Recent Case

[Ronin786]

Figured I would share this recent case.

61yo M with history of ESLD, HRS and ESRD on MWF dialysis, Afib (rate controlled, but not on anticoagulation) and COPD on 3L of home O2. Fell at his nursing home and broke his hip. Ortho has him booked for a hemi-arthroplasty.

INR is 2.0 and PLT count is 67. Hgb is 7.5. Patient is being given Vitamin K to reverse INR prior to scheduled case tomorrow.

What's your plan?

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[Noyac]

Bam. Easy. Can do it in my sleep. Which, by the way, usually is when I get called for these cases.
But I'll stop here and let the youngsters reply.

 

[vector2]

Dialyze before OR if it's a sunday case. RSI with phenylephrine, prop, sux. A-line, second IV, SS femoral with bup 0.25%, ketamine, decadron. Drip in a unit of prbc (and ffp if still 1.7+) at incision. Have some platelets available for ongoing oozing. Make up a stick of vaso 1 unit/ml for any refractory hypotension. Work in a whiff of dilaudid as needed when waking up. Extubate in OR.

edit: also, do we have an echo/pulmonary pressures?

 

[Planktonmd]

Figured I would share this recent case.

61yo M with history of ESLD, HRS and ESRD on MWF dialysis, Afib (rate controlled, but not on anticoagulation) and COPD on 3L of home O2. Fell at his nursing home and broke his hip. Ortho has him booked for a hemi-arthroplasty.

INR is 2.0 and PLT count is 67. Hgb is 7.5. Patient is being given Vitamin K to reverse INR prior to scheduled case tomorrow.

What's your plan?

Excuse my ignorance but what is HRS???

 

[Ronin786]

Hepatorenal Syndrome

 

[deleted59964]

for real?

 

[deleted59964]

 

[Chloroform4Life]

Tell ortho to consult paliative/hospice.

If case proceeds, vitamin k prob won't work. Pt liver can't use it. Can check inr am of surgery, but I would be prepared to give 2 u ffp. Would give a unit of prbc preop as well since ffp will dilute your hb to less than 7. I would also give plt since this procedure can lead to major blood loss in a pt who is already coagulopathic. Goal plt of 100k.

Renally, if pt hasn't gotten dialysis in a couple days, then get dialysis. Get a BMP.

Pulmonary wise, I would warn the pt and family about increased risk of post op respiratory failure due to copd, home o2 need, and likely a component of hepatopulmonary syndrome. Give duo neb preop.

Depends on cardiac status (likely poor given other comorbidities), I'd probably want a preinduction a line. Induce with fentanyl, lidocaine, etomidate, succinylcholine. I don't care about his ponv. He needs rapid sequence induction and his response to a quick bolus of phenylephrine/propofol can be unpredictable.

 

[Ignatius J]

I had an ICU attending in residency who always said INR of FFP is 1.7. Giving it to a patient with an INR of 1.5-2 does very little.

 

[Robotic Wis-Hipple]

Pt's INR is 2 due to ESLD, he's not on AC. I assume this is at a big academic place, so I want a TEG, don't care too much bout INR, can't trust it to actually mean he's hypocoagulable. If he is I'd vote for PCC. Agree Vit K is probably minimally useful.

 

[Chloroform4Life]

I had an ICU attending in residency who always said INR of FFP is 1.7. Giving it to a patient with an INR of 1.5-2 does very little.

While it is true that the in vitro inr of ffp is high (1.6-1.7). I don't know what that would mean in vivo. Furthermore, inr measures only the extrinsic component of the clotting process, which is highly complicated, so I can't say that all the factors ffp contribute would be ineffective for a pt with an inr of 1.5 to 2.0. If the patient's inr is closer to 1.5, I would say yeah, don't transfusion the ffp. But with an inr of 2.0, I'd lean toward transfusion, especially since it's due to liver disease and not Coumadin, meaning that all factors are likely depleted and not just the vitamin k dependent factors.

