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Indian Journal of Transfusion Medicine
  Indian Journal of Transfusion Medicine Indian Journal of Transfusion Medicine

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Blood Transfusion From Blood Relations Can Be Fatal-

                                                                                             Dr. Rajesh Kucheria

                                                                                                                                                       D.C.P. 

Introduction

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

To understand it better, we will see, its mechanism clinical manifestations, treatment, prevention and at risk patients in details.

Mechanism of TA-GVHD

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

1.  Immunological 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. Therefore it depends upon 

1.  The number of transfused leukocytes Vs host number

To support this, there is decreased (90% reduction) incident of TA-GVHD in patients transfused with leucoreduced components. 

2.  Most reported cases have involved relatively fresh  blood components (<48 hrs. old)

Decreased incidence in patients transfused with stored blood may be attributed to loss of leukocyle function with storage. 

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

To support this, most cases of TA-GVHD occure in immuno-supported hosts, who are unable to reject grafts.  An exception to TA-GVHD requiring a immunocompromised  host is when donor cells appear  immunological (HLA) indentical to the recipients cells  but the recipients cells appear foreign to the donor cells. 

This may occur when a donor is homozygous for a given HLA haplotype and recipient is heterorygous for same. And this can occur in blood relatives. 

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.

So, to conclude, 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.

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, diarrhea, abdominal pain, fever & intense pancytopenia. The rash of TA-GVHD usually begins as a central macula popular erruption, subsequently spreads to the extremities and may progress to bullae formation. 

In cases of haematopoietic stem cell transplantation, intense pancytopenia differentiates TA-GVHD from GVHD, in latter the haematopoietic tissue is derived from the donor and is spared from attack by donor derived lymphocytes.

 Patient with, intense pancytopenia on CBC, raised bilirubin & liver enzymes, finding of aggressive uymphocytic infiltration on HPE of skin biopsy in patient with above signs & symptoms following transfusion of blood or any cellular component, should be suspected as a case of TA-GVHD.

Treatment

Various treatment with wide variety of immunosuppressive regimens, including steroids, cytoxan, methotrexate, antithymocyte globulin have been tried without obvious benefits. Cyclosporine has been used in some cases demonstrating recovery. But no specific therapeutic regimen has been found responsible for recovery in few less aggressive TA-GVHD.

Because many therapies have been tried and found to be unsssucessful, prevention is paramount.

Prevention of TA-GVHD by irradiation

  • Principle

To occur TA-GVHD, celluler 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  ymphocytes precludes a significant graft vs host response.

  • Dosage

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. The minimum dose at any  point in the canster must be 15 Gy.

 FDA has stated that the maximum irradiation dose should be 50 Gy. Thus, a dose of 25 Gy would permit a blood component to be irradiated twice and released for transfusion, whereas, if a higher dose were used, a component irradiated twice could not be transfused.

  • Effect of irradiation on unit -

Gamma irradiation, in the doses recommended for the prevention of TA-GVHD, results in some damage to the erythrocyte membrane, so that the permitted storage (expiry) date of the red cell concentrates is 28 day following irradiation (or the usual expiry date, whichever is shorter). There is also a more rapid ccumulation of potassium in the extracellulor fluid of the red cell concentrates. For this reason, for  eonates and young children, it is preferable to gamma irradiate red cell components as close to the timeof transfusion as possible. In these patients, if the units have not been irradiated just prior to transfusion, removal of extracelluler fluid, may be considered.

 Irradiation of platelet units. does not affect the function of platelets. Therefore no change in storage period is necessary for platelet concentrates.

  • Which components may cause TA-GVHD?

Any component that contains sufficient, viable, cytotoxic T cells can mediate TA-GVHD. In practice, only cellular components like whole blood, RBCs, granulocytes and platelet concentrates contain sufficient viable, cytotoxic T cells.

 No case have been reported following administration of Frozen  plasma components (including  ryoprecipitate) and frozen, washed RBCs.

  • Risks involved in irradiation -

Irradiation may result in the maligrant 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 therotically activate latent viruses. No report exist of this occurance from irradiated blood components, the amount of radiation used likely exceeds the amount that could cause this to occur.

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

  • Absolute indications -
  1. Patients with congenital cellular immune deficiency.
  2. Allogenic hematopoietic stem cell recipients.
  3. Autologus hematopoietic stem cell recipients.
  4. Patients with Hodgkin disease.
  5. Granuloyte 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 or  crossmatching.
  • Probable indications -
  1.  Premature neonates weighing < 1200 gms.
  2.  Patients with hematologic malignancies treated with cytotoxic agents. 
  3.   Patients recieving high-dose chemotherapy, radiation therepy and/or aggressive immunotherapy.
  • Contraversial indications -
  1. Solid-organ transplant recipients.
  2. Large volume transfusions and exchange transfusions  to full-form neonates who did not receive IUT.
  3. Aplastic anaemia patients not recieving aggressive immunotherapy. 
  • 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 recieve 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. 

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 TAGVHD.  

Cellular components should be irradiated when - 

  1. A patient is identified as being at risk for TA-GVHD. 
  2. The donor of the component is a blood relative of therecipient.
  3. The donor is selected for HLA compatibility, by typing or cross matching.

 

 

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Dr. RAJESH KUCHERIA
D C P
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