ORIGINAL ARTICLE Transfusion-associated Anaplasma phagocytophilum infection in a pregnant patient with thalassemia trait: a case report Kelsey Shields,1,2 Melissa Cumming,3 Jorge Rios,4 Michael T. Wong,2 Jeffrey I. Zwicker,5 Susan L. Stramer,6 and Carolyn D. Alonso2

CASE REPORT BACKGROUND: Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile illness caused by the bacterium Anaplasma phagocytophilum. Although usually transmitted via tick bite, HGA may rarely also be acquired through transfusion. HGA during pregnancy may pose significant gestational risks due to altered maternal immune status and the potential for perinatal transmission. CASE REPORT: A pregnant 34-year-old Massachusetts woman with β-thalassemia trait was diagnosed at 32 weeks of gestation with transfusion-associated HGA (TAHGA) after receiving nine leukoreduced red blood cell transfusions. She was successfully treated with rifampin therapy and gave birth to a healthy child who tested negative for HGA after delivery. An implicated blood donor was subsequently identified through physician collaboration with the regional American Red Cross and Massachusetts Department of Public Health. DISCUSSION: This is the 11th reported case of HGA in pregnancy and is at least the sixth known case in which leukoreduction did not prevent TAHGA. As seen in this case, nonspecific symptomatology of variable onset can impede diagnosis and treatment. This may increase risk of poor outcomes in maternal HGA patients. Cases of TAHGA, although currently uncommon, may increase as the incidence of HGA in certain parts of the country increases. CONCLUSION: Heightened cross-institutional awareness of the potential risk of TAHGA is warranted. Clinicians need to consider transfusion-associated infections when fever occurs in a transfusion recipient. This case provides additional evidence that leukoreduction does not obviate risk of A. phagocytophilum contamination of donated blood components.

In late September 2012, a pregnant 34-year-old Massachusetts resident was diagnosed at 32 weeks gestation with human granulocytic anaplasmosis (HGA). The patient had β-thalassemia trait and before her diagnosis had been under care for ongoing mild anemia, presyncope, and fatigue. She was gravida 3, para 1 with an uncomplicated delivery 2 years previously. Between May and August 2012 the patient received 9 units of irradiated, leukoreduced red blood cells (RBCs) at Hospital A for symptomatic anemia; her hemoglobin (Hb) had decreased to 7.9 g/dL in the 26th week of pregnancy from a baseline range of 9.5 to 10.7 g/dL. After each of the transfusions the patient reported improvement in fatigue but no change in presyncopal symptoms. Eleven days after her last RBC transfusion, which was prepared from a whole blood donation that took place on

ABBREVIATIONS: ARC = American Red Cross; HGA = human granulocytic anaplasmosis; ID = infectious diseases; IFA = Indirect immunofluorescent antibody; MADPH = Massachusetts Department of Public Health; TAHGA = transfusion-associated HGA. From the 1Division of Gastroenterology, the 2Division of Infectious Diseases, and the 5Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School; and the 3Division of Epidemiology and Immunization, Massachusetts Department of Public Health, Boston, Massachusetts; the 4Massachusetts Region of the American Red Cross Blood Services, Dedham, Massachusetts; and the 6 American Red Cross, Gaithersburg, Maryland. Address reprint requests to: Carolyn D. Alonso, MD, Division of Infectious Diseases, Beth Israel Deaconess Medical Center, 110 Francis Street LMOB GB, Boston, MA 02215; e-mail: [email protected]. Received for publication April 3, 2014; revision received August 2, 2014, and accepted September 6, 2014. doi: 10.1111/trf.12908 © 2014 AABB TRANSFUSION **;**:**-**. Volume **, ** **

TRANSFUSION

1

SHIELDS ET AL.

August 14, 2012, and was administered to the patient on August 23, 2012, the patient developed new onset nausea and fevers (up to 39.3°C). She was treated as an outpatient with intravenous fluids and antiemetics for a presumed viral illness. Treatment was ineffective and 5 days after symptom onset she was admitted to Hospital A at 29 weeks gestation with fever to 39.4°C, nausea, elevated liver enzymes, and poor appetite. On admission her laboratory values included a white blood cell (WBC) count of 4.9 × 109/L (67% neutrophils, 27% lymphocytes, 5% monocytes; WBC nadir 4.6 × 109/L), Hb level of 8.8 g/dL (nadir 7.2 g/dL), platelet (PLT) count of 189 × 109/L (nadir, 150 × 109/L), aspartate aminotransferase (AST) of 127 U/L, and alanine aminotransferase (ALT) of 86 U/L (peak, 92 U/L; Table 1). Throughout her hospitalization the patient experienced leukopenia, decreasing PLT count, and liver function test elevations (Table 1). Diagnostic considerations included tick-borne illnesses, transfusion-transmitted infection, and HELLP (hemolysis, elevated liver enzymes, low PLT count) syndrome. Serologic tests for hepatitis A immunoglobulin (Ig)M/IgG antibodies, hepatitis B surface antigen and core IgM/IgG antibodies, and hepatitis C IgG antibody were negative (Advia Centaur Immunoassay System, Siemens, Malvern, PA). Serologic testing for Lyme disease (Borrelia burgdorferi; Liaison Borrelia burgdorferi assay, DiaSorin, Saluggia, Italy) as well as IgM/IgG antibody and polymerase chain reaction (PCR) testing for babesiosis (Babesia microti; Quest Diagnostics Nichols Institute, Valencia, CA) were also negative. Tests for Anaplasma phagocytophilum were pending at the time of discharge. The patient left the hospital on September 10, 2012, with ongoing low-grade fevers, fatigue, and myalgias. No antibiotics were administered empirically during hospitalization or at discharge. Indirect immunofluorescent antibody (IFA) evaluation of paired serum samples taken at discharge (September 10, 2012) and approximately 1 week later (September 19, 2012)—18 and 27 days after the patient’s receipt of the last RBC transfusion, respectively—revealed increasing titers of antibody specific for A. phagocytophilum (Day 18, IgM < 20/IgG 80; Day 27, IgM 1280/IgG 80; Quest Diagnostics Nichols Institute). The patient’s Day 18 blood sample was also positive for A. phagocytophilum by PCR (Focus Diagnostics, Cypress, CA). The acute-phase PCR and serology results were reported by the commercial reference laboratories to Hospital A on September 14, 2012, and September 15, 2012, respectively. The patient’s convalescent-phase Day 27 serology results were reported by the reference laboratory to Hospital A on September 24, 2012. On September 27, 2012 (17 days after discharge and 35 days after receipt of the last RBC transfusion), these A. phagocytophilum serology and PCR test results from Hospital A became available to the patient’s hematology2

