PCC/OCTAPLEX

1. “Prothrombin complex
concentrates
………………an overview”
Dr. Tanmoy Roy
Consultant Anaesthesiologist & Intensive Care Practitioner
INSTITUTE OF NEUROSCIENCES, KOLKATA

2. INTRODUCTION
Although the various coagulation factors are present at physiological
concentrations in fresh-frozen plasma (FFP) derived from healthy blood
donors, some virally inactivated plasma-derived coagulation factor
concentrates have been available for many years. These latter products
include single coagulation factor concentrates (such as factor VIII
concentrates for the treatment of haemophilia A and factor IX concentrate
for the treatment of haemophilia B) or the so-called prothrombin complex
concentrates (PCC), which are intermediate purity pooled plasma products
containing a mixture of vitamin K-dependent proteins

5. WHAT ARE PCCs ???
PCC are produced by ion-exchange chromatography from the
cryoprecipitate supernatant of large plasma pools after removal of
antithrombin and factor XI. Different processing techniques involving ion
exchangers enable the production of either three-factor (i.e., factors II, IX
and X) or four-factor (i.e., factors II, VII, IX and X) concentrates with a final
overall clotting factor concentration approximately 25 times higher than in
normal plasma. Each PCC vial contains 500 units of Factor IX (equivalent to
two 200-250 cc units of FFP). To prevent activation of these factors, most
PCC contain heparin. PCC may also contain the natural coagulation
inhibitors protein C and protein S.

6. VARIOUS STUDIES………

7. INDICATIONS
› Urgent reversal of acquired coagulation
factor deficiency induced by Vitamin K
antagonist (e.g., warfarin) therapy in
adult patients with acute major bleeding
› Urgent/Emergent management of factor
Xa inhibitor associated bleeding (off-
label): APIXABAN, RIVAROXABAN,
ENDOXABAN
› Given as part of Massive Hemorrhage
protocol (along with pRBC and Platelets),
replacing the FFP component
COMPONENTS
› Factor II
› Factor VII (present only in four factor PCC)
› Factor IX
› Factor X
› Protein C (not present in all formulations)
› Protein S (not present in all formulations)
› Heparin (to prevent factor activation)

8. FORMULATIONS
› PCC3 - Three factor (II, IX, X)
› PCC4 - Four factor (II, VII, IX, X)
PCC4 500 IU (20ml vial) powder and
solvent for solution for infusion
PCC4 1000 IU (40ml vial) powder
and solvent for solution for infusion

9. COMPOSITION
The total protein content per vial is 260 – 820 mg (500 IU vial)/ 520 – 1640 mg (1000 IU vial).
The specific activity of the product is ≥ 0.6 IU/mg proteins, expressed as factor IX activity.
Heparin 100 – 250 IU per 500 IU vial, and 200 - 500 IU per 1000 IU vial

10. PLASMA HALF-LIFE
 Individual dosage requirements can only be identified on the basis of regular
determinations of the individual plasma levels of the coagulation factors of interest, or
on global tests of the prothrombin complex levels(prothrombin time, INR), and
continuous monitoring of the clinical condition of the patient.
 Correction of the vitamin K antagonist induced impairment of haemostasis persists for
approximately 6-8 hours.
 The effects of vitamin K, if administered simultaneously, are usually achieved within 4-6
hours.

11. DOSAGE
• The amount and the frequency of administration should be calculated on an individual patient basis
• Dosage intervals must be adapted to the different circulating half-life of the different coagulation
factors in the prothrombin complex
• Individual dosage requirements can only be identified on the basis of regular determinations of the
individual plasma levels of the coagulation factors of interest, or on global tests
Bleeding and perioperative prophylaxis of bleeding during vitamin K antagonist
treatment:
normalization of INR (≤ 1.2 within 1 hour)
*The single dose should not exceed 3000 IU (120 mL of PCC4).

12. DOSAGE…cont.
Bleeding and perioperative prophylaxis in congenital deficiency of the vitamin K
dependent coagulation factors II and X when specific coagulation factor product is not
available:
One International Unit (IU) of a coagulation factor activity is equivalent to the
quantity in one mL of normal human plasma
• Approximately 1 IU/kg body weight of factor II or X raises the plasma factor II or X activity by 0.02
and 0.017 IU/mL, respectively
• The dose of a specific factor administered is expressed in International Units (IU), which are
related to the current WHO standard for each factor.
Required units = body weight (kg) x desired factor X rise (IU/mL) x 60
Required units = body weight (kg) x desired factor II rise (IU/mL) x 50

13. PREPARATION

14. CONTRAINDICATIONS
- Hypersensitivity to any of the components
- Known allergy to heparin or history of heparin induced thrombocytopenia
- Individuals who have IgA deficiency with known antibodies against IgA

15. FEW WORDS OF CAUTION………
Patients receiving a vitamin K antagonist may have an underlying hypercoagulable state, and infusion
of prothrombin complex concentrate may exacerbate this
The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV. The
measures taken may be of limited value against non-enveloped viruses such as HAV and parvovirus
B19, which may be serious for pregnant women (foetal infection) and for individuals with
immunodeficiency or increased erythropoiesis (e.g. hemolytic anemia). Appropriate vaccination
(hepatitis A and B) is recommended for patients in regular/repeated receipt of PCCs
There is a risk of thrombosis or DIC when patients, with either congenital or acquired deficiency are
treated with human prothrombin complex particularly with repeated dosing
No data are available regarding the use of PCCs in case of perinatal bleeding due to vitamin K
deficiency in the new-born
The safety of human prothrombin complex for use in human pregnancy and during lactation has not
been established

16. FEW WORDS OF CAUTION………cont.
A sudden, allergy induced reduction of the blood platelet count below 100,000/μl or 50 % of the
starting count may be rarely observed. In patients not previously hypersensitive to heparin, this
decrease in thrombocytes may occur 6 - 14 days after the start of treatment. In patients with previous
heparin hypersensitivity this reduction may happen within a few hours.

17. Store below 25°C
Do not freeze
Store in the original package in order to protect from light
3 years of shelf life
Chemical and physical in-use stability has been demonstrated for up to 8 hours at +25°C
From a microbiological point of view, unless the method of opening/reconstitution precludes the
risk of microbial contamination, the product should be used immediately
STORAGE AND STABILITY
COST FACTOR INVOLVED

18. THANK YOU ALL