A comprehensive medical history is important to identify patients at risk of bleeding.4 Significant factors include a family history or the patient suffering bleeding after previous surgery or dental extractions. One study indicated that a positive medical history is much more likely to predict bleeding than any laboratory test. Other significant symptoms may include epistaxis, menorrhagia and or bruising. However von Willebrand disease may be clinically silent and may only manifest itself in situations of stress, such as an operation. A detailed drug history of prescribed medication and alternative medicines is vital.
Haemostatic screening tests, including the platelet count, pro-thrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen are routinely requested when major intracranial or spinal surgery is considered. A platelet count identifies patients with thrombocytopenia, but does not detect platelet dysfunction. In neurosurgical patients, platelet counts of 100 x 109 or more are required to reduce the risk of bleeding complications. The PT is a measure of the extrinsic coagulation pathway and reflects the procoagulant activity of factors II, VII, IX and X. Common causes of prolonged PT are warfarin, liver disease, and vitamin K deficiency. The APTT detects disorders of the intrinsic pathway, such as, the haemophilias or von Willebrand disease (VWD) though may be normal in some cases of mild haemophilia or VWD. Common acquired causes of prolonged APTT include unfractionated heparin and the presence of a lupus anticoagulant. Unlike unfractionated heparin low molecular weight heparins do not reliably prolong the APTT, and anti-factor Xa assays are required if monitoring is necessary. The most common cause of prolongation of both PT and APTT is disseminated intravascular coagulation (DIC). In DIC, D-dimers are usually raised and, in later stages, fibrinogen levels are reduced. Anyone suspected of a bleeding disorder should be referred to a haematologist for assessment so that screening tests might be performed together with specialised investigations. These tests may include bleeding time and coagulation factors assays. Platelet function studies using the platelet function analyser (PFA-100™) or the platelet aggregometer may also be performed.
Drugs are a common cause of bleeding and a history of relevant medication is essential.5 The drugs that need to be considered include anticoagulants, anti-platelet drugs, and non-steroidal anti-inflammatory drugs. Commonly used anticoagulants include warfarin, unfractionated heparin, and low molecular weight heparin.6 Warfarin should be discontinued prior to neurosurgery. Perioperative anticoagulation will be determined by the indication for anticoagulation. In low-risk patients, warfarin is discontinued four days preoperatively, and no bridging anticoagulation is required. Patients at high risk such as those with recent history of thromboembolism or those with mechanical heart valves require appropriate cover with either unfractionated heparin or low molecular weight heparin, when they are off the warfarin. Intravenous unfractionated heparin may be stopped four hours preoperatively, but due to its longer half-life, the last dose of low molecular weight heparin should be at least 24 hours before neurosurgery. On the day of surgery, clotting studies have to be repeated to ensure that values are within acceptable levels.
Anti-platelet agents have widespread use in patients with arterial disease and increase haemorrhagic risk in patients undergoing surgery. The most commonly used agent is aspirin (acetylsal-icylic acid), which acts by irreversibly inactivating the enzyme cyclooxygenase-2 for the life of the platelet. Aspirin should be stopped at least seven days prior to surgery to enable platelets to develop, unaffected by irreversible cyclooxygenase inhibition. Non-steroidal anti-inflammatory drugs (NSAIDs) should be stopped at least two days preoperatively to enable the restoration of any reversible cyclo-oxygenase inhibition they may cause. The new generation of NSAIDs, the cyclooxygenase-2 inhibitors, such as, rofecoxib or celecoxib do not significantly affect platelet function. Clopidogrel, which blocks platelet ADP receptors, is increasingly being used for secondary prevention of myocardial infarction and cerebrovascular accidents. Like aspirin, the anti-platelet effect is irreversible and lasts the lifetime of the platelet. Therefore, discontinuation of the drug 7 to 10 days preoperatively, is essential. Dipyridamole, however, reversibly inhibits phosphodiesterase and may be discontinued only 24 hours before elective surgery.
The advent of aggressive anti-thrombotic treatment as adjuvant to angioplasty or stent placement has increased the risk of haemorrhage associated with these procedures. Glycoprotein IIb/IIIa inhibitors include abciximab, eptifibatide, and tirofibran. Abciximab, a chimeric monoclonal antibody, was the first drug of its class to be developed. Platelet aggregation is almost completely inhibited two hours after treatment is begun and recovery is evident by 48 hours after treatment discontinuation. Mild thrombocytopenia develops in 5% patients and severe thrombocytopenia in 0.7% patients receiving abciximab. In a meta-analysis, major bleeding occurred in 2.4% patients (versus 1.4% placebo). Intracranial bleeding was rare, however, occurringin 0.12% patients as opposed to 0.09% patients receiving heparin alone. A higher rate of intracerebral haemorrhage seems to be associated with neurointerventional procedures than with coronary interventional procedures. This is likely to be related to recent cerebral ischaemic events and reperfusion injury.
When a patient taking anti-platelet agents presents for emergency neurosurgery, and the drug has not been discontinued, platelets should be transfused even if the platelet count is normal. In the anticoagulated patient who requires emergency neurosurgical intervention, for instance, after intracranial haemorrhage, complete reversal of anticoagulation would be indicated.7 If the patient is taking warfarin, a vitamin K antagonist, immediate administration of intravenous vitamin K would be required. Since this takes several hours to be effective, prothrombin complex concentrate (PCC), a virally inactivated plasma product rich in vitamin K dependent coagulation factors, should also be administered. PCC are associated with a small risk of thrombosis and should be avoided in patients with previous history of ischaemic heart disease or thromboembolism. In these patients, fresh frozen plasma (FFP) may be used for immediate reversal of the warfarin effect. In patients receiving unfractionated heparin, coagulation should return to normal within a few hours after discontinuation, due to the short half-life of the heparin; pro-tamine may also be used as an antidote. With low molecular weight heparin the half-life is approximately 18 hours, and only a fraction of the anticoagulant activity may be reversed by protamine. The new generation of anticoagulants, including pentasaccharides, oral direct thrombin inhibitors, and oral anti-Xa inhibitors, do not have a specific antidote.8 If intracranial bleeding occurs, the use of recombinant factor VIIa may be considered in addition to the usual haemostatic measures such as infusion of FFP.9
Neurosurgery may be required in patients with inherited coagulation defects.10 This might be for intracranial haemorrhage due to the bleeding disorder or for treatment of other pathology that has coincidentally occurred in such a patient. In these patients it is essential to work closely with the haematological team to establish the correct diagnosis and define the haemostatic risk preoper-atively. The most common bleeding disorders are von Willebrand disease and haemophilia A and B. In those with haemophilia a pre-operative inhibitor screen is vital to ensure a predictable and satisfactory response to infused factor concentrate. Factor levels should be maintained in the neurosurgical patient as high and long as appropriate. The prescribed factor is infused prior to the surgery, and the factor level is measured before induction of anaesthesia to ensure an appropriate level, usually 100% preoperatively. Continuous infusion of factor concentrate is used increasingly in preference to bolus doses, providing smoother pharmacokinetics and reduced consumption of factor.11 Factor levels must be monitored twice daily initially and then daily to ensure appropriate factor dosage and adequate haemostasis.
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