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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2017  |  Volume : 28  |  Issue : 6  |  Page : 1447-1450
Persistent anemia in a kidney transplant recipient with parvovirus B19 infection


1 Department of Nephrology, Royal Hospital, Muscat, Oman
2 Department of Pathology, Royal Hospital, Muscat, Oman
3 Department of Hematology, Royal Hospital, Muscat, Oman
4 Department of Microbiology, Royal Hospital, Muscat, Oman

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Date of Web Publication18-Dec-2017
 

   Abstract 


Anemia after kidney transplant is not uncommon. This paper reports a case of unexplained anemia in a kidney transplant recipient that persisted for more than two months, and that did not respond to recombinant human erythropoietin treatment but was successfully treated after diagnosing Parvovirus B19 (ParvoV B19) infection. A middle-aged male underwent living-unrelated kidney transplantation from Pakistan in April 2015. He was on triple immuno-suppression therapy consisting of prednisolone, tacrolimus, and mycophenolate mofetil. He presented with anemia which persisted for more than two months that did not improve with Darbepoetin alpha and required blood transfusions. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts characteristic of a ParvoV B19 infection. The serum was highly positive for ParvoV B19 DNA polymerase chain reaction. The anemia resolved completely three weeks after the administration of intravenous immunoglobulin. ParvoV B19 infection should be considered in the differential diagnosis of kidney transplant recipients who present with anemia associated with a low reticulocyte count.

How to cite this article:
Pakkyara A, Jha A, Al Salmi I, Siddiqi WA, Al Rahbi N, Kurkulasurya AP, Mohsin J. Persistent anemia in a kidney transplant recipient with parvovirus B19 infection. Saudi J Kidney Dis Transpl 2017;28:1447-50

How to cite this URL:
Pakkyara A, Jha A, Al Salmi I, Siddiqi WA, Al Rahbi N, Kurkulasurya AP, Mohsin J. Persistent anemia in a kidney transplant recipient with parvovirus B19 infection. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Jul 17];28:1447-50. Available from: http://www.sjkdt.org/text.asp?2017/28/6/1447/220846



   Introduction Top


Anemia after kidney transplant is not uncommon. Severe infection by human parvovirus B19 (HPV-B19) is known to cause anemia in immunocompromised adult transplant patients.[1] Here, we report a case of unexplained anemia in an adult kidney transplant recipient that per sisted for more than two months which did not respond to recombinant human erythropoietin but was successfully treated after diagnosing human ParvoV B19 infection. The persistence of anemia, especially with a low reticulocyte count should alert for a potential ParvoV B19 infection as an early differential diagnosis.


   Case Report Top


A 49-year-old male with a history of type 2 diabetes mellitus (T2DM) and hypertension with chronic kidney disease (CKD) stage V on regular thrice weekly hemodialysis since 2013.

He underwent living-unrelated kidney transplantation from Pakistan on 24 April 2015. He received three doses of Anti-thymocyte globulin (ATG) as induction therapy for immuno-suppression. After transplantation, the maintenance immunosuppression consisted of cyclosporine, mycophenolate mofetil, and prednisone. The medical details of the donor were not known as the place of transplant did not provide any information of the donor medical details.

The immediate posttransplant period was complicated with a huge perigraft hematoma which had to be evacuated surgically. He also had delayed graft function due to acute tubular necrosis requiring hemodialysis. Subsequently, the graft functioning improved. The immunosuppression was modified by replacing cyclosporine with tacrolimus. His kidney functions became normal, but he remained anemic with the hemoglobin dropping to 6.5 g/dL from 11 g/dL over a follow-up period of one month.

On 21 June 2015, that is, two months after the transplantation, he was admitted for removal of the double J ureteric stent. During this admission, his anemia worsened significantly causing increasing fatigue on minimal effort. He was very much pale and dyspneic. Labo-ratory studies showed that the hemoglobin was 5 g/dL (11.55–15.5), hematocrit 14.3% (35–45), leukocytes 6,000/mm3 (2.25–10), neutrophils 4,100/mm3 (15–5), and platelet 321,000/ mm3 (1405–400). His transferrin saturation was 90.1% (205–50), serum iron 344 umol/L (95–30), ferritin 4614 ug/L(185–320), folate 18.3 nmol/L (75–45), and the vitamin B12 was 380 pmol/L (1405–650) suggesting that the anemia was not due to any nutritional or iron deficiency. The hemolytic markers, haptoglobin, and lactate dehydrogenase were normal. He tested negative for Hepatitis B virus (HBV), Hepatitis C virus (HCV), and human immuno-deficiency virus (HIV). Cytomegalovirus (CMV) and BK polyomavirus (BKV) were also negaive. His absolute reticulocyte count was noted to be very low at 5600/mm3. His renal function remained normal with creatinine of 75 umol/L (455–90) and estimated GFR (MDRD) of more than 90 mL/min/1.73 m2.

