Chapter 5 -Concentrates for hemostatic disorders Flashcards
How are clotting factor concentrates sourced?
They can be extracted from pooled donated plasma (plasma-derived) or manufactured using biotechnology (recombinant).
What is the Health Canada Special Access Program (SAP)?
** It allows access to unlicensed or certain licensed clotting factor products that have not undergone Health Canada batch release.**
What is Emicizumab?
Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII and is indicated for routine prophylaxis in hemophilia A patients with or without inhibitory antibodies against factor VIII.
What is the main indication for Emicizumab in hemophilia A patients?
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
What are recombinant clotting factor concentrates (r)?
These are clotting factor concentrates produced using biotechnology, where clotting factor genes are transfected into cultured cell lines to express the factor.
How are recombinant clotting factor concentrates made?
Clotting factor genes are inserted into vectors, **transfected into **cell lines, and the recombinant proteins are purified for therapeutic use.
Non-clotting factor product
1-What is Emicizumab (Hemlibra®)
2- How is Emicizumab produced?
- A bispecific monoclonal antibody to FIX/FIXa and FX/FXa, used as a non-clotting factor product for hemostasis.
- It is manufactured using recombinant technology in Chinese hamster ovary (CHO) cells.
What allergy precautions should be considered with Emicizumab?
Trace hamster proteins (from CHO cells)
Trace bovine proteins (human-animal protein used in cell culturing but removed during the manufacturing process)
What are the criteria for access to Emicizumab through Canadian Blood Services?
Congenital hemophilia A with inhibitors to factor VIII
Severe congenital hemophilia A (intrinsic factor VIII level < 1%) without inhibitors
What is the function of Emicizumab?
It mimics the function of factor VIII in the coagulation cascade to prevent or reduce bleeding episodes in hemophilia A patients.
How does the chromatographic process affect viral load in clotting factor concentrates?
It reduces the viral load during fractionation and purification.
What virus inactivation/partitioning procedures are used in plasma-derived and recombinant concentrates?
Procedures are incorporated to inactivate/partition viruses during manufacturing for plasma-derived and most recombinant concentrates.
What pathogens are effectively targeted by virus inactivation procedures?
Effective against HIV, hepatitis C (HCV), and hepatitis B (HBV).
Since when have virus-inactivated factor concentrates been used in Canada, and what has been the impact?
Introduced in 1985
No cases of HIV or HCV transmission due to concentrates since 1987 and 1988, respectively.v
Are all viruses inactivated by these procedures?
No, non-enveloped viruses such as parvovirus B19 and hepatitis A can be resistant to inactivation processes.
: What vaccines **should be **administered to patients with congenital coagulation deficiency receiving blood products?
Hepatitis B virus (HBV)
Hepatitis A virus (HAV)
What is the theoretical risk associated with plasma-derived concentrates?
The transmission of Creutzfeldt-Jakob disease (CJD) and variant CJD.
Effects and side effects
How do clotting factor concentrates affect hemostasis?
Correct the underlying clotting defect, which may lead to thrombotic complications in patients with clotting factor deficiency and coexisting risk factors for thrombosis or disseminated intravascular coagulation (DIC).
What clotting factor products should be used with caution in patients at risk for thrombosis or DIC?
- FEIBA (Factor VIII Inhibitor Bypass Activity)
- Factor XI (FXI) concentrate
- Recombinant Factor VIIa (rFVIIa)
What are the precautions for using Prothrombin Complex Concentrate (PCC) and Activated Prothrombin Complex Concentrate (aPCC)?
Not indicated for liver disease, DIC, or patients with active arterial/venous thromboembolism or thrombotic risks.
Can cause myocardial infarction or intracardiac thrombus.
Contraindicated in those with a history of heparin-induced thrombocytopenia (HIT) due to heparin presence.
What is the maximum dosage for FEIBA?
Should not exceed 200 IU/kg/day.
What are the risks associated with Hemlibra® (emicizumab) prophylaxis in combination with PCC or aPCC?
Increased risk of thromboembolism and thrombotic microangiopathy (TMA).
aPCC should not exceed 50 IU/kg/dose or 100 IU/kg/day with TMA monitoring.
PCC/aPCC should not be used for 6 months after Hemlibra® has been stopped due to Hemlibra’s long half-life (~4 weeks).
What is the maximum dosage for Factor XI concentrate?
Should not exceed 30 IU/kg per dose.
What has been reported in patients with von Willebrand disease (VWD) treated to raise FVIII levels during surgery?
Thrombosis has been reported when FVIII levels exceed 200 IU/dL (2 IU/ml).
What should be avoided when using PCC and aPCC (including FEIBA)?
Antifibrinolytic therapy should be avoided.
What concentrates contain heparin and should be avoided in patients with a history of HIT?
A:
Factor VII concentrate (Takeda), FX®P (CSL-Behring), FXI concentrate (BPL), FIX Immunine® VH (Takeda), PCC Beriplex® P/N (CSL Behring), PCC Octaplex® (Octapharma), Antithrombin III NF (Takeda).
1- How can minor allergic reactions to protein products be prevented?
2- What should patients on home therapy have on hand to manage serious allergic reactions or anaphylaxis?
1- By pre-medicating with antihistamines.
2- Epinephrine (e.g., Epipen®).
What can be done if an allergic reaction occurs during treatment with a protein product?
A similar concentrate from a different manufacturer can be used for subsequent treatment, which may not cause an allergic response.
Why should caution be exercised with some recombinant concentrates or products?
They may contain trace amounts of non-human proteins. Manufacturers suggest caution in patients with known allergies to these proteins.
What is unique about recombinant porcine FVIII?
It contains porcine protein.
What severe allergic responses may occur in hemophilia B patients?
**Severe allergic reactions, including anaphylaxis, can occur when patients develop inhibitors to factor IX (FIX) concentrates.
When are hemophilia B patients most likely to develop inhibitors and allergic responses?
Usually early on during treatment with FIX concentrate in severe hemophilia B patients.
Where should newly diagnosed severe hemophilia B patients be treated during their initial treatments?
In a setting equipped to manage severe allergic reactions, especially during the first 10-20 treatments.
Storage
What is required for long-distance transportation of clotting factor concentrates stored at 2–8°C?
Transport in validated containers cooled with cold packs.
They are stable until the printed expiration date when stored at the specified temperature.
Can clotting factor concentrates be stored at room temperature (RT)?
Some concentrates can be stored at RT (usually ≤25°C or ≤30°C) for a specified period after removal from refrigeration.
What must be done when clotting factor concentrates are removed from refrigeration for storage at RT?
The date of removal from refrigeration must be clearly marked on the box.
Can RT-stored concentrates be returned to refrigeration?
No, manufacturers do not recommend returning RT-stored concentrates to refrigeration.
Should clotting factor concentrates be stored at freezing temperatures?
No, storage at freezing temperatures should be avoided.
How are clotting factor concentrates packaged for Canadian patients?
Supplied with a kit for reconstitution and infusion, usually with the appropriate diluent.
Almost all clotting factor concentrates available to Canadian patients are supplied in packages containing a kit for reconstitution and infusion, usually with the appropriate diluent.
What proprietary devices do many manufacturers provide for reconstitution?
Devices for transferring diluent into the vial with the lyophilized concentrate and for withdrawing the dissolved concentrate to syringes for infusion.
What should be followed during reconstitution of clotting factor concentrates?
The reconstitution instructions in the product insert and aseptic techniques.
What is the ideal temperature for vials of diluent and concentrate before mixing?
They should be at room temperature or pre-warmed to 20–37°C for refrigerated products.
How should the diluent be added to the vial containing the concentrate?
t should flow down the side of the vial wall, and the mixture should be swirled gently to allow dissolution.
Why should shaking be avoided during reconstitution?
Shaking may create bubbles/foam, which can lead to denaturation of proteins.
