JC 45 (Medicine) - Transfusion complications Flashcards
List Different types of blood products
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)
Acute adverse reactions after transfusion
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
Infections caused by blood transfusion
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)
Red cell concentrate
- Processing
- Pre-transfusion tests
- Storage
- 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
Platelet concentrates:
- Process
- Pre-transfusion testing
- Storage
- 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
Fresh Frozen Plasma
- Content
- Process
- Pre-transfusion testing
- Storage
- Indications
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
Cryoprecipitate
- Content
- Indications
Content: Fibrinogen, Factor 8, vWF
Indications:
- Von Willebrand disease
- Fibrinogen deficiency/ dysfunction
- Factor 8 deficiency
White cell concentrate (buffy coat)
- Processing
- Storage
- Indication
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
List immunological reactions to transfusion
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
List non-immunological reactions to transfusion
Infection
Metabolic effects: Hyperkalemia, Citrate toxicity, Acidosis
Volume effect: Volume overload, Dilutional thrombocytopenia and coagulopathy
Hypothermia
Iron Overload
Air embolism
Reactive hypotension
Ddx fever during/ immediately after transfusion
- Infection (pyogenic infection of blood products)
- Hemolytic reaction (ABO incompatibility)
- Febrile non-hemolytic transfusion reaction
Infective complication of transfusion
- Pathogenesis/ causative agents
- S/S
- Treatment
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:
- Stop transfusion immediately → change set and keep IV line open by NS infusion
- Send to lab: blood unit + IV set
- arrange urgent gram stain of implicated unit
- Monitor: vitals, I/O (Foley’s catheter) → for signs of septic shock
- Broad-spectrum Abx with adequate anti-pseudomonal coverage
ABO incompatible hemolytic transfusion reaction
Pathogenesis
S/S
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
ABO incompatibility transfusion reaction
Investigation
→ 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
Management of ABO incompatibility transfusion reaction
Stop transfusion
Intensive care: monitor vitals, I/O, bloods
Aggressive fluid resuscitation - IV hydration
Alkaline diuresis for AKI
Dopamine infusion for renal perfusion
What is the most common complication of transfusion
Transfusion associated circulatory overload TACO
Transfusion-associated circulatory overload (TACO)
- Cause
- S/S
- Prevention
- Caution in which patients
- Management
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
Febrile non-haemolytic transfusion reactions (FNHTR)
Pathogenesis
S/S
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
Allergic reaction to transfusion product
- Pathogenesis
- Precautions
- S/S
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
Hypotensive reaction to transfusion
Pathogenesis
Precaution
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)
Delayed haemolytic transfusion reaction
- Definition
- Cause
- Pathogenesis
- S/S
- Ix
- Management
definition: reaction occurring >24h afterwards
Cause: non-ABO incompatibility, eg. Rhesus, Kidd, Duffy
Pathogenesis: alloantibodies developed from previous sensitization
- Sensitization: exposure to allogeneic RBCs in pregnancy, sharing of IV needles, prior incompatible transfusio
- Nature: acquired IgG warm antibodies, generally fall in titre after initial exposure
- Re-exposure:
- High titre Ab → immediate haemolysis → AHTR
- Undetectable Ab → anamnestic immune response over a few days → DHTR - 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)
Transfusion-related acute lung injury (TRALI)
Pathogenesis
S/S
Dx
Mx
Pathogenesis:
- donor Antibodies vs recipient WBCs (anti-granulocyte specific, anti-HLA, anti-IgA)
- → activation of recipient WBCs in lung microvasculature → immune activation with lung injury
- 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)
Transfusion-associated graft-versus-host disease (TA-GVHD)
Prognosis
Pathogenesis
S/S
Precautions
Dx
Mx
Prevention
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
Complications following massive transfusions
Hypothermia
Metabolic: Citrate toxicity, Hyperkalemia
Volume effect: Fluid overload, dilutional thrombocytopenia and coagulopathy
Iron overload
Hypothermia following transfusion
Pathogenesis
S/S
Prevention
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
Citrate toxicity following transfusion
Pathogenesis
Precautions
S/S
Treatment
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
Hyperkalemia after transfusion
Pathogenesis
Precautions
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
Transfusion haemosiderosis
- Pathogenesis
- S/S
*
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)
List prevention methods against transfusion complications
- donor DEFERRAL to reduce risk of infection transmission
- Leucocyte reduction before storage (reduce febrile reactions)
- Bedside filtration
- Use of pre-medication: steroids, antihistamines
- Only Male FFP donors
- Irradiation of all blood products before infusion to immunocompromised (prevent GVHD)
- Universal pathogen inactivation
3 pillars of patient blood management (National blood authority)
- Optimize haematopoiesis
- Minimize blood loss
- Optimize patient-specific tolerance of anaemia
3 pillars of patient blood management (National blood authority)
- Optimize haematopoiesis
- Minimize blood loss
- Optimize patient-specific tolerance of anaemia
