Clinical Question of the Day 4/24

[Prolab007]

You have a 50 YO pt receiving chemotherapy (R-CHOP) in the hospital. Hospitalized cancer patients should be on VTE prophy because of hypercoagable state and therefore patient is on Lovenox 30mg daily ( Crcl <30) for DVT prophylaxis. Platelets went from 150k to 60k. Do you suspect HIT? Or is it from chemo? Antibodies come back positive. How would you work up patient from here...

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[UES Girl]

You currently have a patient 50 YO pt receiving chemotherapy (R-CHOP) and is in the hospital. Hospitalized cancer patients should be on VTE prophy because of hypercoagable state and therefore patient is on Lovenox 30mg daily ( Crcl <30) for DVT prophylaxis. Platelets went from 150k to 60k. Do you suspect HIT? Or is it from chemo? Antibodies come back positive. How would you work up patient from here...

hehe. Are you still my patients ? This was literally one of my patients couple weeks ago.

 

[rxlea]

When was the first dose given? Did they have heparin before? How fast did the platelets drop? When was chemo given? Other S/S?

 

[xiphoid2010]

You have a 50 YO pt receiving chemotherapy (R-CHOP) in the hospital. Hospitalized cancer patients should be on VTE prophy because of hypercoagable state and therefore patient is on Lovenox 30mg daily ( Crcl <30) for DVT prophylaxis. Platelets went from 150k to 60k. Do you suspect HIT? Or is it from chemo? Antibodies come back positive. How would you work up patient from here...

What are the 4 T's of HIT? (Does the picture fit?)
What are the 2 tests for HIT and which one is the gold standard?

 

[PharmDstudent]

Hopefully everyone realizes that we all go/went to different pharmacy schools, so the abbreviations in these "clinical" threads are hindering discussion, i.e. I have no idea what S/S means, what the 4 T's are, what picture?, etc.?!... never heard of any of these - in my life!

 

[rxlea]

Hopefully everyone realizes that we all go/went to different pharmacy schools, so the abbreviations in these "clinical" threads are hindering discussion, i.e. I have no idea what S/S means, what the 4 T's are, what picture?, etc.?!... never heard of any of these - in my life!

Signs and symptoms.

The 4 T's are pretty standard, though. This guy has 2 points for the first T but we need info about when the dose was given and if they had heparin before that.

EDIT: lovenox is less likely to induce HIT than regular heparin but we don't know if he was on heparin before and was bridged or what. Prior heparin exposure increases the risk.

 

[awval999]

Hopefully everyone realizes that we all go/went to different pharmacy schools, so the abbreviations in these "clinical" threads are hindering discussion, i.e. I have no idea what S/S means, what the 4 T's are, what picture?, etc.?!... never heard of any of these - in my life!

Students/pharmacists think they are cool when they use abbreviations. Even though JCAHO and CMS very much dislike them and it has been shown in substantially increase errors. But its cool amirite? I'm a big kid with abbreviations.

 

[rxlea]

Students/pharmacists think they are cool when they use abbreviations. Even though JCAHO and CMS very much dislike them and it has been shown in substantially increase errors. But its cool amirite? I'm a big kid with abbreviations.

It's not really a "be cool" thing. More of a time thing. Per Joint Commission:

A. Any reasonable approach to standardizing abbreviations, acronyms, and symbols is acceptable.
Examples include:

• Standardized abbreviations developed by the individual organization.
• Use of a published reference source. However, if multiple abbreviations, symbols or acronyms are used for the same term, the organization identifies what will be used to eliminate any ambiguity.
• A decision that individuals who work in the organization may use any abbreviation, acronym, or symbol that is not on the list of unacceptable abbreviations. However, if multiple abbreviations, symbols, or acronyms exist for the same term, the organization identifies what will be used to eliminate ambiguity.

We use S&S. Do you have anything to add to the clinical discussion?

 

[Praziquantel86]

Students/pharmacists think they are cool when they use abbreviations. Even though JCAHO and CMS very much dislike them and it has been shown in substantially increase errors. But its cool amirite? I'm a big kid with abbreviations.

"4Ts" is actually what the scoring system is called, there is simply nothing else to call it. S/S I'll agree with, though.

To answer the question, you're placed in a tough positition by having that antibody sent (although do you know what type of test it was? IgM vs. pooled Ig? What was the optical density?). The patient scores at least a 2 on the 4Ts system, although we don't know the timing, so it could very well be higher.

Still, having a false-positive antibody test is far less common in the medical population than in surgical, so I have a much higher suspicion that this is something worth considering. I think having the positive test really seals the deal - you have to treat. With poor renal function, I'd probably reach for the bivalirudin and send off an SRA.