 

[BLADEMDA]

OVERVIEW

• FFP has an INR of ~1.6 -> cannot lower below INR 1.7
• The usual volume of 1 unit is ~250 cc = plasma taken from one unit of blood
• Vitamin K dependent factors in concentration of 1 Unit/mL
• FFP must be ABO compatible
• 10-20 cc/kg (4-6 units in adults) will increase factors by ~20%
• It is frozen within eight hours of collection.
• FFP contains all coagulation factors in normal concentrations.
• may be transfused up to 5 days after thawing and contains slightly decreased levels of Factor V (66+-9%) and decreased Factor VIII levels (41+-8%)
• Plasma is free of red blood cells, leukocytes and platelets
• Rh factor need not be considered
• there are no viable leukocytes so plasma does not carry a risk of CMV transmission or GVHD

http://lifeinthefastlane.com/ccc/fresh-frozen-plasma-ffp/

 

[Ignatius J]

While it is true that the in vitro inr of ffp is high (1.6-1.7). I don't know what that would mean in vivo. Furthermore, inr measures only the extrinsic component of the clotting process, which is highly complicated, so I can't say that all the factors ffp contribute would be ineffective for a pt with an inr of 1.5 to 2.0. If the patient's inr is closer to 1.5, I would say yeah, don't transfusion the ffp. But with an inr of 2.0, I'd lean toward transfusion, especially since it's due to liver disease and not Coumadin, meaning that all factors are likely depleted and not just the vitamin k dependent factors.

You actually can say as studies have shown that FFP won't reliably bring below 1.7.

• Toward rational fresh frozen plasma transfusion: the effect of plasma transfusion on coagulation test results. Am J Clin Pathol 126(1):133-139, 2006.
• Effect of fresh frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion 46(8):1279-1285, 2006.

 

[BLADEMDA]

OVERVIEW

• FFP has an INR of ~1.6 -> cannot lower below INR 1.7
• The usual volume of 1 unit is ~250 cc = plasma taken from one unit of blood
• Vitamin K dependent factors in concentration of 1 Unit/mL
• FFP must be ABO compatible
• 10-20 cc/kg (4-6 units in adults) will increase factors by ~20%
• It is frozen within eight hours of collection.
• FFP contains all coagulation factors in normal concentrations.
• may be transfused up to 5 days after thawing and contains slightly decreased levels of Factor V (66+-9%) and decreased Factor VIII levels (41+-8%)
• Plasma is free of red blood cells, leukocytes and platelets
• Rh factor need not be considered
• there are no viable leukocytes so plasma does not carry a risk of CMV transmission or GVHD

http://lifeinthefastlane.com/ccc/fresh-frozen-plasma-ffp/

What is the take home message? Review of recent evidence suggests that FFP does not correct mild elevations in INR, much less reduce INR beyond several hours. Furthermore, elevation of INR does not predict bleeding in the setting of a procedure nor does prophylactic FFP transfusions result in fewer bleeding events. Given the absence of evidence of the benefit of FFP in correcting INR in conjunction with the known risks of FFP, FFP transfusion to non-bleeding patients with mild elevations in INR cannot be supported.

http://www.clinicalcorrelations.org/?p=6458

 

[Chloroform4Life]

You actually can say as studies have shown that FFP won't reliably bring below 1.7.

• Toward rational fresh frozen plasma transfusion: the effect of plasma transfusion on coagulation test results. Am J Clin Pathol 126(1):133-139, 2006.
• Effect of fresh frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion 46(8):1279-1285, 2006.

I don't doubt that statement. For an inr of 1.7 or less, I agree it won't bring the inr down. But what you can't say though is that it won't have an effect on the patient's overall coagulation, which is what I'm concerned about, not the patient's inr per se. His inr tells me that his liver is producing squat. He is depleted of all coagulation factors, so replacing those factors make sense to me, even if his inr doesn't change much.

I agree a Teg would be more useful than inr if available.

 

[Chloroform4Life]

I also don't think inr of 2.0 qualifies as mild elevation.

In addition, even though the patient is not bleeding now, he will be when ortho hacks up his leg.

 

[BLADEMDA]

When compared to FFP in the context of excessive bleed after cardiac surgery, it is superior at correcting the INR and significantly reducing the need for RBC transfusion [8,9,11,12]. 4-Factor PCCs rapidly reverse vitamin K dependent factors within 30 minutes of administration (INR < 1.3) when initial INR > 2 compared to the FFP (12-96 hours) [8,10,12].

http://www.ishlt.org/ContentDocuments/2015FebLinks_Arendt.html

 

[BLADEMDA]

In conclusion, 4F-PCC effectively reverses elevated INRs in trauma patients with warfarin-induced coagulopathy. With appropriate vitamin K use, effects last at least 48 hours. No increase in thrombotic complications was identified.


https://www.cedars-sinai.edu/Patien...ams/Documents/SICU-Articles/kcentra-11316.pdf

 

[BLADEMDA]

 

[BLADEMDA]

 

[BLADEMDA]

 

[BLADEMDA]

So, what would I give this patient?

