Each unit of FFP has approximately 2.5% of activated clotting factors. http://www.psbc.org/therapy/ffp.htm it takes an 80-90% reduction in activated clotting factors for therepuetic inr (Factor 2 72 hour half life one half life 50% decrease two half lives 75% decrease...explains bridging time) So one must replace at least 10% (minimum) in order to move inr toward normal.
Amazing job as always Rob and Joe, you are the master. Joe, I'd be willing to bet you a beer you have either 3-factor PCC or FEIBA in your blood bank right now; most likely both.
We have FEIBAl at our shop in chicago ad use the deaconess protocol: 500U for INR < 5, with repeat INR in 30 minutes. 1000U if > 5, but we only use it for "life-threatening hemorrhages." It reverses the INR almost completely in 30-60 minutes, whether this contributes to improved mortality, or more favorable surgical conditions remains to be answered.
We have FEIBA at our shop and use the deaconess protocol: 500U for INR <5, 1000U for INR >5 with repeat INR in 30 minutes and repeat dose if necessary + 10mg IV vitamin K. This is reserved for "life threatening hemorrhages."
Reverses the INR almost completely in 30-60 minutes, but whether this contributes to improved mortality or more favorable operative conditions just because the numbers are better has yet to be delineated. We're collecting prospective data now.
We use Profilnine (a 3 factor PCC) warfarin reversal. I works great. 25 U/kg for INR 2-4, 35 for INR 4-6, 50 for INR> 6. Reversal in 20 minutes. For the dabigatran and rivaroxaban, we use FEIBA at 50 U/kg.
We did an exhaustive lit review on FEIBA for dabigatran and rivaroxaban for the anticoagulation committee at The Ohio State University. The only data is human exvivo and human volunteer studies and rat tail bleeding model studies. It did work better than rVIIa for both agents. I will be happy to forward the OSU protocol and the lit if anyone wants it. colin.kaide@osumc.edu
We recently got Profilnine at our shop and are working on a dosing regime. Likely it will be a weight based regime. What are the thoughts on dosing of 3 factor PCCs in the obese, still based on total BW or go with ideal BW?
Joe. .. I do believe that octaplex contains protein s c and heparin. Beriplex contains these PLUS anti-thrombin. A recent meta-analysis suggested the thrombotic rate is about 1%. There are multiple regimes. Hamilton( big time researchers and authors of ATT9) use 20 u/kg for inr<3, 30 u/kg for inr 3-5, 40 u/kg for inr > 5. The onset of action should be minutes ( only several.) The national advisory committee has lots of free info on the web and a diffrent guideline published in 2011 for use in Canada. Ffp is considered a bit primitive for inr reversal of warfarin. Ofcourse, this is only for sig bleeding patients. And, prev HIT is a citraindication for plex due to the small amt of heparin. Walter Himmel
Nilesh, I asked my hematology consuntant, Tom Deloughery about the weight based vs IBW based PCC. Here's what he had to say... Found this abstract and I asked also some of my hemophilia center friends and most go with Ideal body weight.
--tom
Critical Care Medicine: December 2011 - Volume 39 - Issue 12 - p 73 doi: 10.1097/01.ccm.0000408627.24229.88 281: WEIGHT-BASED DOSING OF PROTHROMBIN COMPLEX CONCENTRATES FOR THE RAPID REVERSAL OF WARFARIN COAGULOPATHY: A COMPARISON OF IDEAL VERSUS ACTUAL BODY WEIGHT
Hutchison, Emily; Morse, Jennifer; Harris, Serena; Skinner, Joseph; Ellender, Timothy Author Information Indiana University Health-Methodist Hospital (Hutchison) Purdue University (Morse) Spectrum Health–Butterworth (Harris) Indiana University Health-Methodist Hospital (Ellender)
Introduction:
International guidelines recommend Prothrombin Complex Concentrates (PCC) as an option for urgent reversal of warfarin coagulopathy. Although literature supports use of the international normalized ratio (INR) and weight for PCC dosing, use of ideal body weight (IBW) versus actual body weight (ABW) is variable in clinical practice. The purpose of this study is to compare INR reversal with PCC based on INR and either ABW or IBW.
Hypothesis:
We hypothesize that PCC dosed with ABW will have a faster time to INR reversal compared to use of IBW.
Methods:
A retrospective data review from a Level 1 Trauma Center was conducted from June 1, 2010-July 5, 2011. Inclusion criteria were: age >=18 years, initial INR >=1.5, and need for urgent reversal of warfarin coagulopathy. Data collected included reason for INR reversal, serial INR values, PCC dose, patient demographics (age, height, weight, and gender), adjunct therapy given for INR reversal, surgical interventions, bleeding complications, adverse events, and all-cause hospital mortality. Statistical analyses were performed using two-sided Fisher's exact test, Mann-Whitney U test, and the t-test.