 

[janeno]

Couple of questions:
1. When was enoxaparin initiated and when did they observe fall in Plts? When was R-CHOP given?
2. Does the patient have any skin lesions? Was ultrasound performed to rule out thrombosis? What type of cancer is patient getting treatment for?

Based on the given information, HIT cannot be ruled out. I would like to see SRA. In the meantime, it would be reasonable to use argatroban for DVT prophylaxis due to poor renal function. Personally, I avoid using enoxaparin for DVT prophylaxis in patients with CrCl < 30 ml/min.

 

[ucrx]

To answer the previous poster, typically R-CHOP is given for lymphomas.

I also would like to know when chemo was started and how long the patient has been on enoxaparin. Other things to consider: what are the rest of their counts doing? How likely is significant thrombocytopenia with R-CHOP?

Could someone go through the 4ts for people who don't know it? A little hard on my cell.

Is anyone concerned about giving a dti to a patient whose counts are falling?

 

[janeno]

To answer the previous poster, topically R-CHOP is given for lymphomas.

I also would like to know when chemo was started and how long the patient has been on enoxaparin. Other things to consider: what are the rest of their counts doing? How likely is significant thrombocytopenia with R-CHOP?

Could someone go through the 4ts for people who don't know it? A little hard on my cell.

Is anyone concerned about giving a dti to a patient whose counts are falling?

Brief review of HIT: http://en.wikipedia.org/wiki/Heparin-induced_thrombocytopenia

For more in-depth discussion, feel free to pull articles. There are some excellent ones out there.

It would be interesting to see daily trend of PLTs. Typically, DVT prophylaxis contraindicated if PLTs < 30 but PLTs 30 to 50 reaches a gray zone - need risk vs benefit analysis.

 

[Ackj]

Students/pharmacists think they are cool when they use abbreviations. Even though Joint Commission on Accreditation of Healthcare Organizations and Centers for Medicare and Medicaid Services very much dislike them and it has been shown in substantially increase errors. But its cool amirite? I'm a big kid with abbreviations.

fify

Errr... fixed it for you.

 

[Ackj]

4Ts:
Thrombocytopenia - drop >50% is 2 points, 30-50% is 1 point
Timing - onset between 5-10 days or platelet fall <1 day is 2 points
Thrombosis - new thrombosis or skin necrosis is 2 points, progression or suspected thrombosis is 1
Other causes for thrombocytopenia - 2 points if none, 1 point for maybe, 0 points for another clear cause

Then you add up your points, 6-8 is high chance, 4-5 is intermediate, 3 or less low chance. Still not sure how they count the last one as a T, but I guess it's easier to say 4Ts than 3Ts and an O. Maybe it stands for "That's not why they have thrombocytopenia"

 

[owlegrad]

fify

Errr... fixed it for you.

4Ts:
Thrombocytopenia - drop >50% is 2 points, 30-50% is 1 point
Timing - onset between 5-10 days or platelet fall <1 day is 2 points
Thrombosis - new thrombosis or skin necrosis is 2 points, progression or suspected thrombosis is 1
Other causes for thrombocytopenia - 2 points if none, 1 point for maybe, 0 points for another clear cause

Then you add up your points, 6-8 is high chance, 4-5 is intermediate, 3 or less low chance. Still not sure how they count the last one as a T, but I guess it's easier to say 4Ts than 3Ts and an O. Maybe it stands for "That's not why they have thrombocytopenia"

 

[Its Z]

Its no longer called the JCAHO. Now its simply called TJC. The Joint Commission.

Hth

 

[PharmDstudent]

Students/pharmacists think they are cool when they use abbreviations. Even though JCAHO and CMS very much dislike them and it has been shown in substantially increase errors. But its cool amirite? I'm a big kid with abbreviations.

I'd have to agree... or they're just too lazy.

It's not really a "be cool" thing. More of a time thing.

Computers may think in code (1's and 0's), but humans think in words, so translating code into words will take longer.

When was enoxaparin initiated and when did they observe fall in Plts?

^this

fify

Errr... fixed it for you.

acronyms &#8800; abbreviations, that is an abbreviation is not necessarily an acronym

Its no longer called the JCAHO. Now its simply called TJC. The Joint Commission.

Hth

or "Joint Commission"

 

[rxlea]

Fine. I will type out signs and symptoms just for you since it's such an issue. And I'm not lazy, believe me.

Now where is the original poster to answer our questions?

