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Blood Transfusion From Blood Relations Can Be Fatal

Dr Md Mahamudul Hasan

Resident, Phase B

Indian Journal of Transfusion Medicine

Inauguration Issue 2011

                                                                   Dr. Rajesh Kucheria 

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Case Study

A 45-year-old woman presented to the emergency medicine department with history of high-grade fever, oral ulcers, skin rash, and jaundice of 15 days, duration. Subsequently she developed shortness of breath and cough.

She underwent total abdominal hysterectomy 20 days before admission at a private hospital for dysfunctional uterine bleeding. She was transfused one unit of B-positive packed red cells donated by her son.

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Examination findings

At admission, she was found to be very sick looking, icteric, conscious, and coherent. There were milia, exfoliation, and erosions on the skin involving face, neck, arms, forearm, abdomen, and legs. Examination of the oral cavity revealed thrush and cheilitis. She had tachypnoea with a respiratory rate of 40 per min and pulse rate of 120 per min. Blood pressure recorded at the time of admission was 100/70 mmHg. Crepitations were heard all over the chest. Examination of the abdomen revealed a healed scar of the total abdominal hysterectomy.

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Investigations

At admission showed haemoglobin of 7.8 g/dl, with total leucocyte count of only 300 cells/cmm with an absolute neutrophil count of 30 cells/cmm and platelet count of 10,000/cmm. Blood urea and serum creatinine were within normal limits. Serum bilirubin was elevated; however, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum alkaline phosphatase were within normal limits. Blood culture after 24 h developed Gram-negative bacteria which were subsequently identified as Pseudomonas aeroginosa.

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In view of the history of transfusion from a first-degree relative 3 weeks before admission, a clinical diagnosis of TA-GVHD was entertained and bone-marrow aspiration and biopsy were done for pancytopenia. Bone-marrow aspiration and biopsy revealed hypocellularity, scattered histiocytes with erythrophagocytosis and lymphocytes (Fig. 1) which confirmed the diagnosis.

Fig. 1 Bone-marrow biopsy showing marked histiocytosis. H&E

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Intensive care support in the form of ventilator and component transfusion as per requirement were given along with appropriate intravenous antibiotics. Despite close monitoring and supportive care, the patient continued to deteriorate and died after 5 days of hospital stay.

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Discussion

Introduction: Contrary to popular belief that relative’s blood is safest but it may lead to fatal complication-Transfusion associated graft vs host disease (TA-GVHD). Though rare, mortality rate of this complication is 90% and recipient usually succumbs within 3 weeks of occurrence. It is preventable. So preventive efforts to avoid this complication is very important in indicated cases

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Mechanism of TA-GVHD

The three main requirements for the development of TA-GVHD are – 

1.  Immunologically competent donor cells. 

2.  An antigenic difference between graft and host detectable by the donor cells. 

3.  An inability of the host to reject the graft effectively. 

TA-GVHD is basically an immunological battle between  the transfused donor T cells and the host’s immune defense.

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TA-GVHD depends upon 

1.  The number of transfused leukocytes Vs host number

2.  Most reported cases have involved relatively

fresh  blood components (<48 hrs. old)

3.  Occurence of TA-GVHD depends upon immune competence of host & donor

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Blood related donors are directed donors, who donate blood when required for their patients and the blood is usually transfused as fresh blood within 48 hrs of donation to the patient, which increase the risk of TA-GVHD. And if their patient is immunocompromised, or neonate with large volume transfusion, this risk of development of TA-GVHD increases many folds.

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Risk of TA-GVHD increases with

1.  Immuno-suppression in recipient.

2.  Transfusion of blood from blood related donors.

3.  Transfusion of fresh blood.

4.  Transfusion of non leuco reduced components.

Strong stress as of surgery, ageing and transfusion for first time are identify as contributing risk factors.

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Clinical Manifestations

TA-GVHD usually develops 2 to 50 days after  transfusion. Organs at greatest risk of attack are those which are rich in HLA antigens such as skin, liver, gastrointestinal tract, bone marrow, spleen & lymph nodes. Therefore its characteristic signs & symptoms are-

- Rash, - Jaundice,

- Diarrhoea, - Abdominal pain,

- Fever - Intense pancytopenia

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The diagnosis of TA-GVHD is usually made on the basis of ;

  1. History of recent blood transfusion and
  2. Constellation of clinical features.
  3. Investigations : CBC, LFT, Bone marrow study and to exclude differential diagnosis

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Differential diagnoses

  1. Acute viral infection
  2. Hypersensitivity to drugs.
  3. Transfusion-associated viruses like HIV, hepatitis B, and cytomegalovirus can cause similar type of illness.
  4. Dengue fever
  5. Leptospirosis

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Treatment

Includes immunosuppressive drugs

  • Steroids,
  • Cyclophosphamide,
  • Methotrexate,
  • ATG

All have been tried without obvious benefits.

Cyclosporine has been used in some cases demonstrating recovery.

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Prevention of TA-GVHD by irradiation

To occur TA-GVHD, cellular proliferation of the donor   lymphocytes is required. Irradiation with high energy results in ionization that produces chemical cross-links within the DNA of the irradiated cells which prevents cellular reproduction and hence proliferation. Prevention of proliferation of the donor  lymphocytes precludes a significant graft vs host response.

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The intended dose of irradiation should be at least 25 Gy  delivered to the midplane of the canister if a freestanding irradiator is used or to the central midplane of the field if a radiotherapy instrument is used.

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Effect of irradiation on unit

  1. Damage to the erythrocyte membrane, so that the permitted storage (expiry) date of the red cell concentrates is 28 day following irradiation.

  • There is also a more rapid accumulation of potassium in the extracellular fluid of the red cell concentrates.

  • Irradiation of platelet units. does not affect the function of platelets.

.

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Risks involved in irradiation

  1. Irradiation may result in the malignant transformation of  nucleated cells and the data are not sufficient to prove that this risk does not exist in irradiated blood components but the data do indicate that this risk is very small.

  • Secondly gamma irradiation may theoretically activate latent viruses.

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 Indications for irradiation of celluler blood components for prevention of TA-GVHD

  1. Patients with congenital cellular immune deficiency.
  2. Allogeneic hematopoietic stem cell recipients.
  3. Autologus hematopoietic stem cell recipients.
  4. Patients with Hodgkin disease.
  5. Granulocyte transfusions.
  6. Transfusion form blood relatives.
  7. Intrauterine transfusion (IUT).
  8. Transfusion to neonates who have received Intrauterine   transfusion.
  9. The donor is selected for HLA compatibility, by typing
  10. Patient receiving Fludarabine, ATG, purine analogue.

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 Irradiation is not indicated in following conditions

  1. Patients infected with HIV. 
  2. Patients with hemophillia. 
  3. Small volume transfusions to full term neonates who  did not receive IUT. 
  4. Elderly patients. 
  5. Pregnant patients. 
  6. Immunocompetent surgical patients. 
  7. Patients without malignancies receiving   immunosuppressive medications other than   fludarabine or other purine analogs. 

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Conclusion

TA-GVHD is devastating complication of cellular blood   component transfusion. Although TA-GVHD typically occurs in immunocompromised patients, it may develop in immunocompetent patient who recieved blood from blood relatives. The relatively low-cost, los-risk procedure of 25 Gy gamma irradiation has afforded a reliable prevention of TA-GVHD.  

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