BLOOD COMPONENT TRANSFUSION IN CRITICALCARE

UNITBY

DR.MUHAMMAD AKRAM KHAN QAIM KHANIMATERNITY AND CHILDREN HOSPITAL

MAUSADIA, JEDDAH

Together, we can save a life. It is one of the most important things you can do.

DO YOU KNOW ?

Transfusion of blood remained mysteriously unsafe until the discovery of blood groups by K. Land Steiner in 1900Cell separators introduced in 1970sHBsAg screening introduced in 1968

THE COMPONENT SYSTEMMost patient needing transfusion do not require all of the component availableComponent therapy “STRETCHES” the blood supply by allowing prolonged storage of stable factors and permitting several patients to receive the specific component they need from a single donorReduced risk of fluid overload and infection

BLOOD TRANSFUSION

BLOOD COMPONENTRED CELL CONCENTRATE ( PRBCs )LEUCOCYTE POOR RED CELL CONCENTRATEPLATELET RICH PLASMA ( PRP )GRANULOCYTE CONCENTRATEFRESH FROZEN PLASMA ( FFP )CRYOPRECIPITATESINGLE DONOR PLASMACRYO POOR PLASMA

PLASMA DERIVATIVESALBUMINPLASMA PROTEIN FRACTION ( PPF )FACTOR VIII CONCENTRATEFIBRINOGENIMMUNOGLOBULINSOTHER COAGULATION FACTORS

WHOLE BLOOD COMPONENT

Donor blood mixed with anticoagulant preservativeIndicated in emergent restoration of circulating volume and O2 – carrying capacity in massively bleeding patientNowadays its use is based on EMOTIONAL rather than rational argumentMay produce circulatory overload if transfused to a euvolemic patient

FRESH WHOLE BLOODLess than 06-08 hours oldPlatelets become nonfunctional within 24 hours after collectionAfter 48 hours, essentially all factor VIII is depletedWithin 01 week, even the longer lived factor V is depleted30% RBCs may be lost after 03 weeks of storageFresh blood is used to prevent dilutional coagulopathy in massively transfused patients who require 10 or more units of whole blood within 24 hours period A unit of whole blood ( approximately 350 ml) will increase Hemoglobin by about 0.75gm/dl

WHOLE BLOOD

Removing plasma from whole blood leaves a 200-300 ml of PRBCs, having a PCV of 65-75%Used to restore oxygen carrying capacity of bloodOne unit transfused should raise the PCV of an adult patient by 03%Red blood cells may be stored under refrigeration for a maximum of 42 days, or they may be frozen for up to 10 years. Can be infused rapidly by adding 75ml of normal salineAnemia is the primary indication for transfusion of RBCs. Normal hemoglobin levels are between 12 g/dL and 16 g/dL for women, and 14 g/dL and 18 g/dL for menThe hematocrit—the proportion of RBCs in the total volume of blood—can also determine if a patient is anemic. A normal hematocrit value ranges from 37 to 48 for women, and 45 to 52 for menTypically, transfusions are administered at the “10/30 trigger” (hemoglobin, 10 g/dL; hematocrit, 30) Losing large amounts of blood suddenly can cause

Drop in blood pressure and subsequentlyincrease in cardiac output

PACKED RED BLOOD CELLS

The rationale for blood transfusion is rooted in the physiology of oxygen delivery

Oxygen delivery (DO2) = (Hb level x %sat x 1.34) + (PaO2 x 0.003) x C.I.

Hb level is in g/dl, 1.34 is the amount of oxygen in mls carried by one gram of Hb (the Hufner constant), PaO2 is the partial pressure of oxygen dissolved in the blood measured in mmHg and C.I. is the cardiac output standardized to body surface area) better oxygen delivery ought to be the result A reduction in oxygen delivery below a critical level deprives tissues of the oxygen necessary for oxidative metabolism and results in a shift to anaerobic metabolism. The minimum tolerated hemoglobin level is not well established, Conventional transfusion triggers of 10 g/dl have been challenged by reports indicating that aerobic metabolism is supported by hemoglobin levels of 5.0 g/dl or less.

