Factor XIII (Monograph)

Brand name: Corifact
Drug class: Hemostatics
VA class: BL500
Chemical name: Human Factor XIII [A2] homodimer (allele F13A*1B)
Molecular formula: C₃₇₀₈H₅₇₃₅N₁₀₁₃O₁₁₁₁S₂₈
CAS number: 606138-08-3

Medically reviewed by Drugs.com on Feb 19, 2024. Written by ASHP.

Introduction

Preparation of blood coagulation factor XIII derived from pooled human plasma.^{1 7 8}

Uses for Factor XIII

Congenital Factor XIII Deficiency

Routine prophylaxis and perioperative management of bleeding in patients with congenital factor XIII deficiency;^{1 7 8 13 14 15 29 31 33 34 36} designated an orphan drug by FDA for treatment of congenital factor XIII deficiency.¹²

Initial FDA-labeled use based on trough factor XIII levels (5–20%) as a surrogate measure of efficacy; clinical benefit (i.e., prevention of bleeding episodes) established in a postmarketing study.^{1 29 33}

Prophylactic therapy with factor XIII concentrates is recommended in all patients with severe (<1% factor XIII activity) deficiency; considered current standard of care.^{7 8 25 34 38}

Currently available factor XIII concentrates in the US include a plasma-derived (Corifact) and a recombinant (Tretten) preparation.^{1 10 30 31} Some experts recommend preferential use of recombinant preparations because of their potentially superior safety profile with respect to pathogen transmission.³⁰ (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.) When selecting an appropriate factor XIII preparation, consider characteristics of each clotting factor concentrate in addition to individual patient variables.³²

Acquired Factor XIII Deficiency

Has been used to treat acquired factor XIII deficiency^{† [off-label]} associated with various diseases or other conditions.^{2 3 5 9 17 18 19 21 22 25}

Factor XIII Dosage and Administration

Administration

IV Administration

Administer by slow IV injection.¹ (See Rate of Administration under Dosage and Administration.)

Reconstitution

Reconstitute lyophilized powder with manufacturer-supplied sterile water for injection diluent.¹ Prior to reconstitution, allow drug and diluent to warm to room temperature.¹ Gently swirl vial; do not shake.¹

Use reconstituted solution promptly, or no more than 4 hours after reconstitution.¹ Discard unused portion.¹

Rate of Administration

Administer at a rate not exceeding 4 mL/minute.¹

Dosage

Dosage expressed in international units (IU, units) of factor XIII activity.¹ Each vial contains 1000–1600 units of factor XIII (human); actual number of units indicated on each vial and carton.¹

Individualize dosage based on factor XIII levels, presence and severity of bleeding, and clinical response.^{1 35} (See Laboratory Monitoring under Cautions.)

Initial dose of 40 units/kg recommended; adjust subsequent dose in increments or decrements of 5 units/kg based on trough factor XIII activity levels.¹ (See Table 1.)

Pediatric Patients

Congenital Factor XIII Deficiency

Dosage adjustment in pediatric patients <16 years of age may be required due to age-related differences in pharmacokinetics.¹ (See Special Populations under Pharmacokinetics.)

Routine Prophylaxis of Bleeding

IV

40 units/kg every 28 days.¹ Adjust dosage to maintain factor XIII levels of 5–20%.¹ (See Table 1.)

Perioperative Management of Bleeding

IV

Additional dosing may be necessary in patients undergoing surgery depending on the timing of their last prophylactic dose.¹ Individualize dosing requirements based on type of surgery, factor XIII activity, and clinical response.^{1 36}

If last prophylactic dose given within 7 days of surgery, additional dose generally not needed.¹

If last prophylactic dose given 8–21 days previously, an additional partial or full dose is recommended depending on factor XIII levels.¹

If last prophylactic dose was given 21–28 days previously, an additional full dose is recommended.¹

Adults

Congenital Factor XIII Deficiency

Routine Prophylaxis of Bleeding

IV

40 units/kg every 28 days.¹ Adjust dosage to maintain factor XIII levels of 5–20%.¹ (See Table 1.)

Perioperative Management of Bleeding

IV

Additional dosing may be necessary in patients undergoing surgery depending on the timing of their last prophylactic dose.¹ Individualize dosing requirements based on type of surgery, factor XIII activity, and clinical response.^{1 36}

If last prophylactic dose given within 7 days of surgery, additional dose generally not needed.¹

If last prophylactic dose given 8–21 days previously, an additional partial or full dose is recommended depending on factor XIII levels.¹

If last prophylactic dose was given 21–28 days previously, an additional full dose is recommended.¹

Special Populations

Pregnant Women

Achievement of plasma factor XIII activity levels of at least 2–3% (ideally >10%) during early gestation and >30% during labor suggested.^{8 9} Timing and optimum dosage for maintenance of successful pregnancy not fully elucidated.⁸

Cautions for Factor XIII

Contraindications

• Known anaphylactic or severe systemic reactions to human plasma-derived products.¹

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., allergy, rash, pruritus, erythema) observed.¹

Discontinue administration immediately and institute appropriate treatment if manifestations of anaphylaxis or hypersensitivity reactions (e.g., urticaria, rash, chest tightness, wheezing, hypotension) occur.¹

