02 July 2016

Lecture #12: PREPARATION OF DIFFERENT BLOOD COMPONENTS


  
Blood component separation is defined as the fractionation of fresh whole blood into plasma and cells and their respective elements based on sequential centrifugation that take advantage of density differences among the different blood cell types.

Whole blood can provide the following components: red blood cells, platelets, leukocytes, plasma, albumin, anti–hemophilic factor, fibrinogen, gamma globulin, factor II, VII, IX, X concentrate and others.

Component therapy is the use of specific blood product to replace deficient cellular elements.


Advantages of Component Therapy:

1.      Maximum recovery of blood products

2.      Increased service to a wide variety of patients

3.      Transfusion of specific components needed by patients at an adequate dose

4.      Elimination of harmful elements in plasma


Equipment used in the collection of blood and the preparation of blood components:


1.     Blood pack unit

Sterile and pyrogen free bottles or bag containing anticoagulant. A pilot tube which may be used for typing and cross–matching purposes is usually attached to it.


2.     Multiple pack unit or Quadruple blood pack unit

Composed of one large box for blood collection and three small bags (satellite) connected to it through plastic tubings. The satellites are used for transferring smaller amounts of blood and for the preparation of blood components.


3.     Ion exchange blood pack unit

The blood pack is attached to an ion exchange column through the blood donation flows and in which calcium is removed.


4.     Leuko–pak filter

Contains nylon fibers for removal of leukocytes from freshly collected heparinized blood or collected through ion exchange resin.


5.     Plasma extractor

Removes plasma without disturbing the cell pack


6.     Platelet mixer


7.     Refrigerated centrifuge

Especially designed for centrifugation of blood in plastic bags or bottles for the
preparation of blood components. The number of revolution per minutes and temperature are both adjustable to suit the need of the components to be prepared.


8.     Needle (gauge 18)


Components of whole blood

I.       Whole Blood

A.      Packed Red Blood Cell

B.      Fresh Plasma

1.      Platelet–rich plasma

2.      Platelet–poor plasma

a.       Cryoprecipitate (Factor VII, Fibrinogen)

b.      Cryosupernate (Factor II, VII, IX, X)


******  PREPARATION OF DIFFERENT BLOOD COMPONENTS  ******


1.     Whole Blood

a.       Indication:

(1)  Replacement transfusion of infants having hemolytic transfusion of the newborn

(2)  Transfusion to patient having massive replacement therapy secondary to either surgical insult or to total circulatory replacement (liver disease)

b.      Temperature

(1)  If stored: 1 – 6oC
(2)  If transported: 1 – 10oC

c.       Shelf life

(1)  With CPD:                   21 days
(2)  With CPDA–1:            35 days


2.     Packed Red Blood Cell

a.      Indication

(1)  Chronic anemia of any etiology

(2)  Pre–op and pre–delivery transfusion

(3)  Anemic patients with congestive heart failure (low sodium content)

(4)  Anemic patients with liver failure (low NH3 content)

(5)  Uremic patients (low potassium content)

(6)  Bone marrow failure

(7)  Acute massive burns

(8)  Replacement of blood loss

b.     Preparation

Spinning the whole blood and removing 2/3 of its plasma. It has a hematocrit of 60 – 70%.

c.      Speed:

1800 rpm for 4 minutes

d.     Temperature: 20oC

e.      Shelf life:

ACD           21 days
CPD           28 days

2 – 6oC on horizontal position


3.     Washed Red Blood Cell

a.       Indication

(1)  Paroxysmal nocturnal hemoglobinuria
(2)  Autoimmune hemolytic anemia
(3)  Hypersensitivity to plasma proteins

b.      Preparation

Packed RBC washed three times with sterile saline solution

c.       Shelf – life:           24 hours


4.     Frozen deglycerolized RBC

A unit of anticoagulated whole blood less than 5 days old is centrifuged at approximately 4400 rpm for 6 to 7 minutes. The supernatant plasma is removed with a plasma extractor and replaced with a solution of 45% glycerol. The thoroughly mixed glycerolized red cells are then transferred to a suitable freezer – adapted plastic bag and a flat set of stainless canister is placed around the plastic bag. The purpose of the canister is to contain the blood in this specific geometric configuration to simplify storage and permit maximum surface area exposure during the freezing process. The entire unit is then placed in a –80oC storage freezer, where cooling takes place over a period of several hours.

a.      Shelf–life: 10 years at –65oC

b.     Indications

(1)  Alloimmunized patients who have previously experienced non–hemolytic febrile transfusion reactions due to leukocytes or platelets.

(2)  Patient who are allergic to constituents of plasma proteins, such as those with IgA deficiencies.

