Asian Cardiovasc Thorac Ann 2004;12:3-6
© 2004 Asia Publishing EXchange Ltd
Bleeding Following Coronary Surgery After Preoperative Low-Molecular-Weight Heparin
Ulf Myhre, MD,
Roar Stenseth, MD1,
Asbjørn Karevold, MD,
Lise Bjella, MD1,
Per Snorre Lingaas, MD,
Per Olav Olsen, MD1,
Rune Haaverstad, MD,
Idar Kirkeby-Garstad, MD1,
Olaf Walle Levang, MD
Department of Cardiothoracic Surgery
1 Department of Anaesthesia, St Elisabeth Heart Centre, Trondheim University Hospital, Trondheim, Norway
For reprint information contact: Ulf Myhre, MD Tel: 46 31 342 1000 Fax: 46 31 417 991 Email: ulf_myhre{at}yahoo.com Department of Cardiothoracic Surgery, Sahlgrenska Hospital, Gothenburg 413 45, Sweden.
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ABSTRACT
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Low-molecular-weight heparin and acetyl salicylic acid have become an established treatment for unstable angina. A retrospective study on our database of one year was carried out to see what impact preoperative low-molecular-weight heparin versus none had on the postoperative course of 473 patients having coronary surgery exclusively. Apart from the fact that the low-molecular-weight heparin patients had a higher New York Heart Association classification and marginally more grafts, longer bypass and cross-clamp time, the preoperative characteristics and surgery of the two groups were similar. The low-molecular-weight heparin group had twice as many (9.7% versus 4.7%) re-operations for bleeding, 46% versus 26% had blood transfusion and 22.3% versus 12.6% plasma transfusion. The postoperative outcome was otherwise similar. Preoperative treatment of unstable angina with low-molecular-weight heparin carries a definite risk of postoperative bleeding. Although this study did not reveal any serious consequences, bleeding, transfusions and re-operations are associated with infections, wound healing problems and death. The indications and length of treatment with low-molecular-weight heparin in unstable angina patients have to be appropriate and the perioperative management of these patients has to address the bleeding tendency.
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INTRODUCTION
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In 1996 a Fragmin during Instability in Coronary Artery Disease (FRISC) study1 demonstrated a 65% relative reduction in death or infarction over the first 6 days in patients with unstable angina that were treated with low-molecular-weight heparin (LMWH) in a dose of 120 U·kg-1 dalteparin (Fragmin, Pharmacia & Upjohn), subcutaneously every 12 hours. Many of these patients presented for coronary artery surgery while the therapy was still ongoing. If the therapy was just stopped, there was still an effect on coagulation. 1997 was the first year that this therapy became common in the patients presented for surgery at our institution. It was our impression that we were encountering more postoperative bleeding, putting our patients at risk for all the complications associated with this.
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PATIENTS AND METHODS
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At the St Elisabeth Heart Centre, all cardiac surgery is continuously registered pre, per and postoperatively, and the standardized data is entered into a computerized database. Prior to discharge a doctor will assess the quality of the registration. This database was used to see how the preoperative use of LMWH for unstable angina affected the outcome in patients having coronary revascularization surgery exclusively. This group was compared to patients who had not received LMWH who also underwent coronary revascularization surgery exclusively. In 1997, a total of 473 patients underwent coronary revascularization surgery. Of these, 113 were on LMWH therapy upon presentation for surgery. It was not clinical practice to monitor the anticoagulant effect of LMWH preoperatively. Prior to going on bypass, the patients were fully heparinized to an activated clotting time (ACT) of more than 480 seconds. After decannulation, protamine was given at 0.8 to 1 mg·mg-1 heparin used for a target ACT of less than 125 seconds. Another ACT was taken 30 minutes later and additional protamine, usually 50 mg, was given to achieve an ACT of less than 125 seconds. Aprotinin was not used. The patients were retransfused their mediastinal drainage for the first 8 hours postoperatively. The decision to give blood products or re-explore was routinely made on a clinical basis.
Continuous variables are expressed as mean ± standard deviation and Dichotomous variables are shown as percentages. Statistical analysis comparing mean differences were with the two tailed t test and proportional differences with chi-square. A p value of < 0.05 was considered significant.