 

[gotdrugs]

4Ts:
Thrombocytopenia - drop >50% is 2 points, 30-50% is 1 point
Timing - onset between 5-10 days or platelet fall <1 day is 2 points
Thrombosis - new thrombosis or skin necrosis is 2 points, progression or suspected thrombosis is 1
Other causes for thrombocytopenia - 2 points if none, 1 point for maybe, 0 points for another clear cause

Then you add up your points, 6-8 is high chance, 4-5 is intermediate, 3 or less low chance. Still not sure how they count the last one as a T, but I guess it's easier to say 4Ts than 3Ts and an O. Maybe it stands for "That's not why they have thrombocytopenia"

Warkentin came up with it, he did this for the "last T"

oTher

Like you said, easier to remember - if you don't buy it, look at his original papers on it from the early 2000's

 

[Prolab007]

When was the first dose given? Did they have heparin before? How fast did the platelets drop? When was chemo given? Other S/S?

First dose given 10 days ago. No prior heparin. HIT anitbodies come back as positive. Platelets went down on Day 15 of chemo initiation. Over the 10 day course of Lovenox...the platelets dropped.

 

[Prolab007]

Couple of questions:
1. When was enoxaparin initiated and when did they observe fall in Plts? When was R-CHOP given?
2. Does the patient have any skin lesions? Was ultrasound performed to rule out thrombosis? What type of cancer is patient getting treatment for?

Based on the given information, HIT cannot be ruled out. I would like to see SRA. In the meantime, it would be reasonable to use argatroban for DVT prophylaxis due to poor renal function. Personally, I avoid using enoxaparin for DVT prophylaxis in patients with CrCl < 30 ml/min.

Patient being treated for NHL. Facility does not offer SRA. Only Elisa which shows positive.

What is the dose of Argatroban for prophylaxis?

 

[Prolab007]

Fine. I will type out signs and symptoms just for you since it's such an issue. And I'm not lazy, believe me.

Now where is the original poster to answer our questions?

Sorry for delay.

 

[PharmDstudent]

First dose given 10 days ago. No prior heparin. HIT anitbodies come back as positive. Platelets went down on Day 15 of chemo initiation. Over the 10 day course of Lovenox...the platelets dropped.

Why was Lovenox chosen over warfarin with that renal function?

What is the chemo cycle? How much and how often are they getting it?

 

[confettiflyer]

Why was Lovenox chosen over warfarin with that renal function?

You'd still need the bridge until warfarin becomes therapeutic if you go that route. But pretty sure enoxaparin was chosen because of better outcomes in ca. pt's. You can always just dose adjust based on renal function anyway.

An aside on shorthand...I've always used s/s (or s/sx) and 4T's, this was at 3 different health systems while on rotation. Could be a regional thing. The only one that was "odd" was "Px" (prophylaxis).

 

[confettiflyer]

Patient being treated for NHL. Facility does not offer SRA. Only Elisa which shows positive.

What is the dose of Argatroban for prophylaxis?

1mg/kg/min but you titrate to an aPTT of 2-3x baseline. Then you can bridge to warfarin but depending on the pt, I've seen clinicians opt to continue to discharge to the chagrin of our purchasing tech. Also assuming this pt isn't critically ill (on the wards?)

Not familiar w/ bivalirudin, but isn't it renally cleared? This pt doesn't appear to have any hepatic dys. but renal might be an issue.

 

[Prolab007]

Why was Lovenox chosen over warfarin with that renal function?

What is the chemo cycle? How much and how often are they getting it?

R-CHOP every 3 weeks for 8 cycles

 

[Momus]

Students/pharmacists think they are cool when they use abbreviations. Even though JCAHO and CMS very much dislike them and it has been shown in substantially increase errors. But its cool amirite? I'm a big kid with abbreviations.

Hey, I recognize your avatar name from boglehead! lol

 

[Praziquantel86]

1mg/kg/min but you titrate to an aPTT of 2-3x baseline. Then you can bridge to warfarin but depending on the pt, I've seen clinicians opt to continue to discharge to the chagrin of our purchasing tech. Also assuming this pt isn't critically ill (on the wards?)

Not familiar w/ bivalirudin, but isn't it renally cleared? This pt doesn't appear to have any hepatic dys. but renal might be an issue.

Bivalirudin is 80% enzymatically metabolized (by thrombin), 20% renally. We can dose adjust a monitor aPTT (same as we would with argatroban), so renal elimination isn't too great a concern. We get much better contract pricing on bivalirudin, so it's really our workhorse agent.

Transitioning to warfarin would be an absolute PITA in this patient, but I'll let others get into the reasons why.

