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4.2 Blood Transfusion Science > Plasma Products > Flashcards

Plasma Products Flashcards

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1
Q

What are the two main types of frozen plasma used?

A

Octaplas - pooled plasma

fresh frozen plasma - single donor

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2
Q

What are he differences between octaplas and fresh frozen plasma?

A

Octaplas:
- made from pooled plasma
- hence only ABO grouped not Rh -> as no red cells present thus only concerned with what antibodys are present

FFP:
- made from a single donor
- will be Rh typed as there will be a small amount of red cell contamination

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3
Q

What is the new kind of plasma were looking at using?

A

Thawed plasma

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4
Q

What is thawed plasma, whats different about it to ffp?

A

This is frozen plasma which has been thawed and kept for about 5 days in the fridge

Thawed plasma has considerably different coagulation factors but you dont need 100% factor activity for good activation of coagulation pathway

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5
Q

how much % factor activity is needed for activation of the coagulation pathway?

A

About 25% only is needed

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6
Q

What two POC devices are used to monitor need for plasma transfusion?

A

TEG or ROTEM
-> these look at coagulation factors to guide the use of ffp

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7
Q

Talk about the use of cryoprecipitate?

A

We dont use it in Ireland anymore - we use products instead

Most of th world still use cryoprecipitate made from their own plasma though

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8
Q

When was ffp first put into use, what was its initial use

A

FFP has been available since 941
It was initially used as a volume replacement
Plasma used to be given on a formulaic bases e.g. one unit given for x amount of red cells etc -> this isnt done anymore but can often be seen in major haemorrhage packs because of this

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9
Q

When did we stop using FFP as a volume expander?

A

When albumin and hydroxyethyl starch became more available

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10
Q

Nowadays when do we use FFP?

A

We have a better understanding that FFP is contraindicated for volume expansion and instead we use it in cases of excessive bleeding or to prevent bleeding in patients with abnormal coagulation tests that are undergoing an invasive procedure

We usually wont give plasma if patient is bleeding unless there is a coagulopathy

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11
Q

Why did we stop using donor plasma in Irealnd

A

Studies showed that plasma was a major source of prions in 68% of cases while only 26% were present on platelets and the remainder on red cells and leucocytes -> however this sudy has since been contested

There has never been a case of plasma transmitted vCJD

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12
Q

How many mls is a ffp unit when derived from a whole blood donation?

A

1 uni = 250mls

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13
Q

How do we make cryoprecipitate?

A

Made by frezing plasma from whole blood donation
Then thawing the pack to 4 degrees whereby a white precipitate will form in the pack
This precipitate can then be separated and taken off to form cryoprecipitate and cryoprecipitate depleted plasma

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14
Q

What is cryoprecipitate composed of?

A

Its mostly fibrinogen and some von willebrand factor hence why its great for coagulation

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15
Q

Is cryo still available in Irealand?

A

Yes you can still order it from the IBTS
Its used to treat TTP

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16
Q

What is the difference between the treatment of octplas and ffp?

A

Octplas is pathogen reduced by solvent detergent treatment

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17
Q

How is plasma treated in the UK?

A

SD treated using methylene blue

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18
Q

How is fresh frozen plasma produced

A

Separation and freezing to -30 degrees within 6-8 hours of donation

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19
Q

What are the two different types of fresh frozen plasma that can be made, how do they differ from each other?

A

FFP from a whole blood donation
FFP from an apheresis donation

From whole blood only 200-220 mls
Apheresis can be up to 600mls

Apheresis can be stored at -18 degrees for 1 year

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20
Q

How is ffp utilised?

A

Thawed at -37 degrees celsius in a waterbath

Must be transfused asap within 2-4 hours

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21
Q

How can octaplas be stored after thawing

A

can be stored at room temperature for up to 4 hours but can be kept at 4 degrees for up to 8 hours

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22
Q

what is the shelf life of octaplas

A

Since july 2005 it an be stored at -18 degrees celsius for up to 4 years

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23
Q

How is dosage of ffp determined?

