1. Transfusion Medicine

2. “Blood transfusion is like marriage: it should not be entered upon lightly, unadvisedly or wantonly or more often than is absolutely necessary.”
–Robert Beal, past director of International Federation of Red Cross

3. Transfusions: History
1660s: First experiments in blood transfusion, transfused dog blood to humans. Patient died and experiments were banned.
1818: James Blundell, British OBGYN, inspired after seeing women bleed to death from uterine losses. Successfully did human transfusions. Mortality up to 50% likely due to ABO incompatibility.
1900: Karl Landsteiner discovered ABO blood groups.
1940: Red Cross established to help supply blood products during WWII.
Transfusions: History

4. Blundnell’s gravitator (1818)
“On the transfusion of blood by the syringe.”
Source: Blood Journal

5. Blood components & products
Whole blood
Red blood cells (PRBCs)
Fresh frozen plasma (FFP)
Cryoprecipitated AHF
Platelets
Granulocytes
Blood components & products

6. Blood Collection: whole blood

7. Blood collection: apheresis (“a taking away”)

8. Red Blood Cells

9. Red blood cells

10. Red blood cell transfusion
Indications for transfusion
Symptomatic anemia
Red blood cell exchange
Action
Increases oxygen carrying capacity by increasing circulating red cell mass
Dosing
Each unit contains enough Hgb to increase by about 1 g/dL
Each unit contains 250 mg of iron
Administration
Must be ABO compatible
ABO/Rh typing, Ab screen, crossmatch
Initial portion of each unit transfused slowly to look for reactions, then infusion can be as rapid as tolerated
Finish transfusion within 4 hours (do not leave at room temp > 4 hrs)
Red blood cell transfusion

11. Transfusion of Blood Products
Collections and Storage of pRBCs
Half Life of stores platelets is somewhat shorted than normal expected RBC lifespan (120 days)
Lifespan of transfused red cells closer to days
Thought 2/2 to depletion of 2,3 DPG
Stores of ATP are diminished in stored RBCs
Transfusion of Blood Products

12. Blood Groups - ABO First described by Karl Landsteiner in 1900
Won the Nobel Prize in Medicine for his work
First successful, “matched” blood transfusion was done by Dr. Reuben Ottenberg at Mt. Sinai Hospital in 1907.
Blood Groups - ABO

13. Carbohydrate antigens in which the alleles are determined by the end moiety
Addition of n-acetylgalactomine to the base structure yields blood group A
Addition of galactose to the base structure (a galactose moiety) yields blood group B
Lack of any additional moieties yields blood group O
Blood Groups - ABO

16. Minor Antigen Groups

17. Rh Blood Groups RH Blood Group 2nd most important after ABO
Consists of 50 antigens
D, C, c, E, e are most important
RH positive vs negative refers to the presence of absence of the D antigen
Part of the routine Type and Screen and Crossmatch antigens that we test for
Rh Blood Groups

18. Most clinically relevant in hemolytic disease of the newborn
An Rh negative mother with an Rh positive father can result in an Rh positive child
Exposure of fetal cells to mother creates anti- D Abs
Use of RhoGAM has reduced the incidence from close to 16% down to less than 1%
Given at week and again within 72 hrs postoperatively
RH Blood Group

19. Blood Groups Type and Screen
Front type: what antigens are on the patient’s RBCs
Back type: identify Ab in the patient’s serum
A antigen only
Type A
B antigen only
Type B
A and B antigen
Type AB
Neither A or B
Type O
anti-B
Type A
anti-A
Type B
anti-A and anti-B
Type O
neither anti-A or anti-B
Type AB
Blood Groups

20. Screen
Look for red cell alloantibodies that may have formed in pregnancy or after prior transfusions
If screen is positive, need to identify the Ab

21. Blood Groups Type and Cross
Crossmatching involves actually taking donor red cells and mixing with a portion of the patient’s serum to look for a reaction
At least 2 units of PRBCs are crossmatched for the patient and reserved for the patient – these units cannot be used by anyone else
Blood Groups

