1. MANAGEMENT OF MISMATCHED
BLOOD TRANSFUSION AND
MASSIVE BLOOD TRANSFUSION
MODERATOR-DR.MADHUSUDAN[ASSOCIATE
PROFESSOR]
PRESENTOR-DR.RAMYA
1
2. Introduction
Blood is the connective tissue consisting of plasma and cellular components
Average human has 5-6 litres of blood that constitute to 8% of total body weight
It is the transporting fluid that carries vital substances to all parts of the body
2
3. Properties of the blood
Colour- dark red in veins,bright red in arteries
Constitute 8% of body mass
Ph slightly alkaline 7.34-7.45
Temperature 38c
Viscosity-3 to 4 times more viscous tham water
Volume -5 to 6 litres
Osmolarity -280-300 mosm /l
3
4. PLASMA is the pale yellow coloured liquid component of blood that holds the cellular
elements of blood in suspension.
The PH of the plasma is 6.8 -7.7
It consists of water(91%) and 9% solids(1% inorganic molecules and 8% organic molecules) .
Organic molecules –plasma proteins7% (albumin,globulin,fibrinogen,prothrombin).
Inorganic molecules –
sodium,calcium,chloride,bicarbonates,potassium,magnesium,phosphates,iron,copper.
Functions are osmotic balance maintainence, pH buffering, helps in blood clotting .
4
5. RBC
Adult male has 5.4million/microlitre
Adult female has 4.8million/microlitre
In infants 6-7 million/cu mm
In fetus 7-8 million /cu mm
Lifespan is 120 days
Helps in transport of gases and buffering of blood pH
5
6. WBC
Grouped as granulocytes and agranulocytes.
Granulocytes-neutrophils, eosinophils, basophils
Agranulocytes-lymphocytes, monocytes
Neutrophils-helps in phagocytosis
Eosinophils-destroy antigen-antibody complexes,kills parasites,helps in inactivating
inflammatory chemicals.
Basophils –has heparin ,release histamine and other mediators of inflammation.
Lymphocytes-mount immune response by direct cell attack(T-cells) or via antibodies (B-
cells).
Monocytes – helps in phagocytosis and they develop as macrophages in tissues.
Life span is only 18-36 hrs after being released from the marrow
6
7. Platelets
Normal count is 1,30,000 – 4,00,000.
Life span is 9-10 days.
Functions-
forms temporary platelet plugs to stop bleeding and initiating the work of
plasma based clotting factors such as fibrinogen.
Secrete chemicals that attract neutrophils and monocytes to inflammation
site.
Secrete growth factors that stimulate mitosis in fibroblasts , smooth muscle
and help in maintaining blood vessel lining.
7
8. Whole Blood
It is fresh and Metabolically active than stored blood
Stored at 1-4oc.
Shelf life is 35 to 42 days.
In first 4-6hours all the components ate present.
Platelets fall to less than 1% by 4-48 hours.
Labile factor V and VIII also disappear in same time followed by other clotting factors.
Potassium levels increase and ATP levels fall
2,3 DPG levels and pH fall after 5-7days of storage
8
9. Packed RBC
Obtained by apheresis collection or prepared from anticoagulated whole blood.
Following centrifugation,plasma is removed and 100ml of additive solution is added
Each unit contains 200ml RBCs , plasma <50ml , hematocrit of 55-60%.
Shelf life is 21-42 days.
9
11. Platelet concentrates
These are obtained either as pooled concentrations from 4-6 whole blood donations or as
apheresis concentrated obtained from one donor.
If platelets are stored at room temperature ,they can be used up to 7 days after collection.
Random donor unit has 55 × 109 platelets/unit
Apheresis unit has 250 × 109 platelets/unit
11
12. Fresh frozen plasma
It is the most frequently used plasma product.
Produced shortly after donation,generally frozen within 8 to 24 hours.
Thawed plasma is stored at 1to 50 c for upto 5 days.
CONTENTS:-
Factors IV,V,VII,VIII,IX
Protein S,C and antithrombin III
Electrolytes , albumin , immunoglobulins and complement.
