Blood Component Therapy and Apheresis

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Blood Component Therapy and Apheresis Dr. Debasish Gupta Program Director, CHF International

TRANSFUSION THERAPY Used primarily to treat two conditions Inadequate oxygen carrying capacity because of anemia or blood loss Insufficient coagulation proteins to provide adequate hemostasis

Transfusion Therapy The entire donor unit is administered (WHOLE BLOOD) A specific part of the donor unit is selected (COMPONENTS)

BLOOD Fluid part Water Electrolyte Plasma protein Cellular part RBC WBC Platelets

Whole Blood raw material Processing COMPONENT finished product

Blood Component Therapy Transfusion of specific parts of blood, rather than whole blood ` One donated unit can help multiple patients Conserves resources Optimal method for transfusing large amounts of a specific component Sterile, disposable, integrally associated bag, needle and satellite bags

Apheresis Technology Single Donor Multiple units per collection (Red/Plt, Red/plasma, Double platelet, Double Red, etc) Platelets leukoreduced Used to collect granulocytes But anticoagulation, HES, time

Apheresis a + phere (=carry) take out, remove Donation Therapeutic Plasmapheresis Erythrocytapheresi Leukapheresis Plateletpheresis Selective Plasmapheresis Photopheresis

Principles of component therapy Select the blood product that should be as Estimates risks vs. benefits. Identify the cause of deficient component(factor) and administer the same. safe as possible. Monitor side effects of transfusion.

Advantage of component therapy Specific portions of the blood that patients require can be administered Allowing several patients to benefit from one donation Administration of unnecessary or unwanted components is avoided Chances of transfusion associated illness are less

WHOLE BLOOD Improve oxygen delivery over a short time where there is no facility for blood component. Maintain blood volume after massive hemorrhage Exchange transfusion

Red Blood Cells Carry oxygen and Carbon di-oxide Life span of 120 days. Can be stored at 4 0 C for 35 to 42 days

Red blood cells Yes To increase oxygen carrying capacity in anemic patients No For volume expansion In place of hematinics To enhance wound healing To improve general well being

Red Cells Homologous/Allogenic Autologous Directed Whole Blood Packed Red Cells Leukoreduced / Leukodepleted Irradiated CMV negative Antigen Negative Frozen thawed Washed

Packed Red Blood Cells Made by spinning whole blood and expressing off the supernatant Hct 60% (AS-1) and 80% (CPDA-1) 300-350 ml Stored at 1-6 deg C Shelf-life: 21 days (CPD) 35 days (CPDA-1) 42 days AS-1

Packed Red Blood Cells Must be ABO compatible Rh neg should receive Rh neg. One unit Hgb by 1 g/dl or Hct 3% ( in absence of bleeding or hemolysis); Pediatrics: 8-10cc/kg should Hgb by 2 g/dl Restore or maintains oxygen carrying capacity to meet tissue demands e.g. anemia in normovolemic patient Transfusion indications and triggers

Leukoreduced Non-LR RBC contain 1-3 x 10 9 WBC LR contain < 5 x 10 6 WBC and retains 85% of the original cells In many countries all PRBC units are leukoreduced Reduces febrile reactions Reduces HLA immunization (e.g. transplant) Effective in reducing CMV transmission (CMV safe) Cellular immune function preservation Does NOT prevent GVHD!!! Pre-storage vs. Bedside Filtration

CMV negative All neonates (up to 4 months old) Intrauterine Transfusions High risk lung transplant Allogeneic stem cell transplants

Irradiated Prevents Transfusion Associated Graft vs. Host Disease Irradiation for: Units from blood relatives Allo/Auto HPC Transplant Recipients Intrauterine transfusion Neonates undergoing exchange transfusion Hodgkin s Disease Cellular immune deficiency Solid Organ Transplants

Antigen-negative More transfusions, the higher the likelihood of alloimmunization Gets more difficult to find compatible units for patients with antibodies against high frequency antigens (e.g. anti-e) or multiple antibodies Calculate the availability based on the incidence of the antigen in the general population anti-e, 70% of donors are E negative; 7/10 units will be compatible anti-e where <1% of donors are compatible (need to screen 100 units to find one that is compatible) If multiple antibodies, multiply the frequencies e.g. anti-k and anti-e;.7 x.9 = 63% units antigen neg

Platelet Platelets assist the blood to clot in a wound life span of 5-7 days. Stored at 22 0 C for 5 days

Platelet Yes To control or prevent bleeding associated with documented deficiencies in No To treat ITP unless there is life threatening bleeding. TTP platelet number and function.

