Fresh Frozen Plasma

Fresh frozen plasma (FFP) is a blood product made from the liquid portion of whole blood. It is used to treat conditions in which there are low blood clotting factors (INR>1.5) or low levels of other blood proteins. It is also used as part of plasma exchange. The specific batch typically needs to be tested for compatibility before it is given. Use as a volume expander is not recommended. It is given by injection into a vein.

Side effects include nausea and itchiness. Rarely there may be allergic reactions, blood clots, or infections. It is unclear if use during pregnancy or breastfeeding is safe for the baby. Greater care should be taken in people with protein S deficiency, IgA deficiency, or heart failure. Fresh frozen plasma is made up of a complex mixture of water, proteins, carbohydrates, fats, and vitamins. When frozen it lasts about a year.

Plasma first came into medical use during the Second World War. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. In the United Kingdom it costs about £30 per unit. A number of other versions also exist including plasma frozen within 24 hours after phlebotomy, cryoprecipitate reduced plasma, and solvent detergent plasma.

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There are few specific indications for FFP. These generally are limited to the treatment of deficiencies of coagulation proteins for which specific factor concentrates are unavailable or undesirable. In many clinical practices, fresh and frozen plasma contains proteins with two important coagulation factors in it—the V and the VIII. Other documentations indicate FFP has not enough beneficial effect when it is used as a transfusion to stop massive bleeding. In addition, circumstances exist in which FFP has been employed and is believed to be of therapeutic value, but data supporting its efficacy are limited or unavailable (e.g., multiple coagulation protein deficiencies in uncontrollably bleeding). Because such people are often critically ill and satisfactory alternative therapy may not be at hand, FFP may be appropriate

Indications for the use of FFP include the following:

·         Replacement of isolated factor deficiencies FFP is used to treat rare bleeding disorders when specific factor concentrates are not available. FFP is the usual treatment for factor V deficiency

·         Reversal of warfarin effect 

Patients who are anticoagulated with warfarin are deficient in the functional vitamin K dependent coagulation factors II, VII, IX, and X, as well as proteins C and S. These functional deficiencies can be reversed by the administration of vitamin K. For anticoagulated patients who are actively bleeding or who require emergency surgery prothrombin complex concentrate should be used if available FFP (or single-donor plasma) should only be used if more effective alternative treatments are not available. The ASA task force recommends starting with 5-8 mL/kg of FFP for warfarin reversal and rechecking laboratory values.

·         Use in antithrombin III deficiency FFP can be used as a source of antithrombin III in patients who are deficient of this inhibitor and are undergoing surgery or who require heparin for treatment of thrombosis.

·         Treatment of immunodeficiencies FFP is useful in infants with secondary immunodeficiency associated with severe protein-losing enteropathy and in whom total parenteral nutrition is ineffectual. FFP also can be used as a source of immunoglobulin for children and adults with humoral immunodeficiency. However, the development of a purified immune globulin for intravenous use largely has replaced Fresh frozen plasma

·         Treatment of thrombotic thrombocytopenic purpura FFP may be beneficial for the treatment of thrombotic thrombocytopenic purpura.

FFP is not recommended unless there is ongoing bleeding or there is a significant blood clotting problem. That is, FFP is not used in people to reverse warfarin if there is no bleeding, even for an INR > 9 unless they need urgent surgery. It is also not used in elective surgery, or non-emergent surgery.

The risks of FFP include disease transmission, anaphylactoid reactions, and excessive intravascular volume, as well as transfusion related acute lung injury (TRALI) and an increase in infections (including surgical wound infections). The potential viral infectivity of FFP probably is similar to that of whole blood and red blood cells. The rate of posttransfusion hepatitis depends on many factors, including donor selection. In rare instances, human immunodeficiency virus (HIV) is transmitted by blood transfusions and possibly by FFP. Allergic or anaphylactoid reactions can occur in response to FFP administration and may vary from hives to fatal noncardiogenic pulmonary edema.

FFP should be blood type-matched to ensure compatibility, as agglutination reactions are possible, though rare. As with any intravenously administered fluid, excessive amounts of FFP may result in hypervolemia and cardiac failure.

