IN THE NAME OF GOD

THE COMPASSIONATETHE MERCIFUL

M.ALAEI- MD APCPJanuary 2021

Blood Transfusion Research Center, High Institute for research and Education in Transfusion Medicine

Principles of Clinical Transfusion Practices

Blood Transfusion is not without hazards

You should weigh the risk against benefit

Use of right products for the right patient at the right time

Prescribing should be based on national guidelines on the clinical use of blood

Taking individual patient needs into account.

Lab test should not be the sole deciding Factor. Clinical evaluation is important

1. To restore intravascular volume by replacing plasma

2. To restore the oxygen carrying capacity of blood by replacing red blood cells

3. To replace clotting factor

PURPOSE OF BLOOD TRANSFUSION THERAPY

Blood Component Manufacture

• Whole blood donations are commonly manufactured into components.

• This facilitates the treatment of different patients with requirements for RBCs, plasma proteins, or platelets.

• The goals of component manufacture are to maintain viability and function, and to prevent detrimental changes or contamination of desired constituents.

• Cellular Blood Products:

• RBC• Platelets• Leukocytes

• Whole Blood

WB Hct is equal to donor’s Hct (35-45%)WB transfusion should be iso group:containsRBC(Ag) and Plasma(Ab) Needs transfusion standard set(170-260µ filter)

WHOLE BLOODCharacteristics::Contains RBC and Plasma,WBC and Pla.WBC & Pla Not functioning and non viable after 24hrs.Labile clotting fac.(5 and 8) decrease after 2 days storage.Hct:35-45%Blood:450ml-CPD or CPDA-1:63mlApprox. vol.:520mlShelf life:CPDA-1,35 days at 1-6c

Indications for Whole BloodIndications:When both RBC mass (O2 carrying capacity)and plasma vol.(expansion) are needed,active(massive) bleeding with acute loss of more than 15-25%(1000 cc) of blood volume.Rapid flow characteristics.In other words:Massive Transfusion: Replacement of more than one

blood volume (70cc/kg) or more than 4-5lit in 24hrs or ongoing bleeding of more than 150cc/kg/h in an adult.

Exchange Transfusion: Exchange transfusion of the neonate with hemolytic disease of the newborn (HDN) is a special case.

Contra indications for Whole Blood

Congestive Heart Failure

Chronic Anemia

PACKED CELL(RBC)

Characteristics:Packed RBC with reduced plasma vol.(of 200-250cc) Produced by light spin of whole blood or overnight refrigerated sedimentation.WBC,Pla.,clotting fac. As whole blood.Hct:69%(not exeeding 80% for glucose and citrate def.)Approx. vol.:250cc±30 (variable due to donor Hct)Shelf life: 35 days CPDA-1 at 1-6c

*Indications:Increasing RBC mass when symptomatic anemia,chronic anemia(Thal) and normal blood volume is present.*Flow charac:slow due to high Hct.*Use of crystalloids (N/S) possible for increasing transfusion rate in active bleeding or massive transfusion.*One unit increases Hct:3%*

• Packed Red Blood Cell

Red Cell Transfusion• Red blood cells provide oxygen-carrying capacity. • Red cell transfusion may be used to treat acute or

chronic anemia.• A patient’s ability to tolerate anemia depends on the

degree of anemia, physiologic adaptive mechanisms, and cardiac or respiratory disease.

• Transfusion of one unit of RBCs with a Hct of about 69% to an adult patient can usually be expected to raise the Hb by 1 g/dL and the Hct by 3%.

• However, the expected Hct increase may range from about 2%–9%, depending on the patient’s vascular volume.

Red Cell Transfusion Guidelines

• Symptomatic anemia in a euvolemic patient• Acute blood loss of >15% of estimated blood volume• Preoperative Hb <9.0 g/dL with expected blood loss >500 mL• Hb <7.0 g/dL in a critically ill patient• Hb <8.0 g/dL in a patient with an acute coronary syndrome• Hb <10.0 g/dL with uremic or thrombocytopenic bleeding• Sickle cell disease:• Acute sequestration: Hb <5.0 g/dL or decrease of 20% from

baseline• Acute chest syndrome: Target Hb = 10 g/dL, HbS fraction <30%(is

life threatening & exchange transfusion to prevent res failure)• Stroke prophylaxis: Target HbS fraction <30%• General anesthesia: Target Hb = 10.0 g/dL, HbS fraction <60%

Other RBC Products:

• Leukocyte reduced • Washed• Irradiated• Frozen

LEUKOCYTE-REDUCED BLOOD COMPONENTS• Leukocytes present in blood components, particularly RBCs and PCs, may• cause adverse effects, including:• *Febrile nonhemolytic transfusion reactions,(endogenous pyrogens from

present leukocytes)• * Immunization to leukocyte (particularly HLA) antigens with subsequent

refractoriness to platelet transfusions,• * Transmission of leukocyte-associated viruses, • *Graft-versus-host disease. • To minimize most of these adverse impacts, many blood centers and

transfusion services have instituted the use of leukocyte-reduced components for all transfusions(universal leukocyte reduction).