(3)  Neonates or immunocompromised patients in whom the threat of exposure to cytomegalovirus exist

(4)  Patients who need or desire autologous transfusion


5.     Single donor plasma

Separated from a unit of whole blood using a plasma extractor. The separation must occur before the fifth day after the expiration date of the unit of whole blood.

a.      Shelf–life

(1)  CPD at 1 – 6oC (26 days)
(2)  CPDA–1 (40 days)
(3)  At –18oC (5 years)

b.     Indications

(1)  Severe burns
(2)  Hypovolemic shock
(3)  Coagulation defects

6.     Fresh frozen plasma

Fluid portion of 1 unit of human blood that has been centrifuged, separated and frozen at 18oC or colder within 6 hours of collection

a.       Shelf – life

(1)   –18oC within 6 hours after collection
(2)   –30oC within 12 months (optimal storage)

·         If not used within one year of storage at –18oC or not transfused after storage at 1–6oC for 24 hours, it maybe redesignated as SINGLE DONOR PLASMA

b.      Indications

(1)  Massive transfusion
(2)  Single or multiple coagulation protein deficiencies, either prophylactically or in treatment of bleeding.
(3)  Warfarin reversal
(4)  Antithrombin III deficiency
(5)  Treatment of thrombotic thrombocytopenic purpura and immunodeficiencies


7.     Platelet concentrate

Unit of blood collected in triple packs are to be processed immediately and not more than 4 hours after collection without intervening refrigeration.

a.      Preparation

(1)  Centrifuge at 2,500 rpm for 3 minutes in a refrigerated centrifuge

(2)  Express platelet rich plasma into first satellite bag

(3)  Seal and separate red cell container. Label plasma properly before returning red cell container to the refrigerator.

(4)  Centrifuge platelet rich plasma for 5 minutes at 4,000 rpm.

(5)  Express all but 30 to 50 of the plasma into the second satellite bag.

(6)  Check identification, seal and separate between seals.

b.     Shelf–life

48 – 72 hours with constant agitation

c.      Indication

(1)  Active bleeding due to thrombocytopenia

(2)  Cardiovascular surgery

(3)  Surgery with deficient platelets

(4)  Prophylaxis against bleeding when platelet count is below 20 x 109/L or below.


8.     Cryoprecipitate

Units of blood must be collected in triple packs with CPD. The unit is collected within 7 minutes to be suitable for this procedure.

a.      Preparation

(1)  Separate red cells within 4 hours after collection. Centrifuge at 4,000 rpm for 10 minutes in a refrigerated centrifuge. Express plasma in satellite bag.

(2)  Seal and separate red cell pack. Label properly before returning into the refrigerator.

(3)  Freeze satellite bag at 80oC for 15 minutes or until ready to proceed.

(4)  Thaw at 4oC for 24 hours.

(5)  Centrifuge for 10 minutes at 4,000 rpm.

(6)  Express all but 10 ml into satellite bag. Label should include ABO group.

(7)  Seal twice and separate

(8)  Plasma maybe stored at 4oC. Cryoprecipitate is stored at –30oC or lower.

b.     Shelf–life: one year 

c.      Contents

Factor VIII and fibrinogen

d.     Indications

(1)  Hemophilia A and von Willebrand’s disease
(2)  Hypofibrinogenemia
(3)  Hemolytic anemia
(4)  Cardiovascular surgery


9.     Cryosupernate

Prepared from cryoprecipitate poor plasma and stored at –30oC

a.      Shelf–life: one year

b.     Contents:                        Factor II, VII, IX, X

c.      Indications

(1)  Bleeding disorders due to lack of above coagulation factors as in liver disease
(2)  Plasma volume expander


10.  Leukocyte poor blood

Preparation of leukocyte poor blood must be done within 24 hours after donation. Collect blood in twin packs

a.      Preparation:

(1)  Centrifuge blood at 3,000 rpm for 5 minutes (blood pack in inverted position)

(2)  Express about 75% of red cells into satellite pack leaving the plasma and buffy coat in the original container.

b.     Shelf–life: one day

c.      Indications:

(1)  Patients with leukocyte antibodies
(2)  Febrile reactions
(3)  Recipients of tissue transplants


11.  Modified whole blood

Prepared by returning to primary bag (containing the PRBC) the platelet poor plasma. It is considered the same as whole blood.


12.  Fibrinogen

Sterile, freeze dried fraction of normal plasma which in solution has the property of being converted to fibrin upon the addition of thrombin. It contains no preservative and stored at 2–10oC. It has a shelf life of 5 years. It carries a high risk of transmitting serum hepatitis but is more effective than whole blood transfusion for the treatment of chronic hyperfibrinogenemia.


13.  Serum globulin

It is sterile solution of globulin containing those antibodies normally present in adult human blood. Each lot is derived from serum pool of 100 unites. Store between 2–10oC.

