Clinical Aspects of Transfusion Reactions. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Acute haemolytic transfusion reaction. Signs and symptoms. Investigation of serious reactions. Example. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Renal failure. Management of an ABO incompatible transfusion. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Delayed haemolytic transfusion reaction. Definition. Clinical features. Haematological and serological features. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Bacterial contamination. Symptoms. Implicated components/organisms. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Transfusion-associated graft- versus-host disease (TAGvHD). Causes. Clinical features. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Investigations. Indications for gamma irradiation. Components requiring irradiation. Shelf-life post-irradiation. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: IgA deficiency with anti-IgA. Signs and symptoms. Treatment of anaphylactic reaction. Antibody-antigen reactions. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Febrile non-haemolytic transfusion reaction (FNHTR). Signs and symptoms. Causes. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Cytokine generation. The role of cytokines in the pathogenesis of fever. Hypotensive reactions. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Post-transfusion purpura (PTP). Mechanism of autologous platelet destruction. Differential diagnosis. Malcolm Needs CSci FIBMS

This lecture is designed to give an overview of: Course of the disease. Management. Prevention. Malcolm Needs CSci FIBMS

Acute Haemolytic Transfusion Reaction. Malcolm Needs CSci FIBMS

Symptoms: Apprehension. Flushing. Pain at VP site. Pain in chest, abdomen, loin. Malcolm Needs CSci FIBMS

Signs: Fever. Hypotension. Generalised bleeding. Haemoglobinaemia. Haemoglobinuria. Malcolm Needs CSci FIBMS

Investigation of Serious Reactions. Malcolm Needs CSci FIBMS

Re-check patient identity and ABO group. Expiry date. Urine output. Volume, haemoglobinuria, etc. Malcolm Needs CSci FIBMS

Blood samples from patient. ABO group, antibody screen and cross- match. DAT and eluate, even if the DAT is negative. FBC and platelets. Coagulation screen. Blood culture. Biochemistry. Malcolm Needs CSci FIBMS

Example. Malcolm Needs CSci FIBMS

Anti-A reacts with the A antigen. This activates the complement cascade from C1q to C9a. This causes membrane damage. Resulting in intravascular haemolysis. Malcolm Needs CSci FIBMS

Activates clotting factors Neutrophils Complement Cytokines Macrophages Activates clotting factors Thrombosis Consumption of clotting factors Organ failure Bleeding Malcolm Needs CSci FIBMS

Renal Failure. Malcolm Needs CSci FIBMS

Free haemoglobin binds nitric oxide. Hypotension, Shock. DIC. Free haemoglobin binds nitric oxide. Causes excessive vasoconstriction. Malcolm Needs CSci FIBMS

Management of an ABO Incompatible Transfusion. Malcolm Needs CSci FIBMS

Maintain urine output >100mL per hour. IV saline infusion. Treat shock. Monitor urine output. Maintain urine output >100mL per hour. Malcolm Needs CSci FIBMS

Frusemide if urine output <100mL per hour. Dialysis for renal failure. Blood components for DIC with bleeding. Malcolm Needs CSci FIBMS

Delayed Haemolytic Transfusion Reaction. Malcolm Needs CSci FIBMS

Occurs 24 hours or more after the transfusion. Usually >7-10 days due to anamnestic response of red cell alloantigens to which the patient has been previously sensitised. Malcolm Needs CSci FIBMS

Clinical features. Fever. Fall in haemoglobin. Jaundice. Haemoglobinuria. Renal failure (very rarely). Malcolm Needs CSci FIBMS

Haematological and Serological Features. Malcolm Needs CSci FIBMS

Antibody in serum (usually). Antibody eluted from red cells. Spherocytosis. Positive DAT. Antibody in serum (usually). Antibody eluted from red cells. Malcolm Needs CSci FIBMS

Bacterial Contamination. Malcolm Needs CSci FIBMS

Bacterial Contamination of Blood Components. Malcolm Needs CSci FIBMS

Feeling unwell. Fever. Chills. Hypotension. Malcolm Needs CSci FIBMS

Nausea. Vomiting. Dyspnoea. Shock. Malcolm Needs CSci FIBMS

Renal failure. DIC. Death. Malcolm Needs CSci FIBMS

Implicated Components/Organisms. Malcolm Needs CSci FIBMS

Implicated units; RBC/platelets. Organism depends upon type and storage of components. Blood culture, culture of bag. Contact donor; arm swab culture. Malcolm Needs CSci FIBMS

Transfusion-associated Acute Lung Injury (TRALI). Malcolm Needs CSci FIBMS

See separate lecture on TRALI. Malcolm Needs CSci FIBMS

Transfusion-associated Graft-versus-host Disease (TAGvHD). Malcolm Needs CSci FIBMS