1. Kcentra (2500 units or 25 units per Kilogram of actual body weight))- Contains factors 2, 7, 9 and 10
2. 1 of FFP (for other factors like factor 5)
3. Vitamin K IV 10 mg (if he hasn't got any yet)

 

[BLADEMDA]

Figured I would share this recent case.

61yo M with history of ESLD, HRS and ESRD on MWF dialysis, Afib (rate controlled, but not on anticoagulation) and COPD on 3L of home O2. Fell at his nursing home and broke his hip. Ortho has him booked for a hemi-arthroplasty.

INR is 2.0 and PLT count is 67. Hgb is 7.5. Patient is being given Vitamin K to reverse INR prior to scheduled case tomorrow.

What's your plan?

1. Kcentra
2. Vit K
3. 1 unit FFP
4. Platelets- likely
5. Maintain Hgb above 7 probably shoot for Hgb 8.0


Obtain ABG, PFTs (if time allows), Chem-18 (includes LFTs), CBC, CXR, EKG, TTE preoperatively

Anesthetic plan: GA with ETT

Solumedrol 62.5 mg IV preop COPD
Preop FICB under U/S
Arterial Line preop or prior to induction
Good IV access
5% Albumin and Normosol used for IV fluids
2 units Prbcs ready
Platelets ready and started prior or on incision

Extubation at the end of the case or in PACU postop if ABG, Vitals, etc support it.

If the patient's condition is truly HRS type 2 and there is intraop hypotension then intraop TEE may be warranted.

 

[BLADEMDA]

Cirrhotic patients often have a hyperdynamic circulation characterized by increased cardiac output, systemic hypotension and reduced peripheral vascular resistance [21]. Optimizing intravascular volume is essential in managing patients with HRS or at risk of developing HRS. However, intravascular volume expansion, which is often necessary to treat HRS, can potentially lead to worsening of ascites, pleural effusion or heart failure.

Assessment of intravascular volume in HRS is difficult as the standard static hemodynamics measurements of central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) are not reliable markers of circulatory volume [22, 23]. Goal-directed therapy for guiding fluid management has been investigated in patients with HRS with an infusion of 20% albumin significantly increasing central blood volume and cardiac index, without changes in CVP [24]. Pulse pressure variation derived from the arterial waveform and stroke volume variation from the pulse contour, as with other dynamic methods, are predictive of fluid responsiveness during volume-controlled mechanical ventilation [25] but are not as reliable in septic patients on pressure support ventilation [26]. The response to a fluid challenge in cirrhotics, however, is likely to be abnormal, as any fluid bolus which initially expands the intravascular space, will subsequently expand the ‘third space’. Other potential techniques include esophageal doppler, inferior vena caval diameter, right ventricular end-diastolic volume index, left ventricular end-diastolic area index and the global end-diastolic volume index, however, experience with these techniques in patients with cirrhosis remains limited [27–31].

http://ndt.oxfordjournals.org/content/27/1/34.full

 

[BLADEMDA]

Hepatorenal syndrome (HRS) is defined as the occurrence of renal dysfunction in a patient with end-stage liver cirrhosis in the absence of another identifiable cause of renal failure. The prognosis of HRS remains poor, with a median survival without liver transplantation of <6 months. However, understanding the pathogenesis of HRS has led to the introduction of treatments designed to increase renal perfusion and mean arterial blood pressure using vasopressors and albumin, which has led to improvement in renal function in ∼50% of patients.

