Page 1970 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 115

TRANSFUSION OF PLASMA AND PLASMA DERIVATIVES: PLASMA,

CRYOPRECIPITATE, ALBUMIN, AND IMMUNOGLOBULINS

Matthew S. Karafin, Christopher D. Hillyer, and Beth H. Shaz

Plasma and its derivatives are well-established clinical resources, 0%, factor V +1%, factor VII −16%, factor VIII −15%, factor IX
but cost risk of infectious disease transmission, although rare, and +6%, factor X 0%, vWF antigen activity +34%, vWF:ristocetin
other adverse effects mandate their appropriate use. Even to this day cofactor activity +22%, fibrinogen +29 mg/dL, antithrombin 0%,
however, much still remains to be clarified regarding the appropri- protein C −19%, and protein S −5%. A disintegrin and metallopro-
ate clinical use of plasma products. The 2015 National Institute of teinase with a thrombospondin type 1 motif, member 13
Health-National Heart Lung and Blood Institute State of the Science (ADAMTS13) activity level is also equivalent in FFP, FP24, and
Symposium revealed that significant and fundamental gaps in our cryoprecipitate-reduced plasma (discussed later). All of the factors
knowledge regarding the most predictive clinical hemostatic tests evaluated in this study reveal that FP24 immediately postthaw had
(i.e., viscoelastic versus traditional coagulation tests), best products activities above the minimum activity required for safe surgical
(i.e., frozen versus liquid plasma), new products (i.e., freeze dried hemostasis (factor II 97%, factor V 86%, factor VII 89%, factor VIII
plasma), and appropriate clinical indications/protocols for plasma 66%, factor IX 88%, factor X 94%, vWF:Ristocetin cofactor activity
product use remain. Plasma can be separated from red blood cells 123%, fibrinogen 309 mg/dL). Therefore, studies support that FFP
(RBCs) through centrifugation of whole blood at the time of col- and FP24 can be used interchangeably.
lection, or can be collected by apheresis as a single product or as a
by-product of platelet or RBC apheresis. Plasma can be processed into
derivatives through cold ethanol fractionation (method of Cohn). Thawed Plasma
In this chapter, the features and uses of plasma products, which
include fresh frozen plasma (FFP), plasma frozen within 24 hours Coagulation factors are also well maintained in thawed FFP and FP24
of phlebotomy (FP24), thawed plasma, liquid plasma, solvent deter- stored at 1°C to 6°C for up to 5 days, termed thawed plasma. Studies
gent treated plasma (SD-plasma), pathogen-reduced/ inactivated show that during 5 days of storage, most clotting factors, including
plasma as well as plasma derivate, including cryoprecipitate-reduced ADAMTS13, remain stable. However, there is evidence that activity
plasma, cryoprecipitate, albumin, intravenous immunoglobulin levels fall significantly for factors V, VII, and VIII. A review by Eder
(IVIg) and intramuscular immunoglobulin (Ig) are discussed. and Sebock revealed that at day 5, factor V, VII, and VIII activity
The use of plasma-derived clotting factor concentrates as well as levels fell from day 1 on average by 16%, 20%, and 41%, respectively,
coagulation factor concentrates that are genetically engineered as if the FFP was derived from whole blood, and 9%, 4%, and 14%,
therapy for specific clotting factor deficiencies are discussed in respectively, if the FFP was derived via apheresis. Although some
Chapter 120. recent evidence suggests that thrombin generation may be slower in
5-day-old thawed plasma, the decrease in clotting factor activity for
both FFP and FP24 is generally not considered to be of clinical
PLASMA PRODUCTS significance, as the mean factor activity levels for 5-day-old thawed
plasma remain above the minimum activity required for safe surgical
Plasma is the acellular, fluid compartment of blood and it consists of hemostasis (on average, FFP: factor V 67%, factor VII 70%, factor
90% water, 7% protein and colloids, and 2% to 3% nutrients, VIII 43%; FP24: factor V 59%, factor VII 77%, factor VIII 48%).
crystalloids, hormones, and vitamins. The protein fraction contains Stored thawed plasma improves patient care and is more cost-effective
the soluble clotting factors: fibrinogen, factor XIII, von Willebrand than frozen plasma because there is no preparation time required.
Factor (vWF), factor VIII primarily bound to its carrier protein vWF, This difference consequently results in a decreased turn-around time,
and the vitamin K-dependent coagulation factors II, VII, IX, and X. and a substantially reduced wastage rate.
Clotting proteins are the constituents for which transfusion of plasma
is required. Plasma products include FFP, FP24, thawed plasma,
SD-plasma, and pathogen reduced/inactivated plasma which can be Liquid Plasma
used interchangeably. Notably, FFP and FP24 are both termed FFP
in some countries outside of the United States. Liquid plasma is produced from whole blood within 5 days of the
whole blood expiration date. Liquid plasma is maintained at 1°C to
6°C and stored for up to 26 days. It is deficient in labile clotting
FFP and FP24 factors (i.e., factor V, VIII). It is used primarily for immediate treat-
ment of acutely bleeding patients, especially where reversal of the
Plasma frozen at −18°C or colder within 8 hours of donation (6 hours effects of warfarin is required, as the vitamin K–dependent factors
with the use of some storage bags after apheresis collection) can be FII, FVII, F IX, and FX are relatively stable under these storage
labelled as FFP. This product may be stored up to 1 year before use, conditions. Liquid plasma remains rarely used in the United States,
at which time it is thawed at 37°C over 20 to 30 minutes. A second but studies in Europe demonstrate at least comparable efficacy to FFP
type of frozen plasma, the most commonly used in the United States, in urgent situations.
is FP24 plasma. FP24 is frozen at −18°C or colder within 24 hours
of collection. The difference between FFP and FP24, using historic
data, is a reduction in the following factors: fibrinogen 12%, factor Freeze-Dried Plasma (Lyophilized Plasma)
V 15%, factor VIII 23%, and factor XI 7%. More recently, a direct
comparison between FFP and FP24 mean factor activity immediately Freeze-dried plasma is produced and pooled from 10 or fewer apher-
postthaw revealed the following changes in activity levels: factor II esis plasma donors. The plasma undergoes a cryodessication process

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