Vitamin K

[Aznfarmerboi]

---

Members do not see this ad.

I have a patient with multiple problems. He is an 80 year old on mutiple meds. The main ones of importance is flagyl, digoxin, and warfarin.

He was recently given vitamin K because his inr was 3.66 (for warfarin). In addition, his hgb was going down so there was a high chance of him bleeding somewhere. My question is that if his ALT and AST are high, 600ish, but not in the thousand's range. . . , would vitamin K still be efficaous? Vitamin K works by activating clotting factors that is produced via liver. If the liver is near end stage, and cannot produce clotting factors; then how would the vitamin K work? The guidelines recommend that we hold the warfarin (since inr is only 3.66), but the patients HGB is going down.

PS. ALT and AST does not indicate liver disease but rather measures inflammation of the liver specifically.

Concerning the patient's digoxin, his serum concentration came back 0.4 ug/ml, and 0.1 ug/ml. He is being treated for CHF. I am concern about this because the patient was admitted into neurology recently for confused mental alertness, a good sign of digoxin toxicity. In addition, his potassium levels have been going way down in the last few days, (at 3.5 now). If this continues, i am afraid he will be hypokalemic tomorrow or the next day. Yet his serum levels are so low. . .and can be said subtherapeutic. I remember a few formulas to calculate digoxin based on the diseas state, but cant think of anything that would give me a false serum level 2-3 times. The patient isnt on any other medications that are potassium depleting (at least none that i saw).

Patient is also going through ESRD. His crcl is about 41 ml a few days ago, and recent tests show that it is about 35 now. Not there yet, but almost.

Any input is greatly valued.

 

[Moxxie]

Wow. Talk about a post for my case studies class! While I don't feel like I know enough to make any formal recommendations, I do have a couple of thoughts (I'd like to point out that these are all based on class notes/discussions - NOT on any personal experience in a clinical setting - I'm only a P2!):

1) Both his CHF and ESRD can really play havoc with Dig clearance/metabolism - they could be reduced by over 50%. So even if his serum levels are low, he isn't eliminating the dig very quickly, which could be contributing to toxicity.

2) I have a spot starred in my notes that even if a pt is on a therapeutic dose of dig, that they can go toxic (i.e. get an "augmented pharmacological response") if they are hypokalemic, and that Dig can sometimes make hypokalemia worse b/c of the way it affects Na/K transport (obviously,hehe).

3) Under my "factors associated with increased risk for toxicity" I have renal insufficiency, electrolyte abnormalities, advanced age and severe HF. It seems like we're hitting a lot of those on the nose.

So even though I am just a lowly P2, if this was a case in front of me, I'd probably start treating the pt for dig toxicity. I'd start K supplementation to fight that off as well. Also, I'd add FeSO4 as well to combat any hemolytic anemia.

I truthfully have no idea what to say about the Vit K.

Good luck! And if anyone with more experience than me (which would be just about everyone here) has better advice or thinks that my recommendations suck balls, feel free to correct me! 😀

 

[Moxxie]

Hmmm... I just looked up Vitamin K on micromedex (just one source, yeah, I know), and it said that Vit K isn't recommended to lower INR until the INR is b/w 4-10. I wonder if you should just withhold the warfarin and try to treat the underlying cause of his decreasing Hgb? (i.e. with Fe, B12, maybe even EPO?)

Just another thought.

 

[Priapism321]

I have a patient with multiple problems. He is an 80 year old on mutiple meds. The main ones of importance is flagyl, digoxin, and warfarin.

He was recently given vitamin K because his inr was 3.66 (for warfarin). In addition, his hgb was going down so there was a high chance of him bleeding somewhere. My question is that if his ALT and AST are high, 600ish, but not in the thousand's range. . . , would vitamin K still be efficaous? Vitamin K works by activating clotting factors which is produced via liver. If the liver is near end stage and cannot produce clotting factors; then how would vitamin K really work? Usual guidelines recommend that we hold the warfarin (since inr is only 3.66), but the patients HGB is going down.

PS. ALT and AST does not indicate liver disease but rather measures inflammation of the liver specifically.

Concerning the patient's digoxin, his serum concentration came back 0.4 ug/ml, and 0.1 ug/ml. He is being treated for CHF. I am concern about this because the patient was admitted into neurology recently for confused mental alertness, a good sign of digoxin toxicity. In addition, his potassium levels have been going way down in the last few days, (at 3.5 now). If this continues, i am afraid he will be hypokalemia tomorrow or the next day. Yet his serum levels are so low. . .and can be said subtherapeutic. I remember a few formulas to calculate digoxin based on the diseas state, but cant think of anything that would give me a false serum level 2-3 times. The patient isnt on any other medications that are potassium depleting (at least none that i saw).

Patient is also going through ESRD. His crcl is about 41 ml a few days ago, and recent tests show that it is more or less 35 now. Not there yet, but almost.

Any input is greatly valued.

1) His INR is not very high, what are other reasons for his hemoglobin to fall?
2) You have given no indication that his liver does not manufacture clotting factors.
3) You are afraid the patient will "be hypokalemia tomorrow (is this
english?)"
4) 80 year olds get confused
5) Give him 80 mEq of potassium; if the vitamin K works, his liver is functional. Hold the digoxin and see if this has an effect on mental status (I doubt it).