A

Dosage depends on the clinical situation but its typically 10-15mls/kg body weight

Clinical response may be the best monitor but lab tests also important

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24
Q

Talk about the use of the new product, thawed plasma and its storage?

A

Thawed plasma stored at 4 degrees for up to 5 days

NB in trauma packs in the US as well as ireland

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25
Q

What factors have the shortest half lifes?

A

Factor VIII (half life of 12 hours)
Factor VII (half life of 5 hours

i.e. half of the factor is gone after x amount of hours post transfusion -> factors dont remain in patients system for long -> need to be aware of this if patient has a specific deficiency, will need to top up prior to transfusion and need to make sure patient wont run out in the mean time

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26
Q

From who do we get plasma donations?

A

We use volunteer donors from america

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27
Q

Talk about the affect of thawing on plasma, how are factors affected

A

Thawed plasma can be stored for up to 5 days
-> there is no affect on fibrinogen concentration
-> only a 1% drop in FII
-> 16% drop in FV
->20% drop in FVII
->41% drop in FVIII
->6% drop in FX

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28
Q

What is fp24?

A

Frozen plasma which has not been frozen within the initial 24 hours post donation

fp24 ha less FV and protein C but will have more FVIII than fresh frozen plasma

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29
Q

What is the minimum % activity of FV needed for haemostasis?

A

25% activity

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30
Q

What is the minimum activity for haeemostasis of FVIII?

A

30%

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31
Q

What is the main challenge with using plasma?

A

Plasma can be a life saving therapy for patients in need of haemostatic assistance but there is a lack of consensus around definition of the circumstances when this component will truly benefit a patient

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32
Q

How should you choose the right plasma group?

A

FFP is labelled with ABO and RhD groups

First choice would be the same ABO group but if not available then give A or B or vice versa

Avoid group O with high - titre -> should only be given to group O as it will have anti-A and anti-B

AB plasma is very useful and can be given to all -> AB Octaplas was previously known as Uniplas

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33
Q

Talk about factor level differences between blood groups

A

FVIII and vWF levels are up to 25% lower in group O individuals

This increases risk of venous and arterial diseases in A, B and AB individuals

ABO group may effect the rate of synthesis or release of vWF from endothelial cells

ABO Group may affect the proteolytic cleavage of vWF - related to the level of a protease called ADAMTs13 which is higher in group Os

There are ABO sites on both vWF and on ADAMS13 protease

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34
Q

What group is ADAMTS13 highest in?

A

Highest in group Os

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35
Q

Deficiency of ADAMTS 13 results in what condition?

A

TTP

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36
Q

What is ADAMTS13?

A

A protease which is responsibly for the proteolytic cleavage of vWF

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37
Q

How is TTP treated?

A

Cryodepleted plasma is used as it lacks VWF

Exchange transfusion with this plasma

This gives patient the plasma they need without the VWF causing the thrombus

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38
Q

What happens after ADAMTs13 cuts vwf

A

They go around the body attached to factor 8

But there are problems with this in group O

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39
Q

When was octaplas introduced into Ireland

A

Octaplas, a FFP substitute was introduced into Ireland in 2002

This was to help preven the possible transmission of vCJD

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40
Q

Talk about Octaplas

A

A blood specific plasma product

It contains up to 1,500 single donations from unpaid, screened donors

This undergoes a solvent/detergent treatment process

AB Octaplas is not blood group specific though

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41
Q

What is AB Octaplas made of?

A

70% A
20% B
10% AB

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42
Q

What are the steps in the manufacture of octaplas

A

fast thawing
complete cell, cell debris and aggregate removal hrough a 1um filter
SD treatment for 4 hours at 30 degrees
oil extraction and phase separation
clear filtration
hydrophobic bio-interaction chromatography to remove triton x
sterile 0.2um filtration
aseptic sealing and filling of bags
fast freezing to -60 degrees
storage below -30 degrees
complete quality control and batch release

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43
Q

what does SD treatment of octaplas involve?

