TUTORIAL

Blood & Blood Products

Blood & Blood Products

Summary Blood components/ Blood products Guidelines on administration of blood components ASA- 2006, BCSH- 2009 Adverse effects of blood transfusion Safe transfusion practices

History of Transfusions
Blood transfused in humans since mid-1600s

British physician William Harvey discovered the circulation of blood in 1616 (published in 1628)

1818 British obstetrician James Blundell performs the first successful transfusion of human blood to a patient for the treatment of postpartum hemorrhage.

Karl Landsteiner
1930 Nobel Prize Laureate

1900 Blood typing A, B, O

1939 Levine described

the Rh factor This lead to dramatic decrease in the incidence of hemolytic disease of the newborn.

Blood component
A therapeutic constituent of human blood Eg: Cellular

Blood product
Any therapeutic substance derived from plasma

Red cells Platelets White cells (buffy coat) Stem cells

Eg:

Plasma components

Human albumin solution Clotting factor concentrates (Fac Vlll, IX, PCC) Immunoglobulins Anti-D immunoglobulin

FFP Cryoprecipitate Cryo Supernatant Plasma (CSP)

BCSH Guideline on the Administration of Blood Components 2009

Advantages
Better utilization of scarce source Decrease risk of sensitization Effective(higher) dose without volume overload Decrease risk of TTI Cost effectiveness

Differential Centrifugation
First Centrifugation
Closed System

Whole Blood Main Bag

Satellite Bag 1

Satellite Bag 2

First

RBCs

Platelet-rich Plasma

Differential Centrifugation
Second Centrifugation

RBCs

Platelet-rich Plasma

Second

RBCs

Platelet Concentrate

Plasma

Red cell components

Red cell concentrate Leuko depleted red cells Washed red cells Frozen red cells Irradiated red cells

Red cell concentrate

Whole blood is collected in bags containing citrate-phosphate-dextrose-adenine (CPDA) solution. CPDA blood has a Hct of 70-75% , shelf live of 35 days. Store at 2-6 C The PRBCs are prepared by centrifugation of the whole blood.

Red cells in additive Solution Plasma removed & 100ml of additive solution added Lower Hct, 60% Less citrate per unit Longer shelf life, 42 days

One unit of RBCs will increase the Hb 1g/dL and Hct 3%

RBC preparations
Saline-washed RBCs - used for patients that experience reactions to foreign proteins
Plasma replaced by 50-100ml of NS Shelf life 6hrs(prepared by open system)

Indications
For pt getting recurrent severe allergic reactions Ig A deficiency As a method of leuko reduction

Leuko-depleted RBCswhite cells removed by washing, irradiation, or leukofiltration Indications: Hx of recurrent febrile non-haemolytic reactions for RBCs Transfusion dependant patients Eg:Thalassaemia, Sickle cell anaemia

ASA Task Force Guidelines

RBCs should usually be administered when the hemoglobin concentration is low; for example < 6 g/dL in a young otherwise healthy patient and the blood loss is acute; and transfusion is usually unnecessary when the hemoglobin >10g/dL The determination of whether intermediate levels of hemoglobin (between 6-10) justify or require RBCs should be based on any ongoing indication of organ ischemia, potential or ongoing bleeding, patients intravascular volume status and the patients risk factor for complications of inadequate oxygenation

Indications for RCC

Surgical patients Depend of patients clinical condition and the Hb%

Pre-op : Any ptHb<7g/dL Elderly/impaired cardiac and pulmonary functions Hb<9g/dL

Peri-operative: Volume loss >30%

Post op : Hb<7g/dL
BCSH guidelines 2009

Suggested threshold for for RBC transfusion in infants <4 months

Anaemia in first 24h Anaemia in stable patients > 24h Chronic oxygen dependancy Neonate in ICU Cumulative blood loss in 1st week Acute blood loss Hb 12g/dL Hb 7g/dL Hb 11g/dL Hb 12g/dL 10% 10%

FFP (fresh frozen plasma)

The plasma has been separated from freshly donated whole blood and frozen within 24 hours to a temperature that will maintain the activity of all the coagulation factors (including labile factors V and VIII) stored at 30 C or below for up to 24 months or even longer

When needed, the plasma is thawed rapidly at 37 C and then transfused without delay

FFP
DOSE- 15 ml/kg ( 4 units = 1 adult dose)

Up to 30 ml/kg can be used if fluid intake is possible

Achieve a minimum of 30% of plasma factor concentration with 10-15mL/kg of FFP

When the patient cannot be given large volumes of FFP factor concentrates can be used.

FFP
If there is a delay in transfusion after the FFP packs are received
FFP may be stored at 4C in an approved blood storage refrigerator but should be transfused to the patient within 24 hrs. ( FVIII is destroyed in this process)

Before transfusion it is essential to keep the pack out side for it to reach the room temperature. Or use blood warming devices.

