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Products / Services
Plasma Components and Derivatives
There is a wide range of plasma products available with specific indications for their use. For the purpose of clarity, products produced by the component processing laboratories and relying on purely physical separation techniques will be defined as plasma components (e.g. fresh frozen plasma, cryoprecipitate). Those products derived from plasma pools and subjected to more complex chemico-physical processing (e.g. Kistler and Nistchmann alcohol fractionation method) will be referred to as plasma derivatives (e.g. albumin). The various products, usage guidelines and recommended dosage schedules are outlined below. Clinicians should be aware that all the products are antigenic and potentially capable of causing allergic or anaphylactic reactions. The patient should therefore be observed as for cellular products during the initial 15 minutes of any transfusion. The information is provided as a guideline only. For further information please refer to the Medicines Control Council approved package inserts for plasma derivatives.
8.1. Plasma Components
a. Fresh Frozen Plasma (FFP)
Plasma for FFP is separated from anticoagulated whole blood within 18 hours of donation. This is done by centrifuging whole blood in a closed sterile system and freezing the plasma to below -18 oC. It contains all the coagulation factors at normal physiological levels. During the past 5 years, the transfusion services have in most areas introduced a donor plasma retest quarantine program (also for cryoprecipitate and cryo-poor plasma) to minimise the risk of a window period infection. In areas where this program is not in place, only plasma from regular donors is used. No pathogen transmissions have been reported since the introduction of the program. However, patients likely to receive large or repeated doses may benefit from pathogen inactivated plasma (see 8.2).
Table 1
| Product |
Volume |
Content |
Dosage |
| Fresh Frozen Plasma |
Approx 280 ml |
Physiological levels of all coagulation factors |
15-20 ml/kg as an initial dose. Further therapy is dependent on clinical response and laboratory monitoring. |
Table 2: Coagulation factor levels in FFP
| Factor |
Average Levels |
| Fibrinogen |
200mg per unit of FFP |
| Factor II |
1.03 IU/ml |
| Factor V |
0.64 IU/ml |
| Factor VII |
1.21 IU/ml |
| Factor VIII |
0.85 IU/ml |
| Factor IX |
0.95 IU/ml |
| Factor X |
1.25 IU/ml |
| Factor XI |
0.79 IU/ml |
| Antithrombin III |
104 IU/ml |
| Plasma pseudo-cholinesterase |
3000-10 000 IU/ml |
An average unit of FFP will also contain solutes of the anticoagulant from the original unit of whole blood.
Table 3: Solutes in FFP
| Solutes |
Average Levels |
| Glucose |
24.8 mmol/L |
| Potassium |
3.2 mm/L |
| Sodium |
165 mmol/L |
| Chloride |
79 mmol/L |
| Osmolarity |
322 mmol/L |
| pH |
7.9 |
Caution: FFP is hyperosmolar due to the solutes listed. In elderly and very young patients, care should be taken not to precipitate pulmonary oedema if cardiopulmonary function is compromised and tissue oedema is present. Hypernatraemia and hypokalemia may occur if large volumes are transfused.
Table 4: Clinical Indications for FFP
| Indications |
No justification for use of FFP |
| Replacement of inherited single factor deficiencies (if single factor concentrate not available). |
Hypovolaemia |
| Multiple Coagulation factor deficiencies (DIC, massive blood transfusion, liver disease) in presence of active bleeding and abnormal coagulation screening tests. |
Plasma Exchange procedure (except TTP) |
| Thrombotic thrombocytopenic purpura (TTP) (preferably cryo poor plasma). |
Nutritional support and protein losing states |
| Reversal of Warfarin if active bleeding: preferable to use Prothrombin Complex Concentrate (PCC) e.g. Haemosolvex Factor IX |
|
| Vitamin K deficiency associated with active bleeding |
|
| Scoline Apnoea |
|
| Paediatric use: Haemorrhagic Disease of Newborn: use FFP and intravenous Vitamin K |
|
FFP must be administered through a blood giving set after thawing at 30-37 oC. The unit should be transfused as rapidly as possible (15-20 minutes per unit) with a recommended maximum delay after thawing of up to 4 hours, as labile coagulation factors deteriorate within a few hours of thawing or reconstitution. The first choice is to administer FFP of the same ABO blood group as the patient. If not available, a different ABO group can be given provided the anti-A and B titres are low. Blood group 0 FFP should preferably be given only to group 0 patients. Group 0 should especially be avoided in non group 0 neonates since this may result in haemolysis from passive infusion of anti-A and B.
b. Cryoprecipitate
This is the cold insoluble fraction of FFP and is obtained by thawing FFP at 0-4 oC. It is stored at ‹-18 oC for up to 1 year and the mean volume is 0-15ml.
