plavix and platelet inhibition assay, neuraxial recs

[lakersbaby]

If you have a patient with severe COPD, OSA, CAD on plavix/asa. Been off plavix for 3 days continuing asa and platelet inhibition assay (PRU) is in the normal range would you feel comfortable doing a spinal anesthetic for a hip fracture even though it has not been the full 7 days?

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[IlDestriero]

If 10-15% of platelets are replaced each day, after 3 days the patient should have 30-45% new platelets circulating.
How would you feel about a spinal if the patient's platelets were ~1/3 of their lab value? Our oncologists will do a spinal for intrathecal chemo at >15, some want 30. If the assumption is the patient has an effective platelet count of 75+ and is high risk, it should be fine.

 

[BLADEMDA]

Br J Anaesth. 2011 Dec;107(6):966-71. doi: 10.1093/bja/aer298. Epub 2011 Oct 3.
Determination of residual antiplatelet activity of clopidogrel before neuraxial injections.
Benzon HT1, McCarthy RJ, Benzon HA, Kendall MC, Robak S, Lindholm PF, Kallas PG, Katz JA.
Author information

Abstract
BACKGROUND:
Guidelines recommend discontinuation of clopidogrel for 7 days before a neuraxial injection, while other directives suggest that 5 days might be adequate. We examined the time course of antiplatelet activity after clopidogrel discontinuation in patients undergoing epidural injections.

METHODS:
Thirteen patients were studied at baseline, 3, 5, and 7 days after discontinuation of clopidogrel. P(2)Y(12) determinations were performed using the VerifyNow(®) assay (Accumetrics, San Diego, CA, USA), and clot closure times with stimulation by collagen/epinephrine and collagen/adenosine diphosphate using the PFA-100(®) (Platelet Function Analyzer, Siemens Diagnostics, Deerfield, IL, USA). Repeated-measures ANOVA was used to evaluate P(2)Y(12) platelet reaction units, PFA-100 closure times, and per cent P(2)Y(12) inhibition values. Wilcoxon's signed-rank test was used to compare the frequencies of ≥30%, 11-29%, and ≤10% platelet inhibition between the baseline and subsequent sampling points after discontinuation of clopidogrel.

RESULTS:
On day 3 after clopidogrel discontinuation, two subjects had ≥30%, seven subjects had 11-29%, and four subjects had ≤10% platelet inhibition; the corresponding numbers were 0, 3, and 10 subjects on day 5 (P=0.04). There were no differences between the ≥30%, 11-29%, and <10% platelet inhibition groups between days 5 and 7 (0, 0, and 13 subjects, P=1.0). PFA-ADP closure times were normal throughout the study period except in one patient.

CONCLUSIONS:
These findings support the recommendation that discontinuation of clopidogrel for 5 days allows >70% of platelet function and might be adequate before a neuraxial injection is performed.

 

[BLADEMDA]

If you have a patient with severe COPD, OSA, CAD on plavix/asa. Been off plavix for 3 days continuing asa and platelet inhibition assay (PRU) is in the normal range would you feel comfortable doing a spinal anesthetic for a hip fracture even though it has not been the full 7 days?

5 days I would proceed with the SAB. At 3 days I would need the Verify Now PRU and the PFA 100 tests in addition to a large set of balls.

 

[lakersbaby]

PRU on day of surgery was in the 250-260 range which I believe corresponds to only < 10% inhibition? Not sure but guy was severe COPD sat 87% on RA, CAD - s/p CABG along with 10 cardiac stents in the last 4 years. Heavy smoker, morbidly obese, OSA.

Guy could not move at all because of 10/10 pain. Did a fascia iliaca block in preop with 0.5% bupivicaine, was able to go lateral in OR, spinal was done with 15mg isobaric bupi. Done and done. Did have to have big balls because he was pretty fat and I didn't think he would be an easy spinal but basically got lucky with the first pop.

 

[BLADEMDA]

http://www.itcmed.com/uploads/literature/vn-pocketguide_us.pdf

While I'm all for the use of the Verify now test to perform Neuraxial anesthesia I doubt many would do an SAB just 3 days after stopping Plavix. I assume if you would do a SAB after being off plavix for 3 days then why not do the SAB if the patient took Plavix that morning? After all, you are relying on the same test to show whether there is platelet inhibition.

