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MBBS VI - SpC - Medicine > Haematology - Transfusion complications > Flashcards

Haematology - Transfusion complications Flashcards

1
Q

List Different types of blood products

A

Blood components: From fractionation of whole blood
 Red cell concentrate (packed cell)
 Platelet concentrate
 Leukocyte concentrate (buffy coat)
 Fresh frozen plasma (FFP)
 Cryoprecipitate: fibrinogen and coagulation factor concentrated from FFP by controlled thawing → ↓volume overload cf FFP

Plasma Derivatives:
From large pools of human plasma under pharmaceutical manufacturing conditions
 Human albumin
 Clotting factor concentrate
 Intravenous immunoglobulin (IVIg)

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2
Q

Acute adverse reactions after transfusion

A

Transfusion associated circulatory overload TACO
Transfusion associated acute lung injury TRALI

Immune- mediated:
- Allergic reaction vs transfused proteins
- Febrile non-hemolytic transfusion reaction: vs accumulated cytokines in blood products
- ABO incompatibility
- Hypotensive reaction to bradykinin, prekallikreinin
- Infection
- Transfusion associated GvHD
- Delayed hemolytic transfusion reaction

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3
Q

Infections caused by blood transfusion

A

Infections

Bacterial: Pseudomonas fluorescens, coagulase-negative staph, Salmonella enteritidis, Y. Enterocolitica, syphilis

Viral: HBV, HCV, HIV, HTLV-1, CMV, parvovirus B19, Dengue virus, HAV, West Nile virus

Others: prion (vCJD), parasitic (malaria, Chagas disease)

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4
Q

Red cell concentrate

  • Processing
  • Pre-transfusion tests
  • Storage
A
  • Processing: Centrifuge to remove plasma, Additive solution with Citrate-Phosphate-Dextrose-Adenine solution
  • Pre-transfusion tests: ABO and RhD compatibility tests, Infectious agent tests
  • Storage: 42 days at 4oC
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5
Q

Platelet concentrates:

  • Process
  • Pre-transfusion testing
  • Storage
A
  • Process - platelet apheresis donation or 4 whole blood donations (Pooled platelet)
  • Pre-transfusion testing: ABO/ RhD testing, Cultured for 24 hours before release
  • Storage: 4-5 days at 20-24oC on a special agitator rack
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6
Q

Fresh Frozen Plasma

  • Content
  • Process
  • Pre-transfusion testing
  • Storage
  • Indications
A

Content: all soluble plasma proteins and clotting factors (esp fibrinogen, coagulation factors)

Process: Apheresis of blood +/- Methylene blue treatment for viral inactivation

Pre-transfusion testing: ABO compatibility testing (for donor Anti-A or Anti-B)

Storage: up to 2 years at -30oC, must be thawed before use

Indication: TTP, Hepatic failure, Warfarin overdose reversal, Massive hemorrhage in surgery or after transfusion

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7
Q

Cryoprecipitate

  • Content
  • Indications
A

Content: Fibrinogen, Factor 8, vWF

Indications:

  • Von Willebrand disease
  • Fibrinogen deficiency/ dysfunction
  • Factor 8 deficiency
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8
Q

White cell concentrate (buffy coat)

  • Processing
  • Storage
  • Indication
A

Processing: pooled from buffy coat (WBC + platelets) or from apheresis of whole blood → must be irradiated before use

Storage: in room temperature for max 24h

Indication: neutropenia/ neutropenic fever with documented infection that is unresponsive to broad-spectrum Abx + antifungal for ≥48h

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9
Q

List immunological reactions to transfusion

A

Reaction vs RBCs
Haemolytic transfusion reaction: immediate vs delayed

Reaction vs WBCs

  • *Febrile non-haemolytic transfusion reaction (FNHTR)**: due to donor WBCs vs recipient Ab, cytokines during storage
  • *Transfusion-related acute lung injury (TRALI)**: due to donor Ab vs recipient WBCs