It contains the following proteins in concentrated amounts:
- Factor VIII and von Willebrand Factor ± 100 IU per unit
- Fibrinogen 150-250 mg per unit
- Fibronectin
- Factor XIII
It is indicated primarily for treating hypofibrinogenaemia (acquired or congenital) and is usually administered in pools of 10 units and is given through a standard blood administration set. It may also be used for treating hereditary Factor XIII deficiency.
c. Cryosupernatant (cryo-poor FFP)
This is the component available following extraction of cryoprecipitate. It is
stored in limited quantities and is the component of choice in many haematology
units for the treatment (with or without plasma exchange) of thrombotic
thombocytopaenic purpura (TTP). For protocol guidelines, please refer to the
nearest specialist haematology unit.
8.2. Plasma Derivatives
a. Bioplasma FDP (Fresh Human Plasma: lypholised powder for IV infusion)
Bioplasma FDP (from National Bioproducts Institute - NBI) is produced from pooled fresh human plasma from non-remunerated, volunteer donors. It undergoes a pathogen inactivation procedure using a solvent detergent treatment process which inactivates lipoprotein-coated viruses such as HIV, hepatitis B and hepatitis C. After reconstitution with water for injection, each 100 ml contains 4-6 g plasma proteins and a minimum of 0.4 IU/ml of each coagulation factor. Bioplasma FDP has the same clinical indications as FFP at the same recommended dosage. This product is available either as a 50 ml or 250 ml pack size and infused through a standard blood administration set. It can be stored at room temperature (below 25 oC). This product contains no antimicrobial agent or preservatives.
Table 5: A comparison of standard fresh-frozen plasma (FFP) with solvent detergent-treated FFDP
| |
Standard FFP |
Solvent detergent FDP |
| Source |
Single unit format. Voluntary, non-remunerated donors |
Voluntary non-remunerated donors; pools of up to 220 L |
Donation screening
Serology
Genomic |
HIV, HBV, HCV, Syphilis
HIV, HBV, HCV |
HIV, HBV, HCV, Syphilis HIV, HCV, HCV |
| Volume |
±250 ml |
200 ml; 50 ml |
| Coagulation factor content |
Physiological levels, variable between units (see Table 2) |
Constant within batch. All factors > 0.4 IU/ml. |
| Residual additives |
Solutes as per Table 3 |
Residual Levels of solvent detergent not toxic. |
| Allergic reactions |
May be reduced by leucocyte depletion |
Probably less frequent than FFP but no data. |
| Red cell |
Tested for high titre anti-A,B. If > 1 /64 - not used for FFP |
High titre Anti-A,B not a problem since donations pooled. Screen out high titre anti-A,B |
| Cellular content |
No need to Rh-D match. |
No need to Rh D match |
| Product licence |
Not required |
Licensed, batched product |
| Indications |
See Table 4 |
As for FFP – see Table 4 |
b. Coagulation Factor Concentrates
Haemosolvate Factor VIII 300 IU/500 IU
This is an intermediate purity Factor VIII concentrate produced by NBI and prepared from freshly frozen plasma pools. It is reconstituted into 10 ml volumes for direct intravenous injection and is clinically indicated for the treatment of Haemophilia A and von Willebrand's Disease (vWD). It undergoes a viral inactivation step using a solvent-detergent process which inactivates lipid-¬enveloped viruses such as HIV, hepatitis B and hepatitis C. See Table 6 for further details and also refer to the package insert.
Haemosolvex Factor IX
This is a prothrombin complex concentrate produced by NBI and prepared from fresh plasma and contains prothrombin, factor VII, factor X and factor IX. It is reconstituted to a volume of 10 ml for direct intravenous injection. It is indicated in the management of haemophilia B and the treatment of warfarin induced bleeding. It undergoes a viral inactivation step using a solvent-detergent process which inactivates lipid-enveloped viruses such as HIV, hepatitis B and hepatitis C. Refer to Table 6 and the package insert for further details.