A

treatment for 4 hours AT 30 degrees of:
- 1% TNBP
- 1% TRITON-X

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44
Q

Why is the oil extraction and phase separation step of octaplas production needed

A

this is needed to remove the TNBP

45
Q

How is TRITON-X removed from octaplas

A

Hydrophobic bio-interaction chromatography

46
Q

What can be the benefit of using octaplas over fpp from an individual donor

A

You can get the exact coagulation factor levels for a batch of octaplas but you cant for fresh frozen plasma as this is from an individual donor

47
Q

What are some of the indications for the use of octaplas?

A

In bleeding or pre-op patients for:
- replacement of single factor deficits
- neonates with coagulopathy who are bleeding or are facing an invasive procedure
- inherited deficiencies of inhibitor of coagulation where specific concentrates are not available -short term fix
- liver disease
- hereditary angioneurotic oedema

48
Q

Give an example of where plasma can be used in replacement of a single factor deficit

A

e.g. factor V deficiency

We have no virus-safe factor V commercially available

49
Q

Give an example of where inherited deficiencies of inhibitors of coagulation can be treated with plasma

A

AT 111
Deficiencies of inhibitors such as protein C and protein S

Certain hospitals will have concentrates available but other labs wont
FFP should be used though and not octaplas

Can also be used for DIC coagulapathy to stop coagulation -> less of these factors in octaplas

50
Q

Talk about plasma for liver disease

A

PT is used as a guide however plasma is debatable

Plasma is justifiable if liver biopsies are performed with high PTs -> 1.5 x midpoint of reference range in seconds

NB: liver disease is the same as being on warfarin in terms of factors affected

51
Q

what is hereditary angioneurotic oedema?

A

A congenital deficiency of C1-esterase inhibitor

52
Q

What was plasma previously used or

A

Warfarin reversal
-> its use for this today is questionable
-> only really done if evidence of bleeding

53
Q

what product is now used in place of plasma for warfarin reversal?

A

Prothromplex -> known as octaplex in ireland

54
Q

What factors are present in prothromplex?

A

FII, VII< IX and X

55
Q

What are the some specific indications for use of plasma

A

Warfarin reversal where bleeding is evident
DIC if in bleeding stage
Massive transfusion
TTP -> cryoprecipitate
Convalescent plasma for Ebola

56
Q

When is plasma indicated for DIC?

A

Only if bleeding with raised PT/APTT and low fibrinogen

57
Q

Talk about plasma for massive transfusion

A

Has to be guided by lab tests

Also through use of ‘near patient’ devices such as TEG

58
Q

What does TEG stand for?

A

Thromboelastogram

59
Q

Talk about plasma for TTP

A

Plasma as an exchange proecudre is used

Cryo or HMV-VWF poor plasma is ideal

60
Q

Talk about uses of convalescent plasma

A

Was used in covid - used in early treatment - over 1 million units were given in the USA but we neer did this in ireland

Only way of treating Ebola

61
Q

Talk about a use of plasma exchange other than TTP

A

Plasma exchange for myasthenia gravis
- Autoimmune condition caused by antibodies which can be removed through exchange to treat the condition

ITP -> platelets cross placenta during pregnancy

62
Q

What are two POCT devices used to guide plasma transfusion

A

TEG -> used more than rotem nowadays
ROTEM sigma

63
Q

How does ROTEM work

A

sample is loaded into a cuvette
a sensor pins detects clot formation by detecting restriction of pin movement as clot develops

64
Q

How does thromboelastography TEG work?

A

Look this up

65
Q

How does ROTEM present results?