Caused by engraftment and proliferation of donor T lymphocytes in the recipient. Activated donor T lymphocytes produce cytokines, causing inflammation and tissue damage. Malcolm Needs CSci FIBMS

Sharing of HLA haplotypes. Defective recipient cell-mediated immunity. Malcolm Needs CSci FIBMS

Clinical Features. Malcolm Needs CSci FIBMS

Onset 1 to 2 weeks post-transfusion. Fever, skin rash. Diarrhoea. Hepatitis. Pancytopenia. >90% mortality. Malcolm Needs CSci FIBMS

Diagnosis. Skin biopsy. DNA analysis. Bone marrow. Malcolm Needs CSci FIBMS

Investigations. Malcolm Needs CSci FIBMS

Donor samples. Recipient sample. Fresh sample – 10-20mL EDTA. Pre-transfusion (whatever is available). Post-transfusion – 10-20mL EDTA. Hair follicles, nail clippings, etc, as an alternative source of pre-transfusion DNA. Malcolm Needs CSci FIBMS

Skin, affected and unaffected areas. Bone marrow. Spleen (post-mortem). Malcolm Needs CSci FIBMS

Gamma Irradiation; Indications. Malcolm Needs CSci FIBMS

Donations from first or second degree relatives. All HLA selected platelets. Foetus IUT and subsequent exchange/top-up transfusions. Malcolm Needs CSci FIBMS

Infants receiving exchange transfusion. Granulocyte transfusion (Buffy coat). Patients with evidence of an underlying state (except chronic muco-cutaneous candidiasis and HIV). Malcolm Needs CSci FIBMS

Allogeneic BMT from conditioning therapy until GvHD prophylaxis is completed (usually 6 months) or until the lymphocyte count is >1x109L-1. Chronic GvHD can be immunosuppressive. Active chronic GvHD; continue irradiation. Malcolm Needs CSci FIBMS

Patients on purine analogues. Bone marrow donors. Blood transfused to bone marrow donors prior to, or during the harvest. Patients on purine analogues. Malcolm Needs CSci FIBMS

Components Needing Irradiation for Patients at Risk. Malcolm Needs CSci FIBMS

Any other cellular components. Red cells. Platelets. Any other cellular components. Malcolm Needs CSci FIBMS

Shelf-life Post-irradiation. Malcolm Needs CSci FIBMS

Exchange and IUT RBCs = 24 hours. Top-up and other RBCs = 14 days. Platelets = 5 days. Malcolm Needs CSci FIBMS

Not Necessary to Irradiate. Malcolm Needs CSci FIBMS

Fractionated blood products. Fresh frozen plasma. Cryoprecipitate. Frozen red cells. Fractionated blood products. Albumin. Clotting factors. Anti-D immunoglobulin. Malcolm Needs CSci FIBMS

IgA Deficiency with Anti-IgA. Malcolm Needs CSci FIBMS

Signs and Symptoms. Malcolm Needs CSci FIBMS

Immediate reaction. Hypotension. Dyspnoea. Wheeze. Malcolm Needs CSci FIBMS

Stridor. Rash. Angioedema. Malcolm Needs CSci FIBMS

Treatment of Anaphylactic Reaction. Malcolm Needs CSci FIBMS

Maintain venous access. Adrenaline. Piriton. Stop transfusion. Maintain venous access. Adrenaline. Piriton. Malcolm Needs CSci FIBMS

IgA Deficiency with Antibodies. Anaphylactic Reactions. 1 in 700. IgA Deficiency with Antibodies. 1 in 2, 300. Anaphylactic Reactions. 1 in 20x103 to 1 in 50x103. Malcolm Needs CSci FIBMS

Antigen-antibody Reactions. Malcolm Needs CSci FIBMS

Anti-IgA bound to mast cells reacts with IgA. Mast cells degranulate. Histamines. Leucotrines. Cytokines. Brochospasm. Endothelium. Vasodilation. Malcolm Needs CSci FIBMS

IgA Deficient Patient with a History of Severe Anaphylactic Reaction. Malcolm Needs CSci FIBMS

Use IgA-deficient components irrespective of IgA antibody status. Malcolm Needs CSci FIBMS

IgA Deficient Patients With Anti-IgA. Malcolm Needs CSci FIBMS

Red cells - IgA deficient or washed. FFP - IgA deficient. Platelets - IgA deficient or PSM. Malcolm Needs CSci FIBMS