 

[BLADEMDA]

Many HRS patients (the kind we see) are actually HRS type 3:

Munoz proposes that patients with HRS superimposed on chronic renal disease be categorised as having type 3 HRS [22]. Finally, it should be acknowledged that adherence to the IAC criteria is not always possible. As HRS is a diagnosis of exclusion, the diagnostic pathway can be complex at times, labour intensive, and prone to error. Some patients that do not fulfil the full IAC diagnostic criteria may be treated as having “presumed” HRS, based on the index of clinical suspicion. Three studies highlight these challenges. Salerno et al., in a study involving 253 patients with cirrhosis and renal failure, found that the diagnosis of HRS could only be “presumed” in 36% () as not all the IAC criteria could be met [23]. In 17% (), diuretic therapy was tapered but not stopped and in 6% () urinalysis could not be performed due to oligo-anuria or showed red blood cells and/or proteins due to bladder catheterisation or due to previous parenchymal renal disease, while in 7% () ultrasound showed preexisting renal abnormalities [23]. Interestingly, the authors found no significant differences in the clinical characteristics, clinical-pathologic scores, or outcomes between presumed cases compared with cases that met the full criteria [23]. Servin-Abad et al. performed a retrospective analysis on 140 patients diagnosed with HRS from 1996 to 2004. The authors found that only 41 patients (29.3%) met the IAC criteria [24]. Causes of misdiagnosis included parenchymal renal disease (15.2%), acute tubular necrosis (ATN) (35.4%), active sepsis (34.3%), drug induced renal disease (4%), and others (11.1%) [24]. Watt et al. found that only 59% of patients with a clinical diagnosis of HRS met IAC criteria [25].

http://www.hindawi.com/journals/grp/2015/207012/

 

[BLADEMDA]

HRS type 2:

Circulatory disturbances include a hyperdynamic circulation and reduced systemic vascular resistance. This may manifest clinically as low MAP, low jugular venous pressure, tachycardia, a bounding pulse, and wide pulse pressure. The following laboratory findings are suggestive of HRS [26]: elevated plasma renin activity, elevated plasma noradrenaline activity, hyponatraemia, hyperkalaemia, elevated blood urea nitrogen, decreased plasma osmolality, elevated urinary osmolality, and decreased urinary sodium excretion. Serum abnormalities that reflect the severity of the liver disease include hyperbilirubinemia, hypoalbuminemia, and prolonged prothrombin time.

 

[BLADEMDA]

MELD score would be useful:

http://www.mdcalc.com/meld-score-model-for-end-stage-liver-disease-12-and-older/

MELD is the standard used by the Organ Procurement and Transplantation Network (OPTN) and determines who is the highest priority to receive liver transplants in the US.

In interpreting the MELD Score in hospitalized patients, the 3 month mortality is: [6]

• 40 or more — 71.3% mortality
• 30–39 — 52.6% mortality
• 20–29 — 19.6% mortality
• 10–19 — 6.0% mortality
• <9 — 1.9% mortality

 

[Noyac]

My thoughts are:
1) discuss with ortho the options. Can something less invasive and more palliative be preformed?
2) the liver isn't producing clotting factors so I must. Use what you have.
3) dialysis as indicated.
4) lines? This pt will more than likely be difficult. Discuss with renal guys so as not to burn bridges. A-line and Central line are required.
5) pain control - sure if you want to. This pt is going to the unit so this is low on my list of concerns.
6) induction- go slow with whatever meds you want to use. Just mix in some neo and/or vasopressin.
7) Hgb. I would find out where he lives with regard to H/H and keep it there.
8) prepare for war.
9) family should know that he has very little chance of leaving the hospital.

 

[BLADEMDA]

I agree with Noyac:

The first thing is to get FFP (Critical Care) to discuss the likely outcome of this procedure: Death. Patient and family need to prepare for this outcome. Second, is to convince the Orthopod that a Troch Nail/Pinning is the type of procedure the patient needs. In this situation, the Family, Patient and FFP need to either get the Orthopod to agree to a less invasive procedure or ask for a second consult (another Otho doc).

I think this where we fail the most: Not speaking up for the proper procedure or allowing the procedure at all. These days I'm much more vocal about just stating the situation like it is and less worried about upsetting the operating room Provider (like the term). Patients with less than a year to live only need limited, life and death type procedures. If this patient gets a liver transplant he can return in a year or two for an "elective" total hip arthroplasty.

As for induction doses start slowly with propofol 20 mg IV and ketamine 20 mg IV followed by inhalational anesthetics. The preop TTE should provide valuable feedback as to the cardiac status of this patient.

 

[BLADEMDA]

Every postoperative death, whatever the overall incidence might be, makes us wonder about complications, errors, or preventability. Some questions that never fail: Was the surgery advisable or necessary in the first place? Was the patient properly informed of the risks? Were efforts spared in his or her care? In any case, the need to properly calibrate the risk/benefit ratio before each surgery, as opposed to an average across all surgeries or those of a particular type, is undeniable.



