Age: 21.0
Sex: F
Vaccine: FLUX
Symptoms: Blood urea increased, Body temperature increased, Bone marrow failure, Carbon dioxide decreased, Computerised tomogram abdomen abnormal
Clinical narrative: This case was reported by a physician, via another manufacturer (Amgen, # KDL345560) and described the occurrence of bone marrow failure in a 21-year-old female subject who was vaccinated with Influenza vaccine (manufacturer unspecified). The subject's medical history included multiple kidney biopsies, right internal jugular tunneled dialysis catheter placement complicated by vessel damage and traumatic pneumothorax treated with chest tube placement, and living related kidney transplant. Concurrent medical conditions included occasional alcohol use, left upper arm arteriovenous fistula, bone metabolism disorder, chronic allograft nephropathy, dry skin, end stage renal disease secondary to congenital renal dysplasia nos, short-term hemodialysis, high blood pressure, hyperparathyroidism, hyperphosphatemia, metabolic acidosis, and short stature. On an unknown date in 2008, the subject started PROCRIT 5000 units (U) twice a week; exact date, route and baseline hemoglobin (Hgb) were not provided. After an unspecified time of exposure, approximately in May 2008, the subject started experiencing an increase in creatinine (values were not provided). About four months later, on 30 August 2008, creatinine rose to 6.2 and blood urea nitrogen (BUN) was 78. That same day, the subject's Hgb "increased" to 15, and PROCRIT therapy was temporarily discontinued. Approximately two and a half weeks later, on 19 September 2008, the subject started experiencing "failing" of renal transplant and mild metabolic acidosis; Hgb was 14 and creatinine was 5.4. Treatment with sodium bicarbonate orally for metabolic acidosis was initiated. About five days later, on 26 September 2008, the subject experienced a decreased Hgb to 11.9, and one week later, on 03 October 2008, PROCRIT therapy was resumed at 10000 U subcutaneously (SC) every two weeks. Co-suspect medication included Epoetin alfa (PROCRIT and EPOGEN brands). Concurrent medications included Paricalcitol, PHOS-LO, Prednisone, Amlodipine, Heparin, CICLOSPORIN, Dextriferron, CALCITROL, Sodium bicarbonate, Zolpidem tartrate, Laxatives and Mycophenolate mofetil. On 24 October 2008 the subject received unspecified dose of Influenza vaccine (details unknown). On the same date (24 October 2008) blood test showed Hgb of 11.3 (it was not specified whether the test was performed before or after vaccination). It was reported that the subject's anemia was "stable" and the subject had "good response" to PROCRIT. Later that same month, the subject experienced worsening of kidney function with more significant acidosis, hyperkalemia, hyperphosphatemia and pedal edema; creatinine was 6.3, BUN was 66, potassium was 5.2, and phosphorus was 5.8. The hepatitis B surface antigen test was negative. The following month, in November 2008, the subject experienced "allograft failure". On 05 November 2008, Hgb was 10.1 g/dl, white blood cell count (WBC) was 11.95x1000/mcL, platelet count, was 443x1000/mcL, transferrin saturation was 11 percent, serum folate was greater than 24 ng/mL, creatinine was 6.1 mg/dL, BUN was 72 mg/dL, bicarbonate was 17 mEq/L, aluminum was less than 5 mcg/L, intact parathyroid hormone (i-PTH) was 202 pg/mL and hepatitis C (anti-HCV) test was negative. The subject initiated hemodialysis with iron therapy, and immunosuppressive agents (ciclosporin, mycophenolate mofetil and prednisone) started tapered off. Two days later, on 07 November 2008, the subject was switched to EPOGEN at 6600 U intravenously (IV) three times a week (TIW) for an unspecified reason; Hgb was 10.1. Approximately two weeks later, on 19 November 2008, Hgb was 10.5. Four days later, on 23 November 2008, EPOGEN therapy was increased to 8000 U. Ten days later, on 03 December 2008, Hgb was 12.2. EPOGEN was continued. Over the following one month two and a half weeks, Hgb rose to 14.7. Two days later, on 23 January 2009, EPOGEN was temporarily discontinued. That same month, ciclosporin therapy was discontinued as well. The next month, on 06 February 2009, Hgb was 16.8, WBC was 10800, platelet count was 232000, creatinine was 5.91, BUN was 36, glomerular filtration ratio (GFR) was 9. On an unknown date later, the subject developed erythematous rash. Treatment included "moisturizers" and an "antifungal agent" with improvement. Subsequently, in "mid-February" 2009, the subject experienced "acute gastrointestinal illness" with abdominal pain and diarrhoea lasted for about twenty four hours. Treatment details were not provided, and two days later the event resolved. The reporter stated that around the same time prednisone therapy was discontinued. Subsequently, on 25 February 2009, Hgb decreased to 12, and EPOGEN was resumed at 4000 U IV TIW. Over the following three weeks, Hgb ranged from 10.7 to 10, and EPOGEN dose was incrementally increased to 5800 U IV TIW; platelet count 256-266 1000/mcl, WBC was 4.14 x1000/mcL, serum ferritin was 810 ng/mL, serum iron was 206 mcg/dL, unsaturated iron binding capacity (UIBC) was 42 mcg/dL, transferrin saturation was 83%, creatinine was 7.1 mg/dL, BUN was 36 mg/dL, urea reduction ratio was 83%, i-PTH was 748.9 pg/mL and hepatitis B surface antigen test was negative. It was reported that in March 2009 paricalcitol therapy was initiated, and "immunosuppression" therapy was discontinued. On 25 March 2009, Hgb was 6.7, and the reporter stated that anemia became "unresponsive to epoetin" therapy. Treatment details were not provided. Around the same time, the subject started experiencing tiredness when walking upstairs and subsequently became increasingly fatigued and short of breath with exertion. Treatment details were not provided. On 30 March 2009, the dose of EPOGEN was further increased to 7600 U IV TIW. That same day, the subject experienced a low grade fever to 99.3 and was seen in the