Prothrombin Complex Concentrate (PCC)

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Objectives

The purpose of this guideline is to provide recommendations for treatment of inpatients with life threatening bleeding or requiring emergent surgery or procedure with prothrombin complex concentrate (PCC). These guidelines should be used in concert with hematology consultation.

University of Michigan Health System Anticoagulation Program

Guideline for Prothrombin Complex Concentrate Use for Reversal of Anticoagulation

Agent Selection

  1. Kcentra is the preferred PCC agent for use in management of anticoagulant-associated bleeding.
    • Use is restricted to correction of moderate to severe and life-threatening bleeds induced by warfarin
    • Use is restricted to Hematology, Trauma Surgery, Emergency Medicine and Neurosurgery Services and the Stroke Team (pager #90004)
    • Use by all other services requires Hematology approval
  2. Kcentra may be used for reversal of warfarin prior to emergent surgery.
    • Use is restricted to the above services or other surgical services
  3. No specific antidotes are available for the direct thrombin inhibitor, dabigatran, nor the oral factor Xa inhibitors (e.g. rivaroxaban, apixaban). Due to lack of definitive data, PCC can be considered for patients with the above indications using oral direct thrombin or anti-Xa inhibitors.
  4. FEIBA is an activated PCC product that is restricted for use only in concert with hematology consult/approval due to thrombotic risk.

Criteria for use

Inclusion:

  1. Anticoagulant associated major bleeding restricted to neurosurgery, stroke team, emergency medicine, trauma, and hematology
  2. Anticoagulant reversal prior to emergent surgery
  3. Hemophilia patients with inhibitors or other congenital bleeding disorders who currently use PCC at home. These patients do not require approval for use.

Exclusion:

  1. History of anaphylaxis with exposure to factor IX concentrates
  2. Acute thrombosis or embolism
  3. Signs of disseminated intravascular coagulation (DIC)

Caution:

  1. Systemic antifibrinolytic (tranexamic acid or aminocaproic acid) or use of other bypasses within previous 12 hours
  2. Synergy may occur if combined with fresh frozen plasma (FFP) or activated factor VIIa

Pharmaceutical components:1-3

Note: Kcentra is the formulary agent of choice and is the first line agent. FEIBA is restricted to use by hematology only as outlined above.

  1. Factor and heparin concentrations

 

Kcentra™*

Feiba® NF

Factor II

0.76 – 1.6 units per 1 unit Kcentra

1.3 units per 1 unit Feiba

Factor IX

0.8 – 1.24 units per 1 unit Kcentra

1.4 units per 1 unit Feiba

Factor X

1 – 2.04 units per 1 unit Kcentra

1.1 units per 1 unit Feiba

Factor VII

0.4 – 1 units per 1 unit Kcentra

1.5 units VIIa and 0.9 units VII per 1 unit Feiba

 

 

Kcentra™*

Feiba® NF

Heparin

0.016 – 0.08 units per 1 unit Kcentra

None

Protein C

0.84 – 1.64 units per 1 unit Kcentra

1.1 IU/1 unit Feiba

Protein S

0.48 – 1.36 units per 1 unit Kcentra

NA

*Potency of individual factors is labeled on the packaging

Dosing

Note: Kcentra is the formulary agent of choice and is the first line agent. FEIBA is restricted to use by hematology only as outlined above.

Recommended dosing

 

Kcentra™

Feiba®  NF

Dosing for warfarin

INR 2-4: 25 units/kg

50 units/kg

INR  4 – 6 : 35 units/kg

INR > 6:  50 units/kg

Dosing for:

Dabigatran, Rivaroxaban, Apixaban

Limited data and experience, a dose of 50 units/kg would be reasonable

Limited data and experience, a dose of 50 units/kg would be reasonable

Additional doses

Repeat dosing is not recommended

May repeat 50 units/kg Q6-12 hours x 1-2 additional doses for inadequate hemostasis

Maximum dose

INR 2 - < 4:  2500 units

INR 4 – 6:  3500 units

INR > 6:  5000 units

200 units/kg/day

Dosing weight

Total body weight, up to but not to exceed 100 kg

Total body weight

Kcentra

  1. Dosing is based on body weight
  2. Dose based on actual potency as stated on the carton (varies from 20 – 31 Factor IX units/mL).
  3. Doses will be rounded to the nearest whole vial size by a pharmacist prior to dispensing as the amount of product in each vial varies from vial to vial.