Every patient deserves and has the right to as much information as possible about their vulnerability before undergoing a surgical procedure. Everyone understands what it means to have an estimated 20% chance of dying. Such estimates should ideally include CIs that give the provider and patient an expected range for the underlying probability (e.g., 20% chance ±5%). However, this information should be adequately contrasted with the chance expected without surgery, which might be higher in some cases. Moreover, in the preoperative visit, clinicians should provide information to patients of risks other than dying. Some patients with limited life expectancy may prefer not to undergo procedures involving the risk of substantial suffering afterward.


http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2474648

Editorial in the March Edition of Anesthesiology

 

[BLADEMDA]

My thoughts are:
1) discuss with ortho the options. Can something less invasive and more palliative be preformed?
2) the liver isn't producing clotting factors so I must. Use what you have.
3) dialysis as indicated.
4) lines? This pt will more than likely be difficult. Discuss with renal guys so as not to burn bridges. A-line and Central line are required.
5) pain control - sure if you want to. This pt is going to the unit so this is low on my list of concerns.
6) induction- go slow with whatever meds you want to use. Just mix in some neo and/or vasopressin.
7) Hgb. I would find out where he lives with regard to H/H and keep it there.
8) prepare for war.
9) family should know that he has very little chance of leaving the hospital.

1. Agreed. I would insist on a less invasive procedure and counsel the patient/family to get a second opinion if needed.
2. Disagree. The use of KCentra allows LESS VOLUME (significantly less) than 6 units of FFP with better correction of clotting factors. Consider platelets as well.
3. If this is a weekday case then dialysis should have occurred the day before or just prior to surgery.
4. Arterial line. If less invasive procedure planned then no central line. If needed place central line postop.
5. Agreed. FICB or not.
6. I prefer low dose agents followed by inhalation vapor. Give pressors as needed. Hypotension kills. Maint. MAP at all costs.
7. Hgb- I would just give a unit Prbcs and maint hgb of 8.0 Baseline is Hgb 7.5
8. War- More of a skirmish using special forces
9. Agreed. see my previous post.

Good case and discussion.

 

[Planktonmd]

So, what would I give this patient?

1. Kcentra (2500 units or 25 units per Kilogram of actual body weight))- Contains factors 2, 7, 9 and 10
2. 1 of FFP (for other factors like factor 5)
3. Vitamin K IV 10 mg (if he hasn't got any yet)

You do know that you need a liver to produce the coagulation factors regardless of how much vitamin K you give, don't you?

 

[Planktonmd]

Try to avoid having the patient dialyzed the day of surgery unless the potassium is really high.
Don't waste your time on Vitamin K since it's unlikely to work, Kcentra if you have it is a good alternative to FFP here but if you don't have it give a couple of units of FFP and don't even bother rechecking INR.
Make sure you have PRBC and Platelets available.
Take him to the OR, get good IV access, put him to sleep with a small dose of something and intubate him.
Start an Aline, start giving PRBC's ( 2 units + estimated blood loss).
Keep the BP maintained with the usual pressors and some vasopressin if needed.
If bleeding is a problem give platelets (most likely has platelet dysfunction + low numbers)
Let them operate and at the end don't even bother waking him up, just take him to ICU intubated and get some labs, he might need to be dialyzed post op.
Let them wean him off the ventilator gradually.

 

[Planktonmd]

I agree with Noyac:

The first thing is to get FFP (Critical Care) to discuss the likely outcome

So there is a type of physician called FFP???

 

[Noyac]

1. Agreed. I would insist on a less invasive procedure and counsel the patient/family to get a second opinion if needed.
2. Disagree. The use of KCentra allows LESS VOLUME (significantly less) than 6 units of FFP with better correction of clotting factors. Consider platelets as well.
3. If this is a weekday case then dialysis should have occurred the day before or just prior to surgery.
4. Arterial line. If less invasive procedure planned then no central line. If needed place central line postop.
5. Agreed. FICB or not.
6. I prefer low dose agents followed by inhalation vapor. Give pressors as needed. Hypotension kills. Maint. MAP at all costs.
7. Hgb- I would just give a unit Prbcs and maint hgb of 8.0 Baseline is Hgb 7.5
8. War- More of a skirmish using special forces
9. Agreed. see my previous post.