A

Presents different’wine bottle’ shaped results

66
Q

When is plasma not indicated

A

formulaic replacement -> overuse common if this is done

Hypovolamia -> use cheaper crystalloids/colloids instead to increase blood volume

Immunodeficiency states - use of Ig is preferred

Vitamin K deficiency - corection with vitamin K reversal in 6-12 hours

67
Q

What are the adverse effects of plasma

A

Allergic reactions
Overload
Haemolysis due to potent ABO antibodies (FFP)
TRALI
HIV, Hep B, C and bacterial agents (negligible)
Anti-T antibodies when treating infants with necrotising enterocolitis
vCJD -< P-Capt filter from MacoPharma prevents this getting through

68
Q

Talk about allergic reactions to plasma transfusions

A

Anaphylactic reactions

1 in 20,000 recipients is at risk for this reaction since IgA deficiency is the most common congenital immunodificiency

69
Q

What causes TRALI in plasma transfusions?

A

Granulocyte antibodies in plasma causing acute pulmonary injury -> only occurs with FFP and not octaplas

70
Q

Talk about anti-T antibodies

A

T antigens are part of the MNs group
Bacteria with neuramidase enzymes can expose T antigens
Since all adults naturaly have anti-T antibodies against these crypt antigens
When plasma from adult donors is given to children suffering from certain bacterial infections they can have very serious reactions

71
Q

What are the three main strategies of viral inactivation of plasma?

A

Solvent/detergent treatment -> done on large pools

Methylene blue with visible light -> done on single units

Amotosalen -> an alternative to MB FFP fr single-donor virus-inactivated FFP and cryoprecipitate

72
Q

Where is Amotosalen licensed currenly

A

Licensed in Europe

Currently under consideration in the UK

73
Q

What pathogen inactivation is carried out on our products in Ireland

A

All other countries do some kind of vira inactivation of platelets but ireland doesnt do any

Only our octaplas is SD treated in Ireland

74
Q

What does SD treatment involve, how does it work/what does it affect?

A

Tri(n-butyl) phosphate TNBP + Triton-X

This disrupt the ‘lipid’ sructure of enveloped viruses e.g. HBV, HCV, HIV

Non-eveloped viruses are not affected e.g. HAV, Parvovirus B19 not affected

75
Q

Even though SD treatment doesnt work on non-enveloped viruses, why are we not concerned with these

A

Even if there was parvovirus present in the pooled plasma there would be enough anti-parvo antibodies present to negate it -> isnt a problem when transfused

76
Q

How does SD treatment affect clotting factors?

A

There is some loss of clotting factors

Particularly VWF multimers are lost

Protein S functional activity and reduced FVIII activity

77
Q

How does methylene blue with UV light work as a orm of viral inactivation

A

MB has an affinity for nucleic acids and viral core proteins

Visible light illumination then leads to the formation of singlet oxygen, hence photo-oxidative inactivation

Can be used to treat single units

Both enveloped and non-enveloped viruses are disrupted

78
Q

How are coagulation factors affected by Methylene blue

A

30% loss of fibrinogen and of FVIII activity

79
Q

What is theraflex-MB plasma

A

This is a method of MB-visible light vira inactivation

Intercalation of MB into nucleic acids
Excitation of MB by visible light
Oxidation of Guanosine
Degradation of nucleic acids

This blocks transcription and replication of viral RNA and DNA

80
Q

What kind of reaction is the MB + light reaction?

A

Photodynamic process

81
Q

How is MB removed from plasma?

