Blood group : ABO system, Rh system and others Pre-transfusion testing Blood components : whole blood, packed red blood cells, platelets, fresh frozen plasma, cryoprecipitate, granulocyte, plasma derivatives and artificial blood Complications of blood transfusion Immune mediated reactions : acute hemolytic transfusion reaction, delayed hemolytic transfusion reaction, febrile nonhemolytic transfusion reaction, allergic reaction, graft vs host disease, TRALI- transfusion related acute lung injury, post transfusion purpura Non immunological reactions : fluid overload, hypothermia, hyperkalemia, hypocalcemia, iron overload, immunomodulation Infectious complication : bacterial, viral and others National blood safety policy Massive blood transfusion : definition, indications, protocol and mortality

1. TRANSFUSION MEDICINE
Dr Abdullah Ansari

2. Blood group system
&
Pre-transfusion testing

3. ABO blood group system
•1st system discovered in 1900 by Karl Landsteiner
•Gene on chromosome 9p and inherited in Mendelian co-dominant manner
•What is “Bombay” blood group ???
Blood Group Antigen on RBC Antibody in plasma
O None Anti A and Anti B
A A Anti B
B B Anti A
AB A and B None

4. The Rh blood group system
•2nd most important system
•Gene on chromosome 1
•The presence of D antigen confers Rh positivity
•15% lack this antigen
•Exposure of Rh- recipients to Rh+ cells results in production of anti-D antibodies

5. Other blood group systems
•More than 100 systems recognised, composed of more than 500 antigens
•Clinically significant systems are
1. Kelly, Kidd & Duffy system
2. MNS system
3. Lewis & P system
4. I/i system

6. Pre-tranfusion testing
Two stages – “type & screen”
1. Forward type
◦ Determine ABO & Rh phenotype of recipient RBC
◦ Antisera against A, B & D antigens used
2. Reverse type
◦ Determine the antibodies: anti-A, anti-B & anti-D in patient’s serum
◦ Should correlate with ABO phenotype

7. Cont…
1. Antibody screen
◦ Determine antibodies in patient’s serum directed against other RBC antigens
◦ Type O RBC (containing major antigens of most blood groups) is mixed with patient’s
serum
2. Cross-matching
◦ Performed after antibody screen, when the antibodies in patient’s serum are
recognised
◦ Blood selected for cross matching should be ABO compatible and lack the antigens
for which patient has antibodies

8. Bedside procedure for safe transfusion

9. Blood Components

10. Whole Blood
•450 ml donor blood collected as “whole blood” into 63 ml CPDA-1 (citrate
phosphate dextrose adenine) as anticoagulant preservative
•Hematocrit is 30-40%
•Stored at 4°C
•At this temperature, platelets lose viability, granulocytes disintegrate and labile
coagulation factors decline
•Indication: acute hemorrhage with >25% blood loss
•Provide both oxygen carrying capacity & volume expansion

11. Blood component separation

12. Blood components

13. Packed red blood cells
•Volume is 180-200 ml
•Shelf life of 35 days at 4°C
•Hematocrit is 65-75%
•1 unit PRBC raises Hb by 1 g/dL or Hct by 3%
•Increases oxygen carrying capacity in anemic patients but without volume
expansion
•Transfusion threshold is 7 g/dl in normovolumic patients without cardiac disease
and comorbid conditions
•In critical patients, Hb target is 10 g/dl

14. Platelets
•Random Donor Platelets (RDP)/ pooled platelets: prepared from whole blood
by centrifugation
•Single Donor Platelets (SDP)/ jumbo platelets: prepared by plasma apheresis
machine
•Volume of RDP is 50-70 ml & SDP is 200-400 ml
•Shelf life of 5 days at 22°C

16. Platelets cont…
•1 unit of SDP = 6 units of RDP
•1 RDP increases platelet count by 5000-10000, in unsensitised patient without
increased platelet consumption (DIC, splenomegaly, fever)
•Threshold for prophylactic platelet transfusion is 10000
•If patient is without fever or infection (eg ITP), a threshold of 5000 is sufficient
•For invasive procedures & surgeries, platelet target is 50000

17. Fresh frozen plasma
•FFP contains coagulation factors & plasma proteins - albumin, fibrinogen, anti-
thrombin, protein C & S
•Volume is 200-250 ml
•Shelf life of >1 year at -30°C, if thawed can be stored for 24 hr at 4°C
•Indications are coagulation disorders like DIC, liver diseases, congenital bleeding
disorders & reversal of warfarin therapy
•Doze is 10-15 ml/kg body weight
•1 unit FFP raises coagulation factors by 2%
•Transfusion monitored by PT/INR, stopped when INR <1.5