Indications for FFP

Multiple coagulation factor deficiencies
(DIC, advanced liver failure, massive transfusion)

For correction of known coagulation factor deficiencies for which specific correlates are unavailable For urgent reversal of warfarin therapy (5-8ml/kg) For correction of microvascular bleeding in the presence of increased PT/INR & APTT

Indications for FFP

For correction of microvascular bleeding secondary to coagulation factor deficiency in patients with massive transfusion and when PT /APTT cannot be obtained in a timely fashion

For single coagulation factor deficiency when specific factor concentrate are not available(Fac V)
For cases of antithrombin III deficiency Treatment of immunodeficiencies Treatment of TTP (plasma exchange) FFP is contraindicated for augmentation of plasma volume , albumin concentration or nutritional support
Prolonged PT and APTT

Should not be instituted based on laboratory tests alone

Platelets
Platelets are supplied either as single donor units / multiple donors One unit of platelets will increase the platelet count of a 70 kg adult by 5 to 10,000/mm Platelet viability is optimal at 22 C but storage is limited to 4-5 days Platelets have both the ABO and HLA antigens. ABO compatibility is ideal, but not required.

Platelet transfusions
Indications for platelet transfusions
Bone marrow failure ( <10,000 x 109 ) Massive transfusion Acute DIC with bleeding Surgery Platelet count less than 50x109/ l needs transfusion A higher target level of 100 x 109/l has been recommended for those with multiple trauma ,CNS injury or Eye surgery Minor invasive procedure (LP, biopsy, catheter insertion) Platelet functional defect

Platelet dose- 4-8 units ( 1-2 adult doses)

BCSH guidelines / Transfusion Task Force 2007

Platelet transfusion
Platelet pack -50 ml Start the infusion as soon as possible after the pack is received. Infuse over a period of 30 to 60 minutes.
Platelet from single donation is suspended in 50 ml of plasma. Stored at the diffusion of oxygen into the pack, which, with constant gentle agitation, maintains 22C. Platelets are stored in permeable bags that allow aerobic metabolism and reduces the rate of fall of pH.

Do not refrigerate platelet packs

Contraindications for Platelet transfusion

TTP HIT

ITP (relative CI)

Cryoprecipitate
Precipitate remains when the FFP is thawed slowly at 4 C Contains Factor VIII Factor XIII von Willebrand factor (vWF) Fibrinogen Fibronectin Indications Fibrinogen deficiencies / hypo or dysfibrinogenomia Factor VIII deficiency/ hemophilia A Fac Xlll, vWF deficiency Dose- 1-1.5 packs/10 kg (10 units = 1 adult dose)

Cryoprecipitate
1 unit of cryoprecipitate (yield from 1u FFP) contains sufficient fibrinogen to increase fibrinogen level 5 to 7 mg/dL It is stored at -20C and thawed immediately prior to use ABO compatibility is not essential because of the limited antibody content of the associated plasma vehicle (10 to 20 mL) Viruses can be transmitted

Cryo Supernatant plasma

Hypoprotenemic oedema (Nephrotic, Burns) TTP Plasma exchange Haemoplilia B

Prothrombin complex concentrate (PCC)

Combination of blood clotting factors : II, VII, IX , X, and anti thrombotic agents : protein C and S Indications : When rapid correction of prothrombin complex levels is necessary, such as major bleeding or emergency surgery. Reversal of warfarin therapy or vitamin K deficiency in patients exhibiting major bleeding manifestations; and in patients requiring urgent (< 6 hours) surgical procedures
Disadvantage Expensive Lack other clotting factors It has traces of activated clotting factors ( mainly found in older preparations) which may worsen the coagulopathy

Fibrinogen concentrate
Severe hypofibrinogenaemia (<1 g/l) can be treated with a dose of 3 g of Fibrinogen concentrate Expected to raise plasma fibrinogen by around 1 g/l

Recombinant Factor VIIa

An analogue of naturally occurring protease

There are some reports of the successful use of recombinant factor VIIa in patients with DIC and life-threatening bleeding
However, the efficacy and safety of this treatment in DIC is unknown and it should be used with caution.
British Journal of Haematology, 2009 145, 2433

Concentrated WBCS
Prepared by cetrifugation of blood (after separation of RBCS) under controlled conditions Can be stored for up to 24 hours Transfused to treat life-threatening infections in people who have a greatly reduced number of WBCs or whose WBCs are functioning abnormally The use of white blood cell transfusions is rare, because improved antibiotics.

