SQU Med J, May 2011, Vol. 11, Iss. 2, pp. 280-283, Epub. 15th May 11
Submitted 2nd Oct 10
Revision ReQ. 22nd Nov 10, Revision recd. 1st Jan & 19th Feb 11
Accepted 2nd Mar 11

Parvovirus, a single stranded DNA virus with tropism for the erythroid progenitor cells1 is known to cause lytic 
destruction of the proerythroblasts leading to a 
mild anaemia in the immunocompetent person.2 
It is the only known member of the Parvoviridae 
family to be pathogenic to humans.3 Infections occur 
worldwide and especially in the spring and winter 

months. It is so common in the Northern European 
community that by the age of 50 years about 80% of 
this population will have been infected.4

Although it is believed that the virus infects 
only erythroid progenitors, the viral capsid 
antigen  has been demonstrated inside giant 
granulocytes in the bone marrow in patients 
with pancytopenia following bone marrow 

1Department of Hematology & Blood Transfusion, Royal Hospital, Muscat, Oman; 2Department of Nephrology, Sohar Hospital, 
Oman.
*Corresponding Author email: preeni@omantel.net.om

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aBstract: We report a young Omani male who developed severe and persistent anaemia after a kidney 
transplantation while being on immunosuppression therapy, standard practice to prevent rejection of the 
transplanted kidney. His bone marrow aspirate showed the classic morphological changes of pure red cell aplasia 
(PRCA), induced by parvovirus B19 infection which is the presence of giant proerythroblasts with viral inclusions. 
The virus was also demonstrated by polymerase chain reaction in the blood along with IgM antibodies to parvovirus 
B19. He responded dramatically to high dose immunoglobulin with a normalisation of his haemoglobin level 
in two weeks and remained normal until seven months later. Parvovirus B19 induced PRCA can be cured. This 
aetiology must be kept in mind especially when a chronic anaemia, refractory to treatment, is accompanied by 
a reticulocytopenia. The latter reflects the lysis of the  proerythroblasts, preventing maturation of the erythroid 
cells causing anaemia. Early recognition and prompt treatment spares the patient unnecessary exposure to blood  
transfusions, erythropoietin and renal disease caused by the virus. PRCA secondary to parvovirus B19 infection 
following kidney transplantation is reported in the literature, but not in the Omani population. To the best of our 
knowledge, this is the first such report in Oman. 

Keywords: Red cell aplasia, pure; human parvovirus B19; kidney transplantation; Immunosuppuression; Case 
report; Oman

Acquired Pure Red Cell Aplasia caused by 
Parvovirus B19 Infection following a Renal 

Transplant
Arundathi Kurukulasuriya,1 Amal A. Hamed,1 Muhanna Al-Muslahi,1 Asaid Ibrahim2

CASE REPORT



Arundathi Kurukulasuriya, Amal A. Hamed, Muhanna Al-Muslahi and Asaid Ibrahim

Case Report | 281

transplantation.5 Viral growth can also be 
maintained in fetal liver cell cultures.2 In children, 
parvovirus B19 infection causes a transient 
anaemia associated with an erythematous rash 
called the fifth disease or Erythema infectiosum.  
Occasionally, in immunocompetent adults, a 
symmetric polyarthropathy mimicking rheumatoid 
arthritis occurs.3 The tropism to erythroid 
progenitors in the bone marrow is well known to 
cause a transient aplastic crisis (TAC) in individuals 
with an underlying haemolytic anaemia and 
Hydrops fetalis in intrauterine infections.6

In immunocompromised patients, the inability 
to generate an immune response leads to a state of 
persistent anaemia, reticulocytopenia caused by 
lytic destruction of proerythroblasts giving rise to 
an acquired pure red cell aplasia (PRCA). Following 
allogeneic stem cell transplants (ASCT), this 
infection is known to occur most commonly in the 
first year post transplant as the immune suppression 
is at a maximum during this period.7-11 The 
standard treatment for these patients is intravenous 
(IV) gammaglobulin (IVIG). This replaces the 
neutralising antibodies which the patient does not 
possess; however, it is unknown whether the virus 
is always eliminated completely by this treatment. 

Case Report
An Omani man aged 30 had end stage renal disease 
caused by pyelonephritis of the right kidney. He was 
on haemodialysis for three years following which 

Figure 1: Bone marrow smear showing two giant 
proeythroblasts. One intact with intranuclear 
eosinophilic inclusion body like nucleoli. Arrow points 
to ‘dog ear’ cytoplasmic projections. Adjacent is a 
denuded nucleus of a giant proerythroblast. (x 1000).

he had a kidney transplant from a live donor. He 
had a course of antilymphocyte globulin (ALG), 
commenced intraoperatively and was on tacrolimus, 
mycophenolate mofetil and prednisolone as a 
means of immunosuppression. No information was 
available regarding the donor’s parvovirus status 
as the transplant was done in another country. 
Three months later he was referred to our clinic for 
investigation of tiredness on exertion and anaemia 
with a haemoglobin of 5 g/dL. On presentation, 
his renal and liver functions were normal. He was 
afebrile, cheerful and, apart from being very pale, 
was clinically well.