Good case and discussion.

I don't have KCentra. Therefore, I use what I have. I have done cases like this in the past and I have never used KCentra. Every pt made it out of the OR in good shape. Not sure how their postop courses went. But I can speculate.

 

[BLADEMDA]

Let's assume that the patient received Kcentra (2500 units) and Platelets. Upon rechecking the INR it is now 1.3 and the Platelet count is 105,000. Would you consider doing a spinal with isobaric bupivacaine or tetracaine? Let's also assume you don't have TEG or if you do have TEG it is now normal.

 

[BLADEMDA]

I don't have KCentra. Therefore, I use what I have. I have done cases like this in the past and I have never used KCentra. Every pt made it out of the OR in good shape. Not sure how their postop courses went. But I can speculate.

I have Kcentra available at my institution. The data shows it to be superior to FFP in many situations.


http://emcrit.org/wp-content/uploads/2013/12/Kcentra_4FPCC_SPT.pdf

https://www.hosp.uky.edu/pharmacy/formulary/criteria/Critical Bleeding Reversal Protocol.pdf (look at page 3)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127295/

 

[BLADEMDA]

A New Direction in Reversal
Christopher Adams, PharmD, RPh, BCPS, and Andrea R. Resseguie, PharmD, RPh, CACP
Published Online: Tuesday, August 11, 2015


Target-specific oral anticoagulants (TSOACs) dabigatran, rivaroxaban, apixaban, and edoxaban are now being used in a larger and more diverse patient population. Despite the fact that bleeding with TSOACs is not expected to be higher compared with the use of other anticoagulant agents, life-threatening bleeding is still a concern. For most situations, a specific antidote may not be needed due to the short half-life of TSOACs. However, the availability of an antidote is essential for the management of any emergency situation. At this time, there are no clinically available reversal agents and there is a lack of guidance on how to restore hemostasis in the presence of significant bleeding from TSOACs.

Current reversal strategies focus on drug removal and managing bleeding. Immediate discontinuation of all anticoagulant and antiplatelet therapy is standard. Activated charcoal is a possible option if treatment is begun within 2 hours of the drug ingestion. Hemodialysis may facilitate removal of dabigatran if clinically feasible (approximately 60% removed in 2-3 hours). Hemostatic agents used as options for management of bleeding include antifibrinolytics (aminocaproic acid and tranexamic acid) and desmopressin. Other hemostatic agents, including activated prothrombin complex concentrate (aPCC), 3- and 4-factor prothrombin complex concentrate (PCC), and recombinant factor VIIa (rVIIa) have all been investigated, but their roles remain inconclusive.

In various healthy volunteer trials, 3-factor PCC and 4-factor PCC have had variable effects on correcting surrogate lab markers.1,2 A recent study with 3- and 4-factor PCC showed a decrease in prothrombin time in rivaroxaban-treated patients but no effect on abnormal activated partial thromboplastin time or anti-Xa activity.3 aPCC has shown promise in in vitro analyses and was shown to correct abnormal thrombin generation indices in healthy volunteers treated with dabigatran and rivaroxaban.4 Recombinant factor VIIa has also shown variable results in in vitro and ex vivo studies but comes with an increased risk of arterial thrombosis in patients without hemophilia.5

An aPCC, such as Feiba, dosed at 50 units/kg is suggested for patients exposed to dabigatran. For rivaroxaban, apixaban, and edoxaban, a 4-factor PCC, such as KCentra, is suggested at a dose of 50 units/ kg. It is important to remember that factor concentrates are not antidotes; a thrombotic risk is present by creating hypercoagulability, not reversal. One meta-analysis demonstrated a 1.8% risk of thromboembolic events after 4-factor PCC usage,6 and Sarode et al found a 7.8% rate of thromboembolism with use of 4-factor PCC (3.9% deemed related to therapy).7

Idarucizumab and Andexanet Alfa
Idarucizumab and andexanet alfa are 2 agents that have been granted breakthrough therapy status by the FDA. Idarucizumab is a fragmented monoclonal antibody with a high affinity for dabigatran. Theoretically, this agent does not elicit procoagulant effects; however, it did successfully reverse bleeding in animal models.8-10 In a phase 1 study, idarucizumab reversed prolonged clotting times in men and women of various ages and with a range of kidney function.11

