Fluid Resuscitation
Plasma protein fraction (PPF) is used for plasma volume expansion in the treatment of certain types of shock, including those resulting from burns, crushing injuries, abdominal emergencies, or any other cause where there is a predominant loss of plasma fluids and not red blood cells.104 PPF also is effective in the emergency treatment of shock due to hemorrhage.104 Following the emergency phase of therapy, transfusions of whole blood or red blood cells may be indicated, depending on the severity of the blood loss.104 In infants and small children, PPF may be useful in the initial therapy of shock resulting from dehydration and infection.104
Clinical experience indicates that PPF is an adequate replacement for human plasma in the treatment of shock and a suitable means of providing human proteins for their osmotic effect.104 Although PPF has been used interchangeably with 5% albumin human in the treatment of shock, albumin solutions may be preferable because they contain a greater percentage of albumin and, since they are more purified, are less likely to cause hypotensive reactions.
Because PPF is prepared using pooled human plasma, like albumin human, it is associated with a risk of transmission of human viruses or other infectious agents.104 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions: Precautions and Contraindications.)
Administration 
Plasma protein fraction (PPF) is administered by IV infusion, preferably at a site at some distance from any site of infection or trauma.104
As with any plasma volume expander, the rate of administration should be adjusted according to the clinical response of the patient and changes in blood pressure.104 (See Cautions: Adverse Effects.) As plasma volume approaches normal, the rate of administration of PPF should not exceed 5-8 mL/minute, and the patient should be monitored for signs of hypervolemia, including dyspnea, fluid in the lungs, and abnormal increases in blood pressure or central venous pressure. (See Cautions: Precautions and Contraindications.)
PPF solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.104
Dosage
Dosage of PPF depends on the patient's condition and response to therapy.104
In the treatment of hypovolemic shock in adults, the usual minimum effective dose of PPF is 250-500 mL (12.5-25 g of protein).104 In the treatment of hypovolemic shock in infants and young children, an initial dose of 6.6-33 mL/kg (0.33-1.65 g/kg of protein) infused at a rate of up to 5-10 mL/minute has been suggested. Subsequent dosage is determined by the patient's condition.
Adverse Effects
Adverse effects of PPF occur infrequently and may include flushing,104 tachycardia, erythema, urticaria,104 nausea,104 vomiting, chills, fever, headache,104 back pain,104 and hypersalivation.
Hypotension may occur, especially following rapid IV infusion of PPF (i.e., at rates exceeding 10 mL/minute) or intra-arterial administration in patients on cardiopulmonary bypass.104 It is not known if the agent responsible for the hypotensive reactions is present in PPF or generated in the patient. Blood pressure should be monitored during administration of PPF, and the infusion slowed or stopped if sudden hypotension occurs.104 The blood pressure may return to normal spontaneously following slowing or discontinuance of the infusion; vasopressors may also be used to correct the hypotension.104
Precautions and Contraindications
Risk of Transmissible Agents in Plasma-derived Preparations
Because PPF is prepared using pooled human plasma, it is a potential vehicle for transmission of human viruses, including hepatitis viruses, or other infectious agents.104 Although donors are screened for certain viruses (e.g., human immunodeficiency virus [HIV], hepatitis B virus [HBV], hepatitis C virus [HCV]) and PPF undergoes a pasteurization procedure to reduce viral infectious potential, a risk for transmission of infectious agents still remains.104
Studies using plasma-derived coagulation factor preparations indicate that improved donor screening practices and viral inactivation procedures (including pasteurization) have resulted in plasma-derived preparations with greatly reduced risk for transmission of HBV, HCV, HIV-1, and HIV-2.105 No cases of transmission of viral diseases have been identified for plasma-derived albumin and the risk is considered extremely remote.107 However, transmission of nonenveloped viruses, including hepatitis HAV and parvovirus B19, has been documented following administration of plasma-derived coagulation factors.105 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions: Precautions and Contraindications, in Antihemophilic Factor [Human] 20:28.16.)
Risk of Creutzfeldt-Jakob Disease
Because PPF is prepared from human blood, it theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jacob disease (CJD) or variant CJD (vCJD).100,101,102,103,106,107 Although there have been 3 probable cases of vCJD acquired through transfusion of human red blood cells (RBCs) identified by an ongoing epidemiologic review being conducted in the United Kingdom,117 transmission of CJD or vCJD through plasma derivatives (including plasma-derived albumin) has not been documented to date.106,107,108 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions: Precautions and Contraindications, in Antihemophilic Factor [Human] 20:28.16.)