12
13. Each unit of FFP generally increases the level of each clotting factor by 2%-3% in adults.
Initial therapeutic dose is 10-15ml/kg.
Goal is to achieve 30% of normal coagulation factor concentration.
FFP may also be used in patients who received massive blood transfusion and continue to
bleed following platelet transfusion
13
14. Cryoprecipitate
It is prepared when FFP is thawed and the precipitate is reconstituted.
Constituents-1.factorVIIIc(procoagulant activity)
2.von Willebrand factor
3.fibrinogen
4.factor XIII
5.fibronectin which is a glycoprotein that has role in
reticuloendothelial clearance of foreign particles and bacteria from blood.
14
15. All the plasma proteins are present in only trace amounts.
Should be administered through a filter .
Rate of administration should be atleast 200ml/hr.
Infusion should be completed within 6hours of thawing.
15
16. COMPATIBILITY TESTING
Includes ABO-Rh typing
Antibody screen
Cross matching
-Designed to demonstrate harmful antigen-antibody interactions in vitro so
that harmful in vivo antigen-antibody interactions can be prevented.
-Donor blood must be screened for hemolytic anti A and/or anti B antibodies
and Rh antibodies
-Recipient blood must undergo ABO-Rh typing as well as testing for
unexpected antibodies
-Proper selection of donor blood requires a crossmatch to test for
compatibility between recipient and donor blood
16
17. ABO-RH TYPING
Determination of correct blood type is most important because most serious reactions
are usually caused by accidental transfusion of ABO-incompatible blood.
15% of all transfusion related deaths are related to hemolytic reactions due to antibody
incompatibility.
17
BLOOD GROUP Anti -A Anti-B
A + _
B _ +
AB + +
O _ _
18. Antibody Screening
Done to identify unexpected RBC alloantibodies
Patient serum is combined with reagent RBC with an additive that promote
binding of antibodies to the RBC
The mixture is incubated at 37c ,washed and mixed with reagent
containing antibodies to IgG and complement.
The reagent binds to any IgG attached to the RBCs,crosslinking the RBCs
and producing agglutination in vitro.
If the test is positive,follow up testing must be done to identify the target
antigen.
18
20. CROSS MATCHING
Trial transfusion within a test tube in which donor RBCs are mixed with
recipient serum to detect a potiential for transfusion reaction.
The full crossmatch can be completed in 45 to 60 min
Performed in three phases:
Immediate spin phase
Incubation phase
Indirect antiglobulin phase
20
21. IMMEDIATE SPIN PHASE
Conducted at room temperature and is a check against errors in ABO typing.
It detects ABO incompatibilites but insensitive to the presence of other RBC alloantibodies.
Takes 1 to 5 minutes
In emergency situations,this step may serve as a sole confirmatory process to eliminate
reactions that may result from human errors in ABO-RH typing
21
23. INCUBATION PHASE
Helps in detection of incomplete antibodies or antibodies able to attach to a specific
antigen but are unable to cause agglutination in saline suspension of RBC.
Involves incubation of test tube at 37c in albumin for 30 to 45 min or low ionic strength
salt solution for 10 to 20 min.
RBCs are centrifused,resuspended and observed for hemolysis and agglutination
RBCs are then washed and resuspended in solution to remove unbound Igs.
23
24. INDIRECT ANTIGLOBULIN OR INDIRECT COOMBS PHASE
Antiglobulin sera is added to the test tubes
The antihuman antibodies present in the sera become attached to the antibody on the
RBCs causing agglutination
24
25. ABO Incompatible Transfusion Reactions
CAUSES
-Clerical errors: commonest cause
1.Misidentification of recipient –mostly occur
in emergencies,icu,operation theatres
2.Wrong samples/ blood packs
-Technical errors:
1.In grouping of patient or donor blood
2.In cross matching
Mismatched blood transfusion leads to hemolytic transfusion reactions
25
26. HEMOLYTIC TRANSFUSION REACTION
Most severe type of transfusion reactions.categorized into two types
Acute or Intravascular HTR which is due to ABO incompatibility that lead to activation of
complement cascade that destroy donor cells.
