Transfusion requirements for immunocompromised patients

1. TRANSFUSION
REQUIREMENTS FOR
IMMUNOCOMPROMISED
PATIENTS
D R . G . D. A . S A M A R A N AYA K A

2. IMMUNODEFICIENCY
• Primary vs Secondary immune deficiencies
• Congenital vs Acquired
• Cell mediated vs humoral
• Inherited defects requiring transfusions are rare acquired causes are relatively
common.
• Neonates weighing less than 1200 g are physiologically immunocompromised.

3. PRIMARY IMMUNE DEFICIENCIES
• Combined T- and B-cell disorders (SCID)
• Complement disorders
• Antibody deficiencies (CVID)
• Immune dysregulation syndromes (Familial HLH)
• Phagocyte disorders (Kostmann’s Syndrome)
• Innate immunity deficiencies
• Auto-inflammatory disorders (Familial Mediterranean Fever)
• “Well-defined” Syndromes (Wiskott-Aldrich)

4. SECONDARY IMMUNODEFICIENCIES
• HIV / AIDS
• Malignancy AND therapy
• Immunosuppressive therapy
– Auto-immune diseases
– Solid organ transplantation
– Stem Cell Transplantation
• Malnutrition
• Aging

6. HAZARDS OF TRANSFUSION IN
IMMUNOCOMPROMISED STATE
• Transfusion reactions
– Immunological vs non-immunological
– Acute vs delayed
• Special considerations
– Immunological – TA-GvHD, Immunomodulation
– Infectious – CMV, EBV

7. IMMUNOLOGICAL

8. TA GVHD
• Engraftment of viable T lymphocytes in transfused blood & mounting an immunological
response against the host tissues.
• Skin - erythematous maculopapular rash,
generalized erythroderma, bullae
• Gastrointestinal tract - diarrhoea
• Liver - raised liver enzymes and bilirubin
• Suppression of host haematopoiesis –
thrombocytopenia, anaemia, neutropenia
• Fever & lymphadenopathy,

9. TA-GVHD
Factors
1. Immunocompetent viable donor T cells
– Fresh blood, platelets, granulocyte Tx
2. HLA compatibility between donor and recipient
– HLA matched products, Blood from close relatives, share a few common HLA haplotypes
(ex-Japan)
3. Inability of the recipient to reject donor T cells

10. AT RISK PATIENTS
• Recipients of donations from first or second degree relatives.
• Patients receiving HLA-matched components.
• All T lymphocyte immunodeficiency syndromes - SCID
• Intra-uterine transfusion of red cells or platelets.
• Red cell or platelet transfusions – who had in-vitro transfusions - up to the age of 6 months after the EDD.
• Hodgkins disease
• Patients treated with purine analogues, e.g. fludarabine, cladribine or deoxycoformycin.
• Following alemtuzumab (anti-CD52) therapy.
• Aplastic anaemia patients receiving immunosuppressive therapy with ATG.
• Recipients of allogeneic SCT from the time of initiation of conditioning chemoradiotherapy until GVHD
prophylaxis is completed and/or lymphocyte count >1 x109/L.
• Following SCT - chronic GvHD or continued immunosuppressive treatment is required
• All patients undergoing autologous bone marrow transplant or peripheral blood stem cell transplant,
from initiation of conditioning chemo/radiotherapy until 3 months post-transplant (6 months if total
body irradiation)

11. NOT AT RISK
• Solid organ transplant
• HIV
• Solid tumours
• Routine surgery
• Non-Hodgkins lymphoma
• Premature or term infants (unless previous IUT)
• Acute leukemia

12. MANAGEMENT
• Poor prognosis with >90% mortality rate
• Must be treated in a specialized unit
• High dose steroids –First line - antilymphocyte and anti-inflammatory activity
• Methotrexate & Cyclosporine-A – to prevent the disease
• Intravenous immunoglobulins
• Supportive therapy – Antibiotics

13. PREVENTION
• γ-Irradiation - lymphocyte DNA cross linkage.
• Psoralen (S59) + ultra-violet A – used for pathogen inactivation

14. IMMUNOMODULATION
• Transfused leucocytes leading to a decrease of T and B lymphocytes, natural killer cells,
and monocytes.
• Immunomodulation is reported to increase haematological and non-haematological
tumor recurrence
• Increased infection rates after surgery.

15. INFECTIOUS HAZARDS

16. • All blood donations - screened for hepatitis B, C and HIV
– dangerous to all transfusion recipients
• But agents such as cytomegalovirus (CMV), EBV
– few problems in immunocompetent individuals
– serious disease in immunocompromised patients.

17. CMV INFECTION
• Herpes virus - HHV5
• Seropositive rates -30% to 80% in developed countries and nearly 100% in developing
countries.
• Because of the high prevalence - not routinely tested for CMV.
• Asymptomatic infection
• In immunocompetent subjects
– mild or subclinical infection is caused, which may
– persist in latent form in leucocytes.
• In immunocompromised patients -CMV can cause a severe, disseminated infection
– interstitial pneumonitis, hepatitis, retinitis, enteritis, and encephalitis.
– usually treated with gancyclovir and CMV immunoglobulin but mortality is high

18. DETECTION
• Screening - ELISA - IgM or IgG antibody
• viral culture
• antigen detection
• shell vial assay
• polymerase chain reaction.
• IgM - acute infection and IgG - past exposure.
• 3% ± 12% of CMV positive donors may be able to transmit CMV.
• Anti-CMV IgM positive (+/-IgG) donations are more infectious than IgG positive, IgM
negative ones.

19. PREVENTION
1. CMV negative components
• In CMV positive, immunocompromised patients, reactivation of latent, endogenous
infection is more common than transfusion derived infection.
• Hence, such patients and CMV negative recipients of CMV positive stem cell or organ grafts
are not usually given CMV negative components.
2. Leucoreduction
• Equivalent to CMV negative donations if residual leucocytes are <5 × 106 in RBC unit / 1
ATD platelets.
• Centrifugation, washing, freezing, and thawing -insufficient to prevent CMV transmission.

20. 3. Other methods are used to prevent overt CMV
infection (exogenous or reactivation) in allogeneic
stem cell transplant.
– weekly surveillance cultures from day 30 to 100
posttransplant,
– pre-emptive gancyclovir, if surveillance cultures are
positive,
– acyclovir and intravenous IgG from day 7 to 100
post-transplant.

21. EPSTEIN-BARR VIRUS (EBV)
• EBV is latent in B lymphocytes
• Can be transmitted through cellular blood components
– but this is uncommon - presence of neutralizing anti-EBV antibodies in the donation itself.
• Only if the units transfused are exclusively from a donor who does not have such
antibodies, can cause post-transfusion EBV infection
• In immunocompromised patients ->posttransfusion EBV infection - EBV associated
lymphomas.
• Up to 95% of the population is infected by 40 years of age.
• Currently there is no preventive strategy.

22. HUMAN HERPES VIRUS 6,7,8
• HHV 6-8 are also lymphotropic
• biological and epidemiological similarities to CMV including latency
• Reactivations of latent infection -> serious infections
• It is uncertain if HHV seronegative, immunocompromised recipients need HHV
negative transfusions.

23. PARVO VIRUS B19
• Particularly through coagulation factor concentrates.
• Persistent infection with parvovirus B19 - Pure red cell aplasia
• Specially seen in AIDS, Nezelof 's syndrome, and in children in remission after
treatment for acute lymphoblastic leukaemia.
• Thrombocytopenia may also occur.
• Infection is treatable with immunoglobulin infusions.

24. REFERENCES

25. THANK YOU