Andexanet alfa is a recombinant factor Xa derivative that lacks specific binding activity and is currently undergoing development for the reversal of anti-Xa agents.12 In a phase 2 trial, the andexanet dose dependently decreased anti-Xa activity and reduced plasma concentrations of free apixaban compared with placebo.13 Preliminary results of a phase 3 trial displayed reversal of coagulation test abnormalities and restoration of thrombin generation in an older patient population treated with apixaban.14

Aripazine
Aripazine is a small synthetic molecule that binds to all TSOACs, as well as heparins, low molecular– weight heparins, fondaparinux, and argatroban. Aripazine has multiple binding sites present on the molecule for each anticoagulant. This reversal agent is currently undergoing phase 2 trials as a nonspecific reversal agent. It has shown promise in animal models15 and has decreased clotting times in edoxaban-treated healthy volunteers.16

Many factors affect the multimodal strategy to control or reverse clinical bleeding. Understanding what agents are in our armamentarium to combat bleeding in the setting of a TSOAC is vital, especially in an acute situation. The development of specific antidotes is promising and will increase the safety profile of TSOACs, but does not diminish the caution that needs to be practiced with high-risk patients.

 

[Ignatius J]

I don't doubt that statement. For an inr of 1.7 or less, I agree it won't bring the inr down. But what you can't say though is that it won't have an effect on the patient's overall coagulation, which is what I'm concerned about, not the patient's inr per se. His inr tells me that his liver is producing squat. He is depleted of all coagulation factors, so replacing those factors make sense to me, even if his inr doesn't change much.

I agree a Teg would be more useful than inr if available.

INR is a good indicator of bleeding risk. I just think the literature says here that you're teetering on exposing the patient to unnecessary risk. Especially as we are finding out more and more both the detrimental short and long term consequences of transfusions. Give K Centra.

 

[Ignatius J]

What is the take home message? Review of recent evidence suggests that FFP does not correct mild elevations in INR, much less reduce INR beyond several hours. Furthermore, elevation of INR does not predict bleeding in the setting of a procedure nor does prophylactic FFP transfusions result in fewer bleeding events. Given the absence of evidence of the benefit of FFP in correcting INR in conjunction with the known risks of FFP, FFP transfusion to non-bleeding patients with mild elevations in INR cannot be supported.

http://www.clinicalcorrelations.org/?p=6458

EXCELLENT article.

 

[Chloroform4Life]

EXCELLENT article.

Good article, but does not apply to this patient.

 

[ranvier]

Let's assume that the patient received Kcentra (2500 units) and Platelets. Upon rechecking the INR it is now 1.3 and the Platelet count is 105,000. Would you consider doing a spinal with isobaric bupivacaine or tetracaine? Let's also assume you don't have TEG or if you do have TEG it is now normal.

I think there is time to administer factors in whatever chosen form and recheck coags. This speaks to prognosis since a patient that can partially correct their INR is better off than the opposite. That said, no way would I administer a neuraxial from a risk/reward standpoint. Baseline TEG useful for guiding blood products intraop as you note, volume status is tricky in hyperdynamic liver patients. Hepatorenal syndrome is not a good sign and nature is likely to take its course in this type of patient. Agree with palliative discussion with all players...he likely survives the operation but not the journey back to pre-injury status.

 

[Planktonmd]

Let's assume that the patient received Kcentra (2500 units) and Platelets. Upon rechecking the INR it is now 1.3 and the Platelet count is 105,000. Would you consider doing a spinal with isobaric bupivacaine or tetracaine? Let's also assume you don't have TEG or if you do have TEG it is now normal.

Nope!

 

[Ignatius J]

Good article, but does not apply to this patient.

Disagree. Using the article, you can use the formula and see that you will bring this patient down to a INR on average of 1.73. Underwhelming change given the potential adverse consequences of transfusion.

 

[urge]

Figured I would share this recent case.

61yo M with history of ESLD, HRS and ESRD on MWF dialysis, Afib (rate controlled, but not on anticoagulation) and COPD on 3L of home O2. Fell at his nursing home and broke his hip. Ortho has him booked for a hemi-arthroplasty.

INR is 2.0 and PLT count is 67. Hgb is 7.5. Patient is being given Vitamin K to reverse INR prior to scheduled case tomorrow.