 

[Aznfarmerboi]

thank you, sorry. I meant hypokalemic.

I believe his INR isnt high because INR tests the extrinsic clotting factors (first indication that livers are not producing clotting factors). Vitamin K specifically works on the extrinsic pathway. .. (I believe; because extrinsic factors are the fast clotting pathway versus the slow intrinsic pathway. . . and vitamin K needs to work on the fast side to stop the bleeding). That is why I am wondering if vitamin K will be effective here or not. Yet HGB are going down meaning theres got to be some sort of bleeding (I dont see any other disease state for the decrease in hgb). Hence, should vitamin K be administer here, regardless of INR? I recommend to the doctor to hold the warfarin. He still wants to go with the vitamin K (which I got no problem, and would be interested to see what would happen when I go back on Monday).

I do agree 80 year old mental alertness may not be as high; and the diagnosis can go either way.

For the potassium, I alerted the doctor about it. The levels are still within border range right now (3.5). I am sure the doctor will put in the order tomorrow if it drops below that.

Thanks a lot moxie, your inputs were really helpful. I am looking into it right now.

 

[PharmaSynergy]

Interesting case. Here's a few more thoughts for consideration...

• Could be an acid/base disorder, considering his renal status (do we have his ABG values? Has he been treated recently for a metabolic acidosis? i.e., bicarb tx can lead to intracellular shift of K, hence hypokalemia. Any episodes of diarrhea or vomiting that you know of?
• Declining Hgb/Hct due to worsening anemia of chronic renal failure/ESRD
• Metronidazole/Warfarin drug interaction - metro increases the hypoprothrombinemic effect of warfarin
• Renal failure increases the free fraction of warfarin, hence greater effect
• Were there any other signs of bleeding? i.e., bruising, hematuria?
• Besides holding warfarin, might consider a 10-15% dose adjustment based on pt's age, renal function, metronidazole interaction (although I assume he'll be off that soon?)
• Mental confusion/alertness issues possibly related to his acid/base status
• As for the phytonadione (vitamin K), a small dose of 2.5 mg should restore INR to therapeutic range within 24 hrs. The clotting factors issue is interesting... although I believe it's just in cases of severe liver disease that vitamin K might not be effective (see Handbook of Clinical Drug Data: "No effect or worsening of hypoprothrombinemia can occur in severe liver disease, and repeated doses are not warranted if reponse to the initial dose is unsatisfactory.")

Good luck!

 

[group_theory]

Some questions for you to consider

1. Is the patient septic and going through multi-system organ failure? Why is the patient on flagyl?

2. How are you so sure that mental status change was due to digoxin toxicity? The differential for MS change in an 80 yo is HUGE, including but not limited to cerebral vascular events, sepsis, hepatic encephalopathy, etc.

3. Is his drop in hgb/hct an acute drop, an acute on chronic drop, his baseline? Is the patient receiving FFP?

4. Does he have underlying liver disease? How bad is his CHF? What is his underlying kidney disease?

Numbers are important but occasionally, step back and look at the patient and figure out what's going on ... then treat the underlying cause.

 

[JayneCobb]

Some questions for you to consider

Group has very good points. We need to treat the pt, and not the numbers. But as both Group and I are internists in training, we have far more questions than you guys have answers for so far.

To better put this story in context and give much more relevant discussion to this particular scenario, we need to know a few more things.

• A little more history on this acute mental status change, how sudden, any real neurological deficits? detail this part a little more might help us, and give us the history of the 3-4 days leading up to this presentation.
• How acute is the hgb drop? If it wasn't that sudden, I would have just held the coumadin, but if it was fairly brisk and I thought he was actively bleeding, he would have received FFP. There are a few other possibilities to the story as to why he's getting Vit K instead. As far as the Vit K with those LFTs, the fact that he's mounting a transaminitis would not lead me down the cirrhosis path that quick. The rest of his CMP would be helpfulf.
• why is he on coumadin in the first place
• what is his ejection fraction? Is his CHF all systolic dysfunction or is it a diastolic dysfunction. since he's on Dig and coumadin, I'm going to venture that the most likely guess is that he has a low EF and A-fib.
• If the renal dz is chronic, then by your numbers he's stage III-ish, not typically someone you'd see labeled as ESRD. And given that he is hypokalemic, that would seem to indicate that his kidneys do work enough for the dig to make the hypo-k worse. Is this an acute Renal insufficiency? What's his baseline CrCl?
• And why was he on flagyl? C-Diff colitis? and when was he put on Flagyl?
• Were there any medication changes?
• do you have the rest of his labs? CMP? UA? CBC? We do not need an ABG to find an acidosis, and there might be a few other clues as to why he's having multi organ problems.
• Vital signs?

While Dig toxicity is higher on my differential due to the picture you're painting, in someone this age, you have to think about what other potential multi-factorial issues are going on.

 

[PharmaSynergy]

Group has very good points. We need to treat the pt, and not the numbers. But as both Group and I are internists in training, we have far more questions than you guys have answers for so far.

...think about what other potential multi-factorial issues are going on.

Excellent advice and insights! 👍 I wish you guys would join our pharmacy forum discussions more often. It sure would be helpful if we had the answers to all those questions. Perhaps the OP can find out on Monday. 😉