• It must be noted that leukocyte reduction has not been shown to prevent post transfusion graft-versus-host disease and is not used for this purpose. To be considered leukocyte reduced, blood components must be prepared by a method known to reduce the total number of residual leukocytes to fewer than 5 × 106 per unit for RBC and fewer than 8.3 × 105 for whole blood–derived PC.

• Leukocyte reduction is typically accomplished by filtration at the time of component manufacture (prestorage leukocyte reduction) or at the time of transfusion (poststorage leukocyte reduction). Both methods are effective for removing leukocytes.

• However, prestorage leukocyte reduction has the advantage of preventing accumulation of leukocyte-derived biological response modifiers, particularly cytokines, which may cause adverse reactions.

• In addition, filtration at the time of manufacture allows for better process control.

• Leukocyte reduction is not an effective means of preventing graft-versus-host disease .

• Clearly, granulocytes and hematopoietic progenitor cells cannot be leukocyte reduced.

Washed Blood Cells• RBCs and PCs can be washed to remove plasma proteins and

electrolytes.• Washing can be accomplished by manual or automated methods.• Loss of cells during the washing process can be substantial.• In addition, washing of platelets can result in clumping and

activation with reduced viability. • Because this is an open process, washed red cells may be stored for

24 hours at refrigerator temperatures, and washed platelets must be transfused within 4 hours of preparation.

• The main use of washed components is the prevention of severe allergic reactions.

• Washing is not an effective means of leukocyte reduction.

خون و فرآورده ھاي اشعھ دیده

Irradiated products• Transfusion-associated graft-versus-host disease (TA-GVHD) can be

prevented by irradiation of components containing viable lymphocytes (RBCs, PCs, granulocytes, and nonfrozen plasma). This can be accomplished by exposure to γ-rays or X-rays. The minimum dose should be 25 Gy delivered to the center of the blood container and no less than 15 Gy to the periphery.

• Irradiation causes chromosomal damage, which prevents replication of transfused lymphocytes in the recipient. However,irradiated cells are immunogenic. Thus, irradiation is not equivalent to leukocyte reduction.

• Irradiation also causes damage to red cell membranes with increased potassium leakage and decreased posttransfusion survival.

• Irradiated red cells must have the outdate shortened to no more than 28 days from the date of irradiation.

• Platelets appear to sustain minimal damage from irradiation, and so their expiration date need not be altered, although the increment in platelet count may be reduced .

• Clearly, hematopoietic progenitor cells must not be irradiated.• Irradiation is not sufficient to prevent transmission of viral infections,

including cytomegalovirus, or bacterial contamination.

TA)خونانتقالازناشیمیزبانعلیهپیوندبافتواکنش – GVHD )(4)

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:اندیکاسیونهاي مصرف خون و فرآورده هاي اشعه دیده

:بالقوههاياندیکاسیون.شوندمیدرمانسیتوتوکسیکعواملبامواردیکه:هابدخیمیسایر

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Massive transfusionتروماعلتبهCML

Tعلیهباديآنتیکهبیمارانی cellگیرندمی

: عدم اندیکاسیون پیوند ارگان هاي توپرنوزادان ترمHIVبیماران بدون نقص ایمنیتالاسمیهموفیلیcongenital humoral immune deficiency disorder

:فرآورده هایی که باید اشعه داده شوند All viable lymphocyte containing products: Whole Blood ,PRBC Frozen / deglycerolized RBCS Washed RBC Platelet concentrates, pooled Platelet, apheresis Granulocytes Fresh plasma

Cezium

Frozen Red Blood Cells• Red blood cells can be stored in the frozen state after addition of a

cryoprotective agent, such as glycerol. Frozen RBCs can be stored in mechanical freezers or liquid nitrogen for up to 10 years. Frozen units are thawed rapidly at 37° C. The cryoprotective agent must be removed by progressive addition of washing solutions with decreasing osmolality. Failure to properly deglycerolize frozen RBCs can result in hemolysis.

