Haematology JC045: Fever After A Blood Transfusion: Transfusion And Related Problems Flashcards
Types of Blood products
- Red cells
- Platelet concentrates
- Fresh frozen plasma
- Cryoprecipitate (SpC Medicine rich in Factor 8, vWF, Fibrinogen —> less used now because of availability of Factor concentrates)
- Cryoprecipitate-reduced plasma
- Leukocytes (aka Buffy coat)
- Red cells
- One of most commonest used blood products
- Packed red cells with additive solutions (citrate-phosphate-dextrose-adenine) (avoid clotting and RBC dying)
—> **Citrate: anticoagulant
—> **Phosphate-dextrose-adenine: energy + nutrient - All other components of whole blood removed
- Stored at ***4oC
- Shelf life ***42 days
- Platelet concentrates
- Stored at ***room temp (20-24oC)
- Shelf life ***4-5 days
- Require agitation to maintain platelet activity
—> ***platelet agitators machines: moving to keep platelet active
- Fresh frozen plasma
- ***Acellular component of blood (WBC, RBC, Plt removed) —> Yellowish fluid
- Contains ALL ***coagulation factors, proteins
- Stored at ***-30oC
- Must be thawed before use
- Shelf life ***very long
- Leukocytes (aka Buffy coat)
- Must be **irradiated —> inactivate **lymphocyte inside WBC —> prevent transfusion-associated GVHD
- Stored at room temp ***20-24oC
- Shelf life ***8 hours (same day of collection)
Indications (not commonly used):
- ***Neutropenia etc.
***Risks of Transfusion
- ***Volume
- Transfusion associated circulatory overload (TACO) —> Acute pulmonary edema - ***Infection (transmitted from transfusion)
- ***Immunological
- ABO incompatibility
- Febrile non-haemolytic transfusion reactions (FNHTR) —> Leucoagglutinins bind to transfused leukocytes
- Allergic reactions —> IgE mediated Allergic reactions towards transfused protein
- Delayed haemolytic transfusion reaction (DHTR) —> Minor blood group incompatibility (Extravascular haemolysis)
- Transfusion associated acute lung injury (TRALI) —> Anti-Leukocyte Ab in donor plasma bind to pulmonary Ag
- Transfusion associated Graft vs Host disease (TA-GVHD) —> Transfused allogeneic lymphocytes attack recipient - Electrolytes
- Vascular
- Hypotensive reactions —> bradykinin accumulation / prekallikrein activator in plasma products - ***Fe load (chronic heavily transfused patients)
Transfusion associated circulatory overload (TACO)
- ***Commonest complication in transfusion (esp. in elderly: concurrent kidney / heart failure)
- up to 8% of transfusion
Clinical features:
- ***Acute pulmonary edema
Management:
1. Transfuse **ONE unit at a time
2. Be careful in **Elderly, **Renal impairment, **Heart failure
- renal impairment: may have to transfuse during ***dialysis
3. Judicious use of diuretics
4. Close monitoring of haemodynamics and fluid status of patients during + after transfusion
5. Avoid transfusion at night time (when everyone not working)
Fever during / after transfusion
Extremely common complaint
Causes:
1. Infection
- bacterial contamination of blood products (not very frequent)
—> most common in **platelet transfusion (∵ stored at room temp)
—> inspect blood products for any visible damage / discolouration before any transfusion (蛋花湯 appearance)
—> **stop transfusion immediately + send remaining blood product for **culture
—> **microbiological workup of patient + start ***antibiotics immediately
- could be fatal
-
**Haemolytic reaction
- **ABO incompatibility
- fever + shock - ***Febrile non-haemolytic transfusion reaction (most common)
ABO incompatible haemolytic transfusion reaction
- medical incident
- can be fatal
- always do ***Type + Screen properly (turnaround time: 2 hours)
- always give ***Group-specific blood
- naturally occurring IgM, IgG Anti-A + Anti-B
—> these Ab are complement fixing
—> activation of phagocytes + release of inflammatory cytokines (SpC Medicine)
—> **Intravascular haemolysis
—> abrupt onset of “sense of impending doom”, flushing, fever, rigors, loin pain, vomiting, shock, **Haemoglobinuria (dark urine)
—> may develop **DIC + **Acute renal failure —> ***Multi-organ failure
Pathophysiology:
Activation of complements —>
1. **Intravascular haemolysis
—> Free Hb in circulation
—> Activate Plt + Vascular inflammation + binds Nitric oxide causing Smooth muscle dystonia / **Vasodilation + Vascular leak
- Liberate potent Anaphylatoxins + Degranulate mast cells
- Cytokines released from various phagocytes (TNF, IL-6, IL-8 etc.)