Delayed or extravascular HTR –Rh or minor group incompatibility
Extravascular RBC destruction is less serious than that of intravascular
26
27. ACUTE HEMOLYTIC TRANSFUSION REACTION
Acute intravascular hemolysis is usually due to ABO blood
incompatibility,and the reported frequency is 1:38,000 transfusions.
These reactions are often severe and may occur after infusion of little as 10-
15 ml of ABO incompatible blood.
The risk of fatal hemolytic reactions is about 1 in 100,000
transfusions
27
29. Patients under general anesthesia early alarming signs may be
unexplained tachycardia
Hemoglobinuria
Bleeding diathesis
Hypotension
Consequences of intravascular hemolysis:
Acute renal failure
Disseminated intravascular coagulation
Acute renal failure
Usually free hb circulates as complex with haptoglobulin [bind approx 100mg of hb/100ml
of plamsa] which is cleared by RES
As little as 50ml of incompatible blood may exceed binding capacity of haptoglobulin
Plasma with 2mg/dl of hb-faintly pink or light brown
100mg/dl of hb-red
150mg/dl-hemoglobinuria occurs
29
30. Hb gets precipitated to acid hematin in the distal tubule causing mechanical tubular
blockage.
DIC
Intravascular hemolysis leads to release of procoagulant material
from red cell stroma erythrocytin,which activates intrinsic system of
coagulation and leads to fibrin formation.
Subsequently platelets, factor I,II,V and VII are consumed.
Investigation – serum haptoglobulin, plasma and urine
hemoglobulin,bilirubin and direct antiglobulin determinates
30
31. Treatment
Stop the transfusion immediately
Maintain the urine output at a minimum of 75-100ml/hr by the following methods:[since
the magnitude of formation of precipitate is inversely related to ph and volume of urine
flow ]
- Administer fluids intravenously and possibly mannitol
- Administer furosemide if intravenous fluids and mannitol are ineffective
. Alkalization of urine to prevent precipitation of acid hematin in the distal tubules.
.Assay urine and plasma hemoglobin concentrations
31
32. Determine platelet count,prothrombin time,partial thromboplastin time amd serum
fibrinogen level.
Return unused blood to blood bank for repeat crossmatch.
Send patients blood and urine sample to blood bank for cross examination.
Prevent hypotension to ensure adequate renal blood flow.[hypotension may result from
activation of kallikrein system]
32
33. Delayed hemolytic tansfusion reaction
Occurs mainly in recipients sensitized to RBC antigens by previous blood transfusions or
pregnancy.
Antibodies most commonly involved are those in Rh system.
The concentration of antibody is so low that it cant be detected by tests before
transfusion
RBC destruction occurs only when the level of antibody is increased after secondary
stimulus[amnestic response]
Occur days or weeks after blood transfusion
33
34. Jaundice and hemoglobinuria can occur, can cause some impairment in renal function.
Often manifested only by decrease in postransfusion hct .
Suspected in any patient with unexplained decrease in hb 2 to 21 days after
transfusion even without obvious manifestations of hemolysis.
34
35. 35
Management
The treatment of delayed hemolytic reaction is primarily supportive.
The frequency of delayed hemolytic reaction is approximately 1:12,000 transfusions.
Although improved blood banking system, or procedures have decreased the incidence of
immediate haemolytic reactions, the delayed haemolytic reactions are not preventable,
because pretransfusion testing is unable to detect very low level of antibodies present in
potential blood recipient’s.