 

[PharmDstudent]

Transitioning to warfarin would be an absolute PITA in this patient, but I'll let others get into the reasons why.

Prednisone + warfarin is a "significant drug interaction" where prednisone more rapidly metabolizes warfarin... but you can still monitor the patient.



Stupid blue dog. Can't you find a legitimate artist and not one that makes up bull**** about being inspired by the loup garou? It's one thing to want to paint a sad, dead, dog the color blue, but it's another thing to paint blue dogs and then say they're inspired by the loup garou. What a sham!

 

[Praziquantel86]

Prednisone + warfarin is a "significant drug interaction" where prednisone more rapidly metabolizes warfarin... but you can still monitor the patient.



Stupid blue dog. Can't you find a legitimate artist and not one that makes up bull**** about being inspired by the loup garou? It's one thing to want to paint a sad, dead, dog the color blue, but it's another thing to paint blue dogs and then say they're inspired by the loup garou. What a sham!

That's not the reason why it would be a PITA - prednisone is the least of our worries.

And I happen to like my blue dog on a motorcycle, thank you!

 

[janeno]

1mg/kg/min but you titrate to an aPTT of 2-3x baseline. Then you can bridge to warfarin but depending on the pt, I've seen clinicians opt to continue to discharge to the chagrin of our purchasing tech. Also assuming this pt isn't critically ill (on the wards?)

Not familiar w/ bivalirudin, but isn't it renally cleared? This pt doesn't appear to have any hepatic dys. but renal might be an issue.

My source states initial dosing of 2 mcg/kg/min.

 

[psychoandy]

I think you guys need to review the difference between milligrams and micrograms...not snark but that is a huge Med error waiting to happen.

 

[janeno]

Bivalirudin is 80% enzymatically metabolized (by thrombin), 20% renally. We can dose adjust a monitor aPTT (same as we would with argatroban), so renal elimination isn't too great a concern. We get much better contract pricing on bivalirudin, so it's really our workhorse agent.

Transitioning to warfarin would be an absolute PITA in this patient, but I'll let others get into the reasons why.

Once an alternative anticoagulation therapy has been started, overlapping warfarin with a DTI or alternative anticoagulant should continue for a minimum of 4 to 5 days and until the INR is > 2.0 for 2 consecutive days. This is to ensure the adequate reduction of levels of the vitamin K-dependent procoagulant factors II, VII, IX, and X. Patients receiving the DTI argatroban (and, to a lesser extent, lepirudin) will observe that these agents prolong the level of the INR. This can lead to challenges during the transition to warfarin therapy.435 The argatroban package insert advises overlapping with warfarin for a minimum of 4 to 5 days, aiming for an INR of &#8805; 4.0. Once this level is attained, argatroban therapy should be discontinued, and testing of the INR should be repeated approximately 4 to 6 h later to ensure that it remains within the therapeutic range. It also may be advisable to check an INR once lepirudin therapy has been discontinued, although no recommendation is made in the package insert. It must be stressed that the overlap of therapy with both a DTI and warfarin must occur for a minimum of 4 to 5 days.

 

[confettiflyer]

I think you guys need to review the difference between milligrams and micrograms...not snark but that is a huge Med error waiting to happen.

my "c" key was sticky

My source states initial dosing of 2 mcg/kg/min.

our institution guidelines are 1-2 mcg/kg/min, less if they're critically ill.

Bivalirudin is 80% enzymatically metabolized (by thrombin), 20% renally. We can dose adjust a monitor aPTT (same as we would with argatroban), so renal elimination isn't too great a concern. We get much better contract pricing on bivalirudin, so it's really our workhorse agent.

Yeah our angiomax just sits on the shelf, we get argatroban orders 2x/month tops and angiomax gets used once every 6-8 months. it's an option for clinicians if the pt is hepatically compromised.

 

[Praziquantel86]

Yeah our angiomax just sits on the shelf, we get argatroban orders 2x/month tops and angiomax gets used once every 6-8 months. it's an option for clinicians if the pt is hepatically compromised.

Really? Y'all should look into pricing on that.

Plus I think bivalirudin is easier to manage - shorter half life, less effect on the INR. Granted, it's never been studied formally for the treatment of acute HIT, but the literature for argatroban and lepirudin isn't enough to convince me that they're the better options.

 

[confettiflyer]

Really? Y'all should look into pricing on that.

Plus I think bivalirudin is easier to manage - shorter half life, less effect on the INR. Granted, it's never been studied formally for the treatment of acute HIT, but the literature for argatroban and lepirudin isn't enough to convince me that they're the better options.