Platelets Random vs Apheresis HLA-matched Always in short supply Apheresis SDP is 200-400ml (6-8 units)

Platelets Many centers uses only single donor platelets Leuko-reduced because of apheresis collection ABO matched platelets preferable Rh negative receive Rh negative platelets Platelet alloimmunization (XM, HLA matched) Bacterial contamination a problem (RT storage) One RDP increases platelet count by 5000 SDP = 6-8 units random donor platelets should raise 30-40,000

Platelets The need for platelet transfusion is based on: Type and extent of surgery Ability to control bleeding Consequences of uncontrolled bleeding Actual and expected rate of bleeding Presence of factors that interfere with platelet function

Transfusion Criteria Prophylaxis Platelets <15,000 (no ITP,TTP) Platelets <25,000 and neonate Bleeding or invasive procedure Platelets <50,000 If neurosurgery <100,000 Neonates at risk of ICH Platelets <50,000 Massive bleed with no labs available Liver transplant Microvascular bleeding post CPB Platelets <50,000 Thrombocytopathy Medications e.g. ASA

Platelets (dose and administration) Adult : RDP = 6 to 10 units of platelet concentrate SDP (apheresis) = 1 unit Children : 1 unit per 10 kg of body weight Neonate : 1 unit per 2.5 kg After issue store it at room temperature and transfuse as soon as possible. Note: RDP raises the platelet count by 30,000-70,000/ ul 70 kg in adult SDP 1 unit raises 50,000 to 100,000/ ul

White Blood Cells Destroy the germs, which invade the body life span of 7 hours to a few days. Can be stored at 4 0 C(Buffy coat preparations)

Granulocytes Prepared from Buffy coat Prepared from a single donor using apheresis technology with HES as a sedimentation agent Should contain at least > 1.0 x 10 10 granulocytes Stimulated can yield 4-8 x 10 10 granulocytes by GSF They are stored at 24 deg C They must be infused within 24 hours of collection

Granulocytes Transfusion Criteria (limited): ANC <500 Fever Documented infection (bacterial or fungal) for 24-48 hours Unresponsive to appropriate antibiotics Reasonable hope of marrow recovery

PLASMA (pale yellow fluid)

Plasma Fresh Frozen Plasma Liquid Plasma or Cryo-poor Plasma Thawed Plasma Single donor Plasma (by apheresis) Repletion of all known clotting factors Also contains antithrombin, plasma proteins 200-300 ml per unit

Fresh Frozen Plasma Yes To increase level of clotting factors in patients with No For volume expansion As a nutritional supplement documented deficiency or who are at risk of hemorrhage

Fresh frozen plasma FFP is plasma, which has been separated from whole blood within 6-8 hours of collection and snap frozen to 30 C.

FRESH FROZEN PLASMA Laboratory parameters for indications of FFP: PT / PTT > 1.5 x normal. Activated PTT > 55 sec or > 4 sec of control, patient for surgery Coagulation factor deficiency (<25% of normal) Liver transplant

Fresh frozen plasma The accepted dose of FFP for infusion is 12 to 15ml per kg of body weight. FFP after thawing should be transfused as soon as possible preferably within 24 hours of thawing. After thawing store at 1-6 0 C No compatibility testing is required. ABO compatible FFP should be used

Indications Congenital Factor Deficiency Invasive Procedure or Trauma (e.g. factor XI Deficiency) Emergency Warfarin Reversal Microvascular bleeding and elevated PT/PTT Loss of more than one blood volume and no lab values - then give empirically

Not indicated Volume expansion Nutritional Supplement To promote wound healing

Drawbacks Donor exposures Volume Overload Allergic Reactions Transfusion Related Acute Lung Injury (TRALI)

Cryoprecipitate Antihemophilic factor (AHF) Fraction of plasma that does not dissolve on thawing plasma at 4 deg C Rich in fibrinogen, factor VIII, vwf, fibronectin 15ml/unit; adult dose is 10 units or 1U/10kg; NOT concentrated plasma!; Treats low fibrinogen ( 50-100g/dl) No longer used to replace factor VIII or vwf

Transfusion Criteria Fibrinogen <40 g/dl Fibrinogen <100g/dl with bleeding or surgery DIC Abnormal fibrinogen Fibrin glue Factor XIII deficiency vwd with bleeding or surgery

PLASMA ( 150-200 ML / BAG ) Extensive surgery Burns Massive blood transfusion with RBC Dose 12 to 15 ml / kg of body weight ABO compatible plasma preferred

Plasma Derivatives Factor VIII Concentrate Factor IX Concentrate AT Concentrate Humate-P (Factor VIII +vwf) Albumin IVIG RhIg

IRRADIATOR

Clinical transfusion procedures key point Getting the right blood to the right patient at the right time

Ordering blood Assess patient s need for transfusion Emergency Urgent Routine Urgently requested ABO and RhD compatible unit Blood bank may select Group O Requested ABO and and RhD compatible unit To be available at stated time Requested group, Antibody screen and hold

CHECKLIST ask yourself these questions before transfusing What improvement in the patients condition am I aiming to achieve? Can I minimize blood loss to reduce the need of transfusion? Are there any other treatments I should give before considering transfusion

GOOD CLINICAL PRACTICE Whole blood is indicated only to improve oxygen delivery over a short time to maintain blood volume after massive haemorrhage Packed red cells are generally preferable to whole blood to help circulatory overload and transfusion of unnecessary and possibly harmful components

CHECKLIST Have I recorded my decisions and reasons for transfusion on the patients chart and transfusion reaction form?