36. MASSIVE BLOOD TRANSFUSION
- transfusion of 10 or more units of packed red blood cells in a 24hrs period
which almost replaces one blood volume based on the total blood volume
of a 70 kg male
- Transfusion of >4units of prbc in one hour when on going need is there
- Replacement of 50% of total blood volume in within 3 hrs
- Transfusion of one unit blood within 5 minutes
36
37. In children
- transfusion of >50% total blood volume in 3hr
- Transfusion of >100% total blood volume in 24hr
- Traansfusion support to replace on goning blood lossof >10% total blood volume per
minute
37
38. Indications of massive blood transfusion
Trauma
Surgical procedures
Liver transplantation
Cardiothoracic and major vascular surgery
Major cancer and spine surgery
Coagulation abnormalites
Acute traumatic coagulopathy
Clotting factor deficiencies
Dilutional coagulopathy
38
39. Obstetric diseases
Massive obstetrics hemorrhage includes fall in hb conc of >40g/dl or blood loss of >2500ml
or transfusion of >4units RBC
PPH means more than 1000ml blood loss from genital tract within 24hrs of birth
Common etiologies include uterine atony, plaxcenta previa,placenta acreta, placental
abruption, uterine rupture,amniotic fluid embolism leading to DIC
39
41. Purpose of MTP
To provide blood products early in the resuscitation and to treat coagulopathy in an
immediate and sustained manner
Hemostatic resuscitation can be achieved by providing predefined ratio of
RBC:FFP:platelets of 1:1:1
Hemostatic resuscitation has been reported to be beneficial in the trauma setting
41
42. Massive blood transfusion protocol are activated by clinician in response to
massive bleeding.
Generally this is activated after transfusion of 4-10 units.
MTP have a pre-defined ratio of RBCs,FFP/Cryoprecipitate and platelet units
(random donor platelets) in each pack {eg;1:1:1 or 2:1:1} for transfusion.
Once the patient in this protocol,the blood bank ensures rapid and timely
delivery of all the blood components together to facilitate resuscitation.
This reduces the dependency on laboratory testing during the acute
resuscitation phase.
42
44. Coagulation abnormalites
- 1.Consumption coagulopathy mainly caused by dilution of coagulation factors by
volume administration and duration of hypotension and hypoperfusion
- Patients who have adequate perfusion and are not hypotensive for a long period tolerate
administration of multiple units of blood without developing coagulopathy
Signs-oozing into surgical field,hematuria,gingival bleeding, petechiae,bleeding from
venipuncture sites,ecchymosis
44
45. Plasma undergoes progressive loss of coagulation factors during storage particularly factor
v and VIII unless stored at -25c
2.Depletion of platelets
platelet function is rapidly lost during storage of whole blood and virtually there is no
platelet function after after 24hrs
management-
give platelet concentrates when patient shows signs of microvascular bleeding ,when
platelet count falls below 50×109/l
consider platelet transfusion in cases when platelet count falls below 20 109/l even if
there is no clinical evidence of bleeding because of risk of internal bleeding
prophylactic use of platelet concentration patients receiving large volume blood
transfusion is not recommended
45
46. 3.Microaggregates
white cells and platelets can aggregate together in stored whole blood forming
microaggregates
during transfusion particularly a massive transfusion these microaggregates embolise to
the lungs and results in development of ARDS
Management-
Filters can be used to remove microaggregates
Use of buffy coat depleted packed red cells will decrease the likelihood of ARDS
46
47. 4.Disseminated intravascular coagulation
It is abnormal activation of the coagulation and fibrinolytic systems resulting in
consumption of coagulation factors and platelets.
It is less likely due to transfusion itself than due to underlying reasons for
transfusion such as hypovolemic shock,trauma,obstetric complications.
Treatment should be directed at correcting the underlying cause
47
49. citrate intoxication and hyperkalemia
- Citrate binds to calcium and thus lowers the ionized plasma calcium conc
- Leads to hypocalcemia ,dysrhythmia and hypotension
- however ionized calcium levels do not decrease enough to cause bleeding even with
infusion of more than 1unit of blood every 10 minutes
- as citrate metabolism is mainly hepatic ,patient with hepatic dysfunction may demonstrate
hypocalcemia and require calcium infusion during massive transfusion
-treatment:1g calcium gluconate 10% given IV for every 5 units blood/FFP
-Hyperkalemia
- Even though serum k+ levels may be as high as 19 to 50meq/l in blood stored for
21days,the net gain of k+ is approx only 10meq/l,when loss of k+ via blood loss is taken into
account.
