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Low-Molecular-Weight-Heparin before Cardiac Surgery: To Give or Not To Give?

Department of Cardiac Surgery, Alder Hey Children’s Hospital, Liverpool L12 2AP, United Kingdom

I read with great interest the article by Myhre et al¹ suggesting that preoperative treatment of unstable angina with low-molecular-weight heparin (LMWH) carries a definite risk of postoperative bleeding. They deserve praise for their important contribution to the existing literature. However, like most previous contributions on this subject^2–4 they leave the readers confused on the all important issue: whether to give LMWH before cardiac surgery or not?

LMWH has become an attractive therapy for use during acute coronary syndrome (ACS) because of its potential superior efficacy over unfractionated heparin (UFH), its longer activity, and its subcutaneous route of administration. However, because a significant number of patients presenting with ACS may be sent directly to open heart surgery while still on anticoagulation, the potential risk of increased postoperative bleeding and need for re-exploration and transfusion of blood products raises concerns about preoperative use of LMWH. The mechanism of this increased risk is not certain, and the results are complicated by the fact that most studies are retrospective with their inherent limitations. However, a variety of potential explanations can be offered to explain this increased risk. First, the dosage of LMWH (generally 1 mg•kg^–1 subcutaneously twice per day) may induce a greater antithrombotic effect than a standard dose UFH.⁵ Indeed, this may explain its superior clinical efficacy. Additionally, at the standard recommended dose of LMWH, the activated partial thromboplastin time is relatively insensitive to its anticoagulant effect, thereby making it difficult to make individual adjustments to the dose. Second, the longer half-life of LMWH might increase its length of action to well beyond the completion of the surgery and result in increased risk of bleeding.⁵ Third, because of its relative resistance to neutralization by protamine, anticoagulation caused by the LMWH may not be appropriately reversed after surgery, resulting in an increased risk of bleeding.⁵ Regardless of the mechanism, a more than doubling of the risk of surgical re-exploration after open heart surgery¹ is something of potentially significant clinical impact.

This finding, however, does not necessarily call into question the indication for the use of LMWH in ACS. Overall, relatively few patients with ACS actually proceed directly to open-heart surgery. Additionally, the absolute incidence of surgical re-exploration is still fairly low and does not appear to have an impact on overall in-hospital surgical mortality. Moreover, it is important to realize that different formulations of LMWH despite similar pharmacology, have different clinical characteristics and cannot be equally substituted.² Therefore, owing to these differences extreme caution needs to be exercised when interpreting the results of different studies as the findings of one study using a particular formulation of LMWH should not be extrapolated to other formulations of LMWH.

Furthermore, one potential solution to avoid bleeding in patients who need emergent surgery while on LMWH is to perform the operation off-pump if technically and hemodynamically feasible. The other potential method to combat bleeding would be use of hemofiltration or ultrafiltration while on pump, and these methods warrant further investigation.

Thus, until a large, multicenter, randomized, controlled trial to develop appropriate guidelines to address this potentially very important issue is carried out, the available evidence is not robust enough to suggest that LMWH must be withdrawn prior to emergency cardiac surgery.

REFERENCES

1. Myhre U, Stenseth R, Karevold A, Bjella L, Lingaas PS, Olsen PO, et al. Bleeding following coronary surgery after preoperative Low-Molecular-Weight Heparin. Asian Cardiovasc Thorac Ann 2004;12:3–6.[Abstract/Free Full Text]

2. Kincaid EH, Monroe ML, Saliba DL, Kon ND, Byerly WG, Reichert MG. Effects of preoperative enoxaparin versus unfractionated heparin on bleeding indices in patients undergoing coronary artery bypass grafting. Ann Thorac Surg 2003;76:124–8.[Abstract/Free Full Text]

3. Jones HU, Muhlestein JB, Jones KW, Bair TL, Lavasani F, Sohrevardi M, et al. Preoperative use of enoxaparin compared with unfractionated heparin increases the incidence of re-exploration for postoperative bleeding after open-heart surgery in patients who present with an acute coronary syndrome: clinical investigation and reports. Circulation 2002;106(12 Suppl 1):I19–22.

4. Berkowitz SD, Stinnett S, Cohen M, Fromell GJ, Bigonzi F; ESSENCE Investigators. Prospective comparison of hemorrhagic complications after treatment with enoxaparin versus unfractionated heparin for unstable angina pectoris or non-ST-segment elevation acute myocardial infarction. Am J Cardiol 2001;88:1230–4.[Medline]

5. Turpie AG, Antman EM. Low-molecular-weight heparins in the treatment of acute coronary syndromes. Arch Intern Med 2001;161:1484–90.[Abstract/Free Full Text]

This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Shahzad G Raja Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Raja, S. G Search for Related Content PubMed PubMed Citation Articles by Raja, S. G Related Collections Cardiac - pharmacology