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Patients presenting for urological surgery commonly take a combination of antiplatelet medications. Indications for drugs like aspirin, NSAIDs and the newer platelet inhibitors, e.g. platelet glycoprotein receptor inhibitors, are widespread because of the comorbidity in arterial disease associated with advancing age and general medical conditions in this population of patients. Medications are taken to reduce the risk of potentially catastrophic cardiovascular and cerebrovascular events.

Surgery in urological patients can have a thrombogenic influence with a recognized risk of peri-operative vascular events such as deep vein thrombosis, pulmonary embolism, myocardial infarction and stroke. Platelet inhibitors can lead to difficulty in surgical haemostasis through altered platelet physiology. Re-operation for postoperative bleeding is clearly undesirable because of the additional surgical and anaesthetic risks with prolonged hospital stay. The additional cost of further surgery with postoperative high dependency or intensive care is considerable.

The problem is that if a patient is taking antiplatelet therapy, routine screening of coagulation profiles will not reveal an increased bleeding time or reduced platelet function. Many of the antiplatelet drugs are relative newcomers to drug formularies and to date the clinical studies reported are inconclusive about the risk to patients undergoing surgery. This is because of discrepancies arising relating to the heterogeneity of the populations studied, the varied types of surgical procedures and differing dosing strategies [1].

Regional anaesthesia such as spinal or epidural block is frequently the method of choice for many urological procedures. If drugs like clopidogrel (Plavix) or aspirin are prescribed, there may be a risk of haematoma formation, which must be balanced against the risk of vascular occlusion if the antiplatelet therapy is stopped. Platelet transfusion may be required as the first-line therapy if significant bleeding occurs in the operative period [2].

Aspirin and NSAIDs inhibit platelet cyclo-oxygenase, thereby generating blockade in the formation of thromboxane A2. These medications produce a systemic bleeding tendency by impairing thromboxane-dependent platelet aggregation and consequently prolonging bleeding time. Aspirin exerts these effects by the irreversible blockade of cyclo-oxygenase and therefore its effect persists for the circulating lifetime of the platelet. NSAIDs other than aspirin cause reversible inhibition of cyclo-oxygenase. The duration of action depends on dosage, serum level and half-life. The clinical risks of these medications are enhanced by concomitant use of alcohol, anticoagulants and other patient factors, e.g. existing coagulopathies.

More recently, a newer class of irreversible, noncompetitive platelet aggregation inhibitors, e.g. clopidogrel, is becoming increasingly popular. Compared with aspirin, it has been shown to provide a 31% relative risk reduction of vascular death, myocardial infarction, stroke and re-hospitalization in patients with a history of cardiac surgery. It exerts its action through the blockade of adenosine diphosphate receptor, P2T with a maximum of 60% inhibition of ADP-induced platelet aggregation after 3–5 days. Clopidogrel has a favourable safety profile and is associated with a reduction in gastrointestinal haemorrhage, making it an attractive alternative to aspirin. Like other thienopyridine derivatives, patients on this medication have deranged haemostatic functions. Coagulation will gradually return to its normal function only after the affected platelets have being replaced. Consideration should be given to withholding these agents for 7 days before elective surgery [3].

There was a recent case of extensive retroperitoneal haematoma after lumbar sympathetic blockade in a patient with intermittent claudication receiving another thienopyridine derivative, ticlopidine. Another case was of a patient with a history of polyneuropathy, coronary artery disease and stroke, who received lumbar sympathetic blockade after presenting with an acute obstruction of the left femoral artery. In this case, regular clopidogrel was stopped 4 days before the procedure; 12 h after treatment the patient was found pulse-less and an autopsy revealed a massive coagulated haematoma beneath the left psoas muscle [2]. As there appear to be no reliable and sensitive tests to monitor coagulation, the author recommended that irreversible platelet inhibitors should be discontinued for at least 7 days before any invasive procedures, and that patients should be closely monitored for 24 h [2].

A case of acute onset quadriparesis as a result of a large cervical epidural haematoma after cervical epidural injection was reported in a patient taking combined therapy of diclofenac, clopidogrel and possibly aspirin [4].

Aprospective observational study of patients undergoing coronary artery bypass graft surgery reported that the perioperative use of clopidogrel in combination with aspirin resulted in an increased requirement for surgical re-exploration, and the risk of packed cells and cryoprecipitate transfusions after the procedure [5].

Another study also reported an increased transfusion need in patients receiving combined therapies (including aspirin, clopidogrel and low molecular-weight heparin) undergoing elective primary myocardial revascularisation procedures [6].

Conflicting evidence has been generated from clinical studies over time, with a wide variation of practice documented within the speciality. In the more recent past, a study of the haemorrhagic risk of TURP in this patient group concluded that these medications increase the risk of bleeding during and after the procedure, with the recommendation and general acceptance that aspirin and NSAIDs should be discontinued 1 week before invasive procedures [7].

Evidence-based knowledge to date implied that the newer platelet inhibitors also had the potential to generate an increased risk of bleeding, which may be severe in some cases, in an already vulnerable group of patients with significant comorbidities. In view of patient safety, it is not only a recommendation but a responsibility that every practitioner and other members of the team should meticulously assess their patients’ medication history in an open consultation, with full appreciation of the risks and benefits of their surgical and anaesthetic requirements and their associated risks [2].

For patients undergoing elective surgery, it is certainly wise to delay their procedures until the antiplatelet effects of these medications have subsided. Under urgent circumstances, the increased risks associated with these agents should be anticipated, with the goal of minimising adverse effects while maintaining optimal cardiovascular function perioperatively [1].

REFERENCES

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  2. REFERENCES
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    Maier C, Gleim M, Weiss T, Stachetzki U, Nicolas V, Zenz M. Severe bleeding following lumbar sympathetic blockade in two patients under medication with irreversible platelet aggregation inhibitors. Anesthesiology 2002; 97: 7403
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    Russell MW, Jobes D. What should we do with aspirin NSAIDs, and glycoprotein-receptor inhibitors? Int Anesthesiol Clin 2002; 40: 6376
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    Benzon HT, Wong HY, Siddiqui T, Ondra S. Caution in performing epidural injections in patients on several antiplatelet drugs. Anesthesiology 1999; 91: 15589
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    Yende S, Wunderink RG. Effect of clopidogrel on bleeding after coronary artery bypass surgery. Crit Care Med 2001; 29: 22715
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    Wierod FS, Fransden NJ, Jacobsen JD, Hartvigsen A, Olsen PR. Risk of haemorrhage from transurethral prostatectomy in acetylsalicylic acid and NSAID-treated patients. Scand J Urol Nephrol 1998; 32: 1202