VIAHF
This is an intermediate purity Factor VIII concentrate produced by Western Province Blood Transfusion Service (WPBTS) from small pools (5-6 bags) of cryoprecipitate. It is reconstituted into 50 ml volumes with sterile water for injection and is administered through a standard blood administration set. It is indicated for the treatment of Haemophilia A and vWD. It undergoes a viral inactivation procedure (80 oC heating for 72 hours) that has been shown to inactivate HIV, hepatitis B and C viruses.
Table 6: Coagulation factor concentrates
| Product |
Content |
Units |
Volume |
| VIAHF 250 (WPBTS) (Paediatric) |
Factor VIII/vWF |
250 IU |
50 ml after reconstitution with sterile water |
| VIAHF 500 (Adult) (WPBTS) |
Factor VIII/vWF |
400 – 600 IU |
As above |
| Haemosolvate Factor VIII 300 IU (NBI) |
Factor VIII/ vWF |
factor VIII:C 300 IU; factor VIII:vWF ->300 IU;. |
10 ml after reconstitution with sterile water for injection |
Haemosolvate Factor VIII 500 IU (NBI)
Two pack sizes: 500 IU and 2 x 500 IU |
Factor VIII/ vWF |
factor VIII:C 500 IU; factor VIII:vWF ->500 IU |
10 ml after reconstitution with sterile water for injection |
| Haemosolvex Factor IX (NBI) |
Factor IX (also contains II, VII and X) |
factor IX 500 IU (50 IU/ml), factor II > 400 IU, factor VII>65 IU and factor X > 400 IU |
10 ml after reconstitution with sterile water for injection |
c. Dosage schedules and treatment guidelines
For details refer to your local haemophilia centre. It is important that all haemophiliacs or any patient with an inherited bleeding disorder be registered with the South African Haemophilia Foundation and referred to the nearest haemophilia centre.
Haemophilia A
The levels of Factor VIII should be monitored throughout therapy. However, in an emergency or in remote areas dosage schedules may have to be empirically applied. For major surgery in haemophilia and treatment of severe haemorrhage it is strongly recommended that this be undertaken under the supervision of a practitioner experienced in haemophilia care and with reliable laboratory monitoring.
Factor Vlll has an average half-life of 12 hours. Treatment should therefore be given every 8-12 hours for the first 24 hours and then approximately 12 hourly. After major surgery Factor VIII infusions may be required for up to 10 days post-operatively. The dosage (in units of Factor VIII) can be estimated as follows:
Required dose (IU Factor VIII) = body mass (kg) x 0.5 x desired FVIII increase (% of normal).
SA Haemophilia Foundation recommendations:
Dose depends on severity of bleeding
- Minor Bleed : 15-25 IU/kg
- Major Bleed : 40 IU/kg
Expected response: 1 IU/kg = 2% rise in Factor VIII level
Major bleeds often require laboratory monitoring.
- Round off dose to nearest vial/container, do not discard excess concentrate.
Transfusion of factor concentrates should be rapid. Patients should be observed for any adverse reactions, particularly those of an allergic nature.
Continuous infusion regimens have also been utilised and may well provide more consistent haemostatic levels.
Approximately 10% of haemophilia A patients acquire antibodies (inhibitors) to Factor VIII and may not respond to therapy. Emergency referral to a haemophilia centre is required.
von Willebrand Disease (vWD)
Haemosolvate Factor VIII and VIAHF concentrates are the treatment of choice when DDAVP (a vasopressin analogue) is not indicated or ineffective. Both concentrates contain high molecular weight multimers.
Dosage recommendations vary and the best methods of monitoring the response are clinical assessment and measurement of Factor VIII levels. Initial dosage recommendation is 30 IU Factor VIII concentrate per kg body weight. Laboratory monitoring should be every 24 hours with regular interim clinical observation.
If significant bleeding persists despite Factor VIII infusions, cryoprecipitate and platelet concentrates may be efficacious.
Haemophilia B
The clinical picture of haemophilia B (Factor IX deficiency) is identical to that of haemophilia A. The levels required are similar to those for Factor VIII, although slightly lower levels of Factor IX are usually adequate for normal haemostasis. Factor IX has a longer half-life (16-30 hours) and therefore once daily dosage is often sufficient.