CAN WE STORE BLOOD IN THE DOMESTIC REFRIGERATOR? May be stored in the compartment under the chiller NO freezer chiller door Lowest compartment

DURATION FOR WHICH BLOOD CAN BE KEPT AT ROOM TEMPERATURE 30 60 minutes after issuing the blood from the blood transfusion center A frozen blood unit should never be used in transfusion Hot towels should never be used to warm the blood In routine transfusion blood need not be warmed

What are the indications for fresh blood transfusion? There is no absolute indication for fresh blood (<24 hrs) transfusion. However neonates (0-4 months) should be transfused with blood, which is less than 5 days old. Under no circumstances should unscreened blood be issued for transfusion.

What is fresh whole blood? Does it mean one hour old, one day old or two days old? What I am going to achieve? Is it coagulation defect, is it platelet deficiency or improve tissue oxygenation? Let Blood Bank people decide. Tell us what your patient requires. 24hours old whole blood does not contain any viable platelets- denied those platelets to a leukemic patient.

The refrigerator in the ward is out of order. For how many hours can a unit of blood be kept at room temperature before transfusion? Non refrigerated blood units i.e. whole blood and red cell concentrate, should be transfused within 4-6 hours to prevent the risk of bacterial overgrowth. Ideally, transfusion should be started within 30-60 minutes after issuing the blood from the blood transfusion center.

What precautions should be taken during blood transfusion? Before starting the transfusions it is important to check:- (a) The name and hospital number of the patient (b) The donor number on the blood unit (c) The blood group and the expiry date on the blood unit (d) The compatibility report Transfusion through micro aggregate blood filters: have pore size 20 to 40 u which drag most of the micro aggregate composed of white cells, platelets and fibrin threads.

What happens in a remote area where these facilities are not available? Flexibility and adaptability Possible donors are grouped Rapid screening for HIV, HBsAg, anti HCV and VDRL Compatibility is done If the tests are negative, blood is collected and transfused fresh (no provision for component preparation)

Transfusion options summary Option Definition Advantage Disadvantage Autologous Donation Patients blood is collected No Infection Planned in advance Allogenic donation Replacement voluntary donation Availability in emergency Risk of disease transmission Directed donation Selected blood donor by patient Patient feels safe Planned in advance

Non-immune Refractoriness Massive Bleeding Fever Sepsis Splenomegaly DIC Allotransplant Poor storage of plt product Effects of Drugs IV Amphoterocin B TTP

Immune Refractoriness Antibodies to HLA or platelet specific antigens Alloimmunization can follow transfusion, pregnancy, organ transplantation Reduced alloimmunization with leukoreduced products No. of leukocytes more important than No. of donor exposures

Cross-match or HLA-matched Platelets Determine refractoriness with 15 minute or 1- hour post counts; Send off anti-platelet and HLA antibody screen; HLA type patient; inquire about family member r/o possible non-immune causes of thrombocytopenia If screen(+), then go for HLA-A,B match or crossmatched platelets (remember platelets don t express class II); monitor increments Remember that absolute platelet count may not be the endpoint

Anti-platelet Antibody Screen

Guidelines for Red Cell Transfusion

Acute Blood Loss Loss of TBV 15-30% give crystalloids, colloids in young, healthy patients 30-40% Rapid volume replacement RBC transfusion likely needed >40% Life-threatening bleeding Requires rapid volume replacement Requires RBC transfusion

Acute Blood Loss Hgb and Hct Hgb>10, rarely needed Hgb <6, usually needed Hb 6-10 and Co-morbid Conditions indications for transfusion should be based on the patient s risk of inadequate oxygenation from ongoing bleeding and/or high risk factors. CHF, CAD, pulmonary disease, cerebrovascular insufficiency, chemotherapy, sickle cell disease, thal major, tachycardia, weakness, dizziness Don t transfuse based on transfusion trigger

Chronic Anemia Compensatory mechanisms such as increasing 2,3- DPG may allow greater tolerance for anemia Treat the underlying cause (e.g. iron, folate,b12) Try EPO trial if the patient can be observed rather than treated immediately Acute blood loss or peri-operative therapy apply In general: Hgb>10, rarely needed Hgb <6, usually needed Hb 6-10 and Co-morbid Conditions

RBC Transfusion Trigger Why NOT to give PRBC Volume expansion Wound healing Religious objection

Un-crossmatched Blood Used in exsanguination Prefer type specific (takes 5 min) If no time for typing: O+ for males O+ for females beyond childbearing years O neg for females of childbearing years Crossmatching is done retrospectively