1. Transfusion Medicine
Cynthia H. Ho, M.D.
July 2012

2. Introduction Average volume of blood in an adult is 5 liters.
Volume of blood products
Packed red blood cells (PRBCs): mL per unit.
Fresh frozen plasma (FFP): 250–300 mL per unit.
Platelets: 40–50 mL per unit (single donor), mL per unit (pheresis).
Cryoprecipitate: 10–12 mL per unit.

3. Red Blood Cells
RBC antigens are polymorphic, inherited, carbohydrate or protein structures on RBC membranes.
Immunization against blood group antigens occur through transfusion, pregnancy, and needle sharing.

4. What is in a bag of donor blood?
Anticoagulants
Citrate
Heparin
Preservatives
Adenine
Dextrose

5. Byproducts of RBC Storage
Citrate
Causes hypocalcemia when patients are given large volume transfusions.
Potassium
Na/K pump inactivation.
Hemolysis.
Microaggregates of platelets, WBCs, fibrin can cause pulmonary edema.

6. Red Blood Cells
One unit of PRBC will increase Hgb by 1g/dL and increase Hct by 3%.
Indications for transfusion
Acute blood loss: Depends on 1) risk of tissue hypoxia, 2) symptoms, 3) ongoing blood loss, 4) planned interventions, 5) hemoglobin.
Chronic anemia: Hgb is low but plasma volume is normal. Treat underlying illness first.
Critical illness: Consider at Hgb<7.0.
Sickle cell disease: Acute chest syndrome, stroke, perioperative.
Chemotherapy-related anemia: Consider at Hgb<8.0.

7. Perioperative Transfusions
Blood loss
<10% blood loss – usually no need for transfusion.
10-20% blood loss – crystalloids usually sufficient for resuscitation.
>25% blood loss – blood products usually indicated.
No clear cut off, but consider at Hgb<7g/dL. More important to individualize to your patient.
Coronary artery disease – most cardiologists suggest transfusion at Hgb<10g/dL (no studies to support this practice).

8. Red Blood Cells Packed Red Blood Cells (PRBC)
Component of choice for replacement.
Leukocyte-reduced PRBC
Filtered to remove most WBCs.
Decreases risk of alloimmunization, transmission of viruses (including CMV), febrile non-hemolytic transfusion reactions.
Transplant patients, history of febrile nonhemolytic transfusion reactions, transfusion-dependent chronic anemia, patients receiving chemo or XRT.
Irradiated blood
Avoids Graft vs Host disease.
Transplant patients, immunodeficiency, neonates, patients receiving chemo or radiation therapy.
CMV negative
Transplant recipients.
consider in potential transplant patients.

9. Red Blood Cells

10. Platelet Transfusions
Whole blood derived platelets contain 50mL plasma and platelets from 5-6 donors per unit.
Apheresis units are from a single donor.
More expensive.
Circulate longer (gentle handling).
Exposure to fewer donors.
Decreased risk of infections.
Decreased alloimmunization risk has not been substantiated.

11. Platelets One unit raises platelet counts by 5,000-10,000/uL.
Give over minutes (~10mL/min).
Keep >50,000 for bleeding patients.
Consider keep >100,000 for intracranial hemorrhage.

12. Prophylactic Platelet Transfusions
Studies of prophylactic transfusions in leukemia patients with platelet counts of 10,000 versus 20,000 showed no increased risk of bleeding when 10,000 used as cutoff.
Prior to invasive procedures – no randomized trials
Lumbar puncture – 10,000.
Central lines – 20,000-30,000.

13. Prophylactic Transfusions Prior to Surgery
For most surgeries – Keep platelets > 50,000 – based on retrospective studies.
For neurosurgery, retinal surgeries – Keep platelets> 70, ,000 – based on tradition, no studies.

14. Adverse effects of platelet transfusions
Increased risk of bacterial infections compared with other blood products.
Stored at room temperature for 5 days maximum.
1 in 3,000 platelet units have bacterial contaminant.
Clinically apparent bacterial infections occur in 1 in 25,000 transfusions.
Allergic and febrile nonhemolytic transfusion reactions.
Hemolytic transfusion reactions.
TRALI
Rh(D) sensitization

15. Platelet Refractoriness
Non-immune causes
Fever
Sepsis
Bleeding
Splenomegaly
DIC
Immune causes
Antibodies against HLA or platelet specific antigen (HPA)
ABO incompatibility

16. Platelet Refractoriness
Suspect immune cause if hour post-transfusion platelets increased by less than 5,000.
Check post-transfusion platelets 10 minutes to 1 hour after transfusion.
>5,000-10,000 rise suggests non-immune mediated cause.
<5,000-10,000 rise suggests immune-mediated cause.

17. Contraindications to platelet transfusions
TTP
ITP
HIT
Aplastic anemia
MDS
***Unless life-threatening bleeding.

18. Plasma Acellular component of blood
90% water
7% protein and colloids
2-3% nutrients, crystalloid, hormones, and vitamins
Proteins – Fibrinogen, vWF, protein C, protein S, and soluble clotting factors (V,VII,IX,XI).

