Viva Q1(iii)

What is blood plasma?
  • Plasma is the liquid non-cellular part of blood.
  • A pale straw coloured fluid with a specific gravity of somewhere around 1.022-1.026 (compared to the specific gravity of blood which is 1.052 to 1.061). 
How is plasma different to serum?
  • Serum is the liquid potion of blood that remains after the blood has clotted.
  • Most of the time, people refer to plasma instead of serum: "We use the term plasma preferentially to refer to the soluble proteome of the blood because it is the parent mixture" - Anderson & Anderson (2002)
What are the constituents of plasma?
  • Water: 90% by volume
  • Gases: Nitrogen, carbon dioxide, oxygen, traces of nitric oxide and hydrogen sulfide
  • Electrolytes: Sodium, chloride, bicarbonate, potassium, magnesium, calcium
  • Low molecular weight molecules: ​​​​​​Glucose, fatty acids, amino acids, vitamins, hormones
  • High molecular weight molecules: Blood proteins of numerous varieties (~70-80g/L)
What proteins are found in plasma?
  • Albumin
  • Globulins
    • α-1 globulins (α1-foetoprotein, α1-antitrypsin, α-lipoproteins)
    • α-2 globulins (ceruloplasmin, haptoglobin, plasminogen, thyroxin-binding globulin)
    • β-globulins (β-lipoproteins, CRP, transferrin, β2-microglobulin)
    • γ-globulins (immunoglobulins)
  • Fibrinogen (a glycoprotein)

Alternatively, a functional classification:

  • Proteins with primary plasma activity, which are secreted by solid tissue specifically for the purpose of circulating and performing some sort of role in the plasma. Albumin would be a good example
  • Immunoglobulins 
  • Long distance receptor ligands like insulin and erythropoietin
  • Short distance receptor ligands like cytokines and paracrine mediators
  • Temporary passengers which are nonhormone transporters, on their way from one tissue to another (eg. transferrin)
  • Tissue leakage products such as aforementioned myoglobin
  • Aberrant secretion products which are abnormally produced by tumours, for example
  • Foreign proteins which end up in the bloodstream, eg. bacterial proteins
What are the functions of plasma proteins?
How is plasma collected, prepared and stored for re-transfusion?
  • Collected from blood donors,
  • Preparation is by separation from whole blood, either after donation or by apheresis.
  • Must be prepared and frozen within 6-18 hours.
  • In frozen form, fresh frozen plasma (FFP) can be stored for up to 12 months at -25ºC. 
  • It is stored as  250-300ml bags, clearly labelled with the donor blood type.
What is the composition of FFP?

 FFP contains essentially all of the clotting factors except fibrinogen. 

  • Factor VII of the extrinsic pathway (so it will correct the PT)
  • Factors XI and IX of the intrinsic pathway (so, it decreases your aPTT)
  • Factors X and II (Prothrombin) of the common pathway (so, it decreases TT, PT and aPTT)
  • Unfortunately, there isn't much factor VIII. Its solubility is too low at low temperatures, and FFP (once thawed) doesn't contain enough of it.
What are the indications for the use of FFP?
  • To correct coagulopathy where the coagulopathy can't be corrected with a specific factor concentrate
  • To replace plasma extracted in the course of therapeutic plasma exchange, where albumin would not be an appropriate replacement fluid, for example in TTP/HUS
  • To replace a circulating protein which is missing of dysfunctional, eg. where it is given for C1 esterase inhibitor deficiency, or to supplement lacking plasma esterases in cases of suxamethonium apnoea
What is the dose of FFP for the correction of coagulopathy?
  • 10–15 mL/kg per dose
Does FFP need to be blood group typed or crossmatched?
  • Preferably FFP should be ABO-typed
  • Donor plasma in the donated sample may contain anti-ABO antibodies.
  • Crossmatching is not necessary, nor is matching for RhD type
What is cryoprecipitate?
  • The fraction of plasma that loses its solubility at cold temperatures
  • At a temperature of around 1-6ºC (i.e normal refrigerator), some of the plasma proteins remain water-soluble, whereas others become insoluble and precipitate.
  • This cold precipitate is collected and refrozen for storage. 
What are the constituents of cryoprecipitate?

This is a concentrate, meaning to say it is a hyperoncotic solution.

Each unit contains:

  • 160 IU of Factor VIII
  • 260 IU of Von Willebrand factor
  • 380mg of Fibrinogen 
  • Fibronectin, platelet microparticles, and a small amount of immunoglobulin.
What is prothrombinex, and what is in it?
  • Prothrombinex is lyophilised human clotting factor concentrate
  • Presents as a glass vial with powdered concentrate inside, for reconstitution with sterile water. Each vial usually contains 500 units.
  • Each 500 unit vial contains:
    • 500 units of Factor IX  
    • 500 units of Factor II (prothrombin, hence the name)
    • 500 units of Factor X (prothrombinex, get it)
  • When reconstituted, each unit occupies a very small volume (500 units = 50ml)
  • Dose for the reversal of warfarin is 15–50 IU/kg