Adult

Dosage Forms & Strengths

pooled human plasma solution (Octaplas)

  • 45-70mg/mL (as human plasma protein)

Management/Prevention of Bleeding

FFP: 10-20 mL/kg of body weight will increase factor levels by 20-30%

Frequency of transfusion depends on the half-life of the deficient factor(s)

In adults and large children, dosing is rounded to the nearest number of units

Number of units = Desired dose (mL) / 200 mL/unit

Coagulation Factors Replacement

Indicated for replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or those undergoing cardiac surgery or liver transplantation

Octaplas: 10-15 mL/kg IV initially; this should increase plasma coagulation factors by ~15-25%

If hemostasis not achieved, use higher doses and adjust dose based on desired clinical response

Monitor response, including measurement of aPTT, PT, and/or specific coagulation factors

Thrombotic Thrombocytopenic Purpura (TTP)

Indicated for plasma exchange in patients with TTP

Octaplas: Completely replace plasma volume removed during plasmapheresis with Octaplas; generally, 1-1.5 plasma volumes corresponds to 40-60 mL/kg IV

Administration (Octaplas)

Administer via infusion set with filter

Inspect visually for particulates and discoloration; do not use if turbid

Avoid shaking

Not to exceed IV infusion rate of 1 mL/kg/min

Pediatric

Management/Prevention of Bleeding

Octaplas: Safety and efficacy in children not established

Neonates and small children

  • FFP: 10-15 mL/kg of body weight will increase factor levels by 15-25%
  • Transfusion frequency depends on the half-life of the deficient factor(s)
  • Depending on the dose requested, an aliquot of 1 unit, a whole unit or more than 1 unit of plasma may be issued
  • Specific volume to be transfused should be specified to the transfusionist to prevent volume overload in neonates and small children or those at increased risk of volume overload

Large children

  • Please see adult dosing

Contraindications

FFP should not be used solely for volume expansion, or to "correct" a mildly prolonged PT or PTT without active bleeding; patients may have a mildly prolonged PT or PTT and yet have hemostatically stable levels of coagulation factors

Plasma should not be given for replacement of isolated factor or specific protein deficiencies if the appropriate factor concentrates are available

Plasma should not be given for vitamin K deficiency or warfarin reversal if correction can safely be achieved using vitamin K supplementation

Octaplas

  • IgA deficiency
  • Severe protein S deficiency
  • History of hypersensitivity to fresh frozen plasma (FFP) or to plasma-derived products including any plasma protein
  • History of hypersensitivity reaction to Octaplas

Cautions (FFP)

If a transfusion reaction is suspected, the transfusion should be stopped, the patient assessed and stabilized, the blood bank notified, and a transfusion reaction investigation initiated

Massive or rapid transfusion may lead to arrhythmias, hypothermia, hyperkalemia, hypocalcemia, dyspnea, and/or heart failure

Many blood banks utilize P24 and/or thawed plasma interchangeably with FFP; if FFP is specifically needed, it is advisable to inform your institution’s blood bank at the time of request to ensure appropriate product transfusion

Plasma components contain a significant amount of antibodies against the ABO blood group antigens and ABO compatible plasma must be used

Liquid plasma (please see pharmacology for description) may have a significant amount of viable lymphocytes and should be irradiated if the patient is at increased risk of TA-GVHD (see the irradiated blood product monograph)

All transfusions must be given via blood administration sets containing 170- to 260-micron filters or 20- to 40-micron microaggregate filters unless transfusion is given via a bedside leukocyte reduction filter; no other medications or fluids other than normal saline should be simultaneously given through the same line without prior consultation with the medical director of the blood bank

Patient’s should be monitored for signs of a transfusion reaction including vitals pre, during, and post transfusion.

Non-septic infectious risks include transmission of HIV (~1:2 mill), HCV (~1:1.5 mill), HBV (1:300k), HTLV, WNV, CMV, parvovirus B19, Lyme disease, babesiosis, malaria, Chaga’s disease, vCJD

Consult with blood bank medical director or hematologist if you have questions regarding special transfusion requirements

Cautions (Octaplas)

Transfusion reaction may occur with ABO mismatch

High infusion rates can induce hypervolemia with consequent pulmonary edema or cardiac failure

Excessive bleeding due to hyperfibrinolysis can occur due to low levels of alpha2-antiplasmin (ie, plasmin inhibitor); monitor for signs of excessive bleeding in patients undergoing liver transplantation

Thrombosis can occur due to low levels of Protein S

Octaplas is made from human plasma, it may carry a risk of transmitting infectious agents (eg, viruses, vCJD agent); undergoes solvent-detergent purification

Do not inject drugs containing calcium in the same IV line (precipitant may occur)

Citrate toxicity

  • Citrate toxicity can occur with volumes exceeding 1 mL/kg/min of Octaplas
  • Do not exceed infusion rate of 0.02-0.025 mmol/kg/min of citrate (ie, <1 mL/kg/min Octaplas)
  • Symptoms attributable to citrate toxicity (hypocalcaemia) include fatigue, paresthesia, and muscle spasms, especially in patients with liver function disorders
  • Administer calcium gluconate IV into another vein in order to minimize citrate toxicity

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