18. Cryoprecipitate
•It contains fibrinogen, factor VIII & von Willebrand factor
•1 unit cryoprecipitate contains 80 units of factor VIII
•Volume is 10-15 ml
•Shelf life of >1 year at -30°C
•Indications are DIC (serum fibrinogen <100mg/dl), hemophilia A (poor
countries) and von Willebrand disease

19. Granulocytes
•Harvested from donors by apheresis after stimulation by G-CSF &
dexamethasone
•Indicated in febrile neutropenia (ANC<500)

20. Plasma derivatives
•Specific protein concentrates including albumin, intravenous immunoglobulin,
anti-thrombin, and coagulation factors
•Hyperimmune globulins such as anti-D, and antisera to hepatitis B virus (HBV),
varicella-zoster virus, CMV & other infectious agents

21. Artificial Blood
Two main categories of oxygen carrying blood substitutes
1. Hemoglobin based oxygen carriers
2. Perfluorocarbon based oxygen carriers
•In trial stage

22. Complications
of
Blood Transfusion

23. Adverse reactions to blood transfusion
1. Immune-mediated reactions are due to preformed donor or recipient
antibody, however cellular components of stored blood may also cause
immune reactions
2. Non-immune reactions are due to the chemical and physical properties of
stored blood components and its additives like anticoagulant. It include
infections complications

25. Risk of transfusion complications

26. IMMUNE-MEDIATED REACTIONS

27. Acute Hemolytic Transfusion Reactions
Mechanism: The recipient has preformed antibodies that lyse donor RBC
The ABO alloantibodies are responsible for the majority, however, alloantibodies
against other RBC antigens, Rh, Kell, and Duffy are associated with more fatal
reactions
Presentation: Hypotension, tachypnea, tachycardia, fever, chills,
hemoglobinuria, chest pain, flank pain, and discomfort at the infusion site

28. AHTR Cont...
Management:
When suspected, stop transfusion immediately.
Direct Coombs test detects the antibody bound to RBC
Hemolysis studies including serum haptoglobin, lactate dehydrogenase, and
indirect bilirubin levels
Hemolysis causes renal dysfunction. Give intravenous fluids to induce diuresis
Tissue factor released from lysed erythrocytes may initiate DIC. Coagulation
studies including PT, aPTT, fibrinogen, and platelet count

29. Delayed Hemolytic Transfusion Reactions
Mechanism: These patients are previously sensitized to RBC antigens, but have
low antibody levels and negative antibody screen. When re-transfused with the
same antigen, memory response results in early production of antibody (1–2
weeks after transfusion)
The transfused, antibody-coated RBC are removed by the reticuloendothelial
system
Presentation: Mild reaction
Management: No specific therapy is usually required

30. Febrile Non-hemolytic Transfusion Reaction
The most frequent blood transfusion reaction
Mechanism: Antibodies directed against donor WBC, and Cytokines released
from cells within stored blood components
Presentation : Fever with chills and rigors
Management: Use leukocyte-reduced blood products

31. Allergic Reactions
Mechanism: Allergy to plasma proteins in transfused components
Presentation: Urticaria, pruritus, anaphylaxis
Management: Stop transfusion temporarily and administer antihistamines,
corticosteroids if severe.
Prevention: Cellular components washing to remove residual plasma

32. Graft-Versus-Host Disease
Mechanism: Donor T lymphocytes recognize recipient's HLA antigens as foreign
and mount an immune response
Presentation: Fever, cutaneous eruption, diarrhea, and liver function
abnormalities
Management: Resistant to immunosuppressive therapies. Clinical
manifestations appear at 8–10 days, and death occurs at 3–4 weeks
Prevention: Irradiation of cellular components before transfusion

33. Transfusion-related acute lung injury (TRALI)
TRALI is the most common cause of transfusion related fatalities
Definition: TRALI is defined as an acute lung injury (PaO2/FiO2 <300 mmHg) that
is temporally related to a blood transfusion; specifically, it occurs within the first
six hours following a transfusion
Mechanism: The donor anti-HLA class II antibodies bind recipient neutrophils,
these neutrophils aggregate in pulmonary vasculature and release inflammatory
mediators that increase capillary permeability

34. TRALI Cont...
Risk factors: Smoking, chronic alcohol use, shock, liver surgery, mechanical
ventilation and positive fluid balance
Presentation: Symptoms of hypoxia (PaO2/FiO2 <300 mmHg) and signs of non-
cardiogenic pulmonary edema, including bilateral interstitial infiltrates on
chest x-ray
Management: Supportive