I'm certainly not criticizing lakersbaby for doing the SAB but rather pointing out the uncertainty of relying on that test to perform a spinal anesthetic.

(Residual Clopidogrel Responsiveness Within 3 days, > 50% of patients no longer have antiplatelet effect)

 

[BLADEMDA]

Okay, so our ASRA guidelines say 7 days for Plavix in order to do an SAB. But, some (like myself) would do a SAB in a patient off Plavix for 5 days if the Verify Now test was normal.

Would you do the SAB if off Plavix for 3 days without a Verifynow test provided the Platelet count was normal? Well, the guys at Belfast hospital Ireland do just that.


http://onlinelibrary.wiley.com/doi/10.1111/anae.12105/full

 

[BLADEMDA]

Table 6. Belfast Hospitals Trust Guideline for all patients with hip fracture taking clopidogrel

1. Document the indication for taking clopidogrel. If coronary stent insertion in the previous year, contact cardiology for further advice. Otherwise, discontinue clopidogrel and document the reasons (reduced risk of blood loss and neuraxial haematoma, ability to transfuse platelets after 24 h). For patients on dual aspirin and clopidogrel therapy, continue aspirin.
2. Document the date and time of last dose of clopidogrel.
3. Document the full blood picture and coagulation screen.
4. Commence routine thromboprophylaxis with low-molecular weight heparin.
5. If not contraindicated, proceed to surgery under general anaesthesia 24 h after last clopidogrel dose. If excessive bleeding occurs, transfuse one pooled bag of platelets.
6. If general anaesthesia is contraindicated in high-risk group, consider surgery under spinal anaesthesia after 24 h with transfusion of one pooled bag of platelets 1 h pre-operatively.
7. Alternatively, consider waiting 72 h after last dose of clopidogrel and perform spinal anaesthesia with no platelet cover in low-risk group.
8. Recommence clopidogrel on the first morning following surgery provided there is a definite indication for its administration.
9. If excessive bleeding is expected due to surgical procedure or other coagulation abnormality, consider intravenous tranexamic acid 15 mg.kg−1 at induction of anaesthesia and 3 h later.

 

[BLADEMDA]

To the Editor:

We describe the usefulness of the PFA II and P2Y12 assays in determining the residual antiplatelet activity of clopidogrel when neuraxial block is planned. The patient was a 68-year-old man who sustained a left femoral neck fracture and was scheduled for a hemiarthroplasty of the left side of the hip. He had a history of failed intubation because of his ankylosing spondylitis and placement of 3 bare metal coronary artery stents. He has been taking 75 mg of clopidogrel and 81 mg of aspirin daily since stent placement. The clopidogrel and aspirin were stopped 5 days before the surgery, although the patient was administered aspirin on the day of the surgery. Physical examination showed severely limited range of motion of his neck. His platelet count was 235,000/μL. The PFA II result was 87 seconds (reference range, 41-134 seconds). The P2Y12 assay showed 8% platelet inhibition and a platelet reaction unit (PRU) of 250 (reference range, 194-418). We performed spinal anesthesia with 12 mg of hyperbaric bupivacaine, which resulted in a sensory level of T4. He was brought to the post anesthesia care unit with a sensory level of T5, and there was complete sensory and motor recovery 3.5 hrs later. There was no bruising at the site of the spinal anesthesia, and the rest of his recovery was uneventful.