19. Plasma Give transfusions over 20-30 minutes. One unit is 200-280mL.
Give 8-10mL/kg.
If critically ill, give 30mL/kg.

20. Plasma FFP is frozen at -18°C or colder within 6 hours of collection.
Can be stored for one year.
Thawed over minutes.
F24 is most commonly used in the U.S.
Frozen within 24 hours of collection.
Virtually equivalent to FFP except decreased amount of fibrinogen, factors V, VIII, and XI.

21. Indications for plasma transfusion
Give over minutes (~10mL/min).
Bleeding associated with clotting factor deficiencies, prior to invasive procedures, reversal of warfarin.

22. Adverse reactions to Plasma transfusions
Febrile non-hemolytic and allergic reactions.
TRALI.
Anaphylaxis (IgA deficiency).
Infections.

23. Cryoprecipitate
Contains Factor VIII, fibrinogen, fibronectin, von Willebrand's factor and Factor XIII.
Give 2-10 units for every 10 kg -> will raise fibrinogen g/dL.
Indications: Bleeding associated fibrinogen deficiency (<100), e.g. DIC.

24. Transfusion-related labs
Type and cross: Matches patient's blood to specific donor units.
Type and screen: Tests patient's serum for common antigens. Good for 72 hours.
Direct Coomb’s DAT: Tests if patient's cells are IgG or complement coated (e.g. hemolytic transfusion reactions, autoimmune hemolytic anemia). IN VIVO.
Indirect Coomb’s: Tests patient's serum with common antibody (other than ABO) to RBC's (e.g. autoimmune hemolytic anemia, delayed hemolytic transfusion reaction). IN VITRO.

27. Pre-Transfusion Medications
Fever from a transfusion is usually due to febrile non-hemolytic transfusion reaction and responds to antipyretics.
However, fever can also occur with bacterial contamination or more serious transfusion reactions (TRALI). Therefore, do not routinely pre-treat with acetaminophen.
Unless the patient has a history of allergic reactions or shows signs of an allergic component to a febrile non-hemolytic transfusion reaction (flushing, hives, or pruritus) there is no benefit from the use of antihistamines for febrile reactions.
Diphenhydramine should be reserved for pretreatment or treatment of possible allergic reactions in patients who have had a history of a mild allergic reaction.

28. Labs after Transfusion
In the absence of increased red blood cell destruction or sequestration, the expected rise in Hgb is usually not measurable until 24 hours after transfusion, when the plasma volume has had time to return to normal.
Checking platelets 1-2 hours after transfusion may be helpful to determine if platelets increase appropriately or if possible alloimmunization has occurred.
When to draw post-transfusion labs depends on what your goal is, anticipated ongoing losses, anticipated procedures (anesthesia), etc.

29. Transfusion reactions
Hemolytic transfusion reactions
Febrile non-hemolytic transfusion reactions
Allergic transfusion reaction
Bacterial contamination
TRALI
Circulatory overload
Anaphylaxis
Post-transfusion purpura
Graft versus host disease
Hypothermia
Electrolyte abnormalities

32. Febrile Non-hemolytic Transfusion Reaction
Increase in temperature by 1°C with no other explanation.
Antibody-leukocyte or antibody-platelet reactions -> cytokine release -> fever.
Fever and chills usually occur shortly after a transfusion has begun.
Less common, but fever and chills can occur hours after transfusion.
Usually resolves after 8-10 hours.

33. What to do if your patient has a fever during a transfusion
Stop the transfusion
R/o hemolysis
Confirm patient and donor blood type
Repeat type and cross
Evaluation for hemolysis – BMP, CBC, LFT, LDH, DAT, haptoglobin, U/A with microscopy
R/o infection
Examine your patient, consider blood culture is bacterial contamination suspected.
Treatment
Tylenol.
Consider hydrocortisone for patients with history of severe FNTR with fever despite Tylenol.
Consider demerol for patients with significant chills from FNTR

34. Allergic Transfusion Reaction
Can present as urticaria, pruritis, vasomotor instability, bronchospasm, anaphylaxis.
Most common presentation is pruritis followed by urticaria.
Due to antibodies (IgE or other) against donor plasma proteins.
Severity is not dose related.
Common – occurs in 1% of transfusions.
Treatment – stop transfusion, give 25-50mg diphenhydramine, monitor. Restart transfusion if urticaria gone.
Do not restart transfusion if patient has fever, bronchospasm, dyspnea, hypotension, tachycardia.

35. Bacterial Contamination
Contamination occurs from skin at the time of collection.
Some bacteria grow optimally at room temperative but others grow optimally under refrigeration (Pseudomonas, Yersinia, Enterobacter, Flavobacterium).
Presents with fever, rigors, skin flushing, abdominal cramps, myalgias, DIC, renal failure, cardiovascular collapse (warm shock).

