PFA-100® and regional analgesia

Editor—I was interested to read the correspondence from McGlennan and colleagues.1 The specific message conveyed to the readers was unclear. Should we use the platelet function analyser (PFA-100®) as the decision making tool before instituting an epidural?

It is well known that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is associated with platelet dysfunction, resulting in increased bleeding time and closure time (CT). Many short-acting NSAIDs (e.g. ibuprofen) lose their antiplatelet effects within a few hours.2 The patient described by McGlennan and colleagues had taken an overdose of ibuprofen 4 days before and was successfully treated and discharged home. Considering the reversible effects of ibuprofen on platelet function and its short half-life, it was unlikely that the prolonged CT recorded by the authors resulted from an ibuprofen overdose. This test was carried out 4 days after the overdose.

The authors did not describe the method of measurement of CT in sufficient detail.1 I found no logic in declining to insert an epidural on the basis of prolonged CT (which was based on a single measurement) alone.

It is well known that CT has limitations. Despite having 98% negative and 94% positive predictive values, this test is not 100% sensitive to all platelet function defects. False-negative and false-positive results are seen. The PFA-100® is also sensitive to a large number of variables. CT results vary if blood is sampled in the morning or in the afternoon. The CT of blood samples collected in the evening are significantly longer. Haematocrit can affect the CT measurement as well. Two cartridges are used for CT measurements; they are CT/collagen–epinephrine (EPI-CT) and CT/collagen–adenosine diphosphate (ADP-CT). These two cartridges have different sensitivity and specificity for different clinical situations. It is also necessary to duplicate the measurement. Duplicate analysis is associated with a mean coefficient of variation of 5.7% (ADP-CT) or 7.1% (EPI-CT). For complete evaluation of platelet function, it is advisable to perform a whole blood electrical aggregometry test, which is the gold standard for detecting platelet function defects or nucleotide release assays.

The authors1 stated that the normal limits of CT are hospital specific. It would have been useful to publish the upper limit of normal CT in the pregnant population in their hospital. It may not be appropriate to compare this patient's CT with a previously reported CT reference, which was not from their hospital. Thus, the significance of this comparison remained doubtful, especially when the patient did not experience any abnormal bleeding.

Currently, no evidence exists to suggest that regional anaesthesia techniques should be avoided in patients taking aspirin or other NSAIDs in therapeutic doses,3 even though these drugs can prolong the CT by as much as 63%.2 Many patients taking these medications may have a CT as high as 300 s, depending on the type of NSAIDs used.2 There is no evidence that the PFA can estimate the risk of haemorrhage in patients on platelet inhibitors. Neither platelet aggregation nor flow cytometry have been shown to have predictive value with regard to a haemorrhagic risk of antiplatelet agents. Nor are there any reported cases of spinal haematoma attributed to the use of aspirin or other NSAIDs. These drugs have been used for several years in a large number of surgical patients who have undergone epidural/spinal anaesthesia.

N. G. Mandal

Peterborough, UK


 
Editor—we thank you for the opportunity to reply to Dr Mandal. We are pleased that we have succeeded in our aim—to stimulate debate in this area.

We acknowledge that, because of the known reversible effects of ibuprofen, CT should remain unaffected. However, the CT measured was affected, and with the absence of any other clinical cause, we would disagree with Dr Mandal and suggest that it may have resulted from the overdose of ibuprofen.

We did not describe the precise measurement technique of the PFA-100® analyser, and we thank the respondent for the additional information that he has provided.

Dr Mandal is correct in saying that it would be useful to publish an upper limit of normal in the pregnant population of our hospital. However, it must be realized that this is not a common test, and although our hospital had reference ranges for the general population, it does not provide a subdivision for parturients. We did publish reference ranges for the pregnant population from another hospital which had comparable reference ranges for their non-pregnant population to ours.1

Dr Mandal, like many others, may not have agreed with the decision to have denied the patient an epidural. However, we suggest that the logic was plain: we sought clarification from an objective test, which indicated platelet dysfunction, therefore an epidural was denied.

The respondent is correct in his assertion that there is no evidence that the PFA-100® can estimate the risk of haemorrhage. The message that we are trying to convey is that there are dangers in performing tests on platelet function without clinical correlates of true haematoma risk. Our case is an illustration of this danger. The benefits of neuraxial techniques are being extended to a more diverse surgical population. These patients are prescribed an increasing amount of novel preparations that interact with the coagulation process. We need to search for as much information to aid us in what is, after all, a blind technique, and ultimately attempt to correlate results of useful investigations to clinical risk. To be clear, we are not advocating that the PFA-100® analyser is a useful test, we are merely attempting to expand the knowledge base by sharing our experience of it.

A. McGlennan, M. Esler, G. Stocks and V. Pandit

London, UK

References

1 McGlennan A, Esler M, Stocks G, Pandit V. PFA-100® and regional analgesia in a parturient after ibuprofen overdose. Br J Anaesth 2004; 92: 776–7[Free Full Text]

2 van Kraaij DJW, Hovestad-Witterland AHI, de Metz M, Vollaard EJ. A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers. Br J Clin Pharmacol 2002; 53: 644–7[CrossRef][ISI][Medline]

3 Mandal NG, Surapaneni S. Regional anaesthesia in pre-eclampsia. Drugs 2004; 64: 223–36[ISI][Medline]





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