PACKED RED BLOOD CELLS

No justification for transfusion of RBCs required if.

Acutely bleeding patients as might be indicated by:  Rapid (within four hours) blood loss of > 15% of total blood volume regardless of the measured blood hemoglobin or hematocrit value.  This would correspond to a recorded volume lost, or need to replace with intravenous fluids, of 10 ml per kg patient body weight (e.g. 700 ml blood loss with 4 hrs in a 70 kg patient).

PACKED RED BLOOD CELLS

A multi center, randomized, controlled trial, was conducted between 1994 and 1997. In this study euvolemic patients in the intensive care unit were randomized to either a restrictive or to a liberal transfusion policy. In the restrictive group, patients were transfused when the hemoglobin level was less than 7.0 g/dl, with a target hemoglobin level of 7.0 to 9.0 g/dl. In the liberal group, transfusions were given when the hemoglobin level was less than 10.0 g/dl, with a target range of 10.0 to 12.0 g/dl. There were a number of exclusion criteria including patients with ongoing bleeding or chronic anemia and patients undergoing cardiac surgery. when outcome data were analyzed, patients in the restrictive arm exhibited a strong trend toward improved 30-day survival and a significant improvement in hospital survival. The development of new organ dysfunction in the ICU was significantly less in patients randomly assigned to the restrictive arm The best evidence currently available suggests that transfusion can safely be withheld as long as the hemoglobin remains above 70 g/l and the patient is not actively bleeding

THE TRANSFUSION REQUIREMENTS IN CRITICAL CARE (TRICC) TRIAL

Hebert et. al, NEJM, Feb 1999

A multicenter randomized, controlled clinical trial of transfusion requirements in critical care

Designed to compare a restrictive vs. a liberal strategy for blood transfusions in critically ill patients

Methods: Hebert et. al 838 patients with euvolemia after initial

treatment who had hemoglobin concentrations < 9.0g/dl within 72 hours of admission were enrolled

418 pts: Restrictive arm: transfused for hb<7.0

420 pts: Liberal arm: transfused for Hb< 10.0

Exclusion Criteria Age <16 Inability to receive blood products Active blood loss at time of enrollment Chronic anemia: hb< 9.0 in preceding

month Routine cardiac surgery patients

Success of treatment

4.3%1.4%Noncompliance>48hrs

5.6+ 5.32.6+ 4.1# of transfusions

10.7+0.78.5+0.7Average Hemoglobin

Liberal Group

Restrictive Group

Outcome MeasuresRestrictivegroup

Liberal group

Rate of death at 30 days

18.7% 23.3

Mortality rates 22.2% 28.1

Complications while in ICU

restrictive liberal

cardiac 13.2% 21.0%

MI 0.7% 2.9%

Pulm edema 5.3% 10.7%

ARDS 7.7% 11.4%

Septic shock 9.8% 6.9%

Risks of red blood cell transfusion (adapted from British Committee for Standards in Haematology (2001)1)

Risk factor Estimated frequency per unit transfused

Death per million units

Acute haemolytic reactions 1 in 250 000 to 1 in 1 000 000

0.67

Hepatitis B 1 in 100 000 to 1 in 400 000*

<0.5

Hepatitis C 1 in 3 000 000       <0.5HIV 1 in 4 000 000 <0.5Bacterial contamination of red cell concentrates

1 in 500 000 <0.25

* Data from Kate Soldan, National Blood Service and Central Public Health Laboratory.   Data from Dr Pat Hewitt and Dr John Barbara, National Blood Service, North London.