22. So why are these important in transfusion medicine?
Blood Groups - ABO

23. Complications of RBC transfusion
Acute hemolytic transfusion reaction
Febrile nonhemolytic transfusion reaction
Allergic reaction
Anaphylactic reaction
Transfusion related acute lung injury (TRALI)
TACO
Iron overload

24. Blood Groups - ABO Acute Hemolytic Transfusion Reaction Symptoms
Due to ABO incompatibility
Usually due to human ID errors (mislabeling)
Symptoms
Classic Triad: Fevers/Chills, Flank Pain and Red Urine
Also dyspnea, chest/back pain, shock
If patient is in surgery under anesthesia: red urine, hypotension, DIC
Blood Groups - ABO

26. Treatment: supportive
Lab findings:
Hemoglobinuria
Elevated bilirubin
Positive DAT/Direct Coomb’s
Treatment: supportive
Stop transfusion immediately
Notify blood bank to review
Send blood sample from patient along with implicated unit
Maintain/correct BP
Correct coagulopathy, if present
Promote and maintain urine flow

27. Delayed transfusion reaction
Occur in patients who are previously alloimmunized
Antigens on transfused cells provoke antibody production
Usually occurs 2-14 days after transfusion
Signs/symptoms: fever, positive DAT, decrease in H&H, elevated LDH and bili
Most times this is benign and requires no treatment

28. Transfusion Febrile nonhemolytic transfusion reaction
Fever shortly after transfusion (without infection)
Due to cytokines or Abs against WBCs in the transfused blood
More likely to occur if alloimmunized during pregnancy or previous transfusion
Reduce occurrence by using leukocyte reduced RBCs or platelets
Incidence: in less than 1% of LR-RBCs and less than 5% of LR-platelets
Transfusion

29. Anaphylactic reactions
Reported in IgA deficient patients who develop Abs to IgA
Symptoms: hypotension, tachycardia, N/V, diarrhea, bronchospasm, laryngospasm
Use epinephrine, supportive care
Reduce incidence: use washed cellular components

30. TRALI
Thought to be caused by WBC Abs in donors or inflammatory molecules in blood product
Stimulate an inflammatory response in a “primed” donor
Cause injury to alveolar capillary membrane, increased permeability, pulmonary edema
Symptoms: acute onset of hypoxia and non- cardiogenic pulmonary edema within 6 hrs of a transfusion
Treatment: Aggressive supportive care
Reduce occurrence by leukoreducing blood products and preferentially using plasma donated by males.

31. TACO Circulatory overload leading to pulmonary edema
Occurs after transfusing high volumes or at very rapid rates
Higher risk in people with underlying cardiopulmonary or renal disease, very young or elderly, and people with chronic anemia who have low red cell mass and high plasma volume
Treat: supportive, reduce pulmonary edema

32. Bacterial sepsis
Due to gram negative or positive organisms in the transfused product, often skin contaminants
Symptoms: high fever, hypotension, shock during or shortly after transfusion
Treat: stop transfusion, give abx and pressors prn. Send blood cxs from patient and culture specimens from container and blood administration set, report to blood bank.
Occurs more often with platelets (stored at room temp). Most platelets are routinely tested for bacterial contamination.

33. Infectious risks Infection transmission
Blood products are all tested for:
HIV (1 in 1,000,000)
HTLV I and II (1 in 2,000,000)
Hepatitis B (1 in 200,000)
Hepatitis C (1 in 1,000,000)
Syphilis (treponema pallidum)
West Nile Virus
Chagas (trypanosome cruzi)
Other risks: CMV, malaria, bacteria, Lyme, Dengue, Babesiosis, Creutzfeld-Jakob
Infectious risks

34. Blood components & products
Whole blood
Red blood cells (PRBCs)
Fresh frozen plasma (FFP)
Cryoprecipitated AHF
Platelets
Granulocytes
Blood components & products