TRANSFUSION Volume **, ** **

oncology physician affiliated with Hospital B. Upon receipt of these results, a 14-day course of oral rifampin therapy (300 mg per oral twice daily) was initiated and the patient was promptly referred to an infectious diseases (ID) physician affiliated with Hospital B. It is unclear whether the patient completed follow-up at Hospital A after her acute-phase and convalescent specimens were taken, and it is unclear whether her HGA test results were communicated with her providers at Hospital A before their becoming known by providers at Hospital B. Unfortunately, there is nothing in the patient’s medical record to address this apparent delay between testing and initiation of therapy. The patient completed rifampin therapy in October 2012 with complete resolution of low-grade temperature elevations, fatigue, and myalgias. In November 2012 she gave birth to a healthy full-term girl; the baby tested negative for A. phagocytophilum via PCR blood testing. Because the patient denied any known tick bites and reported no tick exposures during her pregnancy, the ID provider at Hospital B alerted the blood bank at Hospital A and the Massachusetts Department of Public Health (MADPH) about potential transfusion transmission of A. phagocytophilum to this patient. The MADPH and the blood bank at Hospital A reported this to the American Red Cross (ARC), which proceeded to defer all future donations from the donors of the RBC units given to this patient and requested that these donors provide blood samples for A. phagocytophilum testing. The ARC also promptly quarantined any remaining in-date cellular components (frozen plasma products have never been implicated in A. phagocytophilum transmission) and alerted the hospitals that received cellular components from the suspected donors. The 9 RBC units involved in this case were each prepared from separate whole blood donations from nine donors residing in Massachusetts, Maine, Vermont, New Hampshire, and Rhode Island. Six of the nine donors were eliminated as the source of the infection based on negative follow-up antibody and PCR tests for A. phagocytophilum (Imugen, Norwood, MA). These donors were allowed to resume blood donation. The three remaining donors either refused testing or were lost to follow-up. These donors were excluded from future donation by the ARC. Two of these three donors resided in Massachusetts, the other donor resided in New Hampshire. On February 14, 2013, one of the lost to follow-up donors residing in Massachusetts contacted the ARC to report that he was diagnosed with acute A. phagocytophilum infection 4 days after his most recent whole blood donation in August 2012. The MADPH verified that this donor had been hospitalized with leukopenia, thrombocytopenia, and 1+ Dohle bodies observed on blood smear with positive A. phagocytophilum PCR testing (Mayo Medical Laboratories, Rochester, MN) at Hospital C 4 days after an August 14, 2012, whole blood

Hospital B provider receipt of IFA results Initiation of rifampin therapy

Inpatient discharge

New-onset fever, nausea Inpatient admission, fever to 39.4°C

Event/symptomatic complaint(s) Receipt of implicated RBC unit

10.4

8.8

8.8 7.8 7.2 8.5 8.4 8.2

9.6

9.9 4.9 4.6 5.2 7 9.6 9.9

Hb (g/dL)

WBCs (×109/L)

26.3

26.7 21.7 22 26.3 26.5 26

29

Hct (%)

205

189 166 150 214 290 232

224

PLTs (×109/L)

5.4

NA 4.6 4.5 5.4 5.7 5.4

NA

Protein (g/dL)

3.5

NA 2.9 2.9 3.3 3.5 3.5

NA

Alb (g/dL)

0.8

0.8 0.5 0.6 0.6 0.6 0.4

NA

Tbili (mg/dL)

98

NA 64 73 95 90 82

NA

AF (I)U/L

29

127 122 108 72 24 26

NA

AST (I)U/L

17

86 79 92 85 27 14

NA

ALT (I)U/L

283

373 NA NA 327 237 250

231

LDH U/L

1:64

1:80

1:1280

1:160

1:80

IgG

Transfusion-associated Anaplasma phagocytophilum infection in a pregnant patient with thalassemia trait: a case report.

Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile illness caused by the bacterium Anaplasma phagocytophilum. Although usually tran...
83KB Sizes 0 Downloads 8 Views