Special RBC’s Leukocyte-reduced= 108 WBCs prevent

FNHTR Leukocyte-depleted= 106 WBCs prevent

alloimmunization and CMV transmission Washed: plasma proteins removed to

prevent allergic reaction Irradiated: lymphocytes unable to divide,

prevents GVHD

A unit of donor whole blood contains 2 billion white cells per ~450 ml unitEven with blood component processing, 90% of these cells remain with RBCsLeukocyte poor RBCs implies the removal of at least 70% of leukocyte, with a loss of ~10% of the red cells.CMV , HTLV-1, and HTLV-II ( Human T cell Leukemia Virus ) are only transmitted by transfusion of cellular component. And if universal leukoreduction is adopted then it would be no longer be necessary to test for these virusesLeukoreduction may occur in two forms : PRESTORAGE and POSTSTORAGE filtration. In USA and Canada pre storage leuko reduction is donePre storage leukoreduction not only decreases the incidence of certain virus transmission but also eliminates the delay associated with filtering blood in a patient requiring urgent transfusionThrough the use of CENTRIFUGATION OR FILTRATION, 99.995% leukocyte reduction can be accomplished

LEUKOCYTE POOR RBCs

WASHED RBCsSaline washing of RBCs results in the removal of majority of platelets and leukocytesIndicated in patients who are sensitive to plasma proteins or when multiple transfusions are anticipated

FREEZING AND DEGLYCEROLIZATIONLeukocyte poor RBCs prepared by freezing and deglycerolization has lower levels of leukocytes than any other methods but it is costly and time consumingThis technique is used for rare units of RBCs

ADVANTAGES OF LEUKODEPLETED PRODUCTSReduced risks of

Febrile Non Hemolytic Reaction ( FNHTR)Sensitization to blood productsDisease transmission like CMV

LEUKOCYTE POOR RBCs

Blood removed from a critically ill patient for testing can average more than 70 ml/day for days or even weeks, depending on the nature and the severity of the illness The presence of an arterial catheter may increase blood testing by as much as one third Waste of blood occurs each time a catheter is aspirated and flushed , and the risk for nosocomial infection is increased both by catheter manipulation and by transfusion of allogeneic packed red blood cell concentrates NONINVASIVE HEMODYNAMIC MONITORING

Pulmonary artery catheterization is employed less frequently now as compared with as recently as 5 years ago, owing to increasing reliance on echocardiography and esophageal Doppler estimates of aortic blood flow, and to evidence that use of pulmonary artery catheters may be associated with increased mortality

BLOOD COSERVATION METHOD IN ICU

Noninvasive measurement of arterial blood pressure is accurate and the technology is widely available. Capnometry and Pulse Oxymetry in ICUs to minimize frequent extraction of blood for ABGsThe yield of 'fever work-ups' in general, and blood cultures in particular, is very low in the early postoperative period (< 72 hours), and therefore evaluation is usually not indicated.

POINT-OF-CARE TESTING ( POC)Testing of blood samples at or near the bedside Very small (i.e. microliter) blood samples are required, and in some cases are not even removed from the patient because indwelling sensors or a closed circuit extracorporeal sampling device is employed to permit return of the sample to the patient after analysis. Most prevalent example of POC testing is glucose monitoring

BLOOD COSERVATION METHOD IN ICU

Limited blood use policyErythropoetinArtificial hemoglobin

Biopure (An HBOC developed by Biopure Corporation, made from bovine blood )HBOC (A hemoglobin oxygen carrier) DCLHBG (Diaspirin cross-linked hemoglobin)

Alternatives to Transfusion

DEFINITIONPlasma separated from whole blood, frozen within 06 hours of collection and stored at -30°C and bellow

FFP contains fibrinogen; clotting factors II, V, VII, IX, X, XI, XIII; and Von Willebrand factorA unit contains 180-300ml of PlasmaINDICATION

PT OR PTT >1.5Multiple coagulation factor deficiencies 2ndry to Liver disease, DIC, TTP, and Dilutional coagulopathy due to massive blood transfusionReversal of Coumarin ( Warfain and Dicumoral ) effectAntithrombin deficieny which may occur due to OCPs, or patients with Liver dissorder

DOSAGE10-15ml/kg May have to exceed in massively bleeding patient The dose advised for reversal of Warfarin is half the dose