He was transfused 500 mL of packed erythrocytes and was on injection Darbepoetin alpha 40 μg once per week. Nevertheless, the hemoglobin remained at 6.5 g/dL. An esophagogastroduodenoscopy (OGD) was performed which was reported as normal.

At this time, the hematologist was consulted, and a bone marrow aspiration was performed which showed hypocellular bone marrow with maturation arrest [Figure 1]. A bone marrow trephine biopsy was also performed and showed hypocellular marrow with reduced and right-shifted erythropoiesis with dysmegakayopoiesis [Figure 2].
Figure 1: Bone marrow aspirate showing hypocellular with reduced erythropoiesis and maturation arrest. Arrow pointing a giant pronormoblast.

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Figure 2: A bone marrow trephine biopsy showed hypocellular marrow with reduced erythropoiesis with dysmegakayopoiesis. Arrow pointing a giant pronormoblast.

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The bone marrow biopsy was thus suggestive of ParvoV B19 infection even though the serology for Parvovirus IgM and IgG assays were negative. However, a qualitative RT-polymerase chain reaction (PCR) test done revealed the presence of ParvoV B19 with more than 50,000,000 copies which were above the upper detection limit of the assay.

The patient was treated with five doses of intravenous immunoglobulin (IVIG) at a dose of 400 mg/Kg body weight /day. In three-week time, the hemoglobin went up to 12.6 g/dL with marked improvement in his well-being [Table 1]. He was discharged on modified doses of the same immunosuppressive medications with well-preserved renal functions and is on regular follow-up in the renal transplant clinic.
Table 1. Showing the levels of hemoglobin, hematocrit, and reticulocyte counts before and after IVIG therapy.

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   Discussion Top


Anemia after kidney transplantation is common and has a multifactorial etiology. Infection with ParvoV B19 is not considered to be a frequent cause of anemia in posttransplant patients. However, the persistence of anemia, especially with a low reticulocyte count should alert for a potential ParvoV B19 infection due to erythrocyte maturation arrest as reported in the present case.[1]

ParvoV B19 was first detected in a healthy blood donor’s serum in 1974.[2] It was subsequently linked to disease in children with sickle cell anemia experiencing transient aplastic crisis[3] and then in children with a contagious exanthema, called erythema infectiosum or “fifth disease.”[4]

The incidence of parvovirus infection in solid organ transplant patients is unknown because of the lack of surveillance studies. Based on the detection of parvovirus DNA in peripheral blood, one study reported a single institution incidence of 12% in kidney transplant patients who had anemia.[5] There is evidence that transmission of ParvoV B19 infection may occur at the time of transplantation. Barzon et al showed that in the majority of 10 pediatric kidney transplant patients, pretransplant parvo-virus serology D+/R-was associated with posttransplant detection of parvovirus DNA in the blood of the recipient.[6] The incubation period ranges from 4–14 days, and individuals with aplastic crisis can be contagious before symptoms until about one week after onset of symptoms.

The common clinical manifestations of ParvoV B19 infection in immunocompromised patients are fever, arthralgia, and rash. However, severe anemia was present in majority of the patients due to lack of reticulocyte response and lack of response to erythropoietin.[8]

ParvoV B19 infection can be diagnosed by serology or direct viral detection.[9] ParvoV B19 IgM antibody was present in only 75% of solid organ transplant recipients at the time of disease onset. The presence of ParvoV B19 IgG antibody alone is suggestive of an earlier infection and is uncommonly seen (7% of patients) among transplant recipients with ParvoV B19 infection.[8] Currently, the use of PCR assays significantly improved the detection of viral DNA.[10]

At present, antiviral drugs are not available for the treatment of ParvoV B19 infection. However, IVIG is found to be beneficial in a large number of solid organ transplant recipients with ParvoV B19 infection. Most patients are treated with 400 mg/kg/day for five days. Patients with recurrence of ParvoV B19 infection have been successfully treated with additional courses of IVIG.[11],[12] The reduction of immunosuppression is believed to contribute to the resolution of infection.[13]