Tests are being developed to detect CJD and vCJD infection in blood and plasma donors.107 Until such donor screening tests are available for these diseases, the US Food and Drug Administration (FDA) has recommended interim preventive measures that include specific guidelines for deferral of blood and plasma donors with possible exposure to CJD and vCJD that are based on geographic considerations and guidelines for product retrieval, quarantine, and disposition that are based on consideration of risk in the donor and product and the effect that withdrawals and deferrals might have on the supply of blood, blood components, and plasma derivatives.107 For further information on CJD and vCJD precautions related to blood and blood products, the FDA's guidance for industry should be consulted ([Web]).107
Risk of West Nile Virus
There is evidence that West Nile Virus (WNV) can be transmitted in transplanted organs (e.g., heart, liver, kidney) and blood products (e.g., whole blood, packed red blood cells, fresh frozen plasma).110,111,113,114 WNV has been isolated from frozen plasma obtained from a blood donor subsequently found to have WNV, indicating that the virus can survive in frozen blood components.111 It is unlikely that WNV would be transmitted through commercially available plasma-derived preparations since WNV is an enveloped virus, like HCV, which is known to be inactivated by the heat and solvent/detergent viral inactivation procedures used in the manufacture of these preparations.111,112
During 2003, a specific test to screen donated blood for WNV became available under an investigational new drug (IND) protocol,115,116 and this test has been used at all US blood centers since July 2003.116 The FDA also recommends additional measures to assess donor suitability to help screen out potential blood donors who have past or present manifestations that suggest WNV illness.111 All potential donors with a medical diagnosis of WNV infection (including diagnosis based on symptoms and laboratory results) should be deferred from blood donation for at least 28 days from onset of manifestations or until 14 days after the condition is considered to be resolved, whichever is later.111 In addition, the FDA recommends that between June 1 and November 30 of each year, potential donors should be asked if they have a history of headache and fever within the last week and they should be deferred for 28 days if the answer is yes.111 This donor questioning should begin earlier in the year if there are local reports of epizootic activity or human transmission of WNV and should end later in states where human infection with WNV is reported in November.111 These recommendations apply to whole blood and blood components intended for transfusion and blood components, including recovered plasma, source leukocytes, and source plasma intended for use in further manufacturing into injectable or noninjectable products.111
Because of the possible transmission of WNV through organ transplants and blood transfusions, any case of WNV that occurs in a patient who received organs, blood, or blood products within the 4 weeks preceding onset of the illness should be reported to CDC through state and local health authorities and serum or tissue samples should be retained for later studies.110,111 In addition, cases of WNV infection occurring in blood or organ donors within 2 weeks after their donation should be reported to CDC.110,111 Prompt reporting of such individuals will facilitate withdrawal of potentially infected products.110,111
For further information on WNV precautions related to blood and blood products, the FDA's guidance for industry should be consulted ([Web]).111
Other Precautions and Contraindications
The manufacturer states that PPF is contraindicated in patients undergoing cardiopulmonary bypass procedures; severe hypotension has been reported in such patients receiving PPF.104 PPF also is contraindicated in patients with severe anemia, congestive heart failure, or increased blood volume.104
Blood pressure should be monitored during PPF treatment and the IV infusion should be slowed or discontinued if sudden hypotension occurs.104
Rapid IV infusion of PPF solutions may cause vascular overload. All patients (especially those with normal or increased circulatory volumes) should be observed for signs of hypervolemia such as pulmonary edema or cardiac failure. In those patients for whom restriction of sodium is indicated, it should be noted that commercially available PPF contains approximately 145 mEq of sodium per liter.104 The rapid rise in blood pressure accompanying administration of PPF following injuries or surgery may reveal bleeding points which were not apparent at the lower blood pressure; the patient must be observed carefully to prevent hemorrhage and subsequent shock. PPF should be used with caution in patients with hepatic or renal failure because of added protein, fluid, and sodium load.
PPF does not contain coagulation factors and, therefore, cannot be used to correct coagulation disorders.104 PPF contains trace amounts of blood groups A and B isohemagglutins; however, these are at such low levels that use of PPF should have no effect on routine blood typing procedures.104
Pediatric Precautions
Although the manufacturer states that safety and efficacy of PPF have not been established in pediatric patients, the protein colloid has been found to be very useful in infants and small children for the initial treatment of shock resulting from dehydration and infection.104
Pregnancy and Fertility
Pregnancy
Animal reproduction studies have not been performed to date with PPF.104 It is not known whether PPF can cause fetal harm when administered to pregnant women, and the protein colloid should be used during pregnancy only when clearly needed.104
Fertility
It is not known whether PPF can affect reproductive capacity.104
Pharmacology
The pharmacologic properties of plasma protein fraction (PPF) are similar to those of its primary constituent, albumin. IV administration of albumin solutions causes a shift of fluid from the interstitial spaces into the circulation and a slight increase in the concentration of plasma protein. Studies in healthy volunteers indicate that that PPF results in an increased blood volume which may last up to 48 hours.104
Chemistry and Stability
Chemistry
Plasma protein fraction (PPF), a protein colloid, is a sterile 5% solution of selected proteins prepared from pooled plasma obtained from healthy human donors.104 PPF meets standards established by the Center for Biologics Evaluation and Research of the US Food and Drug Administration and contains 5 g of selected proteins per 100 mL, of which approximately 88% is normal albumin human; 12% is α- and β-globulins, and no more than 1% is γ-globulin as determined by electrophoresis.104 The protein concentrations result in a solution that is iso-oncotic with normal human plasma and isotonic.104
PPF occurs as a transparent, nearly colorless to slightly brownish, practically odorless liquid which may develop a slight granular or flaky deposit during storage. The solution is buffered with sodium carbonate and stabilized with sodium caprylate and acetyltryptophan.104 PPF contains approximately 145 mEq/L of sodium, 0.25 mEq/L of potassium, and 100 mEq/L of chloride.104 PPF contains no preservatives.104
Plasma used for preparation of PPF undergoes viral screening procedures and PPF is pasteurized at 60°C for 10 hours to reduce the viral infectious potential of the preparation.104 However, no method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations. (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions: Precautions and Contraindications.)