The dosage (in units of Factor IX) can be estimated as follows: Required dose (IU) = body weight (kg) x desired FIX increase (%) x 1.2
SA Haemophilia Foundation recommendation:
- Minor Bleed : 15-25 IU/kg
- Major Bleed : 40 IU/kg
Expected response: 1 IU/kg = 1.5% rise in Factor VIII level Severe bleeds often require laboratory monitoring
If therapy with high doses for >5 days treatment is required, the patient should be carefully monitored for development of thrombosis, which has been reported in some prothrombin complex concentrates. Thrombosis, however, has never been reported in association with Haemosolvex.
d. Plasma volume expanders
Albumin
- Albusol 4% Manufactured by NBI
- Albusol 20% Manufactured by NBI
- WPBTS 20% Albumin Manufactured by WPBTS
Protein Solution
- Stabilised Human Serum (SHS) Manufactured by WPBTS
All the above are prepared from pooled human plasma from volunteer, non¬remunerated donors. Each donation has been individually tested by serologic and nucleic acid amplification technology for HIV, hepatitis B and hepatitis C and is non-reactive for these tests. Albumin solutions are prepared by ethanol fractionation which further reduces the risk of viral transmission. The albumin solutions are sterilised by filtration and finally pasteurised by heat for 10 hours at 60 oC, a process validated and shown to inactivate HIV, hepatitis B and hepatitis C viruses. SHS is prepared by selective absorption of lipoprotein, coagulation proteins and complement components. Potential viral pathogens are reduced by this process and ultra violet irradiation plus a heat treatment step validated as a viral inactivation procedure for HIV.
Albusol 4% is a sterile solution containing 4% m/v human plasma albumin and is available in 200ml volumes (8 g/200 ml). It is stabilised with 0.16 mmol sodium caprylate per gram protein and 3% m/v dextrose. The solution is at pH 7.0 and each litre contains less than 130 mmol sodium, less than 2 mmol potassium and less than 4 mmol citrate.
Albusol 20% is a sterile solution containing 20% m/v human plasma albumin, available in 50 ml (10 g/50 ml) and 100 ml (20 g/100 ml) volumes. It is stabilised with 16 mmol/l acetyl tryptophanate and 16 mmol/l sodium caprylate. The solution is at pH 7.0 and contains less than 100 mmol/l sodium, less than 10 mmol/l potassium and less than 20 mmol/I citrate.
WPBTS'S 20% albumin is a sterile solution containing 20% m/v human plasma albumin and available in 50 ml (10 g/50 ml) and 100 ml
(20 g/100 ml) volumes. It is stabilised with sodium caprylate and is at pH 7.0. It contains less than 130 mmol/l solution and less than 10 mmol/l potassium.
SHS is a stable protein solution containing IgG, IgA and IgM antibodies, albumin and transport proteins. It is available as a 5% solution (50 g/l protein) in 50 ml and 250 ml volumes. The solution is at pH 7.5 and contains 130 mmol/l sodium, 3.5 mmol/l calcium and 130 mmol/l chloride.
Clinical Indications
Blood volume expansion:
Fluid resuscitation in acute clinical conditions associated with hypovolaemia (e.g. trauma) remains controversial. It is not the intention of this guideline to provide a comprehensive review of the subject but the following is a short summary of current opinions and practice.
- The initial resuscitation fluid of choice for volume expansion is a crystalloid solution, probably a balanced salt solution, although an ideal solution does not exist.
- If further therapy is required after 2-3 L of crystalloids have been infused, it is appropriate to continue with a colloid solution. Which colloid to use depends to some extent on the duration of effect required and cost considerations.
- An ideal colloid should have a molecular weight of ± 70 kDa (MW albumin 69 kDa; gelatin 30 kDa; HES 60-70 kDa; Dextrans 40-70 Kda).
- Adverse reactions should be minimal; a meta-analysis published in 2004 showed that albumin proved to be the safest of 4 colloids reviewed (albumin, dextrans, HES, gelatine).
- Costs: synthetic colloids are cheaper than plasma colloids.
- Since there are no clinical trial data to support a clear cut therapeutic advantage for either crystalloids or colloids, the final choice of fluids for resuscitation is ultimately influenced by individual clinician experience and cost considerations.
Replacement fluid following Paracentesis:
- Albumin is beneficial in preventing acute complications of hyponatraemia and renal impairment.
