic acid and aprotinin.
Bleeding after cardiac operations is addressed with a variety of strategies. The majority of the Institutions are following a standard strategy based on a “blind” use of protamine, fresh frozen plasma and platelets, but a considerable number is trying to follow a specific strategy based on point-of-care testing of the coagulation profile. It is interesting to notice that after the operation the most commonly point-of-care tests used address the platelet function (PFA-100 in the operating room; PFA-100 and bleeding time in the ICU), therefore confirming the general feeling that postoperative bleeding is related to a poor platelet function.
However, some Institutions seem to be worried not only by bleeding, but by thromboembolic complications too. AT activity is measured by 23% of the Institutions in the ICU. Low values are corrected with purified AT concentrates in 34% of the Institutions measuring AT activity, with a threshold value at 56%. Interestingly, this value is almost identical to the one (58%) that is associated to an increased morbidity in a recently published article .
Finally, many considerations may be drawn looking at the allogeneic blood products use. The rate of patients receiving packed red cells, fresh frozen plasma, and platelets, greatly varies among Institutions. Of course, this probably reflects many possible differences in the clinical management of patients during and after cardiac surgery: (a) the level of haemodilution during CPB; (b) the transfusion protocol applied, and namely the trigger value of Hb; (c) the rate and severity of postoperative bleeding; (d) the different therapeutic protocols applied in case of bleeding.
As a general comment, the fact that in the European reality there are such impressive differences with respect to transfusional policy reflects, in our judgement, an inadequate understanding of the transfusion effects on the postoperative outcome. There is a growing amount of literature clearly demonstrating that liberal transfusions severely increase morbidity and mortality after cardiac operations [29-33]. Therefore, each transfusion should be the final act in a complex decisional process involving a careful assessment of risk and benefits of this therapy. Institutions with an extremely high (> 70%) rate of patients receiving allogeneic blood products should therefore address the problem, investigating which changes in the daily practice could be suggested.
Conversely, if we look at the final question of this survey, we can find a surprising information: the Institutions which declare a complete satisfaction in their haemostasis/coagulation management are transfusing 60% of their patients; Institutions partially satisfied, 50%…and Institutions completely satisfied, as much as 62%. We can therefore conclude that the rate of patients being transfused is not considered at all when assessing the quality of the clinical management.
The perioperative haemostasis and coagulation management, as well as the transfusional policies, are greatly different among European Institutions. A deeper knowledge of the impact of these issues on the postoperative morbidity and mortality should be reached. The main goals of a correct approach to the problem are (a) limiting perioperative bleeding; (b) limiting allogeneic blood products use, through a specific assessment of the coagulation profile before and after the operation, and through the use of specific transfusional protocols; (c) limiting the risk of thromboembolic complications, by increasing the attention to the heparin management and to the role of natural anticoagulants (AT, tissue factor pathway inhibitor, protein C-S complex).
The following Institutions have contributed to this survey:
Medical University, Graz, Austria; Community Teaching Hospital, Klagenfurth, Austria; Namur Regional Medical Center, Namur, Belgium; Cliniques Universitaires UCL, Mont Godinne, Belgium; Chu Liege, Belgium; University Hospital, Gent, Belgium; University Hospital KULeuven, Leuven, Belgium; Clinical Hospital, Zagreb, Croatia; University Hospital Motol, Prague, Czech Republic; Charles University, Prague, Czech Republic; Olomuc Hospital, Olomuc, Czech Republic; Heart Center Sanchez, Varde, Denmark; University Hospital, Copenhagen, Denmark; North Estonian Regional Hospital, Riga, Estonia; Vasa Central Hospital, Vasa, Finland; Tampere University Hospital, Tampere, Finland; Turku University Hospital, Turku,Finland; Cardiac Surgery Clinic Open Heart, Tbilisi, Georgia; University Hospital Ulm, Ulm, Germany; Otto von Guericke University, Magdeburg, Germany; Charitè University Hospital, Berlin, Germany; German Pediatric Heart Center, Sankt Augustin, Germany; Schuechtermann Klinik, Bad Rothenfelde, Germany; FA University, Erlangen-Nurenberg, Germany; Henry Dunant Hospital, Athens, Greece; Interclinic Hospital, Crete, Greece; Heart Institute, Pecs, Hungary; National Medical Center, Budapest, Hungary; Irccs San Raffaele, Milan,Italy; Irccs Policlinico S. Donato, Milan, Italy; Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; La Sapienza University, Rome, Italy; San Gerardo Hospital, Monza, Italy; Ospedali Riuniti, Trieste, Italy; Ospedale Niguarda, Milan, Italy; Policlinico Hospital, Monza, Italy; Ospedale di Circolo, Varese, Italy; Policlinico Le Scotte, University of Siena, Italy; Poliambulanza Hospital, Brescia, Italy; Azienda Ospedaliera S.Maria, Terni, Italy; Azienda Ospedaliera Papardo, Messina, Italy; Azienda Ospedaliera, Caserta, Italy; Vilnius University Hospital, Vilnius, Lithuania; Ullevaal University Hospital, Oslo, Norway; University Hospital, Trondheim, Norway; Jozef Strus City Hospital, Poznan, Poland; Jagellonian University, Krakow, Poland; Hospital Santa Maria, Lisbon, Portugal; Institute of Cardiovascular Disease Prof Iliescu, Bucarest, Romania; Research Institute of Circulation Pathology, Novosibirsk, Russia; Regional Outpatient of Cardiology, Novosibirsk, Russia; University Hospital German Trias i Pujol, Badalona, Spain; University Hospital Clinic, Barcelona, Spain; University Hospital Orebro, Orebro, Sweden; University Hospital Basel, Basel, Switzerland; Inselspital University of Bern, Bern, Switzerland; Amphia Hospital, Breda, The Netherlands; University Medical Center Groningen, Groningen, The Netherlands; Academic Medical Center, Amsterdam, The Netherlands; Mersin University Medical Faculty, Mersin, Turkey; Turkiye Yuksek Education and Research Hospital, Ankara, Turkey; Hacettepe University, Ankara, Turkey; Dr. Siyami Ersek Hastanesi Hospital, Istanbul, Turkey; Baskent University, Baskent, Turkey; University Hospital of Wales, Cardiff, UK; Barts and the London NHS Trust, London, UK; Southampton General Hospital, Southampton, UK; Castle Hill Hospital, Hull, UK; The Royal Infirmary of Edinburgh, Edinburgh, UK; Manchester Royal Infirmary, Manchester, UK; King's College Hospital, London, UK; Royal Brompton Hospital, London, UK; University Hospital Birmingham, Birmingham, UK.
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Eacta survey on coagulation management in cardiac operations