Fresh Frozen Plasma

https://meditropics.com/fresh-frozen-plasma/

Fresh Frozen Plasma

Rahul Kumar Bairwa

Post Graduate Resident, Department of Medicine, LHMC

 

INTRODUCTION

Blood component therapy allows several patients to benefit from one unit of donated whole blood

Whole blood is the source of component production.

Blood can be separated into various components by different speed centrifugation technique.

Blood components include RBCs, Platelets, FFP, cryoprecipitate, cryo-supernatant etc.

 

PLASMA

Plasma constitutes roughly 55% of whole blood. It contains~ 90-92% of water.

 

PLASMA OR BLOOD PRODUCT COMPONENTS (1)

 -Biological products -prepared by differential centrifugation of whole blood

 E.g., FFP, cryoprecipitate, cryo-supernatant

 

PLASMA DERIVATIVES

 -Products obtained by plasma fractionation process

 E.g., albumin, immunoglobulins, coagulation protein concentrates

 

FRESH FROZEN PLASMA (FFP) (1)

FFP is the fluid portion of one unit of whole blood that is

  1. Obtained either by

 – centrifugation of whole blood   or

 – by apheresis wherein plasma is filtered, and remaining part of blood is pumped back into the donor

 (Both are therapeutically equivalent in terms of haemostasis and side effect profile)

 

  1. Separated         and

 

  • Frozen solid at -30 degree C within 6- 8 hours of collection – to preserve the labile clotting factors

One unit of FFP is around 225-250 ml obtained from one unit of whole blood i.e. 450-500 mL

CONTENT-

  1. Labile (especially factor V and factor VIII) as well as     stable components of coagulation, fibrinolytic and complement system, protein c, protein s and anti-thrombin iii. 
  2. Proteins that modulate oncotic pressure (albumin) and modulate immunity (immunoglobulins).
  3. Fats, carbohydrates, and minerals present in concentration similar to circulation, slightly diluted due to anticoagulant.
  4. Citrate as anticoagulant.

 

ADMINISTRATION-

  • Plasma should be abo compatible (cross matching not required).
  • Group ab plasma can be used for all patients.
  • Once thawed at 37 degree C in a water bath with shaker it should be administered.

            – within 24 hours if refrigerated at 1-6 degree C.

            -within 6 hours if at room temperature

 

SHELF LIFE-

  • 1 year – if stored at -30 degree C.
  • 5 years – if stored at or below -60 degree C.

 

DOSING

  • Initial dosage- 12-15 mL/kg.
  • Adult plasma volume is 40 mL/kg.
  • Haemostasis is not disturbed if coagulation activity is at least 25-30%.
  • One unit of FFP increases level of any coagulation factor by 2-3%.
  • 4 units provide ~10% increase in clotting factors, which is minimum required to produce a change in coagulation status.
  • 12-15 mL/kg is initial required dose – around 4 units for an adult.

 

PLASMA PRODUCTS- SOME OTHER TYPES

  1. FP24 (FROZEN PLASMA 24)-
  • Same as FFP, only difference is- frozen at 8-24 hours after collection.
  • All factors maintained at normal levels except factor viii declines to significant levels.

 

  1. THAWED PLASMA (TP)-

 Derived from thawed FFP or thawed FP24 and maintained for a maximum of 5 days in the refrigerator.

 

  1. JUMBO PLASMA-

500-800 mL plasma obtained from a single donor via plasmapheresis.

 

 

  • CRYOPRECIPITATE-
  • Obtained from FFP by slow thawing at 4-6 degree C followed by hard spin centrifugation.
  • Supernatant plasma is separated in satellite bag and remaining cryoprecipitate is suspended in 10-20 ml of plasma.
  • Refrozen at -30 degree C or lower.
  • Contain- higher conc. Levels of labile clotting factors like- fibrinogen, fibronectin, VWF, factor VIII and factor XIII.

 

  1. PLASMA CRYOPRECIPITATE REDUCED (OTHER NAME- CRYOSUPERNATANT OR CRYO-POOR PLASMA)-

 Contain vitamin K dependant clotting factors but low levels of labile clotting factors like-   fibrinogen, fibronectin, VWF, factor VIII and factor XIII.

 

 

INDICATIONS OF FRESH FROZEN PLASMA

  1. Inherited factor XI deficiency
  2. source of factor V in severe DIC (if platelets, cryoprecipitate do not correct factor V, VIl, fibrinogen consumption defects)
  3. Replacement of specific factor deficiencies: – FFP is effective for the treatment of deficiencies of factors I, V, VII, IX, X and XI – WHEN SPECIFIC FACTORS ARE NOT AVAILABLE
  4. Bleeding from conditions caused by deficiency of multiple coagulation factors
  • Reversal of warfarin effect: Patient anticoagulated with warfarin who are actively bleeding OR who require emergency Surgery, FFP can be used to achieve immediate hemostasis.
  • Vitamin K deficiency with bleeding manifestation- provide vitamin K dependant clotting factors.
  • Massive blood transfusion is very Common to have blood clotting abnormalities – dilutional coagulopathy, after large blood loss in trauma settings. FFP is Commonly recommended in these Se Transfusion in ratio of PRBC:FFP:PLATELETS = 1:1:1
  1. Use in Antithrombin III deficiency – FFP can be used as Source of Anti-thrombin III in patient who are deficient in this inhibitor and are undergoing Surgery or who require heparin for treatment of thrombosis.
  2. Treatment of immunodeficiency – FFP is useful in infants with secondary immuno-deficiency associated with Severe protein losing
  3. Treatment of thrombotic thrombocytopenic purpura (TTP)- act as a source of ADAMTS-13 enzyme- which is deficient in TTP.
  • single volume daily plasma exchange should ideally be begun at presentation and preferably within 24 hrs. of presentation.
  • Daily plasma exchange should continue for a minimum of 2 days after remission is obtained.