Therapeutic plasma exchange:
- Albumin is the replacement fluid of choice for most procedures. The exception is TTP, where FFP or cryosupernatant are indicated.
Burns:
- Often used after the first 24 hours in severe burns but there is a lack of randomised clinical trials.
Nephrotic Syndrome:
- May have a short term limited role in combination with diuretics for the Control of oedema, where diuretics alone have failed.
Refer to package inserts for dosing guidelines.
Albumin solutions appear to have no useful role in malnutrition, cirrhosis and chronic nephrotic syndrome.
The above protein solutions should not be given to any patient with a known sensitivity or allergy to human proteins.
e. Immunoglobulins
Immunoglobulin is the antibody-containing fraction of human plasma obtained by fractionation of pooled plasma units. Each unit has been individually tested and found non-reactive for hepatitis B, HIV and hepatitis C using both serological and nucleic acid amplification technology.
Products
- This is a concentrated IgG immunoglobulin for intravenous use prepared by cold
ethanol fractionation and pH 4.0 pepsin treatment. The pH 4.0 pepsin process has been validated and shown to be effective against enveloped viruses such as HIV, HBV and HCV. It is available as a lyophilised powder and is reconstituted to a 50 ml volume (1 g/50 ml 2% solution); a 100 ml volume (3 g/100 ml 3% solution); a 200 ml volume (6 g/200 ml 3% solution) and a 400 ml volume (12 g/40 ml 3% solution).
Clinical Indications (see Table 7)
- Replacement therapy in primary antibody deficiency syndromes - Myeloma or chronic lymphocytic leukaemia with severe hypogammaglobulinaemia and recurrent infections
- Children with congenital AIDS and recurrent infections
- For immunomodulation in:
- Idiopathic thrombocytopaenic purpura (ITP) in children and adults
- Kawasaki Disease Guillain Barré Syndrome
- Allogeneic bone marrow transplantation
Polygam should be given with caution to patients with antibodies to IgA or selective IgA deficiency, as the small amount of IgA present in Polygam may cause sensitisation. This could lead to a severe allergic reaction and anaphylaxis or subsequent reactions to other IgA containing products.
Immunoglobulins for intramuscular injection (Click here to view Table 8): These are produced from the same donor pool as above and screened in identical fashion. There are various preparations available, mostly hyperimmune globulins with high titres for specific antibodies for passive immune prophylaxis.
Table 7: Intravenous Immunoglobulin (Polygam)
Dosage:
The dose and dosage regimen is dependent on the indication and the in vivo half-life of the IgG molecules in the individual patient. The following intravenous dosage regimens are given as a guideline only:
| Replacement Therapy in Immonodeficiency |
| Indication: |
Dose: |
Frequency of Infusions: |
| Primary immunodeficiency: |
Starting dose:
0,4 – 0,8 g/kg – thereafter:
0,2 – 0,8 g/kg |
every 2 – 4 weeks to obtain IgG trough levels of at least 4 – 6 g/l |
| Secondary immunodeficiency: |
0,2 – 0,4 g/kg |
every 3 – 4 weeks to obtain IgG trough levels of at least 4 – 6 g/l |
| Children with AIDS: |
0,2 – 0,4 g/kg |
every 3 – 4 weeks |
| Immunomodulation: |
| Indication: |
Dose: |
Frequency of Infusions: |
|
Idiopathic Thrombocytopaenic Purpura: |
0,8 – 1 g/kg
or
0,4 g/kg/day |
on day 1, may be repeated once within
3 days
or
for 2 – 5 days. May be repeated if relapse occurs |
| Kawasaki Disease: |
2 g/kg
or
1,6 – 2 g/kg |
as a single dose in conjunction with aspirin
or
in divided doses for 2 – 5 days in conjunction with aspirin |
| Guillain Barré Syndrome: |
0,4 g/kg/day |
for 3 – 7 days |
| Allogeneic bone marrow transplantation: |
| Indication: |
Dose: |
Frequency of Infusions: |
| Treatment of infections and prophylaxis of graft versus host disease: |
Starting dose:
0,5 g/kg
|
every week starting 7 days before transplantation and up to 3 months after transplantation |
| Persistent lack of antibody production: |
0,5 g/kg |
every month until antibody levels return to normal |
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