Reaction vs platelets

  • *Post-transfusion purpura**: due to anti-HPA-1a Ab vs platelet antigens + adsorption of I/C onto recipient platelets
  • *Platelet refractoriness**: due to prior alloimmunization vs foreign platelet antigens

Reaction vs plasma protein

  • *Allergy**: IgE-mediated reaction vs donor plasma proteins
  • *Anti-factor VIII antibody**: in haemophilia A with prolonged replacement therapy or de novo in other individuals

Cell-mediated immunity
Transfusion-associated GVHD (TA-GVHD) due to engraftment of donor lymphocytes attacking recipient HLA-expressing tissues

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10
Q

List non-immunological reactions to transfusion

A

Infection

Metabolic effects: Hyperkalemia, Citrate toxicity, Acidosis

Volume effect: Volume overload, Dilutional thrombocytopenia and coagulopathy

Hypothermia

Iron Overload

Air embolism

Reactive hypotension

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11
Q

Ddx fever during/ immediately after transfusion

A
  1. Infection (pyogenic infection of blood products)
  2. Hemolytic reaction (ABO incompatibility)
  3. Febrile non-hemolytic transfusion reaction
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12
Q

Infective complication of transfusion

  • Pathogenesis/ causative agents
  • S/S
  • Treatment
A

Pathogenesis: bacterial contamination of blood components, can arise from
→ Contamination by skin flora: from donor skin puncture
- Esp. Platelets cannot be refrigerated → cultured for 24h before release to minimize risk
→ Cold-resistant bacteria: Yersinia enterocolitica, Pseudomonas fluorescens and putida

S/S: generally occur in minutes

Systemic: rapid onset of chills/rigors, high fever (usually >2oC), Nausea/ vomiting/ diarrhea, hypotension

Other features: DIC, intravascular haemolysis, renal failure

Treatment:

  1. Stop transfusion immediately → change set and keep IV line open by NS infusion
  2. Send to lab: blood unit + IV set
  3. arrange urgent gram stain of implicated unit
  4. Monitor: vitals, I/O (Foley’s catheter) → for signs of septic shock
  5. Broad-spectrum Abx with adequate anti-pseudomonal coverage
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13
Q

ABO incompatible hemolytic transfusion reaction

Pathogenesis

S/S

A

Cause: majority ABO incompatibility

Pathogenesis:

  • ABO antigens are oligosaccharides → encoded by enzymes that modify H-antigen
  • ABO Ab → IgM cold-reacting Ab with high thermal amplitude → also complement-fixing at 37oC
  • Haemolysis: recipient IgM acting against donor RBC antigens → full complement activation with intravascular haemolysis
  • Free Hb generated > activate platelets and vascular inflammation + binds nitric oxide > hypercoagulation + muscle dystonia
  • Systemic reaction: anaphylotoxin C3a/C5a → mass cell degranulation and cytokine release → systemic inflammation with ↑vascular permeability

S/S: in minutes

  • Systemic reaction: fever/chills/rigors, N/V, agitation/distress, tachycardia/hypotension, headache, dyspnoea, DIC with bleeding
  • Intravascular haemolysis: haemoglobinaemia (pink/dark plasma), haemoglobinuria (pink/dark urine), chest/flank pain, acute renal failure with oliguria, lung peribronchial oedema
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14
Q

ABO incompatibility transfusion reaction

Investigation

A

→ Intravascular haemolysis markers: ↑LDH, ↓haptoglobin, ↑unconj bilirubin, ↑methaemalbumin, haemoglobinemia, urine haemosiderin, haemoglobin

→ Direct Coombs test: +ve

→ CBC, RFT: serial Hb (haemolysis), renal function (AKI)

→ DIC markers: ↑PT/aPTT, ↓fibrinogen, ↑D-dimer, ↓platelets

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15
Q

Management of ABO incompatibility transfusion reaction

A

Stop transfusion

Intensive care: monitor vitals, I/O, bloods

Aggressive fluid resuscitation - IV hydration

Alkaline diuresis for AKI

Dopamine infusion for renal perfusion

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16
Q

What is the most common complication of transfusion

A

Transfusion associated circulatory overload TACO

17
Q

Transfusion-associated circulatory overload (TACO)