- ***Coagulation system activated —> DIC
- Renal failure may be resulted from Vasoconstriction, Hypotension, **DIC (*Not free Hb itself)
Management:
1. Stop transfusion
2. Intensive care
3. Aggressive fluid resuscitation
4. **Alkaline diuresis (treat acidic Haemoglobinuria to rescue kidneys)
5. **Dopamine infusion (inodilator: to preserve renal perfusion)
Febrile non-haemolytic transfusion reactions (FNHTR)
Incidence:
- Red cells 1-12.4%
- **Plt up to 30% (∵ storage temp + more residual WBC)
- more common with patients been **repeatedly transfused
- Correlates with no. of residual leukocytes, storage time, storage temp, rate of infusion
Definition:
- ↑ Body temp by >=***1 oC during / within several hours of transfusion
Clinical features:
- Chills, fever (not ∵ infection), dyspnoea, hypotension, hypertension, rigors
Pathophysiology of Febrile reactions:
1. Leucoagglutinins (Ab in recipients, could be **Anti-HLA class 1 / Granulocyte specific Ab) bind to transfused leukocytes (residual WBC in blood products)
—> activate recipient **monocytes
—> release cytokines with pyrogenic properties
- Could be caused by ***Plasma factors in recipient
- cytokines involved: TNFα, IL-1α, β, IL-6
Management (SpC Medicine):
1. Stop transfusion temporarily
2. Paracetamol
3. **Exclude other causes of fever, esp. AHTR, Bacterial sepsis
4. Use of **Leucocyte-depleted blood products could decrease incidence of FNHTR
5. ***Bedside white cell filter if necessary
Allergic reactions
Different from Febrile reactions
Incidence:
- mild allergic reaction 3%
- anaphylaxis 1 in 20,000
Clinical features:
- From ***Urticaria to Anaphylaxis
Pathophysiology:
- Allergic reactions towards **transfused protein
- **IgE mediated
—> Beware of **IgA deficiency / **Haptoglobin deficient patients (more common in Chinese)
IgA deficient individuals often produce anti-IgA antibodies of IgE or IgG isotypes that can potentially elicit anaphylactic reactions (from Philip Li: very rare, ∵ most anti-IgA Ab are IgG isotype —> not cause anaphylaxis, even IgE isotype seldom cause anaphylaxis)
Delayed haemolytic transfusion reaction (DHTR)
Usually due to Minor blood group incompatibility e.g. **Kidd Ag
- initial Ab titre too low to be detected in Type / Screen (SpC Medicine: referring to AlloAb against minor blood group)
- transfusion of incompatible RBC provokes anamnestic immune response
- Ab causes onset of haemolysis **4-5 days after transfusion
- ***Extravascular haemolysis
Clinical features:
- Fever (may / may not)
- ***Jaundice
- Rapid ↓ in Hb
Investigations:
1. CBP, Reticulocyte, Manual film —> check **Spherocytes
2. Haemolysis screen: **Haptoglobin, Methaemalbumin, Direct / Indirect bilirubin, LDH
3. Direct + Indirect antiglobulin test
4. Extended RBC phenotype (of pre-transfusion sample)
—> able to tell whether haemolysis is due to allogeneic Ab against certain blood group Ag
Transfusion associated acute lung injury (TRALI)
- Transfusion related acute lung injury
- Uncommon (1 in 65,000 ***FFP infusions) but serious complication —> require ICU
- ***Non-cardiogenic pulmonary edema
- now not use female FFP (∵ female donors have higher chance of Anti-Leukocyte Ab in circulation because of ***previous pregnancies)
- ***Diagnosis by exclusion: Need to exclude TACO, Cardiogenic pulmonary edema (SpC Medicine)
Pathophysiology:
2 hit hypothesis (SpC Medicine)
1. Priming of recipient’s neutrophils (e.g. by infection, trauma, surgery etc.) which then adhere to pulmonary vasculature
2.. **Anti-Leukocyte Ab (Anti-HLA / Granulocyte-specific) in **donor plasma —> bind to ***neutrophils bound to pulmonary Ag in recipient —> Activation of neutrophils in recipient —> Release of cytokines —> Capillary leak —> Non-cardiogenic pulmonary edema
Clinical features:
1. Chills, fever, dyspnea, hypotension within **1-2 hours of transfusion
2. Onset of respiratory distress: within **6 hours of initiation of transfusion
3. Radiological evidence of new bilateral pulmonary infiltrates (~ pulmonary edema) but ***absence of circulatory overload
Prognosis:
- After acute phase usually ***full recovery
Management (SpC Medicine):
1. Exclude cardiogenic pulmonary edema
2. Supportive (O2, CPAP)
SpC Medicine:
- Implicated donors will be deterred from future donation
- Use of plasma derived from **male donors / **pooled plasma will decrease the incidence (women: higher chance of having Anti-leukocyte Ab from previous pregnancy / miscarriage causing sensitisation)
- Leukocyte depletion will not decrease incidence of TRALI
Transfusion associated Graft vs Host disease (TA-GVHD)
Transfused allogeneic **lymphocytes attack recipient (esp. T lymphocytes)
—> Attack **BM, Gut, Skin, Liver
—> ***Marrow aplasia, Diarrhoea, Rash, Hepatitis
- ***90% mortality (die of BM failure)
- 4-30 days after transfusion
2 conditions:
1. Immunocompromised recipients
- e.g. BM transplant recipient, patients on immunosuppressants, preterm infants, patients with congenital immunodeficiency
- Immunocompetent recipients receiving blood products from donor who is **homozygous at HLA loci, of which recipient shares the **haplotype
- recipient will see donor as self (∵ share same HLA antigen, esp. homozygous) —> but donor see recipient as foreign (∵ if recipient is heterozygous, donor leukocytes will see as foreign since 1 Ag is different, but host leukocytes cannot see donor leukocytes as different since homozygous)
—> causes: population have limited HLA Ag reservoir (e.g. Japan) / transfusion is from 1st degree relative (近親輸血)
Management:
- **Irradiate blood before transfusion (Gamma irradiation (25 Gy) of **cellular blood components)
Hypotensive reactions
Pathophysiology:
- Reactions towards **bradykinin accumulation / **prekallikrein activator in plasma products
—> **Hypotension, **Vasodilation
Causes:
- Mainly a concern in patients on **ACE-I (bradykinin accumulation)
—> **Bedside filtration of blood products
—> expose plasma to ***charged synthetic surfaces
—> accumulation of bradykinin, prekallikrein activator in plasma
—> ACE-I patients cannot metabolise these cytokines
—> Hypotension, Vasodilation