LAB MONITORING To keep PT/PTT <1.5X normal

FRESH FROZEN PLASMA

INDICATIONPlatelet count <5,000Amegalokaryocytic thrombocytopenia

LeulkemiaHypoplastic Anemia

Dilutional thrombocytopenia e.g. massive blood transfusion with stored bloodDICFunctional Platelet abnormalitiesProphylactic Platelet transfusion are rarely indicated with Platelet count >10KIndicated in bleeding patient when Platelet count is <50,000.If count is between 50 – 100,000, the need for transfusion should be based on the risk of bleedingVaginal deliveries and operations are associated wit insignificant blood loss, may be undertaken if the PLT <50,000

PLATELET TRANSFUSION

Factors affecting a patients response to platelet

transfusion Clinical situation: Fever, sepsis,

splenomegaly, Bleeding, DIC Patient: alloimunization, underlying disease,

drugs (IVIG, Ampho B) Length of time platelets stored 15% of patients who require multiple

transfusions become refractory

Joel Saltzman MD Hematology/Oncology FellowMetro Health Medical Center

Strategies to improve response to platelet

transfusions Treat underlying condition Transfuse ABO identical platelets Transfuse platelets <48 hrs in storage Increase platelet dose Select compatible donor

◦ Cross match◦ HLA match

Joel Saltzman MD Hematology/Oncology FellowMetro Health Medical Center

Platelet Transfusions Reactions

Febrile nonhemolytic transfusion: caused by patients leucocytes reacting against donor leukocytes

Allergic reactions Bacterial contamination: most common

blood product with bacterial contamination

Joel Saltzman MD Hematology/Oncology FellowMetro Health Medical Center

DOSE AND ADMINISTRATIONInfuse over not more than 30 mins.One unit of PLT usually increases platelet count by 5K – 100K in a 70kg.adultThe dose of PLT transfusion should increase the PLT count by 50K, therefore one PLT unit / 10kg.The efficacy of PLT transfusion can be assessed by doing PLT count at one hour. And 4-6/24 Hr. post transfusion an increment of <2K, per unit confirms platelet destructionFollowing formula can help to calculate the Corrected Count Increment( CCI) for PLT transfusion

CCI = Post transfusion PLT – pre transfusion PLT X BSA M²No. of PLT Unit transfused

PLATELET TRANSFUSION

EXAMPLEIf a pt. having a body surface area of 2M² is transfused with 04 unit of PLT with initial count of 15000 and post transfusion count of 55,000

CCI = 55000 – 15000 x 2 = 20K2

PLATELET TRANSFUSION

Platelet transfusions

DEFINITIONIt is the insoluble portion of Plasma left after the FFP has been thawed under controlled conditions

The precipitate contains most of the factor VIII ( about 80 – 100unit ), Fibrinogen ( 250 mg ), and 40 – 60% of the Von Willebrand’s factor present in the original unit Plasma.INDICATION

Hypofibrinogenemic states ( e.g. thrombolytic therapy, Congenital deficiency, and consumptive coagulopathy )Hemophilia A ( factor VIII deficiency )Von Willebrand's disease

CRYOPRECIPITATE

DOSE AND ADMINISTRATIONIn Hypofibrinogenemic state,

one bag of Cryoprecipitate/5 kg.of body weight is a usual doseWhen used for Von Willebrand’s disease, one bag / 10kg is usually adequetNowadays,factor VIII concentrate are favored over Cryoprecipitae for treatment of Von Willebrand’s Disease

CRYOPRECIPITATE

Preapered from the plasma of many ( frequently hundreds ) donors, is used for the treatment of Hemophilia AFor the bleeding hemophilac, factor VIII activity is negligible and should be increased to >50% of normal levels to arrest hemorrhageCALCULATION FOR FACTOR DOSES

The doses may be calculated by replacing 01 unit of factor VIII per milliliter of calculated plasma volume per cent of desired factor VIII

Blood volume ( ml) = wt. in kg. X 70Plasma volume ( ml) = blood volume X ( 1 – PCV fraction )Units of factor VIII = plasma volume X ( desired factor VIII% - current factor VIII% )

◦ Alternatively, the rough calculation may be DOSE ( units ) = 40 X ( wt. in kg. ) X ( % factor VIII activity desired )