Results:
PCC was added to formulary June 1, 2010 and was dosed on initial INR and IBW. Dosing with IBW was changed to ABW on March 1, 2011. Eighty-three patients received PCC during the study period, 63 of these meeting inclusion criteria (45 with IBW and 18 with ABW). Baseline demographics were similar between the two groups. Initial INR was 2.7 in the IBW group and 2.3 in the ABW group (p = 0.66). Median time to obtain an INR <1.5 was 190 min (IQR 80–730 min) in the IBW group and 600 min (IQR 223–705 min) in the ABW group (p = 0.47). There was no difference in the percent of patients who received FFP (p = 0.20), amount of FFP administered (p = 0.57), or INR at 24 hours (p = 0.39). A single adverse event of a superficial clot and venous thromboembolism was identified in the IBW group 9 days following PCC administration.
Conclusions:
Time to INR reversal with PCC was not significantly different when dose was based on INR and ABW as opposed to IBW. PCC dosing with ABW was associated with a similar amount of FFP administration and a low rate of adverse events.
A new 4 factor PCC containing relevant amounts of factor 7 and protein C and S has been approved for use in the United States. It will not be available until the end of 2013. The rationale for adding protein C and protein S is to attempt to balance the hypercoagulable effects of using the PCC to reverse somebody who is anticoagulated. At Ohio State University, we just got the new guidelines for reversal dabigatran and rivaroxaban approved. They both have FEIBA as the main reversal agent in critically bleeding patients. For the uninitiated, FEIBA is Factor Eight Inhibitor Bypassing Activity. It is an activated form of PCC. We are going to use 50 units per kilogram of this drug in patients with severe bleeding. We noted in our guidelines that the evidence supporting FEIBA is minimal however the theoretical rationale is reasonable. You are adding in activated clotting factor and bypassing the ones that are in activated by dabigatran and rivaroxaban. Of note...SIRI on my Mac thinks that dabigatran is "did they get Tran" and rivaroxaban is "river rocks a band." We will give Siri an A for effort and an F on product delivery!
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Preston W. - April 2, 2013 8:25 AM
Each unit of FFP has approximately 2.5% of activated clotting factors. http://www.psbc.org/therapy/ffp.htm it takes an 80-90% reduction in activated clotting factors for therepuetic inr (Factor 2 72 hour half life one half life 50% decrease two half lives 75% decrease...explains bridging time) So one must replace at least 10% (minimum) in order to move inr toward normal.
EMCrit - April 2, 2013 12:40 PM
Amazing job as always Rob and Joe, you are the master. Joe, I'd be willing to bet you a beer you have either 3-factor PCC or FEIBA in your blood bank right now; most likely both.
David B. - April 3, 2013 5:34 AM
We have FEIBAl at our shop in chicago ad use the deaconess protocol: 500U for INR < 5, with repeat INR in 30 minutes. 1000U if > 5, but we only use it for "life-threatening hemorrhages." It reverses the INR almost completely in 30-60 minutes, whether this contributes to improved mortality, or more favorable surgical conditions remains to be answered.
David B. - April 3, 2013 5:37 AM
We have FEIBA at our shop and use the deaconess protocol: 500U for INR <5, 1000U for INR >5 with repeat INR in 30 minutes and repeat dose if necessary + 10mg IV vitamin K. This is reserved for "life threatening hemorrhages."
Reverses the INR almost completely in 30-60 minutes, but whether this contributes to improved mortality or more favorable operative conditions just because the numbers are better has yet to be delineated. We're collecting prospective data now.
Colin K. - April 13, 2013 8:30 PM
We use Profilnine (a 3 factor PCC) warfarin reversal. I works great. 25 U/kg for INR 2-4, 35 for INR 4-6, 50 for INR> 6. Reversal in 20 minutes. For the dabigatran and rivaroxaban, we use FEIBA at 50 U/kg.
Colin K. - April 13, 2013 8:36 PM
We did an exhaustive lit review on FEIBA for dabigatran and rivaroxaban for the anticoagulation committee at The Ohio State University. The only data is human exvivo and human volunteer studies and rat tail bleeding model studies. It did work better than rVIIa for both agents. I will be happy to forward the OSU protocol and the lit if anyone wants it. colin.kaide@osumc.edu
Scott K., D.O. - April 18, 2013 1:37 PM
As usual, Joe Lex, phenomenal!
Nilesh P. - April 23, 2013 6:47 AM
We recently got Profilnine at our shop and are working on a dosing regime. Likely it will be a weight based regime.
What are the thoughts on dosing of 3 factor PCCs in the obese, still based on total BW or go with ideal BW?