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RESULTS
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Age, sex, proportion of redo procedures, preoperative renal failure (defined as serum creatinine > 140 mmol·L-1), diabetes, hypertension, peripheral vascular disease, ejection fraction and end diastolic pressure were all not significantly different between the two groups (Table 1
). Significantly more patients in the LMWH group had unstable angina, 89% versus 15% ( p < 0.001), and they were in a higher New York Heart Association (NYHA) class, 3.6 versus 2.8 ( p < 0.001). In contrast, only 2.6% of the LMWH patients versus 11.7% of the non LMWH patients were on warfarin sodium (Marevan, Nycomed Pharma), ( p < 0.01). 74% of the LMWH patients versus 61% of the non LMWH patients had received acetyl salicylic acid (ASA) (Albyl E, Nycomed Pharma). None had received Clopidogrel.
The LMWH patients received significantly more grafts: median 4 (range, 2–5) versus median 3 (range, 2–4) ( p < 0.05) and they had a longer bypass time, 83 versus 75 min ( p < 0.05). The LMWH patients also had a longer crossclamp time, 46 versus 42 min ( p < 0.05). The core body temperature at arrival in the intensive care unit (ICU) was the same in the two groups.
Postoperatively, the total magnitude of the blood loss in the drains and the amount autotransfused was not significantly different between the groups (Table 2). However, 9.7% of the LMWH patients versus 4.7% of the non LMWH patients ( p < 0.05) had to be brought back and re-explored for bleeding. The reasons for taking the patients back despite similar total loss in the drains were, among other factors, the rate of loss in the drains. Clinical instability with regard to blood pressure, diuresis, metabolic acidosis, the need for pharmacologic circulatory support and signs of tamponade were other important factors in the decision making.
More LMWH patients received blood transfusion, 46% versus 26% ( p < 0.001) and more LMWH patients received plasma transfusions, 22.3% versus 12.6% ( p < 0.05). There was no significant difference in the percentage who received thrombocyte concentrate from 4 donors. The incidence of atrial fibrillation, postoperative myocardial infarction and renal failure, death as inpatient as well as the length of the intubation, ICU stay and total postoperative stay was not significantly different between the groups (Table 3). Bleeding in relation to ingestion of acetyl salicylic acid within the week prior to surgery was also looked at. This was not associated with excess bleeding either alone or in combination with LMWH.
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DISCUSSION
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In many parts of the world, including Scandinavia, many patients are managed medically for unstable angina, at least initially. Thrombotic occlusion is responsible for most acute manifestations of coronary artery disease.2 This was initially addressed by administering acetyl salicylic acid acutely. Acetyl salicylic acid has not been found to be associated with more postoperative bleeding in cardiac surgery.3 Our experience has been as such.
After the findings of the FRISC trial, i.e. a 65% relative reduction in death or infarction over the first 6 days in patients with unstable angina that were treated with LMWH, the management of unstable angina evolved into the widespread use of LMWH among cardiologists referring patients to our institution. An impression of increased bleeding prompted this retrospective study. For the most part our patients had similar preoperative work up, e.g. routine duplex carotid study if indicated from history or clinical examination. There is a surprising, but not significant, difference in that the LMWH patients had fewer carotid stenosis.
In our study we found that preoperative LMWH therapy in the patients referred to us for coronary artery bypass surgery, was associated with a more than twice as frequent rate of re-exploration for bleeding and a much higher consumption of blood products. Some caution has to be applied in interpreting these numbers in that there is some preselection of the patients, such as the LMWH group had much more frequent unstable angina, had more grafts and approximately 10% longer bypass and crossclamp time. These factors may all play some role in postoperative hemostasis. Because of the small number of patients with unstable angina who did not receive LMWH, it would be hard to propensity match unstable angina patients who received LMWH against unstable angina patients who did not, for a more direct comparison. Use of ASA was more common in the LMWH group and use of warfarin sodium was more common in the non LMWH group preoperatively. We did not find any increased re-exploration, loss of blood or transfusion attributable to ASA.
Another large study also found a higher blood transfusion requirement, but not higher re-exploration rate after cardiac surgery, in patients who had been pretreated with LMWH.4 They did however tolerate a higher mediastinal drain blood loss than we did. The decision to re-explore was clinical in our study and different clinical practices may play a role.