 

 

FFP IN ACUTE BLOOD LOSS SETTING

  • Acute massive haemorrhage (2) is variously defined as Loss of
  1. 50% of total blood volume in less than 3 hours Or
  2. Bleeding in excess of 150 mL/minute

(The normal human blood volume in an adult is 70mL/kg; therefore, a 70kg male has a blood volume of approximately 5000mL – a 50% loss is approximately 2500mL)

 

MASSIVE TRANSFUSION PROTOCOL (MTP) (3)

MTP protocol are standard of care in trauma centres. Traditionally defined as

  1. >10 U PRBC given / 24 hours or
  2. > 4U PRBC given / 1 hour with anticipation for requiring more transfusions over next 24 hours

FFP (Plasma) and Platelets are NOT used in the calculation for MTP

QUESTION. When to start MTP?

Calculate ABC score

  • Early prediction of massive transfusion in trauma: Simple as ABC (assessment of blood consumption)

ABC Scoring (4)

  1. Penetrating mechanism/ torso injury
  2. Positive FAST
  3. SBP </= 90 mmHg on arrival
  4. Heart rate >/= 120 bpm on arrival
  • Score >/= 2 is 75% sensitive and 86% specific for predicting massive transfusion
  • As discussed earlier acute massive blood loss- common to have dilutional coagulopathy and dilutional anaemia.
  • FFP is commonly recommended in these Se
  • Higher FFP:PRBC ratio is an independent predictor of survival in massively transfused patients.
  • Aggressive early use of FFP may improve outcome in massively transfused trauma patients.
  • Transfusion in ratio of PRBC:FFP:PLATELETS = 1:1:1

DISADVANTAGES

 

  1. The need for compatibility testing
  2. The need for thawing
  3. Variable content of vitamin K dependent clotting factors.
  4. Side effects
  • Immune reactions- ABO-identical / ABO-compatible
  • Transmission of disease – SAME AS OF WHOLE BLOOD- HEPATITIS B & C, HIV etc.
  • Febrile reactions
  • Anaphylactic reactions – in IgA deficiency with antibodies to IgA

                 Mild- urticaria and rigors

                 Severe- anaphylaxis

  • Volume overload.
  • TRALI (Transfusion related acute lung injury) – Donor antibodies to recipient HLA.

 

CONTRAINDICATIONS

  • SHOULD NOT BE USED
  1. AS BLOOD VOLUME EXPANDER- when other volume expander can adequately and safely be used.
  2. When coagulopathy can be corrected with a more specific therapy
  • Vitamin K or prothrombin complex concentrate (PCC) available for warfarin reversal
  • Factor specific concentrate available (e.g., Recombinant Factor VIll/vWF concentrate for haemophilia or Von Willebrand disease)
  1. As a source of protein/albumin in hypoproteinaemia and hypoalbuminemia or as nutritional supplement
  2. As a source of IMMUNOGLOBULINS in hypogammaglobulinemia
  3. Normalizing abnormal coagulation screen results, in the absence of bleeding.

PROTHROMBIN COMPLEX CONCENTRATE (PCC)

  • This component contains prothrombin (Factor ll), factor Vll, IX and X
  • It is lyophilized and virus-inactivated to reduce the risk of transmitting infections
  • Indications-
  1. Serious WARFARIN overdosage together with Vitamin K (MASSIVE BLEEDING- CNS OR GI BLEED)
  2. Hemophilia B (F IX deficiency)
  3. Coagulation defects due to fulminant hepatitis or liver insufficiency.

 

PCC VS FFP

  • Advantages favoring PCC
  1. Rapid acting (within 30 min)
  2. No thawing needed
  3. No blood group testing and matching required
  4. No volume limitation
  5. fast application
  6. Highly predictable effect (Antagonism of OAC)
  7. No serious side effect of FFP like acute lung injury (TRALI)
  • Disadvantage- Very costly
    • litres of FFP= 60 mL PCC

 

CONCLUSION

  • Blood transfusion is an effect form of therapy.
  • Component therapy allows transfusion of specific portion of blood that the patients requires.
  • Administration of unwanted component is avoided allowing several patients to benefit from one donation.
  • Documented deficiencies of Factors V VII XI XIII can be corrected by FFP/ PF24 though concentrates for Factors XI and XIII are available.
  • FFP is an important component of Massive Transfusion protocol to prevent trauma induced coagulopathy. Aggressive early use of FFP may improve outcome in massively transfused trauma patients.
  • Because FFP is freely available and cost effective it is still an important blood component despite technological advancement to obtain individual factor concentrate.

REFERENCES

  • Eder AF, Sebok MA. Plasma components: FFP, FP24, and thawed plasma. Immunohematology. 2007;23(4):150-7.
  • Schöchl H, Grassetto A, Schlimp CJ. Management of hemorrhage in trauma. J Cardiothorac Vasc Anesth. 2013 Aug 1;27(4): S35-43
  • Teixeira PGR, DuBose J. Surgical Management of Vascular Trauma. Surg Clin North Am. 2017 Oct;97(5):1133-1155. 
  • Yates DW. ABC of major trauma. Scoring systems for trauma. BMJ. 1990 Nov 11;301(6760):1090.