Transfusion Risks
Risks of blood transfusion can be divided into two catagories : Infectious Non-Infectious

Infectious Risks
The transmittable risks are numerous and include: Hepatitis A, B, C, D, E Human T-cell lymphotropic viruses(HTLV-1 & HTLV-2) HIV-1 & HIV-2 Cytomegalovirus West Nile Virus Epstein-Barr virus

Infectious Risks (cont)

Parvovirus B19 GBV-C virus (also called hepatitis G) Transfusion-transmitted virus (TTV) SEN virus Prions including Creutzfeldt-Jakob and variant Lyme Disease Bacterial infections including: malaria, Chagas disease, ehrlichiosis, babesiosis, and syphilis.

Bacterial Contamination
Bacterial Contamination occurs at a much higher frequency than any other infections and is associated with substantial mortality

Rate of bacterial infection/contamination

RBCs 1 : 30,000 Platelets 1 : 2,000

Exposure Estimates
Hepatitis B 1 in 350,000 Hepatitis C 1 in 2,000,000 HIV 1 in 2,000,000 HTLV 1 in 2,900,000 Bacterial reactions from
RBC Platelets 1 in 30,000 1 in 2,000

Noninfectious Risks
Generally immunologically mediated Reactions can occur as a result of the antibodies that are constitutive (Anti-A or Anti-B) or ones that have been formed as a result of prior exposure to donor RBCs, WBC, platelets, or proteins

Noninfectious Risks
Acute hemolytic transfusion reaction (1 : 25,000 -50,000) Delayed hemolytic transfusion reaction (1 : 2,500) Minor allergic reactions (1 : 200 to 250) Anaphylactic/-toid reactions (1 : 25,000 to 50,000) Febrile reactions (1 : 200) Transfusion related acute lung injury (1 : 5,000)

Transfusion-Related Acute Lung Injury (TRALI)

TRALI is a noncardiogenic form of pulmonary edema associated with blood product (any) administration Occurs most frequently with RBCs, FFP, and platelets The incidence is 1 : 5000 (units transfused) TRALI has a mortality of 5 to 8% TRALI was the most common cause of transfusion related death (from 2001-2003)

TRALI (cont.)
TRALI occurs when agents present in the plasma phase of donor blood activate leukocytes in the host Those agents are usually antileukocyte antibodies in donor blood formed as a result of a previous transfusion or pregnancy TRALI usually requires a preexisting condition such as sepsis, trauma or surgery

TRALI (cont.)
The clinical appearance is similar to ARDS Symptoms usually begin within 6 hours after the transfusion and often more rapidly, the patient develops dyspnea, cyanosis, chills, fever, hypotension and noncardiogenic pulmonary edema CXR reveals bilateral infiltrates Severe pulmonary insufficiency can develop

TRALI (cont.)
Treatment is largely supportive The transfusion should be stopped if the reaction is recognized in time The patient should receive oxygen and ventilatory support as necessary, usually with a low tidal volume strategy

Other Non-Infectious Risks

Hypothermia Volume Overload Dilutional coagulopathy Decrease in 2,3-DPG Acid-Base changes Hyperkalemia Citrate Intoxication Microaggregate Delivery

Safe transfusion practices

Time limits:
RBC :-4hrs Platelets:-within 30 min Plasma :- 2-4 hrs

Blood warming / avoid hypothermia: Indications:

Rapid & multiple transfusions >50ml/kg/hr Exchange transfusion in infants Children transfused with >15ml/kg/hr Severe cold agglutinin disease Rapid infusion via CV line Uncontrolled warming could cause death

Avoid hypothermia
Hypothermia has profound effects on the coagulation system . Even modest hypothermia can greatly augment bleeding and needs to be treated or prevented. Prevention pre-warming of resuscitation fluids temperature controlled blood warmers patient warming devices such as warm air blankets

Apheresis
Process which whole blood is collected from a donor and separated into components. Some of these components are retained and the remainder returned to the donor Blood component donation Eg: Plasma (plasmapheresis), Platelets(plateletpheresis), Leukocytes (leukapheresis).

Avoid undesirable practices

Eg: Blood warming by hot water Delay in transfusing after issue from blood bank Lack of monitoring of patient during transfusion Use of unmonitored refrigerator for storage in nursing station Routine pre-transfusion medication Addition of medicined to bag

Optimise Oxygenation Cardiac output Tissue perfusion Metabolic state

Monitor (every 30-60min) FBC Coagulation screen Ionised Calcium levels ABG

Aim for Temp >35 C pH > 7.2 Base excess < -6 Calcium level >1.1mmol/L Lactate level <4mmol/L Platelet >50,000/cc PT/APTT/INR <1.5 Fibrinogen level>1g/dl

Safe transfusion practices

Rational use of blood & blood components to treat conditions leading to significant morbidity and mortality that cannot be prevented or managed effectively by other means.

Thank you