A

Removed by filtration with Blueflex

Then frozen

82
Q

What is the principle of Amotosalen

A

Blocks the reproduction of pathogens by crosslinking DNA and RNA

83
Q

What are the four steps Amotosalen

A

Amotosalen targets helical regions of nucleic acid

Docking into DNA strands

Permanent crosslinking of DNA

Locked DNA/RNA now unable to replicate

84
Q

What is the Intercept system

A

the method of carrying out SD treatment of plasma using Amotosalen HCL

-> Amotosalen added, illuminated, CAD added and storage etc

85
Q

What is the new method of viral inactivation being looked at

A

Riboflavin and UV light

86
Q

Talk about Riboflavin and UV light viral inactivation

A

No removal after treatment is required as its just vitamin B6

Riboflavin damages any nuclear material when light is shone on it

87
Q

Talk about Riboflavin and UV light viral inactivation

A

No removal after treatment is required as its just vitamin B6

Riboflavin damages any nuclear material when light is shone on it

88
Q

Why dont we use riboflavin in Ireland

A

The IBTS trialed this for platelets but werent impressed with the platelet quality

89
Q

Talk about the concept of FFP donor retested

A

This concept allows for a window period after supposed infectivit of donor

Donor isnt paid for first donation

First unit is stored frozen for approximatelt 112 days

Donor is recalled to donated and is tested again

If still negative then your presuming first was negative

90
Q

What is the ideal product for TTP

A

Cryo-reduced plasma

91
Q

How many precipitates are pooled to make a pack of croprecipitate?

A

Between 4 and 6 units are pooled

92
Q

Where is cryoprecipitate commonly used?

A

Commonly used in the UK

93
Q

What do we use instead of cryoprecipitate in Ireland

A

We use commercial fibrinogen

However this is a lot more expensive so were looking at using cryo again

94
Q

Talk about the discovery of cryo

A

Originially developed in the 1960s as an advance on fresh whole blood treatment for haemophilia A

Prepared bby ‘slow thawing’ of FFP at 4 degrees/24 hours

Formed the source of fibrinogen for primitive ‘fibrin sealants’

95
Q

What exactly is cryoprecipitate?

A

An insoluble precipitate containing significants amount of fibrinogen, FVIII, vWF, FXIII

96
Q

What are currently the issues with using cryoprecipitate?

A

Difficult to virally inactivate
Difficult to standardise the factor content

97
Q

What are some indications for the use of cryoprecipitate?

A

Deficiency of fibrinogen, FVIII or vWF in massive bleeds

98
Q

When should cryo be used to replace fibrinogen

A

In congenital fibrinogen deficiency
In massive transfusion
Less often in DIC -> if bleeding

99
Q

When did we discontinue use of cryoprecipitate?

A

July 2009

100
Q

What did we replace cryoprecipitate with in Ireland?

A

Haemocomplettan P

RiaSTAP

101
Q

Talk about RiaSTAP

A

Most commonly used commercial fibrinogen
Fibrinogen of human origin
Heat and detergent treated unlike cryoprecipitate

102
Q

When was lyophilised plasma first used, why was it discontinued

A

First described and used in the 1930s

Became contraindicated as novel Blood-borne pathogens were discovered

103
Q

How is lyophilised plasma used?

A

Its reconstitued at point of transfusion within hospitals or in a pre-hospital setting

104
Q

Who uses lyophilised plasma today?

A

Only Germany and wales

Lyoplas-W-N by German Red Cross
-> lyophilised plasma from individual donors
-> used in flying squad -> for use in ‘golden hour’ -> can be the difference between someone bleeding out on a montain and making it through air lift to hospital etc

105
Q

How is lyophilised plasma stored?

A

Stored at 2-8 degrees for up to 2 years

Reconstituted in 200ml sterile water -> totoal preparation of 10 minutes

106
Q

What are the advantages and disadvantages of lyophilised plasma?

A

advantages:
- reduced preparation time
- ease of storage
- administration

disdvantages:
- no prion removal
- 10% reduction of clotting factor activity
- has same risk of adverse reactions as liquid plasma

107
Q

What is the alternative to lyophilised plasma now being looked at?

A

Spray Dried Plasma

108
Q

Talk about spray dried plasma

A

Forms a fine powder
redissolves much quicker than lyophilised -> less effort to reconstitute
250mls of saline needed
Not in use anywhere as of yet -> only being tested atm

4.2 Blood Transfusion Science (13 decks)

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