- For clinically significant hyperkalemia to occur banked blood mut be given at a rate of
120ml/min or more
49
50. Hypothermia
Administration of blood that has been stored at 4c can decrease the
recipient temperature
Interfere with coagulation process by impairing coagulation factors and
platelet functions
If temperature decreases to <30c ,ventricular irritability and cardiac arrest may
may occur.
Shivering from even mild hypothermia increases metabolic demands and is
counterproductive to tissue perfusion
Prevention-warming the blood to body temperature before transfusion
50
51. Acid base abnormalites
-Ph of storage media is very acidic [ph 5.5 for CPD]
- When this solution is added to unit of freshly drawn blood ph of blood immediately
decreases from 7.4 to 7.1
- Ph of banked blood continues to decrease to 6.9 after 21 days of storage as a result of
accumulation of lactic and pyruvic acids by rbc metabolism and glycolysis
-Empirical administration of sodium bicarbonate is not indicated ,administation should be
guided by analysis of arterial blood gases
- Blood transfusion provides citrate which can lead to endogenous generation of bicarbonate
leading to metabolic alkalosis
51
52. TRALI
Transfusion related acute lung injury presents as acute hypoxia and non cardiac
pulmonary edema occurring within 6hours of blood product transfusion.
No evidence of acute lung injury prior to transfusion
Hypoxemia is defined as PaO2/FiO2 less than or equal to 300mm hg , oxygen
saturation less than 90% on room air.
Radiographic evidence of bilateral infiltrates without evidence of left atrial
hypertension.
52
53. Symptoms-
fever,dyspnea ,fluid in ett, severe hypoxia are typical
Management-
stop blood transfusion, institute supportive measures
supplemental o2 for mild cases
Mechanical ventilation with low tidal volume and plateau pressure for moderate to severe
cases
IV corticosteroids to reduce complement mediated granulocyte activation
Blood bank should be notified to provide blood components from different donor and to
quarantine all units from donor in question
All records should be reexamined and the results of patient HLA testing should be
reevaluated if possible
Although most patients recover within 96hrs,TRALI remians the leading cause of
transfusion related deaths
53
54. Transfusion associated circulatory overload
Excessive administration of blood volume leading to pulmonary edema with evidence
for increased left sided cardiac filling pressures
Elevated brain natriuretic peptide
Elevated central venous pressure
Evidence of left heart failure
Acute respiratory distress.
Raised JVP
Widened pulmonary vascular pedicle on chest x ray.
54
55. Non hemolytic transfusion reactions
Febrile or allergic
Febrile reactions are most common
Caused by pyrogenic cytokines and intracellular contents release by donor leucocytes
Symptoms-chills,fever,headache,myalgia, nausea and non productive cough,hypotension,
chest pain, vomiting, dyspnea
Radiographic evidence of prehilar nodule formation and lower lung infiltrates along with
overt pulmonary edema is seen
A direct antiglobulin test differentiates hemolytic reaction from febrile reaction as this test
rules out attachment of antibody to transfused donor donor RBC
Use of leukoreduced blood has lowered the incidence of febrile reactons
55
56. Allergic reactions-
Can be minor,anaphylactoid or anaphylactic.
1. Most allergic reactions are minor and is Caused by the presence of foreign protein in
transfused blood
- Most common symptom is utricaria associated with itching.ocasionally facial swelling
- Transfusion usually need not to be discontinued .anti histamines are used to relive the
symptoms
2.Anaphylactoid are similar to anaphylaxis but are not mediated by IgE
3. Anaphylaxis is more severe form which is due to transfusion of IgA to patients who are IgA
deficient and has formed antiIgA
- Symptoms –dyspnea ,hypotension, laryngeal edema ,chest pain,shock
- These patients should be given transfusion with washed RBC so that all traces of donor
IgA have been removed or with blood that lacks IgA protein
56
57. Transfusion –Transmissible Infections
Donor screening-attempts to reduce the ris of transfusion –transmissible diseases and to
protect the donor from an adverse reaction due to donation
High risk categories for potential transmission of a infectious agent :
1.significant travel histoy
2.history of injection drug use
3.Recent tattoos
4.men who have had sex with men in previous 12 months
57
58. Infectious disease testing for blood
Discontinue serum alanine aminotransferase testing
hepatitis c antibody testing
antibody to hepatitis b core antigen
HIV type1
HIV type 2
HIV antigen [p24]
human t cell lymphotrophic virus type 1 and 2
serological tests for syphilis
58
59. Post Transfusion Hepatits
90% of posttransfusion hepatitis is caused by hepatitis C.