emergency room for "fatigue and generalized weakness". Anemia work up revealed Hgb of 5.6. Treatment details were not provided. Outcome details of the event fever were not provided. The subject was subsequently hospitalized on 01 April 2009 for five days for anemia. That same day, blood test showed Hgb of 6, WBC of 2800, absolute neutrophil count of 1.2, platelet count of 283000, potassium of 3.2, CO2 of 32, creatinine of 2.51 and GFR of 24.2. Peripheral blood smear showed predominantly normochromic normocytic erythrocytes with rare target cells. No increased polychromasia, nucleated blood cells, erythrocyte fragments and microspherocytoses were observed. The white blood cells were decreased with no early white blood cell forms detected, and the neutrophils did not have increased granulation or vacuoles; no giant platelets were identified. Faecal occult blood test x1 was negative. Urinalysis revealed small blood, positive protein, positive leukocyte esterase, five to ten white blood cells and few bacteria. Urine culture showed no bacterial growth at 24 hours. EPOGEN therapy was increased to 24000 U IV TIW. Additional treatment details were not provided. The following day, on 02 April 2009, Hgb was 6, blood erythropoietin was 3607, WBC was 2.4, absolute neutrophil count was 1.3, platelet count was 242000, folate was 5.7, total protein was 6.3, chloride was 98, CO2 was 33, creatinine was 3.78, GFR was 15, thyroid stimulating hormone level was 22 and vitamin B12 was 1051. The subject was negative for serum parvovirus B19 antibodies, and the results of blood cultures x2 were pending. Repeated blood smear test showed significant artifact, and no increased red blood cell fragments were identified. The subject was diagnosed with hypoproliferative anemia and leukopenia. It was reported that the subject was reluctant to proceed with red blood cell transfusion due to concerns of "alloimmunization compromising her changes for second transplant". Transfusion with red blood cells was planned for Hgb of 5.5 or less or in case of developing of worsening of symptoms. The subject also experienced abdominal pain, and a computed tomography scan of abdomen with oral and intravenous contrast was done. The results revealed focal fatty infiltrate within the liver adjacent to the falciform ligament and severely atrophic, and cystic kidneys. A left ovarian cyst and congenital deformity at the lumbosacral spine with dysgraphism were noted as well. The lung bases were clear. No acute intra-abdominal abnormality was identified. Treatment and outcome details were not provided. The subject also experienced hair loss. Treatment and outcome details were not provided. The next day, on 03 April 2009, Hgb was 5.5, WBC was 2.7, platelet count was 241, serum iron was 183, iron saturation was 93, total iron binding capacity was 196, transferrin was 140, ferritin was 630, creatinine was 6.31, BUN was 33, GFR was 8.3, total protein was 6.5 and phosphorus was 6. Hepatitis B core IgM, hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus 1 and human immunodeficiency virus 2 tests were negative. Cytomegalovirus DNA was not detected as well. Protein electrophoresis revealed no monoclonal proteins and decreased IgG and IgA components. For evaluation of the subject's shortness of breath computed tomography scan of the chest without the use of contrast was performed. The results showed a duplicated left superior vena cava extending along the left mediastinum to the left heart border, 8 mm hypodense lesion of left thyroid, constipation and atrophic kidneys consistent with end-stage renal disease; no pleural effusion, gross mediastinal or hilar adenopathy were detected; lungs were clear with no pneumothorax. No findings to explain the subject's shortness of breath were identified. That same day, the subject received two units of unspecified transfusion. The following day, on 04 April 2009, Hgb was 8.5, WBC was 3.5, platelet count was 228, creatinine was 4.72 and GFR was 11.7. Repeated faecal occult blood test was negative. Urine immunofixation electrophoresis showed a polyclonal increase in free kappa and/or free lambda light chains; no monoclonal free light chains (Bence Jones Protein) were identified. On 05 April 2009 Hgb was 8.4, WBC was 4.2, platelet count was 214, and the subject was discharged. The next day, on 06 April 2009, Hgb was 8, and EPOGEN therapy was decreased to 20000 U IV TIW. Over the following two and a half weeks, Hgb ranged from 6.8 to 9.1. The subject received two units of unspecified transfusion and required incremental increase in EPOGEN dose to 28000 U IV TIW. On 23 April 2009 bone marrow aspirate, clot sections and core biopsy revealed normocellular (60-70 percent) bone marrow with trilineage hematopoiesis, left shifted granulopoiesis, marked erythroid hyperplasia and mild megakaryocytic hyperplasia; increased storage iron; mild paratrabecular reticulin fibrosis, 1+/4+; no atypical non-hematopoietic cells or granulomas were identified, scattered erythroid and myeloid precursors were present. Peripheral blood smear revealed anemia and leukopenia. Flow cytometric analysis showed no significant immunophenotypic abnormalities. The pathologist commented that low grade myelodysplastic syndrome cannot be completely ruled out. Over the following ten days, Hgb steadily declined from 8.5 to 6.5, and EPOGEN therapy was permanently discontinued on 04 May 2009. Two days later, on 06 May 2009, Hgb was 6.1. The subject received two units of unspecified transfusion. The latest Hgb level on 08 May 2009 was 10.5; WBC was 5.1 and platelet count was 266. Antibody testing was requested. The subject was hospitalized and the physician considered the events were clinically significant (or requiring intervention). At the time of reporting the outcome of the events was unspecified. The physician stated that there was a reasonable possibility the event anemia was related to EPOGEN therapy. There was no causality statement provided for Influenza vaccine.