36. Bacterial Contamination
Treatment
Stop transfusion, check labs (r/o acute intravascular hemolysis)
Send culture of donor blood
Start broad spectrum antibiotics
Between 1998 and 2000
Transfusion transmitted bacteremia
9.98 per million single donor platelets
10.64 per million pooled platelets
0.21 per million RBC units
Fatal reactions
1.94 per million single donor platelets
2.22 per million pooled platelets
0.13 per million RBC units

37. Transfusion Related Acute Lung Injury
Occurs in 1,000 to 5,000 transfusions.
Range in presentation - mild dyspnea, desaturation, fever, chills, hypotension, respiratory failure.
CXR with acute development of bilateral infiltrates.
Develops within 1-6 hours of transfusion.
Non-cardiogenic pulmonary edema (PCWP<18).

39. Circulatory Overload
More common among elderly and patients with predisposition to volume overload (renal failure, CHF).
As a general rule, unless a patient is actively hemorrhaging, do not transfuse faster than 2-3mL/kg/hour.
Slowest rate of transfusion in 4 hours per unit of PRBC. Can ask blood bank to give blood in smalller aliquots if needed to slow down the rate further.

40. Post-transfusion Graft versus Host Disease
Occurs in bone marrow transplant patients.
Immunocompetent donor WBCs attack host tissues.
Fatal in 90% of cases.
Occurs 8-10 days after transfusion.
Pancytopenia, rash, liver test abnormalities, multiorgan failure.
No effective treatment.
Irradiated leukocyte reduced PRBC decreases risk of GVHD.

42. Post-transfusion Purpura
Rare, self-limited cause of thrombocytopenia after transfusion.
Patients with history of exposure to platelet specific antigen (usually PLA1) that they lack form an antibody.
With subsequent exposure to the platelet specific antigen, the antibody destroys donor platelets and triggers an autoimmune response to host platelets as well.
Treatment – IVIg, plasma exchange, steroids, splenectomy.
If bleeding and transfusion needed, give platelets without the platelet specific antigen that the host is lacking.

43. Risk of Transmission of Viral Infections
HBV – 1 in 137,000
HCV – 1 in 1,000,000
HIV – 1 in 1,900,000

44. Type Signs/Symptoms Treatment Acute hemolytic Delayed hemolytic
Fever, chills, back pain, hypotension, intravenous site burning, pallor, jaundice, dark urine.
Occurs during or immediately after transfusion.
Evidence of immune-mediated hemolysis (DAT positive, indirect hyperbilirubinemia, high LDH, low haptoglobin, elevated retic, urine dipstick positive blood without RBC)
Stop transfusion, maintain BP & volume.
Delayed hemolytic
Pallor, jaundice, fever.
Occurs days to weeks after transfusion.
Evidence of immune-mediated hemolysis (DAT+).
Stop transfusion, monitor for severe hemolysis, send pink top tube to blood bank.
Non-immune hemolytic
Pallor, dark urine.
Evidence of hemolysis (DAT negative).
Stop transfusion, supportive treatment.
Febrile non-hemolytic
Fever, chills, malaise.
Once hemolysis ruled out, give anti-pyretics.
Allergic reaction
Hives, rash, pruritis, wheezing, anaphylaxis.
Hold transfusion, monitor for signs of more serious allergy, give diphenhydramine.
If rash only, should resolve in 30 min after treatment and can resume transfusion.
This is the only reaction that a transfusion reaction work-up does not need to be sent.
Anaphylaxis or Anaphylactoid
Sudden onset flushing, wheezing, and hypertension followed by hypotension, edema, respiratory distress, and shock.
No evidence of incompatibility (DAT negative).
Watch for DIC, ARF, respiratory failure, hyperkalemia.
Stop transfusion, give 1ml/kg im epinephrine (0.01mg/kg) of 1:1000 solution.
Hydrocortisone 1mg/kg iv.
Maintain BP and volume, consider dopamine, O2.
Consider IgA deficiency.

47. Summary RBC transfusions Platelets Plasma Cryoprecipitate
One unit increases Hgb by 1g/dL.
Give over 2-3mL/kg/hour, slowest is one unit over 4 hours.
Leukocyte reduction decreases risk of CMV and FNHR.
Irradiation decreases risk of GVHD.
Platelets
One unit increases platelets by 5,000-10,000.
Check platelets after 1 hour if concern for immune mediated cause of refractoriness to platelet transfusion.
Plasma
Transfuse for bleeding patient with decreased clotting factors.
Cryoprecipitate
Transfuse for bleeding patient with decreased fibrinogen <100.
Transfusion reactions
Can be acute or delayed, hemolytic or non-hemolytic.
Stop transfusion, call the blood bank!

48. Reference
Hoffman: Hematology: Basic Principles and Practice, 5th edition Churchill Livingstone, An Imprint of Elsevier.