LOGO In the Name of GOD

LOGO مصرف پلاکت و فرآورده های پلاسمائی شیراز خرداد 1393 دکتر آزیتا آذرکیوان متخصص کودکان؛ فوق تخصص هماتولوژی انکولوژی

Whole Blood

Blood Products خون کامل با حجم 450 سی سی سانتریفیوژ شده و فرآورده های خونی از آن مشتق می شوند گلبول قرمز متراکم پلاکت پلاسما

LOGO Platelets

Platelet Incubator Stored in room tempreture with constant agitation

8 Platelet Random donor Platelets Whole blood 1 unit Platelet Concentrate 1 unit > 5.5 x platelets in ml of plasma 3 days Single donor platelets 1 Donor Platelet concentrate > 3 x platelets in ~ 300 ml of plasma 3 Days

Platelet Pheresis

Single Donor Platelet Volume ~ 300 ml

Platelet Threshold For plt Tx  Platelet count 100’000/μl in pt who need Surgery or unstable condition  Platelet count 50’000/μl in pts who need invasive lab. Procedure  Platelet count 50’000/μl in pts With Active bleeding  Platelet Dysfunction with manifested bleeding

Platelet Tranfusion  In The Domain of bleeding disorders :  Platelet Transfusion needs just in the field of Congenital platelet Dysfunction  They need chronic platelet tx, BUT there is the risk of p.refractoriness So it is better to tx p. just on bleeding threatening life,  If there is possible use from alternative drugs such as antifibrinolytic drugs  It is better to have some HLA matched donor platelets

Platelet Refractoriness Definition Failure to achieve the expected platelet increment after 2 successive platelet transfusions Corrected count Increment (CCI) (post tx plt ct- pre tx plt ct) = BSA X No of plts transfused (10 11 )  1hr Increment is <7500 or <4500 at 24 hrs

Definition  Platelet refractoriness: Inappropriately low increment in platelet count following a transfusion.  Formula to determine platelet response:  1 hour Increment < 5,000-7,500.  Corrected Count Increment (CCI): Expected > 7500 at minutes or >4500 at hours.  Less than predicted platelet increment on 2 occasions: Fresh platelets: < 72 hours. ABO compatible.

Low Post-transfusion Platelet Increment  1 hour post (platelet recovery) poor  platelet alloantibodies  platelet autoantibodies  hepatosplenomegaly  24 hour post (platelet survival) poor  infection, bleeding  DIC, fever

Platelet Refractoriness Non Immune S epsis, drugs, DIC, poor quality non- viable platelets, splenomegaly Immune Alloimmunisation to HLA Class I antigen HLA Bw4/ Bw6 ABO incompatibility Platelet specific antibody

LOGO Plasma Products

Fresh Frozen Plasma

Plasma Processing Whole Blood Collection: cc of plasma can be obtained after the procssing of one unit of whole blood depending on the volume & RBC content of the unit collected Single donor Plasmapheresis: cc of plasma depending of donor’s wt

Fresh Frozen Plasma  FFP Contains  II, V, VII, VIII, XI, X, XI  Protein C, Protein S, ATIII and various other components  Fresh frozen plasma contains a normal concentration of fibrinogen and the labile coagulation factors VIII and V.

Indications for FFP Transfusion  Usually If the pt is known case of hemophilia Donot need to FFP  Sever Factor Deficiency With Bleeding No Factor available  Sever Protein C deficienc  FFP is not completely Safe

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Cryo precipitate  Volume of 15 ml, frozen  Contain VWF, FVIII, FXIII, Fibrinogen  Usually use in :  Hypofibrinogenemia, of dysfib,  FXIII deficiency  VWD  1 unit for every 5 kg

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Cryoprecipitate (Cryo) Cryoprecipitate Pooling Cryo

Treatment of Hemophilia Fresh Frozen Plasma Cryoprecipitate Concentrates of Factor Plasma-derived Biotechnology Vials of of 250 to 3000 unit é s 1 FFP (200 ml) = 200 units of F8 1 ml FFP = 1 unit of F8

Plasma Derived Fractionation

Plasma derivatives are produced on an industrial scale from plasma pools consisting of thousands of donations

Major Plasma Derived Products

 Proteins associated with vitamin K  Thrombin  Antithrombin III  Factor XI  Fibrinogen  Factor XII  Alpha-1-antitripsin  C1-Inhibitor  Immunoglobulin M

Immigration and Demographics Immigration: 1)Human 2)Plasma Need To Pathogen Clearance

3 walls protecting from transmission of pathogens donor criteria testing inactivation, removal

Recognise that any system has gaps  Swiss cheese model of safety TTVI

Blood Safety Strategies Testing vs. Inactivation

Pathogen Reduction  Removal Method  Inactivation Method

 Virus Removal  Plasma fractionation  Filtration methods  Various chromatographic methods  Pathogen Inactivation  Pasteurization  Solvent / Detergent (S/D) treatment  High salt, alcohol or acid treatment  Vapour heat treatment Company name Pathogen Reduction

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Specific Inf Removal Tx : Nanofiltration Bacteria µm 0.2 µm Filtration Virus nm Nanofiltration Protein Å Ultrafiltration

Virus inactivation methods  Dry Heating  Wet Heating  Pasteurization  Low/High pH  Gamma Radiation  UV Radiation  Nanofiltration  Solvent/Detergent  Beta Propiolacton  Caprylate Photochemical inactivation Chemical inactivation

Gene introduced into plasmid Plasmid then transfected into cells New DNA integrated into DNA of cells Cells producing large amounts of rFactor selected and cultivated by fermentation Factor protein secreted into media cells grown in, and harvested

plasma-Derived products – Country of plasma origin – Donor selection – Viral screening by antibody – Antigen and nucleic acid amplification testing – Viral screening and inactivation in pooled plasma – Establishing safety of the cell line – Eliminating exogenous human or animal proteins – Viral removal and inactivation,steps designed to reduce the risk of viral contamination Recombinant products Minimizing infection risk

Recombinant Factor Infectious safety Good supply More costly Greater inhibitor risk??? Plasma-derived Factor As safe as recombinant Less inhibitor risk??? Superior inhibitor eradication Cheaper Recombinant VS Plasma derived

Second generation Animal- and human- derived proteins in cell culture No albumin in final product First generation Animal- and human- derived proteins in cell culture Human albumin in final product Third generation No animal- and human-derived proteins in cell culture, processing or final product

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