Storage and reconstitution

Characteristics of available PCC products

2º – 25º C (36º – 77º F) do not freeze

Characteristic

Kcentra™

Feiba®  NF

Source material

Pooled human plasma

Pooled human plasma

How supplied

Single use vials with sterile water, Mix2Vial filter transfer set, alcohol swab

BAXJECT device, sterile water, and single dose vial

Microbial reduction

heat-treated; nonofiltered, lyophilized

Vapor heated; nanofiltered

Preservative

None

None

Latex

Does not contain latex

Rubber stoppers contain latex

Diluent

Sterile water (20 mL)

Sterile water (20 mL)

Reconstitution

Use within 4 hours of reconstitution

Allow drug and diluent to reach room temperature before reconstitution. Use within 3 hours of and do not refrigerate after mixing

Storage

Room temp ≤ 77°F in original package to protect from light

Administration

  1. Kcentra
    • Administer by intravenous infusion at a rate of 0.12 mL/kg/min (~ 3 units/kg/min)
    • Maximum infusion rate = 8.4 mL/min (~210 units/min)
  2. Feiba
    • Maximum infusion rate = 2 units/kg/min
    • For a 75 kg patient this corresponds to infusion rate of 2.5-7.5 ml/min depending on units per vial.

Monitoring

NOTE: Coagulation tests like INR, aPTT, and whole blood clotting time may not correlate with hemostatic efficacy or clinical improvement when treating with PCC. For this reason, attempts at normalizing these values by increasing doses of PCC may not be successful and may provoke thromboembolic events.

  1. Baseline monitoring
    • aPTT, INR/PT, platelet count, and hemoglobin/hematocrit
  2. On-going monitoring
    • Resolution of bleeding
    • Assess efficacy of first dose 15 minutes after the end of the infusion of the dose as there should not be a delayed effect
    • INRs should be monitored every 4 hours due to half-lives of therapeutic agents/clotting factors
    • Thrombosis or embolism

Use of PCC with additional supportive therapies

  1. Vitamin K
    • For patients receiving PCC because of warfarin-associated bleeding, administer 10 mg vitamin K slow IVPB x 1 dose over at least 30 minutes
    • Consider risk for vitamin K resistance in patients with mechanical heart valves
  2. Fresh frozen plasma (FFP)
    • Could consider in patients deemed to have inadequate response to 1-2 doses of PCC (refer to section V above for Kcentra and Feiba dosing)
  3. Recombinant activated Factor VII (NovoSeven) (rfVIIa)
    • Not routinely recommended
    • May consider use in patients who have failed both PCC and FFP administration

Drug Interactions:1-3

No compatibility studies have been performed with these agents; do not mix with other solvents or products

Management of PCC-associated thrombotic complications:1-3

  1. If the patient has signs or symptoms of thromboembolism, discontinue PCC infusion immediately
  2. Provide supportive care

Special Thanks

Attribution

If reusing this content please use the following information to provide credit to the content authors:  

  1. Title: Prothrombin Complex Concentrate (PCC)
  2. Author:  Michigan Medicine
  3. Source: https://ecosystem.tactuum.com/
  4. License: “CC BY-NC 4.0”

Prothrombin Complex Concentrate (PCC),  Michigan Medicine, Dept of Surgery,  “CC BY-NC 4.0”

Last reviewed: 09 June 2021