FACTOR VIII CONCENTRATES

Because factor VIII has a half life of only 08 – 12 hours, close monitoring of clinical signs of bleeding and factor VIII level is necessary

FACTOR VIII CONCENTRATES

Transfusion Reactions

Clinical Signs and symptoms

( of a blood transfusion reaction ) Increased pulse Hypertension

Hypotension Congestive Heart Failure Cyanosis Chills Dyspnea Fever (a 2°rise is

considered a Chest pain febrile reaction) Nausea Hemoglobinuria Vomiting Rash Back pain Heat or pain along the Flushing vein of transfusion Urticaria Other symptoms that would cause concern

to the nurse or patient

Hemolytic transfusion reaction◦ The destruction of transfused red cells. The most common

cause of acute hemolytic reactions is transfusion of ABO incompatible blood, resulting from identification errors occurring at some point(s) in the transfusion process. Type and cross matches are done to try to prevent this type of reactions.

Acute hemolytic reaction◦ Characteristically begin with an increase in temperature and

pulse rate; symptoms may include chills, dyspnea, chest or back pain, abnormal bleeding or shock. Instability of blood pressure is frequent, the direction and magnitude of change depending upon the phase of the antigen-antibody event and the magnitude of compensatory mechanisms

Transfusion Reaction

Delayed Hemolytic reactions:

Occur in previous alloimmunized patients in whom antigens on transfused red cells provokes anamnestic production of antibodies that reaches a significant circulating level while the transfused cells are still present in the circulation;

the usual time frame is 2 to 14 days after transfusion. Signs may include unexplained fever, development of a

positive direct antiglobulin test, an unexplained fall in hemoglobin/hematocrit. Hemaglobinemia and hemoglobinuria are uncommon, but elevation of LDH or bilirubin may be noted. Most delayed hemolytic reactions have a benign course and require no treatment.

Transfusion Reaction

Transfusion ReactionFebrile non-hemolytic reaction

Typically manifested by a temperature elevation of >1°C or 2°F occurring during or shortly after a transfusion and in the absence of any other pyrexic stimulus. This may reflect the action of antibodies against white blood cells or the action of cytokines, either present in the transfused component or generated by the recipient in response to transfused elements. Febrile reactions may accompany about 1% of transfusions; they occur more frequently in patients alloimmunized by transfusion or pregnancy and in patients immune dysfunction due to neoplasm or autoimmunity. Patients who experience repeated, severe febrile reactions may benefit from receiving luekocyte reduced components.Allergic Reactions Usually occurs as urticaria, but may also include wheezing or angioedematous reactions.

Massive Transfusions• Transfusing 1 blood volume replacement (10-20

units for most adults) in less than a 24 hour period or as an acute administration of more than ½ the patient’s EBV per hour

• Main objective is to improve and maintain adequate oxygen carrying capabilities, hemostasis, oncotic pressure, and biochemistry

• Multiple studies show 18-30% of massively transfused patients develop a coagulopathy

• There is debate whether or not to prophylactically replace platelets and coagulation factors or wait until there is abnormal micro vascular bleeding and laboratory evidence of coagulation factor deficiencies

Complications• Metabolic acidosis is uncommon unless there is inadequate

resuscitation• Blood pH is 6.9 after 21 days of storage, due to continued

RBC metabolism of glucose to lactate and pyruvate and bags are impermeable to CO2. pH 6.9 after 21 days and 6.71 after 35 days

• Metabolic alkalosis (MA) is the most common pH abnormality after massive blood transfusions

• Progressive MA results as citrate & lactate in the transfusion convert to bicarbonate in the liver

• MA most likely to occur in patients with renal dysfunction since kidneys are responsible for HC03 elimination.

• If alkalosis occurs, there is a left shift for O2 affinity, and a possibility for cellular hypoxia. There is also a decrease in 2,3 DPG for a left shift of O2

• Compensation for these abnormalities by increasing CO2 and increase O2 delivery

WHAT TIME IS IT? So how much

time has passed since we started?

Many, many people have needed blood.

Remember, the only way for someone to receive blood is for another person to donate it.