• After deglycerolization, red cells can be stored for up to 1 day at 1°–6° C if processed by an open method, or up to 14 days if processed by a closedmethod.

• The main use of frozen RBCs is to maintain an inventory of rare antigen-negative units.

Frozen deglycerolized RBCNeed wash and thaw procedure. Characteristics: RBC, no plasma , no pla.95% WBC removed. Up to 20% RBC loss during procedure. Appr. Vol:250cc Shelf life:10 yrs at -65c• 24 hrs at 1-6c after wash. Indications: Rare blood ,Autologous blood

donation.

Random Donor Platelet: from whole blood

Single Donor Platelet: from Apheresis

Platelete Concentrate

Platelet Concentrate

PLATELET CONCENTRATES• Platelet concentrates (PCs) are prepared from whole blood by centrifugation of

platelet-rich plasma and expression of platelet-poor plasma.• Platelet concentrates must contain at least 5.5 × 1010 platelets per unit. They are

stored at room temperature (20°–24° C) because platelets stored at refrigerator temperature (1°–6° C) have greatly diminished posttransfusion survival.

• Current FDA regulations allow PCs to be stored for up to 5 days with continuous gentle agitation, otherwise clumping occurs.

• Platelet concentrates typically contain a small number of red cells, which are visibly apparent and can cause alloimmunization to red cell antigens. PCs contain 30–50 mL of plasma.

• It is typically necessary to pool five or more PCs to obtain a therapeutic dose for a typical adult patient.

• PCs that are pooled using an open system must be transfused within 4 hours. • PCs can be pooled and leukocyte reduced at the time of manufacture , using a

system that maintains sterility, often referred to as prepooled platelets. Because the integrity of the container is not compromised in this process, prepooledplatelets can be stored for up to 5 days.

Random Donor Platelet Concentrate

Characteristics:Platelets(5.5x1010),some WBC,(lym),50cc plasma, few RBC(Hct0.5%)Should be prepared as soon as 6-8 hrs after collection of blood.Blood bag first light spinned for separation of Packed RBC(250cc) and pla. Rich plasma(200-250cc),then plasma heavy spinnedfor pla.button(50cc) and Pla. Poor plasma(200cc).

Random Donor Platelet Concentrate

App. Vol:50ccShelf life:5 days,room temp.(20-24c),with gentle constant agitation for maintaining func.Indications:for quantitative and qualitative pla. disorder.1.Correct TCP as prophylaxis for CNS hemorrhage in ex. Leukemia patients.(pla.<100000)2.Bleeding patient (surgery or trauma,Pla.<40000)3.Thrombocytopathy(qualitative def.)

*Blood components can also be collected by apheresis. The advantage of apheresis donation is that a greater volume of the desired components may be obtained from a single donation. * The most common use of apheresis donation is the collection of platelets (commonly called single donor platelets). Plasma may also be collected, typically concurrently with platelets.* Apheresis donation allows for the collection of two

units of RBCs from suitable donors.* Leukocytes may also be collected by apheresis. This is most commonly utilized for the collection of hematopoietic progenitor cells for autologous or allogeneic transplantation. * Granulocytes or mononuclear cells may be collected by apheresis for special applications.

• PCs prepared by apheresis (platelets,apheresis, or single-donor platelets) are stored and handled in the same manner as platelet concentrates prepared from whole blood.

• Each apheresis platelet unit should contain a minimum of 3.0 × 1011 platelets.

• It is possible to collect two platelet units in a single apheresis session from some donors.

• One apheresis platelet unit will typically provide a therapeutic dose for an adult patient.

Single donor pla. Concentrate by apheresis

Characteristics:Pla.(3x1011),some WBC(lym):possible GVHD,250cc plasma,few RBC(Hct 0.5%).App. Vol.:250-300ccShelf life:5 days at room temp. constant agitation.Indications:As for random donor.Most useful in platelet Immunologic refractory patient.

Platelet Transfusion Guidelines

• Thrombocytopenia due to decreased production• Stable patient: platelet count <10,000/μL• Fever: platelet count <20,000/μL• Bleeding, invasive procedure, or surgery: platelet

count <40,000–50,000/μL• Retinal or central nervous system (CNS) bleeding:

platelet count <100,000/μL• Microvascular bleeding due to platelet

dysfunction

Major ABO compatibility is less of an issue in platelet transfusion than in red cell transfusion. ABO antigens are expressed weakly on platelets. ABO incompatible platelet transfusions may result in lower post transfusion survival, although this usually is not clinically significant.

Failure to achieve an expected platelet count increment after platelet transfusion on two or more occasions is commonly considered refractoriness.

Failure to respond with an appropriate increase in platelet count after transfusion (platelet refractoriness) may be due to immune causes (HLA or platelet-specific antibodies), non immune clinical causes (bleeding, splenomegaly, disseminated intravascular coagulation [DIC], medications), product-specific causes (ABO incompatibility; older products give lower increments).

A poor Increment following a single platelet transfusion must not be presumed to be due to alloimmunization. The refractoriness is often multifactorial and changes with the patient’s underlying condition and therapy. HLA antibodies are the most common cause of immune-mediated platelet refractoriness.

HLA class I antigens are expressed on platelets, and class I antibodies are common in patients who have been previously pregnant or transfused with non–leukocyte-reduced blood components.

Antibodies to platelet-specific antigens are a relatively rare cause of platelet refractoriness.

• Transfusion of one apheresis platelet unit, or an equivalent pool of whole blood–derived platelet concentrates, can typically be expected to raise the platelet count of an adult by 20,000–40,000/μL.

• Consumption(DIC) or bleeding, splenomegaly, platelet antibodies, and drugs are all causes of a poor response to platelet transfusion. Drugs that can cause an inadequate platelet increment include antibiotics, heparin, anti platelet agents (clopidogrel, tirofiban), quinidine, and antithymocyte globulin, along with many others.

• In assessing platelet transfusion effectiveness, it is useful to take into account dose and body size by calculating the corrected count increment (CCI).

• CCI= (Pla count after transfusion- Pla count before transfusion)x BSA------------------------------------------------------------------------------------------

No of transfused Pla• CCI >7500 at 1 hour or a CCI >4500 at 24 hours generally indicates a successful transfusion.

Obtaining a platelet count within 1 hour of completing the transfusion may be helpful in distinguishing immune from Non immune causes of platelet refractoriness. Typically, immune refractoriness will result in an inadequate platelet increment when measured at 1hour. Typical nonimmune refractoriness will manifest as an adequate CCI at 1 hour but shortened survival time, so that the platelet count by 24 hours may be back to baseline.

• It must be appreciated that the CCI does not indicate that an adequate platelet count has been achieved. It indicates only the adequacy of a platelet count increment in relation to the number of platelets transfused.

Platelet Transfusion• Platelet transfusion is indicated for prevention or treatment of

hemorrhage due to thrombocytopenia or platelet dysfunction.

• The platelet transfusion is relatively contraindicated inImmune Thrombocytopenic Purpura(ITP),an auto immune disorder with Ab to platelet Ags.. In this setting, posttransfusion platelet survival is extremely brief, and platelet transfusion is indicated only if there is severe hemorrhage.

• Clearly, transfusion in the setting of intravascular platelet consumption (DIC)should be undertaken with great caution.

• Platelet transfusion in heparin-induced thrombocytopenia (HIT),a condition with thrombotic tendency, or thrombotic thrombocytopenic purpura (TTP), Ab to ADAMS13 enzyme which prevents vWF cleavage, can be deleterious.

LEUKOCYTE COMPONENTS• Granulocytes can be prepared by apheresis.

Granulocytes may be stored at room temperature for up to 24 hours. However, after even brief in vitro storage, granulocytes may have reduced ability to circulate and migrate to areas of inflammation.

• It is desirable that they be transfused as soon as possible after collection.

• Donor stimulation with granulocyte colony-stimulating factor (G-CSF) is usually necessary to obtain a sufficient number of granulocytes to be a therapeutic dose for an adult .

• Granulocyte units contain a substantial number of RBCs and must be ABO compatible with the recipient.

• Mononuclear cells collected by apheresis can be a source of hematopoietic progenitor cells (HPCs) for autologous or allogeneic transplantation.

• The number of circulating HPCs can be increased by growth factor (G-CSF or granulocyte-macrophage colony-stimulating factor[GM-CSF]) stimulation, recovery from chemotherapy.

• Autologous HPCs for transplantation in patients with lymphoma or other malignancies are typically collected when the bone marrow is recovering from chemotherapy because there are relatively high numbers of circulating stem cells at that time.

• HPCs may be stored frozen after addition of a cryoprotectiveagent, such as DMSO, for an extended period of time.

• After thawing at 37° C, HPCs should be transfused as soon as possible.

BLOOD COMPONENT THERAPY

• All transfusion decisions are clinical judgments that should be made while taking into account clinical and laboratory data. There are no absolute indications, and few contraindications, to blood transfusion.

THANK YOU