The American Society of Regional Anesthesia consensus guidelines recommend the discontinuation of clopidogrel for 7 days before a neuraxial injection. There is a case report of a caudal steroid injection 5 days after discontinuation of the clopidogrel; no test of platelet activity was performed before the injection.1 In our patient, we performed a spinal anesthesia in view of the 8% platelet inhibition and a P2Y12 PRU that showed no residual antiplatelet activity of the clopidogrel. The numbers representing residual platelet reactivity (≥68 seconds for the PFA II and ≥264 P2Y12 PRU for the P2Y12 assay) were determined in 1267 patients by comparing the 2 assays with the light transmission aggregation test, the standard test for the determination of antiplatelet activity of drugs.2 It was also noted that there was a better correlation of the P2Y12 assay with light transmission aggregation than the PFA test.2 The PFA test cost $154.00, whereas the P2Y12 assay costs $459.00. Another test, the platelet mapping portion in the thrombelastography, has been used, but limitations in its clinical usefulness have been noted.3 Our 1 case of an uneventful spinal anesthesia does not guarantee the safety of neuraxial injections 5 days after clopidogrel is stopped. If a neuraxial injection has to be performed before 7 days after clopidogrel is stopped, then either the PFA II or the P2Y12 assay, preferably the P2Y12 assay if available, should be considered to determine the residual antiplatelet activity of clopidogrel. Further studies are required to determine the clinical appropriateness of these tests.

Honorio T. Benzon, MD

Robert Fragen, MD

Hubert A. Benzon, MD

Jason Savage, MD

Jennifer Robinson, CRNA

Lalit Puri, MD

Departments of Anesthesiology and

Orthopaedic Surgery

Northwestern University

Feinberg School of Medicine

Chicago, IL

 

[BLADEMDA]

Clopidogrel: Metabolism, Mechanism of Action and Indications

Despite the difficulty of interpreting the results in the literature, it appears that currently between 5% and 9% of patients with hip fracture are taking clopidogrel [14-17].

Clopidogrel is absorbed via the intestine and metabolized in the liver cells to convert it in active form. This process involves several enzymes, including those in the cytochrome P450 pathway. Clopidogrel covalently binds to the structure of the platelet P2Y12 receptor, which is inactivated throughout the platelet’s lifetime [18]. The recovery of platelet activity after discontinuation of clopidogrel treatment is gradual and requires platelet renewal. According to Metzler et al. [19], 53% of patients recover platelet function within three days of treatment withdrawal, and 85% of patients within five days.

The absorption and metabolism of clopidogrel are subject to genetic factors, and so the drug’s bioavailability and activity vary widely. In addition, age, certain pathologies and the use of certain drugs which are metabolized by the same enzyme pathway further increase the biological variation [20,21].

The laboratory tests that are currently available to measure platelet function in response to antiplatelet agents are not sufficiently sensitive for routine use in clinical practice.

Clopidogrel is prescribed for the prevention of cardiac, cerebrovascular and peripheral vascular disorders. Its action can only be reversed with platelet transfusion, and its withdrawal increases the risk of thromboembolism [1,22].

http://www.esciencecentral.org/jour...g-clopidogrel-2329-8790.1000141.php?aid=26643

 

[teeva]

I follow guidelines. They're not standard of practice, but they're easy to follow, require little thought process, and let me sleep comfortably at night. Those with smarter minds can do the science and research, and change the guidelines as needed.

 

[GaseousClay]

I follow guidelines. They're not standard of practice, but they're easy to follow, require little thought process, and let me sleep comfortably at night. Those with smarter minds can do the science and research, and change the guidelines as needed.

A guideline is a "guide" it is not an absolute. Sometimes you have to use clinical judgement and in this case I think with the plavix assay the decision was a justifiable one given the patients comorbid conditions. pretty weaksauce statement teeva

 

[Consigliere]

Okay, so our ASRA guidelines say 7 days for Plavix in order to do an SAB. But, some (like myself) would do a SAB in a patient off Plavix for 5 days if the Verify Now test was normal
Well, the guys at Belfast hospital Ireland do just that.


http://onlinelibrary.wiley.com/doi/10.1111/anae.12105/full

Well, the guys in Belfast, Ireland are in a completely differenct malpractice environment than the guys in the USA.

 

[Consigliere]

You guys do whatever floats your boat. Hopefully you'll never have a patient develop an epidural/spinal hematoma with subsequent paralysis after waiting 5 days after Plavix discontinuation. If it happens though, there will be some smarmy lawyer projecting the ASRA guidelines 5 feet tall and wide in the courtroom asking you why you did a spinal.

