history of ih & gen functions of blood 2
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RBC FREEZING
Frozen preservation of RBCs with _________isprimarily used for storing units with rare blood typesand autologous units
Frozen cells can be effectively stockpiled for militarymobilization or civilian disasters, but the high cost andthe 24-hour shelf life after deglycerolization make themless useful for routine inventory management
Recently, an effectively closed system was approvedwith a 2-week postthaw shelf life when the blood iscollectedin_________________________________________________________________________
glycerol
CPDA-1, frozen within6 days and stored at -80 degrees C
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RBC FREEZING
Addition of cryoprotective agent to RBCs thatare
Cryoprotective agent is added_____________________________________________________therebyenabbling the cryoprotective agent to
permeate the RBCs
Cells are then rapidly
less than 6 days old
slowly to the RBCs with vigorous shaking
frozen and stored in the freezer
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RBC FREEZING
Deglycerolization process ( Done if unit is going to be used fortransfusion)
-wash RBCs with decreasing percentages of salinea) 12% saline
b) 1.6% saline
c) 0.2% dextrose in saline
-removal of glycerol or cryoprotective agent
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(commonly used)
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RBC FREEZING
ADVANTAGES DISADVANTAGES
Long-term storage A time-consuming process
Maintenance of RBC viability andfunction
Storage requirements (-65C )
Removal of significant amounts ofplasma proteins
higher cost of equipments and
materials
low residual leukocytes and platelets
higher cost of product
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REJUVENATION
Principle
Rejuvenating solution is not intended for intravenousadministration; after warm incubation with the solution, the redcells are washed and either glycerolized for frozen storage or kept at
-rejuvenation is a process to restore depleted metabolites and improve the
function and post transfusion survival of stored red cells
1 to 6 degrees C for transfusion within 24 hours
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REJUVENATION The rejuvenating solution approved by the Food and Drug
Administration contains pyruvate, inosine, phosphate, and adenine
Its use is permitted only with RBCs prepared from Whole Bloodcollected into CPD, CP2D, or CPDA-1, and it may be added at anytime between 3 days after collection of the blood and 3 days after theexpiration of the unit
The use of the rejuvenation solution with RBC units before 14 daysof storage is not routinely accepted because the treated cells maydevelop supranormal levels of 2,3-diphosphoglycerate, whichimpairs oxygen uptake.
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ABO Blood Types
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Hemolytic Disease of Newborns (HDN)or Erythroblastosis Fetalis
*1st pregnancy-exposure*infuse-rhogam (prevent mother form creating Abs.)
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IMPROVED ADDITIVE SOLUTIONS
Longer storage periods could improve thelogistics of providing RBCs for clinical use
Hess and Greenwalt and coworkers : Customized solutions containing sodiumbicarbonate, sodium phosphate, adenine, dextrose,mannitol, and sodium chloride and the use of higher
pH (alkaline range) is providing for better retentionof ATP levels
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RBC Substitutes
Hemoglobin based oxygen carriers and the PFCs
Function: Carry and transfer oxygen in theabsence of intact RBCs
In recent years, referred to as oxygentherapeutics
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Advantages and disadvantages of
Stroma-Free Hemoglobin solutions
ADVANTAGES DISADVANTAGES
Long shelf life Short intravascular half-life
Very stable Possible toxicity
No antigenicity (unlessbovine)
Increased oxygen affinity
No requirement for bloodtyping procedures
Increased oncotic effects
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Hemoglobin-based oxygen carriers
In advanced clinical testing are chemicalymodified hemoglobin solutions
One product: Polymerized bovine hemoglobin
Others are prepared from modified humanhemoglobin
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PFCs
Hydrocarbon structures in which all the H+
atoms have been replaced with fluorine
Chemically inert
Excellent gas solvents
Carry O2 and CO2 by dissolving them
(perfluorochemicals)
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Advantages and Disadvantages of PFCs
ADVANTAGES DISADVANTAGES
Biologic inertness Adverse clinical effects
Lack of immunogenicity High O2 affinity
Easily synthesized Retention in tissues
Requirement for O2administration when infused
Deep-freeze storage
temperatures
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Platelet Anatomy and Function
Disc-shaped
of blood
Alpha Granules:
Dense Granules:
: 2-4 microns in diameter
150,000 to 400,000 microliter
contain clotting factors,pH-derived growth
factors
contain ADP, ATP,
calcium, serotonin,
fibro-stabilizing factor
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Steps in Vascular Damage and ClottingResponses
Vascular Spasm: contraction of smoothmuscle in arteriole walls to reduce bloodflow.
Platelet plug formation:
1. Platelet adhesion:Platelets contact and stick to freecollagen fibers of the damagedblood vessel
2. Platelet release reaction:Activated platelets extend manyprojections that enable them tocontact and interact with one another.They then liberate their granules.
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Steps in Vascular Damage and ClottingResponses
Liberated ADP and thromboxane A2help activate other platelets.
Serotonin and thromboxane A2function as vasoconstrictors helping todecrease blood flow.
3. Platelet aggregation: LiberatedADP makes new platelets sticky; thesenewly-recruited and activatedplatelets adhere to the originally-activated platelets. The process causes
the formation of a platelet plug.
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The Blood Clotting Cascade
Extrinsic Pathway (Fastacting)1.________________________
______is released by tissue cellsoutside of the damaged vessel.
2. TF begins a chemical reactionpathway that activatesThrombokinase (___).____combines with Proaccelerin(_____) to form the enzymeProthrombinase.
t ssue actor or t rom op ast n
FX
FX
FV
-common pat way
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The Blood Clotting Cascade
Intrinsic Pathway (slowacting)Activated by factors within theblood or vesselsAntihemophilic factor D orHageman factor (F12) is activatedby contact with collagen fibers.F12 starts a chemical cascade thatultimately activates F10 or
Thrombokinase.F10 combines with Proaccelerin(F5) to form the enzymeProthrombinase.
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The Blood Clotting Cascade
The Common Pathway
Prothrombinase catalyzes theconversion of Prothrombin (F2) toThrombin.
Thrombin converts the solubleplasma protein fibrinogen in theinsoluble protein fibrin (loosethreads).
Thrombin also activates FibrinStabilizing Factor (F13) whichconverts the loose threads intostable threads.
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The Problems withClotting Cascade
Hemophilia A:Deficiency of Factor VIIIaccounts for 85% cases. Almost exclusively in males.
Females are usually carriers caused by a gene mutation on
the X chromosome. Occursin about 1/10,000 male births
Other Hemophiliasaccount for another 15% Hemophilia B
Hemophilia C
Hemophilia D
actor
actor
(Factor XII)
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The Problems with Platelets andAbnormal Clotting
Thrombocytopenia: Abnormally low levels of platelets. Usually
below 50,000/ul of blood. In many cases, specific antibodies are produced
against platelets destroying them
Thrombus: Abnormal clot that develops in a blood
vessel.
Embolus: Free thrombic clots carried in the blood that
usually get caught in arterioles in the brain,kidney, and lungs.
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