It is also caused by hepatitis B and rarely D ,which are parenterally transmitted
diseases.
SIGNS AND SYMPTOMS
Fatigue(67%)
Hepatomegaly(67%)
Chronic hepatitis(23%)
Chronic active hepatitis(51%)
Hepatocellular carcinoma(11%)
59
61. Cytomegalovirus
It is double stranded DNA virus belonging to herpiviridae family,acts as a
normal flora in healthy adults.
Infection with CMV virus is limited to human, transmitted through contact with
body fluids of a previously infected individual survives best within the cells and
persists in its latent form in the monocytes of people with antibody evidence of
of previous exposure infection
61
62. The recipients who are at high risk for CMV transmission
are
Pregnancy (multiple)
Immaturity or immunosuppression (premature neonates)
Allograft recipients
Post splenectomy
CMV causes a heterophile antibody negative response that closely
resembles infectious mononucleosis in many respects.
An infectious mononucleosis like syndrome that can occur 1 to 2 months
after open heart surgery is known as post perfusion syndrome or post
transfusion mononucleosis
62
63. Management
To prevent this transmission in high risk populations
Use of leukocyte reduced blood, use of frozen deglycerolized RBCs, screening
for CMV antibody negative donors.
63
64. Zika virus
Most recently, transfusion transmissible zika virus infection has been of
concern.
Transmitted by aedes mosquito ,its infection is associated with
GBS,microcephaly in newborn whose mother were in infected during
pregnancy.
80% of infected persons are asymptomatic that pose a potential threat to
blood supply.
PREVENTION;FDA issued guidance that all donations collected in the
united states to be tested for zika virus using NAT.
64
65. Bacterial infections
Bacterial contamination of blood products is the second leading cause of
transfusion associated mortality.
The prevalence of positive blood products ranges from 1:2000 for platelets to
1:7000 for PRBCs and may be due to inadequate antisepsis during phlebotomy.
Both gram positive(staphylococcus) and gram negative(Yersinia and
citrobacter) bacteria can contaminate the blood transfusions and transmit the
disease.
PREVENTION:Blood products should be administered over a period shorter
than 4hr to avoid the possibility of bacterial contamination.
Syphilis,brucellosis,salmonellosis,yersiniosis and ricketsiosses are the specific
bacterial disease rarely transmitted by blood transfusion from donors.
65
66. Parasitic infections
Parasitic diseases that can be transmitted by transfusion include;
Malaria
Toxoplasmosis
Chagas disease.
66
67. Other non infectious risk of blood transfusion
MICROCHIMERISM:
Chimerism refers to more than one cell line in an individual organisms.
Significantly,donor lymphocytes may persists in a patient.
The outcome of the patients with microchimerism is not known.
POST TRANSFUSION PURPURA
This refers to recipient alloantibodies attacking donor platelets antigen and
is treated with intravenous immunoglobulin.
HYPOTENSIVE TRANSFUSION REACTIONS;
Activation of coagulation pathways activates production of bradykinin and
allergic reactions.
67
68. REFERENCES
Millers Anesthesia [ninth edition]
Morgan and mikhails clinical anesthesiology-
edition
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![MANAGEMENT OF MISMATCHED
BLOOD TRANSFUSION AND
MASSIVE BLOOD TRANSFUSION
MODERATOR-DR.MADHUSUDAN[ASSOCIATE
PROFESSOR]
PRESENTOR-DR.RAMYA
1](https://image.slidesharecdn.com/mismatchedbloodtransfusionfinal-240201033316-611c0637/85/mismatched-blood-transfusion-hunkkb-finalpptx-1-320.jpg)