We did not find that the increased blood product requirement and re-exploration rate had a significant impact on in hospital 30 day postoperative death, complications or length of stay. However the trends were there and it may have reached significance in a larger series. Transfusion and re-exploration are known risk factors for complications.5–8
We regard the consequences of preoperative LMWH therapy to be serious, therefore careful assessment of indications for and administration of LMWH has to be made in unstable angina patients. Tailoring the LMWH therapy by risk stratification in relation to sex, smoking, C reactive protein, fibrinogen and troponin T & I may be helpful in this regard.9–15 The benefits of long term LMWH therapy are also rather uncertain.
Once a patient who has been on LMWH presents for surgery, it is important to be aware of the extra bleeding risk and carry out the surgery and postoperative management with attention to this. Preoperatively measuring activated prothrombin time and newer methods of monitoring the anticoagulant effect of LMWH, such as anti-activated factor X heparin concentration,4 may be helpful in this respect. Anticoagulant and antiplatelet therapy given because of unstable angina or because of tentative or partial Percutaneous Coronary Angioplasty,4,16 are important factors to pay attention to in the preoperative assessment of a patient. It has implications for perioperative management and risk of surgery.
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REFERENCES
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- FRISC Study Group. Low-molecular-weight heparin during instability in coronary artery disease (FRISC). Lancet
1996;347:561–8.[Medline]
- Turpie AG. New frontiers in the management of unstable coronary artery disease. Am J Cardiol
1997;80:21E–24E.[Medline]
- Tuman KJ, McCarthy RJ, O’Connor OJ, McCarthy WE, Ivankovich AD. Aspirin does not increase allogeneic blood transfusion in reoperative coronary artery surgery. Anesth Analg
1996;83:1178–84.[Abstract]
- Clark SC, Vitale N, Zacharias J, Forty J. Effect of low molecular weight heparin (fragmin) on bleeding after cardiac surgery. Ann Thorac Surg
2000;69:762–4.[Abstract/Free Full Text]
- Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M. Re-exploration for bleeding is a risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg
1996;111:1037–46.[Abstract/Free Full Text]
- Zacharias A, Habib RH. Factors predisposing to median sternotomy complications. Deep vs superficial infection. Chest
1996;110:1173–8.[Abstract/Free Full Text]
- Dacey LJ, Munoz JJ, Baribeau YR, Johnson ER, Lahey SJ, Leavitt BJ, et al. Re-exploration for hemorrhage following coronary artery bypass grafting: incidence and risk factors. Northern New England Cardiovascular Disease Study Group. Arch Surg
1998;133:442–7.[Abstract/Free Full Text]
- Leal-Noval SR, Rincon-Ferrari MD, Garcia-Curiel A, Herruzo-Aviles A, Camacho-Larana P, Garnacho-Montero J, et al. Transfusion of blood components and postoperative infection in patients undergoing cardiac surgery. Chest
2001;119:1461–8.[Abstract/Free Full Text]
- Toss H, Wallentin L, Siegbahn A. Infl uences of sex and smoking habits on anticoagulant activity in low-molecular-weight heparin treatment of unstable coronary artery disease. Am Heart J
1999;137:72–8.[Medline]
- Toss H, Lindahl B, Siegbahn A, Wallentin L. Prognostic infl uence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. FRISC Study Group. Circulation
1997;96:4204–10.[Abstract/Free Full Text]
- Lindahl B, Venge P, Wallentin L. Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC Study Group. Circulation
1996;93:1651–7.[Abstract/Free Full Text]
- Lindahl B, Venge P, Wallentin L. Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. FRISC Study Group. J Am Coll Cardiol
1997;29:43–8.[Abstract]
- Lindahl B, Andren B, Ohlsson J, Venge P, Wallentin L. Non-invasive risk stratification in unstable coronary artery disease: exercise test and biochemical markers. FRISC Study Group. Am J Cardiol
1997;80:40E–44E.[Medline]
- Lindahl B, Venge P, Wallentin L. The FRISC experience with troponin T. Use as decision tool and comparison with other prognostic markers. Eur Heart J
1998;19:N51–8.
- Nageh T, Sherwood RA, Harris BM, Thomas MR. Cardiac troponin I for risk stratification following percutaneous coronary artery intervention in acute coronary syndromes. Catheter Cardiovasc Interv
2002;55:37–42.[Medline]
- Hongo RH, Ley J, Dick SE, Yee RR. The effect of clopidogrel in combination with aspirin when given before coronary artery bypass grafting. J Am Coll Cardiol
2002;40:231–7.[Abstract/Free Full Text]
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ABSTRACT
INTRODUCTION