  • Cause
  • S/S
  • Prevention
  • Caution in which patients
  • Management
A

Cause: due to volume overload from any blood component, usu in pre-existing HF/CKD

S/S: respiratory distress (SOB, orthopnoea) in 6-12h of completing transfusion;

↑CVP with pulmonary oedema picture in TACO

Prevention: transfuse one unit at a time

Caution: Elderly, renal impairment, heart failure

Management: O2, diuretics ± ventilation if hypoxia

18
Q

Febrile non-haemolytic transfusion reactions (FNHTR)

Pathogenesis

S/S

A

Pathogenesis: immunological reactions involving donor WBCs esp if repeated transfusion

  • Donor leukocyte react against recipient HLA or granulocyte-specific Ab
  • Cytokines released from donor leukocytes during storage (Longer storage = worse)
  • Host Leucoagglutinin bind to transfused leucocytes > activate monocytes and release cytokines with pyrogenic properties

S/S:

  • Mild fever: 1oC rise
  • Flushing, tachycardia, mild dyspnea, rigor, fluctuating BP
19
Q

Allergic reaction to transfusion product

  • Pathogenesis
  • Precautions
  • S/S
A

Pathogenesis - immediate IgE-mediated reaction against plasma proteins

Precautions

  • IgA deficiency
  • Haptoglobin deficiency

S/S

→ Mild: flushing, urticarial rash, pruritus
→ Severe: angioedema, SOB, wheezing, laryngeal oedema with stridor, anaphylaxis with shock

20
Q

Hypotensive reaction to transfusion

Pathogenesis

Precaution

A

Pathogenesis:

Vasodilation due to reaction to bradykinins or prekallikrenin activator in plasma product

Bedside filtration of blood product exposes plasma to charged synthetic surfaces

Precaution:

ACEi user (cannot metabolize prekallikrenin)

21
Q

Delayed haemolytic transfusion reaction

  • Definition
  • Cause
  • Pathogenesis
  • S/S
  • Ix
  • Management
A

definition: reaction occurring >24h afterwards

Cause: non-ABO incompatibility, eg. Rhesus, Kidd, Duffy

Pathogenesis: alloantibodies developed from previous sensitization

  1. Sensitization: exposure to allogeneic RBCs in pregnancy, sharing of IV needles, prior incompatible transfusio
  2. Nature: acquired IgG warm antibodies, generally fall in titre after initial exposure
  3. Re-exposure:
    - High titre Ab → immediate haemolysis → AHTR
    - Undetectable Ab → anamnestic immune response over a few days → DHTR
  4. Haemolysis: generally non-complement fixing (IgG) → extravascular haemolysis, mainly in the spleen

S/S: 4-5 days after transfusion

  • Low-grade fever and jaundice
  • NO evidence of intravascular haemolysis,eg. no haemoglobinemia/uria

Ix:

  • CBC, RET
  • Haptoglobin, methaemalbumin, direct/ indirect bilirubin, LDH
  • Direct/ Indirect antiglobulin test
  • Red cell phenotype

Mx:

none (self-limiting)

22
Q

Transfusion-related acute lung injury (TRALI)

Pathogenesis

S/S

Dx

Mx

A

Pathogenesis:

  1. donor Antibodies vs recipient WBCs (anti-granulocyte specific, anti-HLA, anti-IgA)
  2. → activation of recipient WBCs in lung microvasculature → immune activation with lung injury
  3. Non-cardiogenic pulmonary edema

S/S:

  • sudden onset, usually during or shortly after (<6h) transfusion
  • ARDS: SOB with hypoxaemia, pulmonary oedema on CXR, dry cough
  • Systemic upset: fever, chills, hypotension, cyanosis

Dx:

