Usage
Human Prothrombin Complex (PCC) is prescribed for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonists (VKAs), such as warfarin, in adults with:
- Acute major bleeding.
- Need for an urgent surgery or invasive procedure.
It is also indicated for the treatment and prophylaxis of bleeding in congenital deficiency of any of the vitamin K-dependent coagulation factors when purified specific coagulation factor products are not available.
Pharmacological Classification: Antihemorrhagic agent, Vitamin K-dependent coagulation factor replacement.
Mechanism of Action: PCC provides a source of Vitamin K-dependent clotting factors (II, VII, IX, and X), thereby replacing the deficient factors and promoting hemostasis. Some PCCs also include proteins C and S, which provide additional antithrombotic effects.
Alternate Names
- Factor IX Complex
- Prothrombin Complex Concentrate
Brand Names:
- Kcentra
- Balfaxar
- Beriplex
- Octaplex
- Profilnine
- Confidex
- Prothromplex TOTAL
How It Works
Pharmacodynamics: PCC increases the plasma levels of Vitamin K-dependent clotting factors (II, VII, IX, and X). This leads to a shortening of the prolonged prothrombin time (PT) and international normalized ratio (INR) caused by VKA therapy, effectively restoring the coagulation process. The presence of Proteins C and S in some PCCs contribute towards anticoagulant effects.
Pharmacokinetics:
- Absorption: Administered intravenously, PCC achieves peak plasma concentrations rapidly, usually within minutes.
- Metabolism and Elimination: The individual factors within PCC have different half-lives. Factor VII has the shortest half-life (approximately 4-6 hours), while Factor II has the longest (approximately 60-72 hours). The other factors have intermediate half-lives. The elimination pathways are not fully understood, but they likely involve normal protein catabolism mechanisms in the liver.
Mode of Action: PCC directly replaces the deficient Vitamin K-dependent clotting factors in the coagulation cascade, restoring the ability of the blood to clot. It doesn’t involve receptor binding, enzyme inhibition, or neurotransmitter modulation, but directly supplements depleted coagulation factors. This effect is temporary.
Elimination pathways: The exact mechanisms of elimination of PCC are not fully elucidated, but it likely involves normal protein catabolism and hepatic clearance.
Dosage
Standard Dosage
Adults:
Dosing is individualized based on the patient’s pre-treatment INR and body weight (up to 100 kg). The dose is expressed in international units (IU) of Factor IX.
- INR 2 to <4: 25 IU/kg IV (maximum 2500 IU).
- INR 4-6: 35 IU/kg IV (maximum 3500 IU).
- INR >6: 50 IU/kg IV (maximum 5000 IU).
Children:
Safety and efficacy have not been established in pediatric patients. Limited guidance suggests individualized dosing based on the clinical condition and coagulation profile.
Special Cases:
- Elderly Patients: No specific dose adjustments are recommended, but monitor closely for adverse effects.
- Patients with Renal Impairment: No specific dose adjustments are indicated, but monitor carefully.
- Patients with Hepatic Dysfunction: Use with caution. Monitor closely.
- Patients with Comorbid Conditions: Individualized dosing and close monitoring are essential.
Clinical Use Cases
Dosing is individualized based on the patient’s specific clinical situation, INR, and other relevant factors. Consult with a hematologist or expert in coagulation disorders for guidance.
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Dose adjustments should be made based on INR, patient response and presence of any co-morbidities.
Dosage Adjustments
Dose modifications are needed based on INR response, bleeding severity, and patient-specific factors.
Side Effects
Common Side Effects:
- Headache
- Nausea
- Vomiting
- Joint pain (arthralgia)
- Hypotension
Rare but Serious Side Effects:
- Thromboembolic events (myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis)
- Allergic reactions (anaphylaxis)
- Hypercoagulability
Long-Term Effects:
- Development of inhibitors to coagulation factors.
Adverse Drug Reactions (ADR):
- Anaphylaxis
- Thromboembolism
Contraindications
- Known hypersensitivity to any component of the product (including heparin).
- Disseminated intravascular coagulation (DIC).
- Heparin-induced thrombocytopenia (HIT).
Drug Interactions
- Anticoagulants (e.g., heparin, warfarin, direct oral anticoagulants): May antagonize the effects of PCC.
- Antithrombin: May cause additive or synergistic effects.
- Thrombolytic agents (e.g., alteplase): May increase the risk of bleeding.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C. Use only if the potential benefit outweighs the potential risk to the fetus. Not known if excreted in breast milk; breastfeeding is generally not recommended during treatment.
Drug Profile Summary
- Mechanism of Action: Replaces deficient vitamin K-dependent clotting factors (II, VII, IX, X), promoting hemostasis.
- Side Effects: Headache, nausea, vomiting, arthralgia, hypotension, thromboembolic events, allergic reactions.
- Contraindications: Hypersensitivity, DIC, HIT.
- Drug Interactions: Anticoagulants, antithrombin, thrombolytics.
- Pregnancy & Breastfeeding: Category C; use with caution if benefits outweigh risks; breastfeeding not recommended.
- Dosage: Individualized based on INR and body weight (see above).
- Monitoring Parameters: INR, PT, signs of bleeding or thrombosis.
Popular Combinations
- Vitamin K: Administered concurrently with PCC to restore Vitamin K-dependent clotting factor production.
Precautions
- Monitor closely for signs of thromboembolic events and allergic reactions.
- Use with caution in patients with a history of thromboembolic events.
- Administer via slow intravenous infusion.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Human Prothrombin Complex?
A: Dosing is individualized based on INR and body weight (up to 100 kg). INR 2 to <4: 25 IU/kg (max 2500 IU); INR 4-6: 35 IU/kg (max 3500 IU); INR >6: 50 IU/kg (max 5000 IU).
Q2: What are the common side effects of PCC?
A: Headache, nausea, vomiting, joint pain, and low blood pressure.
Q3: What are the serious side effects of PCC?
A: Thromboembolic events (blood clots), allergic reactions including anaphylaxis, and DIC.
Q4: What are the contraindications for PCC use?
A: Known hypersensitivity to any component, disseminated intravascular coagulation (DIC), and heparin-induced thrombocytopenia (HIT).
Q5: Can PCC be used in pregnant or breastfeeding women?
A: It should be used with caution during pregnancy only if clearly needed when the benefits outweigh the risks. Breastfeeding is generally not recommended.
Q6: How is PCC administered?
A: Administered intravenously, through slow infusion as per manufacturer instructions.
Q7: What are the key monitoring parameters for PCC?
A: INR, PT, aPTT, fibrinogen levels, and clinical signs of bleeding or thrombosis.
Q8: What is the mechanism of action of PCC?
A: PCC provides a source of vitamin K-dependent clotting factors, thereby promoting hemostasis.
Q9: What is the difference between 3-factor and 4-factor PCC?
A: 3-factor PCC typically contains factors II, IX, and X. 4-factor PCC additionally includes factor VII. 4-factor PCC, like Kcentra, also contains proteins C and S.
Q10: Can PCC be used in patients with liver disease?
A: Use with caution in patients with liver disease due to their potential for impaired coagulation factor production. Careful monitoring is crucial.
