fresh frozen plasma

Plasma is the liquid component of blood, the medium that keeps blood flowing. Plasma is a straw-colored fluid that remains when all the blood cells including red blood cells, white blood cells and platelets are removed from the blood. Plasma makes up approximately 55% of the total blood volume and 92% of plasma is water.

Plasma contains electrolytes, minerals, amino acids, vitamins, proteins, enzymes, hormones, organic acids and other substances required for sustaining life. Plasma also contains certain specialized proteins known as coagulation factors that regulate the clotting process to prevent excessive bleeding from an injury and also prevent abnormal clotting. Plasma carries nutrients to the cells and the metabolic wastes to the kidneys, liver and lungs for excretion. Plasma maintains adequate blood volume, blood pressure and biological stability (homeostasis).

Fresh frozen plasma (FFP) is plasma separated by centrifugation from whole blood taken from donors, and frozen withing 8 hours of collection. Liquid plasma is plasma that is never frozen and is immediately administered. Another plasma product is P24 plasma, which is essentially the same as FFP except that the separation and centrifugation occurred between 8 and 24 hours of collection. The Octaplas brand of plasma product undergoes treatment with solvent-detergent agents to inactivate any enveloped viruses in the blood, and sterilized before freezing.

Before administration, fresh frozen plasma is thawed in a water bath at 30 to 37 Celsius over 20 to 30 minutes or in an FDA-cleared device in just 2 to 3 minutes. Thawed plasma should be administered immediately, or may be stored at 1 to 6 degrees Celsius for up to 24 hours, and should be discarded if not used in that period of time.

Fresh frozen plasma is administered as an intravenous transfusion based on ABO blood group compatibility. The uses of fresh frozen plasma include the following:

• Management and prevention of bleeding in adult and pediatric patients
• Replacement of coagulation factors in adults with acquired deficiencies
  • Due to liver disease
  • Undergoing cardiac surgery or liver transplantation
• Plasma exchange in adults with thrombotic thrombocytopenic purpura (TTP), a condition that causes small blood clots to form in the small arteries all over the body

• Do not administer fresh frozen plasma to patients with:
  • History of hypersensitivity to pooled plasma (human), fresh frozen plasma, or to plasma-derived products including any plasma protein
  • Deficiency of immunoglobulin A (IgA), a type of antibody
  • Deficiency of protein S, a blood protein that prevents excessive coagulation
• Fresh frozen plasma should not be used only to increase blood volume, in the absence of active bleeding.
• FFP administration must be based on ABO blood group matching. ABO mismatch can cause transfusion reactions.
• Patients should be monitored for signs of a transfusion reaction, including vitals, before during, and after transfusion. Transfusion should be stopped if transfusion reaction is suspected, the patient should be assessed and stabilized, and the blood bank notified to initiate an investigation.
• Plasma should not be given for:
  • Replacement of isolated factor or specific protein deficiencies if the appropriate factor concentrates are available
  • Vitamin K deficiency or warfarin reversal if correction can safely be achieved using vitamin K supplementation
• Liquid plasma may have a significant amount of viable lymphocytes and should be irradiated if the patient is at increased risk of transfusion-associated graft-versus-host disease (TA-GVHD), in which the donor lymphocytes attack the host tissue.
• High infusion rates can induce excessive blood volume (hypervolemia) and lead to pulmonary edema or cardiac failure. Patients should be monitored and treated appropriately.
• 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.
• Thrombosis can occur if protein S levels are low. Monitor for signs and symptoms of thrombosis in patients at risk.
• Plasma carries a risk for the transmission of infectious organisms.
• Excessive bleeding due to fibrin destruction (hyperfibrinolysis) can occur due to low levels of alpha2-antiplasmin (i.e., plasmin inhibitor); monitor for signs of excessive bleeding in patients undergoing liver transplantation.
• Do not inject drugs containing calcium in the same intravenous line with plasma because precipitants may block the line.
• Volumes exceeding 1 mL/kg/min of Octaplas can cause citrate toxicity, especially in patients with liver function disorders, resulting in low calcium (hypocalcemia) with associated symptoms of fatigue, muscle spasms, skin tingling and numbness. Citrate toxicity may be minimized with calcium gluconate IV into another vein.

Common side effects of fresh frozen plasma include:

• Transfusion-transmitted infections and septic reactions
• Hemolytic transfusion reactions that destroy red blood cells
• Feverish (febrile) non-hemolytic reactions
• Transfusion related acute lung injury (TRALI)
• Transfusion-associated graft-versus-host disease (TA-GVHD)
• Transfusion-associated circulatory overload (TACO)
• Allergic reactions such as:
  • Hives (urticaria)
  • Itching (pruritus)
• Severe allergic reaction (anaphylaxis)
• Post-transfusion bruising (purpura)

Common side effects of Octaplas include:

• Urticaria
• Pruritus
• Nausea
• Headache
• Abnormal skin tingling or numbness (paresthesia)

Less common side effects of Octaplas include:

• Hypersensitivity reactions including anaphylactoid and allergic type of reactions
• Hyperfibrinolysis, a process that breaks down fibrin, the clot-forming protein, which results in high bleeding risk
• Cardiac arrest
• Circulatory overload
• Rapid heart rate (tachycardia)
• Blood vessel block from clots (thromboembolism)
• Bronchospasm
• Fluid in lungs (pulmonary edema)
• Shortness of breath (dyspnea)
• Rapid breathing (tachypnea)
• Respiratory arrest or failure
• Vomiting
• Abdominal pain
• Excessive alkalinity of body fluids (alkalosis)
• Fever
• Chills
• Chest discomfort or pain
• Rash
• Skin redness (erythema)
• Citrate toxicity
• Passive transfer of antibodies
• Passive transmission of analytes (e.g., beta-human chorionic gonadotropin which can give misleading positive pregnancy results)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Pooled Human Plasma Solution (Octaplas)

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

Adult:
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 intravenously (IV) initially; this should increase plasma coagulation factors by approximately 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 correspond 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

Dosing Considerations

• Administer based on ABO-blood group compatibility

Other Indications and Uses

• Fresh Frozen Plasma, Plasma Frozen within 24 hours, Thawed Plasma, Liquid Plasma (FFP, P24, TP, LP) may be used to treat bleeding due to acquired multiple factor deficiencies such as seen due to large volume bleeding or DIC.

Plasma transfusion is indicated for

• Management of bleeding or to prevent bleeding prior to an urgent invasive procedure in patients requiring replacement of multiple coagulation factors
• Massively transfused patients who have clinically significant coagulation deficiencies and hypovolemia
• Patients on warfarin therapy with bleeding or that need to undergo an invasive procedure before vitamin K could reverse the effects of warfarin or who need only transient reversal of warfarin effects
• For transfusion or plasma exchange in patients with thrombotic thrombocytopenic purpura (TTP) and some cases of hemolytic uremic syndrome (HUS)
• Management of patients with selected coagulation factor deficiencies, congenital or acquired, for which no specific coagulation concentrates are available (i.e., factors II (2), V (5), VII (7), X (10), XI (11), Proteins C or S
• Management of patients with rare specific plasma protein deficiencies, such as C1 inhibitor, when recombinant products are unavailable
• FFP is the product of choice for patients specifically requiring replacement of the labile clotting factors or other proteins with poor storage stability because the other plasma products may be deficient in these factors during liquid storage; deficiencies due to consumption/hemodilution rarely fall to levels that are inadequately treated with non-FFP plasma components; consultation with a hematologist or transfusion medicine physician is recommended for assistance with indications 3-6

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

• See adult dosing

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Fresh Frozen Plasma has no listed severe, serious, moderate or mild interactions with other drugs.

Octaplas:

• Do not inject drugs containing calcium in the same intravenous line with Octaplas because precipitants may block the line.
• Passive transmission of analytes (e.g., beta-human chorionic gonadotropin) may result in misleading positive results
• The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.
• It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There is no information about fresh frozen plasma transfusion during pregnancy; may be administered if clearly needed.
• Fresh frozen plasma may be given to increase blood volume in women with severely depleted blood volume (hypovolemia) due to post-partum hemorrhage, who also have greatly reduced coagulant factors (coagulopathy).
• There is no information about fresh frozen plasma transfusion in nursing mothers.