Nilesh
Walter M. H., M.D. - April 25, 2013 1:03 PM
Joe. .. I do believe that octaplex contains protein s c and heparin. Beriplex contains these PLUS anti-thrombin. A recent meta-analysis suggested the thrombotic rate is about 1%. There are multiple regimes. Hamilton( big time researchers and authors of ATT9) use 20 u/kg for inr<3, 30 u/kg for inr 3-5, 40 u/kg for inr > 5. The onset of action should be minutes ( only several.) The national advisory committee has lots of free info on the web and a diffrent guideline published in 2011 for use in Canada. Ffp is considered a bit primitive for inr reversal of warfarin. Ofcourse, this is only for sig bleeding patients. And, prev HIT is a citraindication for plex due to the small amt of heparin. Walter Himmel
Rob O - April 29, 2013 11:17 AM
Nilesh, I asked my hematology consuntant, Tom Deloughery about the weight based vs IBW based PCC. Here's what he had to say...
Found this abstract and I asked also some of my hemophilia center friends and most go with Ideal body weight.
--tom
Critical Care Medicine:
December 2011 - Volume 39 - Issue 12 - p 73
doi: 10.1097/01.ccm.0000408627.24229.88
281: WEIGHT-BASED DOSING OF PROTHROMBIN COMPLEX CONCENTRATES FOR THE RAPID REVERSAL OF WARFARIN COAGULOPATHY: A COMPARISON OF IDEAL VERSUS ACTUAL BODY WEIGHT
Hutchison, Emily; Morse, Jennifer; Harris, Serena; Skinner, Joseph; Ellender, Timothy
Author Information
Indiana University Health-Methodist Hospital (Hutchison)
Purdue University (Morse)
Spectrum Health–Butterworth (Harris)
Indiana University Health-Methodist Hospital (Ellender)
Introduction:
International guidelines recommend Prothrombin Complex Concentrates (PCC) as an option for urgent reversal of warfarin coagulopathy. Although literature supports use of the international normalized ratio (INR) and weight for PCC dosing, use of ideal body weight (IBW) versus actual body weight (ABW) is variable in clinical practice. The purpose of this study is to compare INR reversal with PCC based on INR and either ABW or IBW.
Hypothesis:
We hypothesize that PCC dosed with ABW will have a faster time to INR reversal compared to use of IBW.
Methods:
A retrospective data review from a Level 1 Trauma Center was conducted from June 1, 2010-July 5, 2011. Inclusion criteria were: age >=18 years, initial INR >=1.5, and need for urgent reversal of warfarin coagulopathy. Data collected included reason for INR reversal, serial INR values, PCC dose, patient demographics (age, height, weight, and gender), adjunct therapy given for INR reversal, surgical interventions, bleeding complications, adverse events, and all-cause hospital mortality. Statistical analyses were performed using two-sided Fisher's exact test, Mann-Whitney U test, and the t-test.
Results:
PCC was added to formulary June 1, 2010 and was dosed on initial INR and IBW. Dosing with IBW was changed to ABW on March 1, 2011. Eighty-three patients received PCC during the study period, 63 of these meeting inclusion criteria (45 with IBW and 18 with ABW). Baseline demographics were similar between the two groups. Initial INR was 2.7 in the IBW group and 2.3 in the ABW group (p = 0.66). Median time to obtain an INR <1.5 was 190 min (IQR 80–730 min) in the IBW group and 600 min (IQR 223–705 min) in the ABW group (p = 0.47). There was no difference in the percent of patients who received FFP (p = 0.20), amount of FFP administered (p = 0.57), or INR at 24 hours (p = 0.39). A single adverse event of a superficial clot and venous thromboembolism was identified in the IBW group 9 days following PCC administration.
Conclusions:
Time to INR reversal with PCC was not significantly different when dose was based on INR and ABW as opposed to IBW. PCC dosing with ABW was associated with a similar amount of FFP administration and a low rate of adverse events.
Ricky G - May 30, 2013 6:54 PM
Can I assume being on any of these new anticoagulants is an absolute contraindication to tPA?
Colin K. - June 5, 2013 8:43 AM
A new 4 factor PCC containing relevant amounts of factor 7 and protein C and S has been approved for use in the United States. It will not be available until the end of 2013. The rationale for adding protein C and protein S is to attempt to balance the hypercoagulable effects of using the PCC to reverse somebody who is anticoagulated.
At Ohio State University, we just got the new guidelines for reversal dabigatran and rivaroxaban approved. They both have FEIBA as the main reversal agent in critically bleeding patients. For the uninitiated, FEIBA is Factor Eight Inhibitor Bypassing Activity. It is an activated form of PCC. We are going to use 50 units per kilogram of this drug in patients with severe bleeding. We noted in our guidelines that the evidence supporting FEIBA is minimal however the theoretical rationale is reasonable. You are adding in activated clotting factor and bypassing the ones that are in activated by dabigatran and rivaroxaban. Of note...SIRI on my Mac thinks that dabigatran is "did they get Tran" and rivaroxaban is "river rocks a band." We will give Siri an A for effort and an F on product delivery!