35. Fresh Frozen Plasma Plasma: FFP
Contains all plasma proteins including all coagulation factors
10-15 mL/kg raises factors ~25%
Ready to use after thawing, must be discarded after 24 hrs or stored as thawed plasma
Indications for use
Preop or bleeding patients who need replacement of multiple factors (liver disease, DIC)
Patients taking warfarin who need transient reversal of warfarin before Vit K would take effect
TTP (transfuse or plasma exchange)
Patients with plasma protein or factor deficiencies, if no specific factor concentrate or recombinant product is available
Fresh Frozen Plasma

36. Fresh Frozen Plasma FFP precautions
One unit is about 250 mL (can be up to 600 mL if apheresis derived). High risk for volume overload.
Plasma must be ABO compatible with the patient’s red cells.
Average INR of FFP is 1.5. Will not correct INR below this value.
Fresh Frozen Plasma

37. Fresh Frozen Plasma FFP: complications/hazards
Infection (bacterial, viral)
Allergic reactions
Febrile reactions
TACO
TRALI
Fresh Frozen Plasma

38. Blood components & products
Whole blood
Red blood cells (PRBCs)
Fresh frozen plasma (FFP)
Cryoprecipitated AHF
Platelets
Granulocytes
Blood components & products

39. Cryoprecipitate Cryoprecipitated anti-hemophilic factor
That FFP  recover the precipitate
Contains:
Fibrinogen
Factor VIII
Factor XIII
vWF
Fibronectin
Each unit contains 80 IU Factor VIII and 150 mg fibrinogen in 5-20 mL plasma
Cryoprecipitate

40. Cryoprecipitate Indications: Control bleeding due to low fibrinogen
Treat Factor VIII deficiency when recombinant proteins not available
Second line therapy for vWD and hemophilia A
ABO compatible preferred
Dose: 1 bag per 10 kg of body weight will raise fibrinogen by mg/dL
Cryoprecipitate

41. Blood components & products
Whole blood
Red blood cells (PRBCs)
Fresh frozen plasma (FFP)
Cryoprecipitated AHF
Platelets
Granulocytes
Blood components & products

42. Platelet Transfusions
Platelets needed for normal hemostasis
Platelets are collected from a single donor (separated from whole blood) or pheresed and pooled from different donors (1 unit = 4-6 single donor units)
Platelet Transfusions

43. Platelet Transfusions
Indications for transfusion:
Thrombocytopenia
Dysfunctional platelet bleeding
Active platelet related bleeding
Prophylactic use for high risk of bleed
Hematologic conditions
Patients on ECMO or cardiopulmonary bypass
Do not use:
In HIT, TTP, or ITP, unless patient has significant bleeding
Platelet Transfusions

44. Platelet Transfusions
Compatibility testing not routinely necessary
Therapeutic dose:
1 unit apheresis platelets
4-6 units of whole blood derived platelets
Should raise platelets by 5-10k
Transfused platelets have a short lifespan! 3-5 days
Platelet Transfusions

45. Platelet Transfusions
Platelet alloimmunization
Platelets have HLA and platelet specific antigens on their surface
Patients who get transfusions often develop HLA antibodies and may become refractory to platelets
Check CBC minutes post transfusion  if Abs present, will not see response
If poor response is due to splenomegaly, sepsis, fever, or DIC, will usually see early response to transfusion but reduced 24 hr survival
Can do tests to look for presence of Ab against platelet antigens
Platelet Transfusions

46. Factor Concentrates Prothrombin Complex Concentrate (PCC)
Contains Vitamin K dependent factors (II, VII, IX, X)
Used to reverse the effects of Vitamin K antagonists
Factor Concentrates

47. Special scenarios Massive transfusion for severe hemorrhage (trauma)
Transfuse RBCs, platelets, plasma in 1:1:1 ratio
Need FFP otherwise clotting factors will be diluted and worsen coagulopathy
Blood is anticoagulated with sodium citrate and citric acid.
In massive transfusion, can get metabolic alkalosis and hypocalcemia from excessive citrate.
Hypothermia can develop when transfusing more than 3 units  use a blood warmer.
Special scenarios