history of ih & gen functions of blood 2

7/29/2019 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


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


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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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 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.

history of ih & gen functions of blood 2

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