Transfusion medicine handbook

5. Fractionated Products

5.1.3 Beriplex NZ

Beriplex NZ is presented as a powder, containing human prothrombin complex, in packs of 500 IU Factor IX, for reconstitution with a vial of diluent (Water for Injections). It is made from New Zealand plasma. It contains up to 343 mg (approximately 15 mmol) sodium and up to 200 IU heparin per 100 mL reconstituted solution.

• Beriplex NZ has the following coagulation factor content per vial [1]:
• Factor II, 400 – 960 IU
• Factor VII, 200 – 500 IU
• Factor IX, 400 – 620 IU
• Factor X, 440 – 1200 IU
• Protein C, 300 – 900 IU
• Protein S, 240 – 760

It should be noted that Beriplex NZ is a ‘4 factor’ prothrombin complex concentrate compared to Prothrombinex-VF which is a ‘3 factor’ product. Furthermore, Beriplex NZ contains Protein C and Protein S.

Indications for Use

• Beriplex NZ is indicated for the treatment and perioperative prophylaxis of bleeding in acquired deficiency of the prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists, or in case of overdose of vitamin K antagonists, when rapid correction of the deficiency is required.

Dose

These are general dosage guidelines only. Treatment should be initiated under the supervision of a doctor experienced in the treatment of coagulation disorders. The dosage and duration of the substitution therapy depend on the severity of the disorder, on the location and extent of bleeding and on the patient’s clinical condition.

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-lives of the respective 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 of the prothrombin complex levels (e.g. International Normalised Ratio (INR)), and a continuous monitoring of the clinical condition of the patient.

Bleeding and perioperative prophylaxis of bleeding during vitamin K antagonist treatment

• The dose will depend on the INR before treatment and the targeted INR. The pre-treatment INR should be measured as close as possible to the time of dosing in order to calculate the appropriate dose of Beriplex NZ.

1. Pre-treatment INR 2.0–3.9

• Approximate dose 1 mL / kg body weight or 25 IU (factor IX) / kg body weight

2. Pre-treatment INR 4.0–6.0

• Approximate dose 1.4 mL / kg body weight or 35 IU (factor IX) / kg body weight

3. Pre-treatment INR >6.0
   • Approximate dose 2 mL / kg body weight or 50 IU (factor IX) / kg body weight.

Dose is based on body weight up to but not exceeding 100 kg. For patients weighing more than 100 kg the maximum single dose (IU of factor IX) should not exceed 2500 IU for an INR of 2.0–3.9, 3500 IU for an INR of 4.0–6.0 and 5000 IU for an INR of >6.0.

The correction of the vitamin K antagonist-induced impairment of haemostasis is commonly reached approximately 30 minutes after the injection. The simultaneous administration of vitamin K should be considered in patients receiving Beriplex® NZ for urgent reversal of vitamin K antagonists since vitamin K usually takes effect within 4–6 hours. Repeated dosing with Beriplex NZ for patients requiring urgent reversal of vitamin K antagonist treatment is not supported by clinical data and therefore not recommended [1]. If a repeat dose is considered within 14 days then it should be discussed with an NZBS TMS/ Medical Officer.

Precautions 

• Hypersensitivity reactions

If allergic or anaphylactic-type reactions occur, the administration of Beriplex NZ should be stopped immediately.

• Thromboembolic risk

There is a risk of thrombosis or disseminated intravascular coagulation when patients, with either congenital or acquired deficiency, are treated with human prothrombin complex. The risk may be higher in treatment of isolated factor VII deficiency, since the other vitamin K dependent coagulation factors, with longer half-lives, may accumulate to levels considerably higher than normal.

Close monitoring should be undertaken in patients with a history of coronary heart disease or myocardial infarction, liver disease, in the peri- or postoperative periods, neonates, and patients at risk of thromboembolic phenomena or disseminated intravascular coagulation or simultaneous inhibitor deficiency.

• Disseminated Intravascular Coagulation (DIC)
• Resumption of anticoagulation

Reversing vitamin K antagonists exposes patients to the risk of the underlying disease. Resumption of anticoagulation should be carefully considered as soon as possible.

• Heparin-Induced Thrombocytopenia type II
  • Characteristic signs of HIT are a platelet count drop >50% and/or the occurrence of new or unexplained thromboembolic complications during heparin therapy. Onset is typically from 4 to 14 days after initiation of heparin therapy but may occur within 10 hours in patients recently exposed to heparin (within the previous 100 days).