 

[Hoya11]

You guys do whatever floats your boat. Hopefully you'll never have a patient develop an epidural/spinal hematoma with subsequent paralysis after waiting 5 days after Plavix discontinuation. If it happens though, there will be some smarmy lawyer projecting the ASRA guidelines 5 feet tall and wide in the courtroom asking you why you did a spinal.

agree with the above. guidelines dont directly support it, they are 7 days for a reason, so dont do it. Especially for a case that can easily be done under general. AND with a block, whats the point of doing the spinal? Prob cause FI blocks suck. Hard to piece all of the reasoning together here. Just tube the guy. Laboring woman where baby's fate matters, probably do the spinal.

 

[BLADEMDA]

agree with the above. guidelines dont directly support it, they are 7 days for a reason, so dont do it. Especially for a case that can easily be done under general. AND with a block, whats the point of doing the spinal? Prob cause FI blocks suck. Hard to piece all of the reasoning together here. Just tube the guy. Laboring woman where baby's fate matters, probably do the spinal.

Evidence supports the use of SAB after discontinuing Plavix for 5 days provided the Verify now test shows no platelet inhibition. The science behind 5 days makes perfect sense especially when combined with the Verify now test.

I'll continue to follow this routine in all patients where the risks/benefits of an SAB make sense over a GA. Fortunately, the number I encounter is small and I have done this only twice in my practice. As for being off Plavix for 3 days followed by an SAB I won't be going down that road regardless of the platelet inhibition test. Those patients will get a GA.

 

[lobelsteve]

Evidence supports the use of SAB after discontinuing Plavix for 5 days provided the Verify now test shows no platelet inhibition. The science behind 5 days makes perfect sense especially when combined with the Verify now test.

I'll continue to follow this routine in all patients where the risks/benefits of an SAB make sense over a GA. Fortunately, the number I encounter is small and I have done this only twice in my practice. As for being off Plavix for 3 days followed by an SAB I won't be going down that road regardless of the platelet inhibition test. Those patients will get a GA.

Reviewing the literature for pain blocks in the epidural space as well as epidural anesthesia, the risk is only 1/3000 for epidural hematoma after epidural procedure while on Plavix. The generally accepted risk for epidural hematoma while not on Plavix is 1/150,000.

We start with a low risk no matter what (1/3000). Realizing that risk in the hospital can lead to surgery if noted in time, but as an outpatient is more likely to lead to delay in Dx and paralysis. To take the risk is a clinical decision and to realize the risk is going to get you malpractice suit that might be winnable. But ultimately you have to make that decision on a case by case scenario.

 

[lakersbaby]

i understand and appreciate all your points. I don't really disagree with any of you but I really felt this guy was super high risk of a downward spiral. He's had 4 separate thrombotic events of his stents. He looked like one of the unhealthiest people out there. I thought long and hard about it and I discussed with surgeon and patient all the concerns and my thought was that if spinal turned out to be difficult then GA was going to be the way to go. Luckily things worked out great for this case. I made a judgement call and I think it was justifiable and I don't really regret it. That doesn't mean I am a cowboy; I agree with all the guidelines we have, but sometimes you have to do what you think is right for the pt.

 

[BLADEMDA]

i understand and appreciate all your points. I don't really disagree with any of you but I really felt this guy was super high risk of a downward spiral. He's had 4 separate thrombotic events of his stents. He looked like one of the unhealthiest people out there. I thought long and hard about it and I discussed with surgeon and patient all the concerns and my thought was that if spinal turned out to be difficult then GA was going to be the way to go. Luckily things worked out great for this case. I made a judgement call and I think it was justifiable and I don't really regret it. That doesn't mean I am a cowboy; I agree with all the guidelines we have, but sometimes you have to do what you think is right for the pt.

I'm curious as to your rationale behind the decision. You trust the Verify now/PRU that much to base your clinical decision on it? Sure, the odds are overwhelmingly in your favor that nothing bad would happen as a result of the SAB but 3 days is aggressive. I like it. But, here in my part of the woods, I doubt many would do the same due to the aggressive malpractice lawyers. The ACA hasn't changed that reality for me one bit.