It is noteworthy that the development of recombinant human ParvoV B19 vaccine composed of VP1 and VP2 capsid proteins is underway.[14]


   Conclusion Top


ParvoV B19 infection should be strongly considered as a differential diagnosis of persistent anemia, unresponsive to erythropoietin in postkidney transplant patients. The true incidence of this infection may be underestimated as B19 serological tests may fail to detect B19 infection in immunosuppressed patients. Hence, ParvoV B19 PCR to detect the virus should be considered early to improve diagnostic sensitivity and to guide adequate treatment. This is of special relevance as there is an increasing trend for kidney transplantation throughout the world as CKD population is on the rise.

Conflict of interest: None declared.



 
   References Top

1.
Bertoni E, Rosati A, Zanazzi M, et al. Severe aplastic anaemia due to B19 parvovirus infection in renal transplant recipient. Nephrol Dial Transplant 1995;10:1462-3.  Back to cited text no. 1
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2.
Geetha D, Zachary JB, Baldado HM, Kronz JD, Kraus ES. Pure red cell aplasia caused by parvovirus B19 infection in solid organ transplant recipients: A case report and review of literature. Clin Transplant 2000;14:586-91.  Back to cited text no. 2
[PUBMED]    
3.
Cossart YE, Field AM, Cant B, Widdows D. Parvovirus-like particles in human sera. Lancet 1975;1:72-3.  Back to cited text no. 3
[PUBMED]    
4.
Pattison JR, Jones SE, Hodgson J, et al. Parvovirus infections and hypoplastic crisis in sickle-cell anaemia. Lancet 1981;1:664-5.  Back to cited text no. 4
    
5.
Anderson MJ, Lewis E, Kidd IM, Hall SM, Cohen BJ. An outbreak of erythema infectiosum associated with human parvovirus infection. J Hyg (Lond) 1984;93:85-93.  Back to cited text no. 5
[PUBMED]    
6.
Ki CS, Kim IS, Kim JW, et al. Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients. Clin Transplant 2005;19:751-5.  Back to cited text no. 6
[PUBMED]    
7.
Barzon L, Murer L, Pacenti M, et al. Detection of viral DNA in kidney graft preservation and washing solutions is predictive of post-transplant infections in pediatric recipients. J Infect Dis 2009;200:1425-33.  Back to cited text no. 7
[PUBMED]    
8.
Bell LM, Naides SJ, Stoffman P, Hodinka RL, Plotkin SA. Human parvovirus B19 infection among hospital staff members after contact with infected patients. N Engl J Med 1989;321:485-91.  Back to cited text no. 8
[PUBMED]    
9.
Eid AJ, Brown RA, Patel R, Razonable RR. Parvovirus B19 infection after transplantation: A review of 98 cases. Clin Infect Dis 2006; 43:40-8.  Back to cited text no. 9
[PUBMED]    
10.
Bredl S, Plentz A, Wenzel JJ, et al. False-negative serology in patients with acute parvovirus B19 infection. J Clin Virol 2011;51:115-20.  Back to cited text no. 10
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11.
Manaresi E, Gallinella G, Zuffi E, et al. Diagnosis and quantitative evaluation of parvovirus B19 infections by real-time PCR in the clinical laboratory. J Med Virol 2002;67: 275-81.  Back to cited text no. 11
[PUBMED]    
12.
Jordan SC, Toyoda M, Kahwaji J, Vo AA. Clinical aspects of intravenous immunoglobulin use in solid organ transplant recipients. Am J Transplant 2011;11:196-202.  Back to cited text no. 12
[PUBMED]    
13.
Kumar J, Shaver MJ, Abul-Ezz S. Long-term remission of recurrent parvovirus-B associated anemia in a renal transplant recipient induced by treatment with immunoglobulin and positive seroconversion. Transpl Infect Dis 2005;7: 30-3.  Back to cited text no. 13
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14.
Liefeldt L, Buhl M, Schweickert B, et al. Eradication of parvovirus B19 infection after renal transplantation requires reduction of immunosuppression and high-dose immunoglobulin therapy. Nephrol Dial Transplant 2002;17:1840-2.  Back to cited text no. 14
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Correspondence Address:
Issa Al Salmi
Department of Nephrology, Royal Hospital, Muscat
Oman
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DOI: 10.4103/1319-2442.220846

PMID: 29265066

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