Background
- Haemophilia B is a bleeding disorder caused by a deficiency of clotting factor IX
- Incidemce 1:30,000 male
- x5 rarer than Haemophilia A
- Female carriers may have low FIX levels and ⅓ have levels similar to mild haemophilia (5-40% or 0.05-0.40 IU/ml)
- These affected females may also need treatment for bleeding, menorrhagia or prior to surgery or labour and delivery.
Severity
| Severity | Factor IX Activity Level |
|---|---|
| Severe disease | <1% (<0.01 IU/ml) |
| Moderate disease | 1–5% (0.01-0.05 IU/ml) |
| Mild disease | >5% (>0.05 IU/ml) |
Treatment Admin.
- Ensure to prescribe correct clotting factor concentrate e.g. i.e. Alprolix for FIX deficiency
- Not all may require clotting factor so consider an alternative e.g. TXA
- Confirm the patient's treatment of choice with the CCC (see Haemophilia A)
Clotting Factor Concentrate - Alprolix
Alprolix is the clotting factor concentrate used as the 1st line treatment and prophylaxis of bleeding in patients with FIX deficiency. Alprolix comes as a powder with an accompanying solvent of sodium chloride solution. Alprolix is administered as a bolus infusion.
Alprolix dose calculation
Bolus Dosing in FIX Defic. CFC: Alprolix
Rise required = desired level of factor concentrate (%) minus baseline factor level (%).
(Note: 100% = 1.0 IU/ml, 50% = 0.5 IU/ml, 5% = 0.05 IU/ml).
K factor for FIX = 1
Example
| Bleeding Site | Target post Rx FVIII & FIX factor levels |
|---|---|
| Major bleed | 1.0 IU/ml (100%) |
| CNS or bleed involving peripheral nerve | 1.0 IU/ml (100%) |
| Ileopsoas / retroperitoneal | 1.0 IU/ml (100%) |
| Tongue / neck / retropharyngeal | 1.0 IU/ml (100%) |
| Gastrointestinal | 1.0 IU/ml (100%) |
| Haemarthrosis | 0.5 – 0.7 (50% - 70%) IU / ml |
| Minor bleed | 0.5 IU / ml (50%) |
| Laceration requiring suturing / ROS | 0.4 IU / ml (40%) |
| Haematuria | ↑ fluid intake ± rise to 0.3-0.5 IU/ml (30%-50%) |
| Minor surgery (angiogram, LP) | 1.0 IU/ml (100%) |
| Liver Bx or central venous catheter | 1.0 IU (100%) |
| Major surgery | 1.0 IU (100%) |
Alprolix dose admin.
- Given slow IV push (max 10mL/min)
- A sample for post treatment factor level should be drawn 20 minutes' post administration (two coagulation samples sent to local laboratory for forwarding to the CCC for analysis)
- Liaise with CCC regarding the post treatment level result in case further treatment is required.
TXA - Tranexamic Acid (Cyklokapron)
TXA (PO or IV) is an anti-fibrinolytic agent, indicated in patients with haemophilia for short-term use (2-8 days), to reduce or prevent haemorrhage.
TXA dose
- PO (500mg tablets) given as 1g q8h
- IV (500mg in 5ml ampoule) given as 10mg/kg q8h
PO TXA contraindications/cautions
PO TXA Contraindications
- Severe renal impairment
- SAH
- Hx venous or arterial thrombosis
- Fibrinolytic conditions
- Hx of convulsions
- Hypersensitivity to TXA/tablet
PO TXA Cautions
- ↓dose in renal impairment
- Caution in upper GU massive haemorrhage
- Caution when active intravascular coagulation
- Caution in high VTE risk (eg PE/DVT Hx)
- Caution if on OCP (↑risk thrombosis)
IV TXA contraindications/cautions
IV TXA Contraindications
- Hypersensitivity to TXA/ingredient
- Acute venous or arterial thrombosis
- Fiibrinolytic conditions except in those with predominant activation of the fibrinolytic system with acute severe bleeding
- Severe renal impairment
- Hx of convulsions
- Intrathecal and intraventricular injection, intracerebral application (risk of cerebral oedema and convulsions)
- TXA should not be given IM
IV TXA Cautions
- Convulsions
- Visual Disturbances
- Haematuria
- Thromboembolic events
- On OCP (↑ risk thrombosis
- DIC
- More at National treatment guidelines (CUH Intranet)
Caution when giving TXA to receiving FEIBA or recombinant factor VIIa (risk of thrombosis)
Patients with Factor IX deficiency and inhibitors
- Inhibitors (antibodies against infused FIX concentrate) occur less commonly in FIX deficiency (Haemophilia B) in comparison to FVIII deficiency (Haemophilia A)
- Incidence of inhibitor development ≈3%
- Rarely occurs after 150 exposure days
- A very small number of patients have persistent, high responding inhibitors and these patients cannot receive FIX concentrate to treat or prevent bleeding but should receive alternative treatment with bypassing agents (see below)
- It is important to identify patients with FIX deficiency that have a current or past Hx of inhibitors
- The presence of inhibitors in Factor IX deficiency may be associated with anaphylactoid reactions and the development of nephrotic syndrome
In all cases where there is a history of an inhibitor, it is crucial to contact the patient's CCC to confirm the patient's optimal treatment regimen
Please ask about:
- Is inhibitor present currently or in past history?
- What is patient's current treatment of choice?
- Has patient ever received Immune tolerance treatment? If yes, when was this given and did the patient achieve eradication of the inhibitor?
- Does the patient have a history of anaphylactoid reactions or of nephrotic syndrome following Factor IX administration?
Mx options in Factor IX patients with inhibitors
Bypassing agents (BPA) are clotting factor concentrates designed to "bypass" the need for FIX and are given when the patient's inhibitor titre means that FIX concentrates will not be effective (high responding inhibitors).
There are two bypassing agents available in Ireland:
- Feiba – an activated prothrombin complex concentrate (aPCC) containing factors II, VII, IX and X. The clotting factors are present in their inactive (zymogen) form and also in an activated form, as activation occurs as part of the manufacturing process. Feiba is derived from human blood donations and the product is dual virally inactivated
- NovoSeven – recombinant activated factor VII (rFVIIa) can activate Factor X on the surface of activated platelets and thus, overcome the absence of FIX. The dose of activated factor VII is supra-physiological (about 10 times the normal level of FVII in the blood). NovoSeven is a fully recombinant clotting factor and does not contain human derived material
Please leave dosing, administration and management of these complicated cases to the haematologists.
More information at National treatment guidelines (CUH Intranet).