You've got PM

It's a comfort thing, our clinicians are comfortable managing the INR bump and are entirely too comfortable w/ argatroban in general.

and +1 for the lit on the agents, granted we're boxed into a corner w/ HIT in terms of options.

 

[CUpharmD2013]

Once an alternative anticoagulation therapy has been started, overlapping warfarin with a DTI or alternative anticoagulant should continue for a minimum of 4 to 5 days and until the INR is > 2.0 for 2 consecutive days. This is to ensure the adequate reduction of levels of the vitamin K-dependent procoagulant factors II, VII, IX, and X. Patients receiving the DTI argatroban (and, to a lesser extent, lepirudin) will observe that these agents prolong the level of the INR. This can lead to challenges during the transition to warfarin therapy.435 The argatroban package insert advises overlapping with warfarin for a minimum of 4 to 5 days, aiming for an INR of &#8805; 4.0. Once this level is attained, argatroban therapy should be discontinued, and testing of the INR should be repeated approximately 4 to 6 h later to ensure that it remains within the therapeutic range. It also may be advisable to check an INR once lepirudin therapy has been discontinued, although no recommendation is made in the package insert. It must be stressed that the overlap of therapy with both a DTI and warfarin must occur for a minimum of 4 to 5 days.

Good response, but you forgot that you don't want to start the warfarin until the platelets have recovered to >150k.

 

[janeno]

I just posted this from an article...

 

[psychoandy]

Transitioning to warfarin would be an absolute PITA in this patient, but I'll let others get into the reasons why.

transition to warfarin -> get a couple chromogenic factor X, nbd unless its a sendout

my "c" key was sticky

our institution guidelines are 1-2 mcg/kg/min, less if they're critically ill.

Yeah our angiomax just sits on the shelf, we get argatroban orders 2x/month tops and angiomax gets used once every 6-8 months. it's an option for clinicians if the pt is hepatically compromised.

its all good, i just wanted to stress that it's really important to know the right dose due to the complicated dosing. moreso if using paper orders, no decision support, "freetexting" titration/dose ranges, etc.

i would definitely much rather use bivalirudin over lepirudin in liver dz but due to unfamiliar dosing it doesn't really fly in my institution (even though we have a cath lab that uses plenty of it...). lots of posters at midyear regarding cost savings with bivalirudin. the problem is, once you mention the slight renal dosing with attendings, nooooope. i don't get it

 

[awval999]

Hey, I recognize your avatar name from boglehead! lol

It's me. I enjoy the every other month postings of 26 year olds that make $125k that want to go back to medical school and ask the bogleheads for advice. The bogleheads always try to guess their profession (the OP never gives it). I know from the start. A retail pharmacist. Always. Good times.

 

[Praziquantel86]

Good response, but you forgot that you don't want to start the warfarin until the platelets have recovered to >150k.

Why might that be a difficult to do in this patient?

transition to warfarin -> get a couple chromogenic factor X, nbd unless its a sendout



its all good, i just wanted to stress that it's really important to know the right dose due to the complicated dosing. moreso if using paper orders, no decision support, "freetexting" titration/dose ranges, etc.

i would definitely much rather use bivalirudin over lepirudin in liver dz but due to unfamiliar dosing it doesn't really fly in my institution (even though we have a cath lab that uses plenty of it...). lots of posters at midyear regarding cost savings with bivalirudin. the problem is, once you mention the slight renal dosing with attendings, nooooope. i don't get it

That's why it has to be done at a P&T level - individual attendings aren't familiar with it for this indication in most cases, and will always reach for argatroban because it's "the" drug for this indication. Once you present the cost savings and propose a titration protocol with initial renal dosage, you're good to go. It also helps to have hematology on board as backup when you, the pharmacist, are questioned.

 

[PharmDstudent]

That's not the reason why it would be a PITA - prednisone is the least of our worries.

And I happen to like my blue dog on a motorcycle, thank you!

OK. Good. But I would think it would be a problem, because of the disruptive chemo cycle.

I'm sick and tired of seeing it all over this state... My old neighbors founded the Art Market in NOLA, and they have me convinced that the artist is a big liar.

Good response, but you forgot that you don't want to start the warfarin until the platelets have recovered to >150k.

...which is basically where the patient was to begin with...

It seems to me that if you have a therapy that could put the patient at risk for low platelets, like chemo!, then you shouldn't use a heparin-based therapy for treatment or prophylaxis because of the risk of HIT. Talk about risk and stacking up the odds against you. But maybe that's just my lowly, simpleton, retailer point-of-view.