Shelf – life:     three years

Hyperimmune globulin available

a.       Tetanus immune globulin
b.      Rho immune globulin


14.  Serum albumin

Fractionation of human plasma is carried in different laboratories. It is prepared by varying the ionic strength of the supernatant left after the other fractions have been removed by altering its pH to 4.8. This forms a precipitate known as fraction V. By reworking fraction V, human serum albumin is prepared. From 3 liters of plasma, 200 ml of 25% human serum albumin can usually be prepared.

a.      Clinical uses

(1)  Treatment of severe burns and shock and in exchange of transfusion to infants to assist in binding unconjugated bilirubin

b.     Storage

(1)  Five to ten years in a liquid state at 5oC and as such shows no evidence of deterioration






****** OTHER TRANSFUSION PRACTICES  ******


1.     Pheresis

A procedure in which whole blood is removed from a donor, separated and a portion retained with the remainder being returned. The retained product may be plasma, platelets or leukocytes and the associated process is called plasmaphereis, plateletpheresis and leukapheresis.


2.     Autologous transfusion

Autologous transfusion refers to procedures for transfusing blood or blood products derived from the recipient’s own blood. Many hazards of transfusing blood from homologous donors, particularly hepatitis transmission are thereby avoided. Using conventional drawing and storage methods, patients may pre–deposit autologous blood products which are then available to meet future needs. Autologous transfusion may be the only suitable manner to supply blood products to patients who react adversely to all homologous blood, to patients of extremely rare blood types, or to patients who refuse blood from homologous donors because of religious beliefs. Autologous blood products may also be obtained through salvage of blood lost during surgery or following trauma (intra–operative salvage). This blood is collected from the interior of the body by instrumentation and returned to the patient after filtration. Under no circumstances should this latter procedure of blood salvage be instituted if the blood is possibly contaminated.


3.     Massive Transfusion

Massive transfusion can be defined as transfusion of patients’ blood volume during a twelve hour interval.

Effects of massive blood transfusion

a.       Antigen–antibody reaction

(1)  Formation of immune antibodies by the patient
(2)  Reaction between plasma and red cells of donor’s blood

b.      Pulmonary edema and cardiac arrest due to circulatory overload (when a patient’s blood volume could not be bought at normal within 24 hours).

c.       Changes in hemostatic function due

(1)  Depression of coagulation factors
(2)  Abnormalities of platelet function

d.      Biochemical changes such as hypocalcemia, hyperkalemia and increase in citrate

e.       Hypothermia

f.        Pulmonary dysfunction may result due to transfused cellular microaggregates


4.     Pediatric Transfusion

Children who are not actively bleeding should receive red blood cells for the same reason that red blood cells are superior to whole bloods for adults. If transfusion of small volumes of blood are to be administered, one donor unit can be collected into a small multiple container and divided into small volumes needed.


5.     Universal Donor Transfusion

The practice of routine and indiscriminate transfusing all recipients with Group O blood regardless of groups is advocated by almost no one.

There are nevertheless, instances where use of Group O, Rho negative blood, a universal donor is not only advisable but necessary. The chief indication of use of Group O Rho negative blood without regard to the recipient’s typing is in case of massive hemorrhage with attending shock. There is nevertheless an element of risk. The safety factor is the presence of low titer anti–A and anti–B agglutinins in Group O blood.

Blood group specific substances A and B (Witebsky substances) are also used as an aid in the use of universal donor. In order to neutralize the anti–A and anti–B agglutinins of the Group O type, purified Group A and B specific substances derived from hog and horse stomachs respectively are added to the blood. This produce is available in a 10 ml vial for injection into the blood, react immediately prior to transfusion.

However, not all are complete in agreement on the advisability of injecting the Witebsky substance. Some immunologist believe that transfusion with O blood with A and B specific substances added may result in a high immune anti–A or anti–B antibody titer in subsequent pregnancies.


***********  RED CELL SUBSTITUTES  ************


Characteristics of an ideal blood substitutes

1.      It should be non–toxic, non–pyrogenic, non–allergic, sterile and easy to store at normal temperatures.

2.      Must be equivalent to human blood in viscosity and osmotic pressure and retained in the vascular system for a sufficient time to exert the required therapeutic effect

3.      Must be eliminated by normal metabolism or excretion and must not affect normal hemostasis

4.      Must be relatively cheap to produce and easily administered


Synthetic red blood cells surrogates


1.     Emulsions of perfluorocarbons

Perfluorocarbons (PFCs) are large organic compounds in which all the hydrogen atoms have been replaced by fluorine atoms. They are chemically inert, immiscible in water and not metabolized. Oxygen transported by a PFC is carried in solution and has approximately 20 times the solubility for oxygen and carbon dioxide as does water, which is almost three times the oxygen carrying capacity of blood.