Stability
PPF should be stored at a room temperature not exceeding 30°C and should not be frozen.104 Solutions which have been frozen should not be used.104 Since PPF contains no preservatives, the protein colloid should not be used if it appears turbid, if more than 4 hours have elapsed since the container was first entered, or if the vial is cracked or damaged.104
PPF is compatible with whole blood, packed red blood cells, and standard carbohydrate and electrolyte solutions intended for IV administration.104 However, PPF should not be mixed with protein hydrolysates or solutions containing alcohol.104 Norepinephrine bitartrate is reported to be incompatible with PPF. Specialized references should be consulted for specific compatibility information.
Only references cited for selected revisions after 1984 are available electronically.
100. Nightingale SL. Dear doctor letter regarding withdrawal of certain plasma products. Rockville, MD: Department of Health and Human Services. Public Health Service. Food and Drug Administration; 1995 Mar 29.
101. Department of Health and Human Services, Food and Drug Administration. Precautionary measures to further reduce the possible risk of transmission of Creutzfeldt-Jakob disease by blood and blood products. 1995 Aug 8. Memorandum.
102. Department of Health and Human Services, Food and Drug Administration. Precautionary measures to further reduce the possible risk of transmission of Creutzfeldt-Jakob disease by blood and blood products. 1995 Aug 8. (Supplemental recommendations to 1987 Nov 25 memorandum on deferral of donors who have received human pituitary-derived growth hormone.)
103. Vidor A. Dear customer letter regarding withdrawal of certain lots of Buminate® 25%. Lakewood, NJ: Baxter Healthcare Corp; 1997 Mar 13.
104. Talecris. Plasmanate® (plasma protein fraction [human] 5%) prescribing information. Research Triangle Park, NC; 2005 Jan.
105. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations concerning the treatment of hemophilia and other bleeding disorders (revised October 2005). MASAC recommendation #165. From National Hemophilia Foundation website. [Web]
106. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations regarding the use of recombinant clotting factor products with respect to pathogen transmission (June 3, 2006). MASAC recommendation #169. From National Hemophilia Foundation website. [Web]
107. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) by blood and blood products. January 2002. From FDA website. [Web]
108. Ricketts MN, Cashman NR, Stratton EE et al. Is Creutzfeldt-Jacob disease transmitted in blood? Emerg Infectious Dis . 1997; 3:155-63.
109. Brown P, Will RG, Bradley R et al. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns. Emerg Infectious Dis . 2001; 7:6-16.
110. Centers for Disease Control and Prevention. West Nile virus activity—United States, October 10-16, 2002, and update on West Nile virus infections in recipients of blood transfusions. MMWR Morb Mortal Wkly Rep . 2002; 51:929-31. [PubMed 12403410]
111. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Revised recommendations for the assessment of donor suitability and blood and blood product safety in cases of known or suspected West Nile virus infection. May 2003. From FDA website. [Web]
112. National Hemophilia Foundation. West Nile virus fact sheet. From National Hemophilia Foundation website. [Web]
113. Harrington T, Kuehnert MF, Kamel H et al. West Nile virus infection transmitted by blood transfusion. Transfusion . 2003; 43:1018-22. [PubMed 12869105]
114. Iwamoto M, Jernigan DB, Gausch A et al. Transmission of West Nile virus from an organ donor to four transplant recipients. N Engl J Med . 2003; 348:2196-203. [PubMed 12773646]
115. Chiron. New test developed to screen donated blood for West Nile virus by July 1 deadline. Press release. 2003 June 18.
116. Centers for Disease Control and Prevention. Questions and answers: blood transfusions and organ donations. From the CDC website. [Web]
117. Hewitt PE, Llewelyn CA, Mackenzie J et al. Creutzfeldt-Jakob disease and blood transfusion: result of the UK transfusion medicine epidemiological review study. Vox Sang . 2006; 91:221-30. [PubMed 16958834]