Sex: M
Vaccine: PNC13
Symptoms: Coombs direct test negative, Cryoglobulins absent, Dyspnoea, Dyspnoea exertional, Electrophoresis protein normal
Clinical narrative: Cold antibody autoimmune hemolytic anemia; This is a literature report from the Clinical Case Reports. This is the first reported case of cold antibody autoimmune hemolytic anemia due to anti-Pr autoantibodies attributed to Pneumococcal vaccination in an adult patient. The patient presented 1 week after receiving the vaccination with low hemoglobin, jaundice, and dyspnea with no prior history of anemia. Extensive workup including ruling out infectious and malignant causes was unremarkable, and his treatment consisted of transfusions and a course of steroids. An autoantibody anti-Pr was identified with persistence but decreased reactivity up to 3 months after his initial presentation.  The patient is a 72-year-old man who presented with jaundice and increasing dyspnea on exertion and was found to be anemic with hemoglobin of 7.4 g/dL. His symptoms began approximately 1 week after receiving the pneumococcal 13-val conj vac (dipht crm197 protein) (PREVNAR 13) vaccination. The patient had been in stable health with a documented hemoglobin level of 13.9 g/dL at the time of his implantable cardioverter-defibrillator (ICD) placement 2 months prior. His past medical history included congestive heart failure with ejection fraction of 10%, type II diabetes mellitus, and hypertension. His medication regimen had been stable for several years and included low strength aspirin, naproxen, lisinopril, carvedilol, furosemide, potassium chloride, simvastatin, metformin, glipizide, gabapentin, omeprazole, docusate sodium, folic acid, and a daily multivitamin. He had no prior history of anemia and had never before required a blood transfusion. At presentation, the patient was jaundiced with stable vital signs (temperature of 98.8 degree F, heart rate of 88 beats/minute, blood pressure of 112/61 mm Hg, and oxygen saturation of 97% on room air). Laboratory results were significant for a low RBC count (2.60 M/CUMM; normal range: 4.15-5.75 M/ CUMM), reticulocyte count of 0.5 percent, elevated lactate dehydrogenase (LDH; 445 U/L; normal range 125-243 U/L), decreased haptoglobin (<8 mg/dL; normal range 30-200 mg/ dL), and elevated total bilirubin (5.2 mg/dL; normal level up to 1.2 mg/dL). A peripheral blood smear was remarkable for spherocytosis. Direct antiglobulin testing was negative on two separate occasions for IgG as well as complement C3 components. A cold autoantibody was identified that reacted to all panel cells. The antibody was nonreactive with enzyme-treated RBCs and identified as anti-Pr The patient was diagnosed with cold antibody AIHA most likely secondary to recent administration of the pneumococcal vaccination (PREVNAR 13). Further workup was unremarkable including the following: hepatitis serology testing, serum protein electrophoresis with immunofixation, general flow cytometry screening, Cryoglobulin testing, iron studies, folate, and B12. Parvovirus showed positive IgG and negative IgM, consistent with prior infection. Polymerase chain reaction testing for Parvovirus was negative. Computed tomography scan of the chest, abdomen, and pelvis demonstrated several borderline mediastinal lymph nodes measuring up to 1.3 cm, a left implantable cardioverter- defibrillator (ICD) in place, a moderately enlarged heart, no obvious lung abnormalities or nodules, and a normal appearing liver and spleen with no abdominal or pelvic lymphadenopathy. He had a white blood cell count of 3.5 K/ CUMM (normal range 3.3-10.5 K/CUMM) and platelet count of 215 K/CUMM (normal range 150-400 K/CUMM). During his hospitalization, the patient's hemoglobin dropped to 6.6 g/dL, and his bilirubin increased to 6.6 mg/ dL with a normal direct bilirubin of 0.5 mg/dL. The patient was transfused with one unit of packed red blood cells and discharged home in stable condition with a post-transfusion hemoglobin level of 7.5 g/dL. At follow-up, 11 days after his transfusion, his hemoglobin had dropped to 6.8 g/dL. He received two additional units of packed red blood cells with rise in hemoglobin to 9.3 g/dL. The patient was also treated with a course of prednisone with taper over 2 months. His hemoglobin level continued to rise, reaching 13.8 g/dL 3 months after discontinuation of steroid treatment. A blood sample at that time showed persistence of anti-Pr, though with overall decreased reactivity strengths. The patient's laboratory studies showed no evidence of hemolysis with a normal LDH of 187 U/L and RBC of 4.61 M/CUMM. Information on the batch number has been requested.; Sender's Comments: Based on the information currently available (hemolytic anemia occurred one week post vaccination with Prevnar 13 and positive cold autoantibody identified against Pr antigen the antigenic determinants of which have been found on almost all RBCs), it cannot be excluded that Pneumococcal vaccination with Prevnar 13 may elicit the formation of Pr specific autoantibody thus triggered the occurrence of cold antibody autoimmune hemolytic anemia.  The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate