Case report: A. phagocytophilum transmitted via blood transfusion

Bacteria causes the tickborne rickettsial disease human anaplasmosis.

In the first confirmed case of its kind, an elective knee arthroplasty and synovectomy patient in Minnesota who received a blood transfusion developed symptoms of human anaplasmosis and was confirmed to carry the bacteria Anaplasma phagocytophilum. Epidemiologic and laboratory analyses traced the bacteria to a specific donor. The case was reported in the CDC’s Morbidity and Mortality Weekly Report.

A. phagocytophilum is a gram-negative, obligate intracellular bacterium that attacks neutrophils. Typically it is transmitted to humans via bites from ticks in the Ixodes genus, including the blacklegged tick in the Northeast and upper Midwest United States and the western blacklegged tick on the West Coast. Anaplasmosis onset generally occurs between five and 21 days after a tick bite. Initial symptoms include sudden onset of fever, headache and myalgia, along with thrombocytopenia, leukopenia and elevated liver transaminases. Severe or untreated infections can lead to seizures, renal failure, hemorrhages and death.

Case details

Although the authors report that one previous case of transfusion-transmitted anaplasmosis exists, it did not include confirmed tests of both the blood donor and recipient. In this case, a 68-year-old man underwent elective knee arthroplasty and synovectomy on Oct. 12, 2007. Soon after the procedure, bleeding at the surgical site and coagulopathy required transfusion of multiple blood components. Over the course of nine days, he received 34 units of nonleukoreduced red blood cells, four units of leukocyte-reduced apheresis platelets, 14 units of fresh frozen plasma and seven units of cryoprecipitate; donations came from 59 different donors.

Seven days following the initial procedure, the patient developed sepsis and multisystem failure. Eleven days after that, physicians found he had worsening thrombocytopenia. On October 31 his platelet count was 178,000/mm³, and by November 5 it had declined to 54,000/mm³. He also developed hypotension and fever, and a blood smear on November 3 indicated the possibility of A. phagocytophilum infection. A review of a previous smear, from three days after the initial procedure, showed no evidence of the bacteria.

The patient received doxycycline treatment, resulting in steadily improving platelet count until a return to normal on November 10. Following rehabilitation, he was discharged on Dec. 3, 2007.

One infected donor

Polymerase chain reaction (PCR) and immunofluorescence assay tests on blood samples from all 34 red blood cell samples and eight of 14 fresh frozen plasma samples received by the patient showed that one woman donor tested positive for A. phagocytophilum infection. According to the report, “the donor did not recall being bitten by a tick, but had spent time in wooded areas of northeast Minnesota where anaplasmosis is endemic within the month before her donation. She reported no history of fever during the month before or after her donation.” No whole blood samples from other donors had evidence of the bacteria, although two red blood cell donors’ sera tested weakly positive by immunofluorescence assay (IgG titers 1:64, vs. 1:512 for the PCR-positive donor, where 1:32 and above was considered positive). Neither donor tested positive by PCR and neither reported any exposure to ticks or illness in the period prior to blood donation.

“The case described in this report provides strong presumptive evidence that A. phagocytophilum infection in this patient was acquired through blood transfusion,” the authors wrote. There was no conclusive evidence that the patient’s blood was free of the infection prior to blood transfusion, but he reported limited outdoor exposure that might involve tick contact. Furthermore, the suspected incubation period for anaplasmosis of five to 21 days strongly suggests that the infection was transmitted during the patient’s hospital stay.

Looking forward

This case and other unpublished reports suggest that some patients — such as those who are immunocompromised — might be at risk for some tickborne diseases, which can often survive in refrigerated red blood cell samples. The rarity of transfusion-related cases, however, makes specific tests or screening of blood donors — especially in areas of high tick concentration — cost ineffective. The authors noted that patients with anaplasmosis often do not recall specific tick bites or even possible tick exposure.

Notably, the reported incidence of anaplasmosis and other tickborne illnesses has risen in recent years. In 2007 in Minnesota, 322 cases of anaplasmosis were reported. “As the incidence of tickborne diseases increases, physician vigilance for possible transmission of these agents via transfusions also should increase,” the investigators wrote. “In addition to more common etiologies, physicians should suspect possible rickettsial infections if transfusion recipients develop acute thrombocytopenia posttransfusion, especially if accompanied by fever. Such signs should lead to rapid assessment for rickettsial agents and empiric treatment with doxycycline.” – by Dave Levitan

This interesting case reinforces the teaching that any organism that has infected a blood donor can potentially be transmitted to a recipient. Although viral infections and bacterial infections (particularly from platelet concentrates) are of greater concern in the U.S. blood supply, other infectious agents including parasites and rickettsia can cause transfusion transmitted disease. These infections can be commonplace in endemic areas as with malaria or unusual as seen in the current case. The finding of an unusual infectious agent in the blood of a patient should prompt the clinician to review recent transfusions and report to the transfusion service if a transfusion transmission is suspected. If a cluster of cases occurs, blood collection agencies can consider screening donors by history or laboratory testing to prevent further transmissions; in the current case, it is not likely that donor questions or testing would be effective or cost-effective and false positive answers to screening questions would result in loss of many potential donors.

Since it will never be possible to prevent the transmission of all infectious agents by transfusion using questions and laboratory tests, many transfusion authorities are hoping that pathogen reduction technologies will become available in the near future. There are systems available in Europe to reduce pathogens in platelets but they are not licensed in the United States; pathogen reduction systems for red cells are under development by several companies and may become available in the future if safety and efficacy can be established.

– Paul M. Ness, MD

HemOnc Today Editorial Board member

For more information:

• CDC. MMWR. 2008;57:1145-1148.
• Kemperman M, Neitzel D, Jensen K, et al. Anaplasma phagocytophilum transmitted through blood transfusion --- Minnesota, 2007.