35. Chest X-ray of
TRALI...
Bilateral interstitial
infiltrates

36. Post-transfusion Purpura
Mechanism: Anti-platelet antibodies are produced that react to both donor and
recipient platelets
Presentation: Delayed thrombocytopenia 7–10 days after platelet transfusion
Management: Intravenous immunoglobulin to neutralize the antibodies, or
plasma exchange to remove the antibodies

37. NON-IMMUNOLOGIC REACTIONS

38. Fluid Overload
Blood components are excellent volume expanders, and transfusion may quickly
lead to transfusion-associated circulatory overload (TACO)
Dyspnea with SpaO2 <90%, bilateral infiltrates on chest x-ray, and systolic
hypertension are found with TACO
Monitoring the rate and volume of transfusion and using a diuretic can minimize
this problem

39. Hypothermia
Refrigerated (4°C) or frozen (−18°C or below) blood components when rapidly
infused
Cardiac dysrhythmias on exposure of the SA node to cold fluid
An in-line warmer will prevent this complication

40. Electrolyte Toxicity
Hyperkalemia:
•RBC leakage during storage increases the potassium concentration in blood unit
•Prevented by using fresh or washed RBCs in high risk patients like renal failure
Hypocalcemia:
•Citrate, used as anticoagulant, chelates calcium and inhibits coagulation
•Hypocalcemia manifest by circumoral numbness and tingling sensation of
fingers and toes

41. Iron Overload
Each unit of RBCs contains 200–250 mg of iron
Symptoms and signs appears after 100 units of RBC transfusion (total-body iron
load of 20 g)
Prevent by using alternative therapies (eg erythropoietin in CKD) and judicious
transfusion
Chelating agents, such as deferoxamine and deferasirox, used but response is
often suboptimal

42. Immunomodulation
Transfusion of allogeneic blood is immunosuppressive.
Transfusion-related immunomodulation is thought to be mediated by
transfused leukocytes.
Leukocyte-depleted cellular products may cause less immunosuppression

43. INFECTIOUS COMPLICATIONS

44. National blood safety policy
Testing for every unit of blood is mandatory for
1. HIV
2. Hepatitis B
3. Hepatitis C
4. Malaria
5. Syphilis

45. Viral contamination
1. Hepatitis C (HCV): antibodies to HCV and HCV RNA.
2. Human immunodeficiency virus (HIV): antibodies to HIV, p24 antigen and
HIV RNA
3. Hepatitis B (HBV): HbsAg antigen
4. Other Hepatitis viruses
5. West Nile virus
6. Cytomegalovirus (CMV)
7. Human T lymphotropic virus (HTLV) type 1
8. Parvovirus B19

46. Bacterial Contamination
Most bacteria don’t grow well at cold temperatures, hence not common with
PRBC and FFP. However, some gram-negative bacteria can grow at 1–6°C, eg
Yersinia, Pseudomonas, Serratia, Acinetobacter and Escherichia species
Platelet, stored at room temperature are more likely to contain skin
contaminants eg coagulase-negative staphylococci
Presentation: Fever and chills, which can progress to septic shock and DIC
Treatment: stop transfusion immediately if suspected, manage shock and give
broad-spectrum antibiotics
Sent blood component bag for culture and Gram stain

47. Other Infectious Agents
Various parasites, including those causing malaria, babesiosis, and Chagas’
disease and syphilis can be transmitted by blood transfusion

48. Massive Blood
Transfusion

49. Massive Blood Transfusion Definition
The replacement of one blood volume (equivalent to 10 units of blood) in any
24 hour period,
or
Half of the blood volume (5 units of blood) in four hour period in an adult

50. Massive transfusion indications
1. Severe trauma
2. Ruptured aortic aneurysm
3. Vascular/aortic surgeries
4. Obstetric complications

51. Massive Transfusion Protocol
These parameters should be measured frequently (every 30‐60 minutes, or
after transfusion of blood component).
1. Temperature
2. Acid‐base status
3. Ionised calcium (Ca)
4. Haemoglobin
5. Platelets (Plt)
6. PT/APTT (activated partial thromboplastin time)
7. Fibrinogen

52. Mortality
Mortality is high in massive transfusion
Its etiology includes hypotension, acidosis, coagulopathy, shock and underlying
condition of the patient
The lethal triad of acidosis, hypothermia and coagulopathy have the highest
mortality rate
It is often the underlying cause and consequences of major hemorrhage that
result in complications, rather than the transfusion itself