Hereditary factor X deficiency

The dose and duration of the treatment depend on the severity of the factor X deficiency (i.e. the patient’s baseline factor X level), on the location and extent of the bleeding and on the patient’s clinical condition.

Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes.

Not more than 60 IU/kg daily should be administered in any age group.

In adults and adolescents at least 12 years of age, the expected in vivo peak increase in factor X level expressed as IU/dL (or % of normal) can be estimated using the following formulae:

Dose (IU) = body weight (kg) x desired factor X rise (IU/dL or % of normal) x 0.5

OR

Increase in factor X level (IU/dL or % of normal) = [total dose (IU)/body weight (kg)] x 2

The following examples assume the patient’s baseline factor X level is <1 IU/dL:

1. A dose of 2000 IU coagulation factor X administered to a 70 kg patient should be expected to result in a peak post-infusion factor X increase of 2000 x {[2 IU/dL]/[IU/kg]}/[70 kg] = 57 IU/dL (i.e. 57% of normal)
2. A peak factor X level of 90% of normal is required in a 70 kg patient. In this situation, the appropriate dose would be:

70 kg x 90 IU/dL/{[2 IU/dL]/[IU/kg]} = 3150 IU.

The dose and frequency should be based on the individual clinical response. Patients may vary in their pharmacokinetic (e.g. half-life, in vivo recovery) and clinical responses to coagulation factor X. Although the dose can be estimated using the calculations above, whenever possible appropriate laboratory tests, such as serial factor X assays, should be performed to guide dose adjustments.

Control of Bleeding Episodes

Adults and adolescents aged 12 years or more for treatment of bleeding episodes: 25 IU/kg coagulation factor X should be injected when the first sign of bleeding occurs or just before the expected onset of menstrual bleeding. Repeat at intervals of 24 hours until the bleed stops. Judge each individual bleed on its own severity.

For secondary prophylaxis against re-bleeding or short-term prophylaxis prior to anticipated physical activity or dental appointments: 25 IU/kg coagulation factor X should be injected and repeated as required.

Routine prophylaxis of bleeding episodes

Due to inter-and intra-patient variability, it is recommended that trough blood levels of Factor X should be monitored at intervals, especially in the first weeks of therapy or after dosage changes. Adjust dosage regimen to clinical response and trough levels of Factor X of at least 5 IU/dL.

There are limited data on the use of coagulation factor X for long periods of prophylaxis in adults. There are no data available on routine prophylaxis in paediatric patients aged >12 to <18 years. 25 IU/kg twice weekly is the proposed starting dose for prophylaxis in patients >12 years of age with dose levels and dosing intervals to be adjusted as clinically indicated. Depending on individual clinical response, longer intervals, e.g. once weekly, might be adequate.

Perioperative Management (Adults and adolescents aged at least 12 years of age)

Pre-surgery: calculate dose of coagulation factor X to raise plasma factor X levels to 70-90 IU/dL. The careful control of dose and duration of treatment is especially important in cases of major surgery.

Required dose (IU) = body weight (kg) x desired factor X rise (IU/dL) x 0.5

The desired factor X rise is the difference between the patient’s plasma factor X level and the desired level, and based on the observed recovery of 2 IU/dL per IU/kg.

Example: to raise plasma factor X level from 15 IU/dL to 90 IU/dL in a 70 kg patient, the appropriate dose is:

70 x (90-15) x 0.5 = 2,625 IU.

Post-surgery: dose as necessary to maintain plasma factor X levels at a minimum of 50 IU/dL until the subject is no longer at risk of bleeding due to surgery.

It is recommended that post-infusion plasma factor X levels are measured for each patient before and after surgery, to ensure that haemostatic levels are obtained and maintained.