Immunogenicity

Although frequency low,³⁴ inhibitory antibodies against factor XIII detected in patients receiving factor XIII (human).^{1 2} Presence of inhibitory antibodies may manifest as inadequate response to treatment.^{1 2}

Monitor patients for possible development of inhibitory antibodies.¹ If expected plasma factor XIII activity levels not attained or breakthrough bleeding occurs during prophylaxis, measure factor XIII inhibitory antibody concentrations.¹

Thromboembolic Complications

Thromboembolic complications reported.¹ Closely monitor patients with known risk factors.¹

Risk of Transmissible Agents in Plasma-derived Preparations

Factor XIII (human) is prepared from human blood and may carry risk of transmitting infectious agents (e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease [CJD] agent).¹ Also potentially capable of transmitting unknown infectious agents.¹

Report any suspected infections associated with factor XIII (human) to CSL Behring Pharmacovigilance Department at 866-915-6958 or FDA at 800-FDA-1088 or [Web].¹

Laboratory Monitoring

Monitor patient’s trough factor XIII activity level during treatment.¹ Also monitor during and after surgery.^{1 34}

If breakthrough bleeding occurs or expected peak plasma factor XIII activity levels not attained, perform investigation to determine presence of factor XIII inhibitory antibodies.¹

Specific Populations

Pregnancy

Category C.¹

Safety and efficacy during labor and delivery not established;¹ however, has been used throughout pregnancy in some women with congenital factor XIII deficiency to prevent spontaneous abortion and obstetrical hemorrhagic complications.^{7 8 16 26}

Lactation

Not known whether factor XIII (human) is distributed into human milk.¹ Use caution.¹

Pediatric Use

Has been used in some children <2 years up to 16 years of age.¹

No apparent differences in safety profile in children compared with adults.¹ However, differences in pharmacokinetic profile observed; dosage adjustments may be necessary in patients <16 years of age.¹ (See Special Populations under Pharmacokinetics.)

Geriatric Use

Safety and efficacy in geriatric patients not established.¹

Common Adverse Effects

Hypersensitivity reactions (i.e., rash, pruritus, erythema), joint inflammation, hematoma, arthralgia, headache, elevated thrombin-antithrombin levels, increased blood LDH.¹

Drug Interactions

No formal drug interaction studies to date.²⁸

Factor XIII Pharmacokinetics

Absorption

Duration

IV dose results in increased plasma factor XIII activity levels for approximately 28 days.¹

Plasma Concentrations

Mean increase (from baseline) in plasma factor XIII activity levels after third dose (steady state) given every 28 days: 83% (range: 48–114%).¹

Elimination

Half-life

5–12 days (mean: 6.6 days).^{1 7 8 9}

Special Populations

Patients <16 years: Possible shorter half-life and faster clearance than in adults.¹

Stability

Storage

Parenteral

Powder for Injection

2–8°C; avoid freezing.¹ Store in original carton and protect from light.¹

Stable for 24 months at 2–8°C, up to the expiration date on carton and vial label.¹

May store at room temperature (≤25°C) for up to 6 months.¹ Do not use beyond the expiration date on carton and vial labels or beyond the period of room temperature storage, whichever comes first.¹

Do not return product to refrigerator after storage at room temperature.¹

Reconstituted solutions: Use within 4 hours after reconstitution.¹ Do not refrigerate or freeze.¹

Actions

• Preparation of blood coagulation factor XIII derived from pooled human plasma.¹

• Congenital factor XIII deficiency is a rare but serious bleeding disorder manifested by a lifelong bleeding tendency that typically includes umbilical bleeding during the neonatal period, delayed soft tissue bruising, mucosal bleeding, poor wound healing, recurrent miscarriage, and intracranial hemorrhage.^{7 9 10 13 14 16 20 23 24 27 34}

• Factor XIII circulates in plasma as a heterotetrameric glycoprotein consisting of 2 A-subunits and 2 B-subunits.^{1 8} Enzymatic activity resides in the A-subunit; B-subunits function as carrier molecules for the A-subunits.^{1 6 7 8 9 10}

• Factor XIII is a proenzyme that is activated in the presence of calcium by thrombin cleavage of the A-subunit to become activated factor XIII (factor XIIIa).^{1 2 7}

• Factor XIIIa promotes cross-linking of fibrin and other proteins, resulting in a fibrin clot that is more elastic and resistant to fibrinolysis.^{1 2 4 6 8 10}

• Factor XIIIa also cross-links α₂-plasmin inhibitor to the α-chain of fibrin, resulting in protection of the fibrin clot from degradation by plasmin.^{1 6 8}

Advice to Patients

• Possible risk of transmission of infectious agents (e.g., viruses, and theoretically, the CJD agent).¹

• Importance of reporting signs and symptoms of hypersensitivity reactions (e.g., urticaria, rash, tightness of the chest, wheezing, hypotension, anaphylaxis) experienced during or after injection of factor XIII (human).¹

• Importance of informing patients of the signs and symptoms of immunogenicity (e.g., breakthrough bleeding).¹

• Importance of informing patients of signs and symptoms of thrombosis (e.g., swelling of limb or abdomen and/or pain; chest pain; shortness of breath; loss of sensation or motor power; altered consciousness, vision, or speech).¹

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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