  • acute (≤6h) onset of ARDS following transfusion
  • Radiological evidence of bilateral pulmonary infiltrate without circulatory overload

Mx:

  • Stop transfusion
  • Ventilatory support with 100% oxygen
  • Exclude circulatory overload (TACO is similar in presentation)
23
Q

Transfusion-associated graft-versus-host disease (TA-GVHD)

Prognosis

Pathogenesis

S/S

Precautions

Dx

Mx

Prevention

A

Prognosis: 90% mortality

Pathogenesis: Transfused allogeneic lymphocytes attack recipient, causing marrow aplasia, diarrhea, rash and hepatitis

S/S: 4-30 days after transfusion

  • Skin: erythematous MP rash progressing into generalized erythroderma
  • GI: anorexia, vomiting, diarrhoea, abdominal pain, dLFT, hepatomegaly
  • Marrow: pancytopenia, BM aplasia, infection, bleeding

Precaution:

  • Immunocompromised state
  • Partial HLA matching between donor and recipient with shared haplotype (e.g. 1st degree cousins)

Dx: Tissue biopsy

Mx: None, manage as GVHD in HSCT

Prevention:

  • 25Gy γ-irradiation of cellular blood components in at-risk individuals
  • AVOID transfusion from close relatives
24
Q

Complications following massive transfusions

A

Hypothermia

Metabolic: Citrate toxicity, Hyperkalemia

Volume effect: Fluid overload, dilutional thrombocytopenia and coagulopathy

Iron overload

25
Q

Hypothermia following transfusion

Pathogenesis

S/S

Prevention

A

Pathogenesis: Transfusion of large volume of blood >> lower core temp. down to 27.5 degrees

S/S: Arrhythmia, cardiac arrest, platelet dysfunction and coagulopathy

Prevention: Blood warmer

26
Q

Citrate toxicity following transfusion

Pathogenesis

Precautions

S/S

Treatment

A

Pathogenesis - citrate in stored blood act as anti-coagulant > citrate chelates calcium > hypocalcaemia in donor

Precautions: Infants, liver impairment patients

S/S: Hypocalcemia S/S e.g. prolong QT and arrhythmia

Treatment: replace calcium with 10% calcium gluconate

27
Q

Hyperkalemia after transfusion

Pathogenesis

Precautions

A

Pathogenesis:

  • Potassium released from red cells with storage
  • Extracellular K in a unit of RBC stored for 1 month is 10.2 mmol

Precautions:

  • Infants
  • Patients with renal impairment
28
Q

Transfusion haemosiderosis

  • Pathogenesis
  • S/S
    *
A

Pathogenesis: Massive transfusion (1 unit = 200mg iron) causing iron overload

S/S: Iron overload
Chronic liver disease: hepatomegaly, cirrhosis, HCC
Endocrine and metabolic: Hypogonadism, hypothyroidism, bronze diabetes
Leaden-grey skin pigmentation
Infection by siderophilic bacteria
Heart failure

Ix and Dx:

  • MRI T2W Liver and Heart (gold-standard)
  • Liver biopsy
  • Ferritin (but acute phase reactant)

Tx:

Iron chelation (oral or subcutaneous)

29
Q

List prevention methods against transfusion complications

A
  1. donor DEFERRAL to reduce risk of infection transmission
  2. Leucocyte reduction before storage (reduce febrile reactions)
  3. Bedside filtration
  4. Use of pre-medication: steroids, antihistamines
  5. Only Male FFP donors
  6. Irradiation of all blood products before infusion to immunocompromised (prevent GVHD)
  7. Universal pathogen inactivation
30
Q

3 pillars of patient blood management (National blood authority)

A
  1. Optimize haematopoiesis
  2. Minimize blood loss
  3. Optimize patient-specific tolerance of anaemia
31
Q

3 pillars of patient blood management (National blood authority)

A
  1. Optimize haematopoiesis
  2. Minimize blood loss
  3. Optimize patient-specific tolerance of anaemia

MBBS VI - SpC - Medicine (80 decks)

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