What's your plan?

Pent sux tube.

Use ffp, prbcs, and platelets as iv fluid.

 

[deleted171991]

So there is a type of physician called FFP???

I must admit that I am flattered that when he thought about Critical Care he typed FFP. I actually laughed out loud when I read it at work.

This is an excellent thread (this is what one gets with smart people), and Blade's contributions to it are remarkable (as usual).

One thing I want to point out though is that INR is less reliable as a coagulation marker in cirrhosis, the reason being that everything is so F-ed up with their coagulation system (the synthesis of all proteins is decreased, not only procoagulant ones), that it's actually difficult to figure out the risk of bleeding vs thrombosis. A TEG would tell us much more (theoretically, I have never used one).

For the same reason, it's more important to keep platelets above 50,000, and fibrinogen over 150-200. I would give vitamin K (it doesn't hurt), I just wouldn't count on it doing anything. PCC is definitely the better choice over FFP, especially in a dialysis patient (but it's about $4-5K a dose). I would not do neuraxial in this guy; cirrhotics are hyperdynamic low SVR people even at baseline, and this guy is also hepatorenal on top of it.

Unless the patient is on the liver transplant list, I would have a very strong discussion with the family and ortho about palliative or less invasive treatments (e.g. IM nailing).

 

[Ronin786]

Try to avoid having the patient dialyzed the day of surgery unless the potassium is really high.
Don't waste your time on Vitamin K since it's unlikely to work, Kcentra if you have it is a good alternative to FFP here but if you don't have it give a couple of units of FFP and don't even bother rechecking INR.
Make sure you have PRBC and Platelets available.
Take him to the OR, get good IV access, put him to sleep with a small dose of something and intubate him.
Start an Aline, start giving PRBC's ( 2 units + estimated blood loss).
Keep the BP maintained with the usual pressors and some vasopressin if needed.
If bleeding is a problem give platelets (most likely has platelet dysfunction + low numbers)
Let them operate and at the end don't even bother waking him up, just take him to ICU intubated and get some labs, he might need to be dialyzed post op.
Let them wean him off the ventilator gradually.

Bingo. I know the reflex is to have dialysis done pre-operatively, but it can make things even more challenging intra-operatively as I've had happen a few times recently. Especially if the K is alright. And especially because most internal medicine services will aggressively dialyze patients in order to "prepare them for the OR".

In response to a few things in this thread. Pre-operative MELD score was 38. INR was pretty much unaffected by Vitamin K. Patient had a surprisingly normal heart and decent METS prior to breaking his hip.

In our situation, he underwent dialysis the day before surgery then showed up the following day in pre-op in a-fib to the 120s and hypotensive to the 70s. The case was postponed for a day (which is when I became scheduled to take care of him).

Does this change anything for you guys?

 

[Ignatius J]

I must admit that I am flattered that when he thought about Critical Care he typed FFP. I actually laughed out loud when I read it at work.

This is an excellent thread (this is what one gets with smart people), and Blade's contributions to it are remarkable (as usual).

One thing I want to point out though is that INR is less reliable as a coagulation marker in cirrhosis, the reason being that everything is so F-ed up with their coagulation system (the synthesis of all proteins is decreased, not only procoagulant ones), that it's actually difficult to figure out the risk of bleeding vs thrombosis. A TEG would tell us much more (theoretically, I have never used one).

For the same reason, it's more important to keep platelets above 50,000, and fibrinogen over 150-200. I would give vitamin K (it doesn't hurt), I just wouldn't count on it doing anything. PCC is definitely the better choice over FFP, especially in a dialysis patient (but it's about $4-5K a dose). I would not do neuraxial in this guy; cirrhotics are hyperdynamic low SVR people even at baseline, and this guy is also hepatorenal on top of it.

Unless the patient is on the liver transplant list, I would have a very strong discussion with the family and ortho about palliative or less invasive treatments (e.g. IM nailing).

One thing I'll add is that cirrhosis can have hypersplenism and chew up platelets. If you're giving platelets, better give a Big Gulp's worth.

 

[Noyac]

Well, I'm not sure I wouldn't do a spinal.

If the case has been delayed for new onset Afib then let cards handle it. Rate control or conversion, I don't care.

As far as dialysis goes, they can do it but leave the pt euvolemic.