IgA Deficient Patients Without Anti-IgA. Malcolm Needs CSci FIBMS

Occasional transfusions. Regular transfusions. Occasional transfusions. Urgent. Elective. Malcolm Needs CSci FIBMS

Febrile Non-haemolytic Transfusion Reaction (FNHTR). Malcolm Needs CSci FIBMS

Patient experiences chills. The fever may develop between ½ hour to several hours after the start of the transfusion. It is usually self-limiting. Malcolm Needs CSci FIBMS

Differential diagnosis. Haemolysis of transfused red cells. Bacterial contamination of blood components. Malcolm Needs CSci FIBMS

Causes of FNHTR. Malcolm Needs CSci FIBMS

30% of patients have no detectable antibody in their plasma. Antibodies directed towards granulocyte and HLA antigens have been implicated as major causes of this immune-mediated event. 30% of patients have no detectable antibody in their plasma. Malcolm Needs CSci FIBMS

This is inconsistent with an immune-mediated response. It is not uncommon for patients who have had no previous transfusions or pregnancies to have an FNHTR during their first platelet transfusion. This is inconsistent with an immune-mediated response. Malcolm Needs CSci FIBMS

Cytokine Generation. Malcolm Needs CSci FIBMS

RBCs stored at 4oC (+/-2oC). Platelets stored at 22oC (+/-2oC). The levels of cytokines measured in stored blood were lower, compared with cytokines measured in stored platelet concentrates. Malcolm Needs CSci FIBMS

The Role of Cytokines in the Pathogenesis of Fever. Malcolm Needs CSci FIBMS

Circulatory pyrogenic cytokines IL-1β, IL-6 and TNF-α stimulate prostoglandin (PG) E2 production in the anterior hypothalamus. PG reach the thermoregulatory neurons in the preoptic area of the anterior hypothalamus by diffusion. Malcolm Needs CSci FIBMS

Aspirin/indomethacin block the generation of fever (PG inhibitors). Malcolm Needs CSci FIBMS

Most reactions occur during, or immediately after transfusion. The frequency of NHFTR with platelet transfusions is up to 30%. The incidence is higher with pooled platelet products than with apheresis units. Malcolm Needs CSci FIBMS

Frequency of NHFTR with RBC transfusion: General hospital population = 0.5%. Patients with haematological malignancies = 0.6%. Malcolm Needs CSci FIBMS

Hypotensive Reactions. Malcolm Needs CSci FIBMS

Recently described. Blood pressure <10mmHg baseline Recently described. Blood pressure <10mmHg baseline. Resolved quickly when transfusion discontinued. Causes: Associated with ACE drugs (breakdown bradykinin). Filters with net negative charge (activates kallikrein, causing bradykinin release). Malcolm Needs CSci FIBMS

Treatment: Positioning. Normal saline. Malcolm Needs CSci FIBMS

Post-transfusion Purpura (PTP). Malcolm Needs CSci FIBMS

PTP is an acute episode of severe thrombocytopenia occurring about a week after a blood transfusion. It usually effects HPA-1a negative women who have previously been alloimmunised by pregnancy. Malcolm Needs CSci FIBMS

The transfusion precipitating PTP cause a secondary immune response, boosting the HPA-1a antibodies. Malcolm Needs CSci FIBMS

PTP typically occurs in middle-aged or elderly women (average 57 years, range 21 to 80 years). Malcolm Needs CSci FIBMS

Mechanism of Autologous Platelet Destruction. Malcolm Needs CSci FIBMS

Bystander mechanism (immune destruction). Adsorption of soluble platelet antigens from donor plasma. Immune complexes bind to autologous platelets. Transient auto-antibody formation. Malcolm Needs CSci FIBMS

Differential Diagnosis. Malcolm Needs CSci FIBMS

ITP, TTP. DIC. Marrow failure. Malcolm Needs CSci FIBMS

Heparin-induced thrombocytopenia (HIT). Drug-related thrombocytopenia. Blood components implicating PTP: Most reported cases involve RBCs. Malcolm Needs CSci FIBMS

Course of the Disease. Malcolm Needs CSci FIBMS

Usually self-limiting. Mortality 7-10% (early in the course). If not treated, lasts, on average 2 weeks (range 1 to 4 weeks). Remission (platelet count >100x109L-1) is, on average, 24 days (range 6 to 70 days). Malcolm Needs CSci FIBMS

Management. Malcolm Needs CSci FIBMS

IV steroids/plasma exchange. IVIgG (2gdL-1 over 2 days). 85% respond. IV steroids/plasma exchange. Malcolm Needs CSci FIBMS

Prevention. Malcolm Needs CSci FIBMS

HPA-compatible blood. Leukodepleted blood. Malcolm Needs CSci FIBMS