Pure Red Cell Aplasia Caused by Parvovirus B19 Infection in an Early Kidney Transplant Recipient

Abstract

Dear Editor, Posttransplant anemia has a wide range of etiologies and may be associated with higher morbidity and mortality rates. Parvovirus B19 (PV B19) has an affinity for infecting erythroid progenitor cells and causes severe hypoplasia or aplasia, leading to anemia. The bone marrow cytology examination provides an early clue for the possibility of PV B19; additionally, serological estimation of immunoglobulin M and IgG antibodies, complement levels, and molecular amplification techniques to detect PV B19 DNA aid in the diagnosis of PV B19. In the 1st month after kidney transplant, we encountered a patient with pure red cell aplasia caused by a PV B19 infection. A bone marrow aspirate cytology, low complement levels, and PV B19 DNA real-time polymerase chain reaction aided us in the early identification of the disease and a prompt reduction in immunosuppression resulted in a favorable outcome without the need for blood transfusion. A 39-year-old male with end-stage renal disease due to diabetic nephropathy who was on maintenance hemodialysis for the past 2 years underwent a deceased donor renal transplantation. He received anti-thymocyte globulin (ATG), cumulative dose of 2 mg/kg body weight and methylprednisolone, cumulative dose of 1.25 g, as induction therapy. He also received tacrolimus (trough level of 7.2 μg/l by the 5th postoperative day [POD]), mycophenolate mofetil (MMF, 2 g/day) from the day 0, and prednisolone (15 mg/kg) POD 3. He also received cotrimoxazole and valganciclovir as part of standard prophylaxis against pneumocystis and cytomegalovirus (CMV). The allograft kidney functioned well and serum creatinine reached a trough of 0.9 mg/dL from a pretransplant level of 6.5 mg/dL [Figure 1]. During his follow-up visit on POD 25, it was found that he had developed anemia. His hemoglobin level steadily dropped from 14.5 g/dL to 6.5 g/dL by POD 52 [Figure 2]. He was asymptomatic and his systemic examination was unremarkable except for pallor. Peripheral blood smears showed normocytic, normochromic RBCs. Other hematological blood parameters such as total white blood cell and platelet counts were normal. The complement levels (C3 and C4) were low. Biochemical parameters such as serum iron studies, Vitamin B12, and folic acid levels were normal. The viral serology for HIV-1, HIV-2, anti-hepatitis C antibody, and hepatitis B surface antigen were nonreactive. Reverse transcription polymerase chain reaction (RT-PCR) for CMV was undetectable (<57.1 copies/mL) by RT-PCR. A bone marrow aspiration (BMA) was performed and it showed cellular marrow with erythroid hypoplasia with maturation arrest. Many basophilic pronormoblasts with intranuclear inclusions were seen. Few cells showed pseudopod/dog-ear-like projections that favored PV B19 infection [Figure 3]. PV B19 was detectable by RT-PCR. The immunosuppression dose was reduced following the bone marrow cytology and RT-PCR results. The dose of prednisolone was reduced to 10 mg/day and MMF was completely withheld for a fortnight. The dose of tacrolimus remained unchanged. Following this intervention his hemoglobin, which was hitherto continuously decreasing, stabilized at 6.8 g/dl. MMF was reintroduced in a dose of 500 mg once a day after a complete abstinence of 15 days, while keeping a close watch on his allograft kidney function. His graft kidney function remained stable and his hemoglobin started to increase from POD 59 and by POD 148 it reached 15.8 g/dl. He did not need either intravenous immunoglobulin or hospitalization or blood transfusion. It is now 6 months since PV B19 was detected and he has a stable graft function with no recurrence of infection.Figure 1: Creatinine trend before transplant and after transplantFigure 2: Hemoglobin trend during transplant and after transplantFigure 3: Bone marrow aspiration cytology smears showed erythroid hypoplasia, giant pronormoblast with basophilic cytoplasm (a: Blue arrow), Pronormoblast with intranuclear inclusion (b: Blue arrow), (c and d: Green arrow) pronormoblast with pseudopod or dog-ear like cytoplasmic projectionDespite PV B19 being a common infection in the general population, it is infrequently suspected as a cause of anemia in postrenal transplant population due to the lack of typical immune-mediated symptoms such as fever, arthralgia, and rash in a patient with anemia. The most common conditions suspected to cause anemia during this period are allograft dysfunction, infections with viruses like CMV or drugs like ATG, rituximab, MMF, or cotrimoxazole and rarely blood loss.[1] PCR assay to detect viral DNA is preferred over serological assays.[2,3] Since we had a high index of suspicion, we requested for an RT-PCR which turned out to be positive. We also performed a BMA which showed features helpful for us to diagnose PV B19.[4] Complement levels, C4 in particular, decrease early along with a decrease in the haemoglobin concentration in PV B19 infection and this was noticed in our patient.[5] We were quick in reducing the immunosuppressive medications, a complete withdrawal of mycophenolate in particular, along with a significant reduction in the dose of prednisolone and this resulted in an improvement in hemoglobin levels. Though our patient received ATG for induction, it is interesting to note that the incidence of PV B19 is more in patients who received basiliximab rather than ATG. To conclude, Infection with PV B19 is a well-known but infrequent condition in the renal transplant group. The high index of suspicion, as well as morphological features of bone marrow aspirate with a low complement (C4) level, provide an early clue for PV B19 infection and assist in preventing unnecessary investigations. Declaration of patient consent The patient consent has been taken for the participation in the study and for the publication of clinical details and images. Patients understand that the names and initials would not be published and all standard protocols will be followed to conceal their identity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.