The PFC solution Fluosol–DA 20% has a circulation half–life of about 13 hours and a tissue half–life of 9 days.


Advantages of PFCs:

a.       Contain no antigens; no typing and crossmatching necessary.

b.      Easily synthesized from readily available materials.

c.       Free of infectious diseases.

d.      Do not carry carbon monoxide and could provide oxygen to a carbon monoxide victim until the patient replaces abnormal cells.

e.       Small particle size enables the suspension to penetrate occluded vessels in conditions such as cerebral ischemia or myocardial infarction.

f.        It may be useful as an adjunct to radiation therapy in inoperable tumors and in angioplasty procedures.


Disadvantages of PFCs:

a.       Potentially cause oxygen toxicity.

b.      Unstable in–vitro – need to be frozen

c.       Retention by the liver and spleen causes pulmonary hypertension, bronchospasms and cytotoxicity.

d.      Have not been proven beneficial in severely anemic patients.

e.       The emulsifying agent Pluronic F–68 may cause a clinical reaction involving the activation of complement. The stability of the current emulsion limits the shelf – life, even though it can be stored frozen for up to 1 year.


2.     Stroma–free hemoglobin

This is prepared by slowly lysing washed red cells with a buffered solution of water, followed by high–speed centrifugation and micropore filtration. This procedure separates the fragmented cell membrane into relatively large pieces that can be removed.


Advantages of SFH

a.       Excellent volume expanders
b.      Potential candidate for an emergency resuscitive fluid.


Disadvantages of SFH:

a.       Toxicity (this can be improved by coupling the beta chains of hemoglobin through an organic phosphate).

b.      Can activate the complement system.

c.       Short half–life in the circulation (less than 8 hours).

d.      Significant oncotic effect and unacceptably high affinity for oxygen.

e.       Must be refrigerated or frozen.


3.     Polymerized hemoglobin


Advantages of Poly SFH–P

a.       Relative simplicity of preparation

b.      Approximates the oxygen carrying capacity of whole blood and has a half-life of 38 hours.

c.       Can be infused without altering the plasma oncotic pressure

d.      Near normal plasma hemoglobin

e.       Longer intravascular persistence than any unpolymerized product.

f.        Tissue oxygenation effect is significantly improved in comparison to stroma– free hemoglobin.


Disadvantage of PolySFH–P

a.       A higher affinity for oxygen than erythrocytes

b.      A higher content of non–functional methemoglobin

c.       Nephrotoxicity

d.      May be immunogenic


4.     Liposome–encapsulated hemoglobin

This can be done with the use of liposomes which can be prepare from a single phospholipid, a mixture of phospholipids or mixtures of phospholipids and neutral lipids, for example, phosphatidylcholine plus cholesterol. A 10 g/dl quantity of hemoglobin encapsulated in an artificial cell results in an intracellular environment comparable to that of normal red blood cells.

Another way of encapsulating hemoglobin is with the use of neohemocytes, which are microcapsules containing purified human hemoglobin and 2,3– diphosphoglycerate. The size range (0.1 – 1.0 um) is small enough to allow free passage through capillaries. With this specification, they are qualified as prototype artificial cells.

Specifications for prototype cells

a.       The microcapsule membrane must be biodegradable and physiologically compatible

b.      The encapsulation process must avoid significant hemoglobin degradation.

c.       The oxygen affinity of hemoglobin must be reduced relative to that of free hemoglobin.

d.      The encapsulated hemoglobin must be sufficiently concentrated (more than 33% of that in erythrocytes)

e.       There should be no evidence of overt intravascular coagulopathy

f.        The artificial cells must be small enough to pass unrestricted through normal capillaries.

Overall clearance process of neohemocytes

a.       Clearance resulting from irreversible binding to tissues followed by breakdown

b.      Clearance caused by rapid or early destruction or breakdown

c.       Clearance from uptake by mononuclear phagocytic system

Advantages of encapsulated hemoglobin

a.       Reduced permeability and rate of aggregation

b.      Increased resistance to hydrodynamic shear and chemical disruption

c.       Apparent thromboresistance

d.      Substantially smaller than erythrocytes

Disadvantage of encapsulated hemoglobin

a.       Toxicity

b.      Stability

c.       Storage

d.      Questionable cost–effectiveness

Ideal biophysical criteria for artificial red cells

a.       Adequate oxygen carrying capacity and appropriate oxygen affinity

b.      Rapid gas exchange

c.       Satisfactory circulating half–life and thromboresistance

d.      Biologic inertness (low pathogenic potential)

e.       Chemical and physical stability

f.        Satisfactory viscosity

g.       Low immunogenicity







No comments: