Escolar Documentos
Profissional Documentos
Cultura Documentos
Leukemia
Case Report
Open Access
Abstract
Aplastic anemia (AA) is a type of bone marrow failure characterized by peripheral pancytopenia and bone
marrow hypoplasia. The complications of AA include infections and bleeding. A rare association between dengue
fever and AA has been reported. Dengue fever is a disease endemic to the western region of Saudi Arabia. In the
literature 8 cases of Dengue fever induced Aplastic anemia has been reported and treated conservatively, but none
has received allogeneic bone marrow transplant .In the context of this background, we report the first case of dengue
feverinduced severe AA (SAA) salvaged by an allogeneic bone marrow transplant (BMT).
J Leuk
ISSN: 2329-6917 JLU, an open access journal
Discussion
Only 2 cases of dengue feverinduced SAA have been reported in
Citation: Khoj L, Baksh R, Aslam M, Kelta M, Albeirouti B, et al. (2013) A Case of Dengue Fever-Induced Severe Aplastic Anemia Salvaged by
Allogeneic Bone Marrow Transplant. J Leuk 1: 120. doi:10.4172/2329-6917.1000120
Page 2 of 2
the literature in patients aged 8 and 11 years [2,3] both patients were
diagnosed with AA following a dengue virus infection, and both were
successfully treated with chemotherapy alone. In the first case, BMT
was planned but could not be done because an HLA-matched donor
was not available [2]. However, to our knowledge, the present case is
the first ever case where allogeneic BMT was performed for dengue
feverinduced SAA. The patient tolerated the transplant well, with no
major complications or graft-versus-host disease. There are only a few
reported cases of AA due to dengue fever in the literature. Albuquerque
et al. reported similar cases from Latin America, and Ramzan et al.
reported a case from India [2,3]. In both articles, the diagnosis of AA
was confirmed by IgG and IGM; however, none of the patients received
a BMT. Hemorrhagic episodes in patients with aplastic anemia occur
usually secondary to thrombocytopenia and require frequent support
with platelet concentrates and other blood products. Infection with
dengue virus (particularly dengue sero type-2 of South Asian genotype)
is associated with dengue hemorrhagic fever. Dengue infection further
worsens the disease process in patients with aplastic anaemia due to
uncontrolled hemorrhagic diathesis and major organ failure, which
may prove fatal in these already immunocompromised patients, if not
treated appropriately [4].
In our case, the patient presented with bleeding due to
thrombocytopenia. Upon investigation, the patient was found to be
pancytopenic, the dengue virus serology was positive for both IgG
and IgM, and the bone marrow biopsy showed SAA. Other causes
of AA, such as PNH and myelodysplastic syndrome, were excluded
from consideration. Hence, a diagnosis of dengue feverinduced AA
was made. The defects could be the result of an autoimmune response
mediated by cytotoxic T lymphocytes (CD8), which are detectable
in the blood and bone marrow of AA patients. As is known in many
autoimmune diseases, an acute viral illness can trigger this autoimmune
response.
Most acquired AA is the result of an immune-mediated destruction
of hematopoietic stem cells that causes pancytopenia and aplastic bone
marrow. The severe form of aplastic anemia is a life-threatening bone
marrow failure disorder that, if untreated, is associated with a very
high mortality rate. An immune response dominated by oligoclonal
expanded cytotoxic T cells targets hematopoietic stem and progenitor
cells, inducing their cell death via apoptosis and hematopoietic failure
[5]. Again, this can be triggered by a dengue virus infection.
Other viruses causing SAA, including parvovirus B19 and
hepatitis, also share the same immunologic pathogenesis outlined
above. Two hypotheses can be made concerning the pathogenesis of
parvovirus B19induced AA. The first hypothesis involves the direct
effect of parvovirus B19, suggesting that all 3 precursor cell lines
in the bone marrow might become the target cells [6]. The second
hypothesis is based on immunologic mediation. In virus-associated
hemophagocytic syndrome with an acute parvovirus B19 infection,
raised levels of cytokines such as interferon would impair regulation
of the phagocytic system, resulting in pancytopenia and/or decreased
Conclusion
Allogeneic BMT is the transplant method of choice for SAA
in younger patients, and it was achieved successfully in our case.
The transplant was done following a priming regimen with
cyclophosphamide and antithymocyte Globulin and was made feasible
because of a well-established collaboration and good organization
between different health institutions. In addition, finding an HLAmatched donor in our country is not challenging because most patients
have a large number of siblings. Regarding the serious association
between dengue fever and SAA, the importance of eradicating the Aedes
aegypti mosquito, which is the main carrier of dengue fever, cannot
be overemphasized. Efforts should be placed to decrease morbidity
and mortality related to dengue virus, and this could be established
by proper sanitation and by having an effective vaccine and specific
antiviral treatment.
References
1. Segel GB, Lichtman MA (2010) Aplastic anemia: acquired and inherited.
(8thedn). Williams Hematology. McGraw Hill Professional, New York.
2. Ramzan M, PrakashYadav S, Sachdeva A (2012) Post-dengue fever severe
aplastic anemia: a rare association. Hematol Oncol Stem Cell Ther 5: 122-124.
3. Albuquerque PL, Silva Jnior GB, Digenes SS, Silva HF (2009) Dengue and
aplastic anemia--a rare association. Travel Med Infect Dis 7: 118-120.
4. Ullah K, Satti TM, Ahmed P, Raza S, Tariq WU, et al. (2007) Successful
allogeneic stem cells transplantation in severe aplastic anaemia complicated
by dengue Fever. J Coll Physicians Surg Pak 17: 635-636.
5. Young NS, Scheinberg P, Calado RT (2008) Aplastic anemia. Curr Opin
Hematol 15: 162-168.
6. Young NS (1996) Parvovirus infection and its treatment. Clin Exp Immunol 104
Suppl 1: 26-30.
7. Osaki M, Matsubara K, Iwasaki T, Kurata T, Nigami H, et al. (1999) Severe
aplastic anemia associated with human parvovirus B19 infection in a patient
without underlying disease. Ann Hematol 78: 83-86.
8. Lu J, Basu A, Melenhorst JJ, Young NS, Brown KE (2004) Analysis of T-cell
repertoire in hepatitis-associated aplastic anemia. Blood 103: 4588-4593.
9. Pham AM, Langlois RA, TenOever BR (2012) Replication in cells of
hematopoietic origin is necessary for Dengue virus dissemination. PLoS
Pathog 8: e1002465.
J Leuk
ISSN: 2329-6917 JLU, an open access journal