He received a transfusion of two units of packed 
red blood cells. Despite this his anaemia persisted at 
an Hb of 6.9 g/dL. The doses of immunosupressive 
drugs (tacrolimus and mycophenolate mofetil) 
were reduced. Other laboratory investigations were 
as follows; red cell count - 2.93 x 109/L (4.5–6.6); 
white blood cells - 4.0 X 109/L (4–11); platelets - 
353 x 109/L; absolute reticulocyte count- 3 x109/L 
(5–200); haptoglobin Level - 1817 mg/L (360 – 
1950mg/L); lactate dehydrogenase level - 322 (95–
190 IU/L); folate Level - 30.7 (4.8–30.5 nmol/L), 
vitamin B12 – 130 (139–651 pmol/L); iron profile 
– normal; direct and indirect antibody tests - no 
antibodies detected; antibodies for parvovirus B19 
– positive;  IgM antibodies and polymerase chain 
reaction (PCR) parvovirus - positive. Figure 1 shows 
the bone marrow aspirate, Figure 2 shows bone 
marrow trephine biopsy with giant proerythroblast 
with a megakaryocyte at the left hand end of the, 
and Figure 3 positive glycophorin stain for giant 

Figure 2: Trephine biopsy. Arrow points to three giant 
proerythroblasts with a megakaryocyte at the left hand 
end of the row ( x1000).



Acquired Pure Red Cell Aplasia caused by Parvovirus B19 Infection following a Renal Transplant

282 | SQU Medical Journal, May 2011, Volume 11, Issue 2

proerythroblasts.
The above investigations show the absence of an 

aetiology of haemolytic anaemia (immune mediated 
and non immune), iron deficiency, vitamin B12 or 
folate deficiency for the anaemia in this patient.     

The persisting anaemia, with a reticulocytopenia, 
no evidence of myelodysplasia, haemolysis, 
nutritional deficiency, the morphological evidence 
of parvovirus B19 infection, of gigantoblasts 
containing viral inclusion bodies and the  
absence of late normoblasts in the bone marrow 
confirmed the diagnosis of parvo virus B19 
by morphology. Positive staining of giant 
proerythroblasts with the glycophorin stain, 
established the large cells as being erythroid 
in nature. Further confirmation was made 
by the presence of the anti parvovirus B19  
immunoglobulin M (IgM) and positive polymerase 
chain reaction (PCR) for a high load of parvovirus 
B19. 

The cornerstone of treatment for this disease is 
passive transfusion of IVIG to enrich the humoral 
immunity of the patient supported with packed red 
blood cell transfusions. In the immune competent 
host, 0.4g/kg/day of IVIG is given for 3 days. In the 
immunocompromised host, prolonged treatment 
with IVIG reduces the viral levels to undetectable 
levels by repeated PCR. A higher dose of 1g/kg/day is 
used for 5 days in these patients and when necessary 
for a longer period. Patients generally respond after 
two weeks of treatment. Some patients may require 
more than one course of immunoglobulin therapy 
and some may benefit from alteration of their 
immunosuppressive therapy.12-16

Other immunomodulatory approaches such 

as rituximab, steroids, (ALG), cyclophosphamide, 
and methotrexate have also been used in chronic 
PRCA. This is especially the case if it present as the 
primary haematological disorder, with no obvious 
cause, or in association with other disease ssuch as 
lymphorproliferative disorders, connective tissue 
diseases, thymoma, solid tumours, pregnancy, or 
following bone marrow transplantation, but rarely 
in patients with parvovirus B19 infection.15

Our patient was treated with 1g of IVIG /kg /
day for 5 days and packed red blood cells. His 
haemoglobin levels recovered in two weeks. He 
was completely well with a normal complete blood 
count (CBC) seven months later, at time of writing.                                                            

Discussion
In immunocompetent persons with normal red 
cell life spans, parvovirus B19 infections cause a 
5–10 day erythropoietic aplasia, but do not cause 
significant anaemia as their red cell life span is 
120 days.6 However, in patients with haemolytic 
anaemias whose red cell life spans are shortened, 
for example 15 days in hereditary spherocytosis, 
a transient decompensated erythropoiesis leads 
to a severe anaemia.6 In immunocompromised 
patients, such as our patient, the infection can 
persist leading to chronic anaemia. Congenital 
immunodeficient states, human immunodeficiency 
virus (HIV) infections, post organ transplants, 
lymphoproliferative disorders are some of the other 
known immunodeficient states associated with 
PRCA caused by parvo virus B19.   

The diagnosis rests on the presence of a 
persistent anaemia, with normal other blood cell 
counts, a reticulocytopenia, giant proerythroblasts 
(gigantoproerythroblasts) with prominent 
eosinophilic viral inclusions in the bone marrow, 
serum anti parvoviral IgM/IgG and positive PCR 
for parvoviral DNA. The neutralising antibodies are 
able to clear the infection usually by 5th to 10th day 
of infection. It is proposed that with the rising titres 
the virus is cleared and the giant proerythroblasts 
are replaced by regenerating erythroid cells.6

Parvoviridae are difficult to culture, but 
can be grown from the bone marrow. In 
the immunocompromised host, parvoviral 
antibodies maybe difficult to demonstrate,6  
although the presence of anti parvo viral IgG 
makes persistent infection improbable. In 

Figure 3: Trephine biopsy - glycophorin stain giant 
proerythroblasts  staining positive (x1000).



Arundathi Kurukulasuriya, Amal A. Hamed, Muhanna Al-Muslahi and Asaid Ibrahim

Case Report | 283

PRCA caused by other aetiological causes like 
thymoma, large granular lymphocytic leukaemia, 
systemic lupus erythematosus and rheumatoid 
arthritis, giagantoproerythroblasts are not seen. 
Parvoviral infections are also associated with 
glomerulonephritis and a nephrotic syndrome such 
as protein-losing kidney disease. 

Conclusion
In isolated persistent anaemia in 
immunocompromised adults, accompanied by 
a reticulocytopenia and no other aetiological 
evidence for the anaemia, a parvovirus B19 induced 
PRCA should be excluded, particularly as there is 
no vaccine for protecting those at risk.

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