Final Diagnosis -- A 24-day-old Term Infant with DiGeorge Syndrome


FINAL DIAGNOSIS:

Twenty-four-day old infant with DiGeorge syndrome, transfusion related graft versus host disease, and multiorgan failure with disseminated intravascular coagulation.

DISCUSSION:

This 24-day-old, normal appearing, term infant with DiGeorge syndrome received unirradiated packed red blood cells and developed transfusion related graft versus host disease. During the hospital course the infant never developed diarrhea and maintained liver enzyme levels in the normal range until three days prior to his demise. He was cultured throughout his stay and failed to develop clinical evidence of septicemia, although urine and tracheal aspirate cultures grew Candida species and E. cloacae, respectively. Transfusion related graft versus host disease was evidenced by an erythematous rash with desquamation, increasing liver enzyme and pancytopenia.

Transfusion related graft versus host disease (TR-GVHD) results from the transfusion of T lymphocytes; the recipient fails to recognize the cellular components from the donor as "non-self", and as a result donor-derived cytotoxic T cells injure various organs.

TR-GVHD results in significant morbidity and mortality in 80-90% of individuals affected1. Although there is general agreement regarding most categories of patients who should receive irradiated blood components, there is lack of consensus regarding others.2

Current transfusion guidelines for neonates indicate that irradiated blood components are required for premature infants, those suspected of having a congenital immunodefiency, those receiving blood from a first or second degree relative, and those with an acquired immunodeficiency as a result of a malignancy, stem cell transplantation or solid organ transplantation. Our patient showed no obvious clinical signs of immunodefiency prior to receiving cellular blood components. However, he had hypocalciumia suspected as a cause of seizures, DiGeorge syndrome might have been diagonsed earlier.

Irradiation of cellular blood products is currently the only accepted methodology to prevent TR-GVHD. Ionizing radiation penetrates nucleated cells and damages nuclear DNA, preventing postinfusion proliferation and aborgating the potential GVHD. The FDA recommends that 2500cGy to the center of a canister (free-standing irradiator) or to the center of an irradiation field (linear accelerator) with a minimum of 1500cGy elsewhere be used to irradiate cellular blood components.3

As seen in our case, characteristic histologic features of TR-GVHD are identical to those seen in typical graft versus host disease, with the addition of pancytopenia.

There have been conflicting data regarding effective treatment for TR-GVHD. Yasukawa et al reported successful treatment with anti-CD3 monoclonal antibody and cyclosporin A in an adult immunocompetent patient who received cellular blood components with a shared HLA type.4

To our knowledge there is no known effective treatment for neonatal TR-GVHD reported in the literature and , therefore, clinical practice is focused on its prevention.

A unique feature of our case is that of associated disseminated intravascular coagulation in TR-GVHD. To our knowledge, only two other cases in the literature have been reported.5 Our case showed no evidence of septicemia, although tracheal aspirates and urine cultures grew organisms. Histologic evidence of disseminated intravascular coagulation manifested as microvascular thrombosis and perivascular fibrin deposits are commonly seen in allogeneic immune reactions. It is unclear whether our patient suffered from disseminated intravascular coagulation as a result of rapid deterioration and multiorgan failure secondary to TR-GVHD or disseminated intravascular coagulation was responsible for the rapid progression of TR-GVHD. Although speculative, Murakawa et al6 reports rapid progression of multiorgan failure in TA-GVHD secondary to diffuse intravascular coagulation. They describe a mechanism whereby gamma-interferon, released from activated donor T cells, enhances the procoagulant activity in monocytes and vascular endothelial cells, in addition to tumor necrosis factor-alpha and gamma interferon stimulating the expression of class I and II antigens on vascular endothelial cells. Recipient cells provide targets for activated donor T-cells, causing endothelial damage.

REFERENCES:

  1. Transfusion Medicine Reviews, Vol 11, No. 1 (January), 1997:pp15-26.
  2. Transfusion Medicine Reviews, Vol 11, No. 1 (January), 1997:pp15-26.
  3. Transfusion Medicine Reviews, Vol 11, No. 1 (January), 1997:pp15-26.
  4. British Journal of Hematology, Vol 85, 1994:pp831-835.
  5. Murakawa et al Annals of Clinical and Laboratory Science, Vol. 25, No.1, 1995:pp 31-38.
  6. Murakawa et al Annals of Clinical and Laboratory Science, Vol. 25, No.1, 1995:pp 31-38.

Contributed by Valerie A. Lyons, M.D. and Paul Dickman, M.D.


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