A fatal case of transfusion-transmitted babesiosis in the State of Delaware.

BACKGROUND: Most cases of human babesiosis in North America are caused by Babesia microti, which is endemic in the northeastern and upper midwestern United States. Although the disease is usually transmitted by a tick bite, there has been an increase in the number of transfusion-transmitted cases reported. We describe a fatal case of transfusion-transmitted babesiosis in a nonendemic state, Delaware. CASE REPORT: The patient was a 43-year-old Caucasian woman with history of transfusion-dependent Diamond-Blackfan syndrome, hepatitis C, and splenectomy. She was admitted initially for presumptive pneumonia. The next day, a routine examination of the peripheral blood smears revealed numerous intraerythrocytic ring forms, consistent with Babesia. The parasitemia was approximately 5% to 6%. The diagnosis was confirmed by positive polymerase chain reaction (PCR) for B. microti DNA and high titer of antibody to B. microti (1:2048). Despite aggressive therapy including clindamycin and quinine antibiotics, the patient expired 3 days after admission. Subsequently, 13 blood donors were tested for B. microti. All tested donors were negative by PCR. However, one donor living in New Jersey had a significant elevated B. microti antibody titer (1:1024). CONCLUSIONS: We believe that this is the first reported case of transfusion-transmitted babesiosis in Delaware, a nonendemic state. Our case illustrates that clinicians should consider babesiosis in the differential diagnosis of immunocompromised patients who have fever and recent transfusion history, even in areas where babesiosis is not endemic. It also demonstrates the need for better preventive strategies including more sensitive, specific, and rapid blood donor screening tests to prevent transfusion-transmitted babesiosis.

Roles of low specificity and cofactor interaction sites on thrombin during factor XIII activation. Competition for cofactor sites on thrombin determines its fate.

Factor XIII is activated by thrombin, and this reaction is enhanced by the presence of fibrin(ogen). Using a substrate-based screening assay for factor XIII activity complemented by kinetic analysis of activation peptide cleavage, we show by using thrombin mutants of surface-exposed residues that Arg-178, Arg-180, Asp-183, Glu-229, Arg-233, and Trp-50 of thrombin are necessary for direct activation of factor XIII. These residues define a low specificity site known to be important also for both protein C activation and for inhibition of thrombin by antithrombin. The enhancing effect of fibrinogen occurs as a consequence of its conversion to fibrin and subsequent polymerization. Surface residues of thrombin further involved in high specificity fibrin-enhanced factor XIII activation were identified as His-66, Tyr-71, and Asn-74. These residues represent a distinct interaction site on thrombin (within exosite I) also employed by thrombomodulin in its cofactor-enhanced activation of protein C. In competition experiments, thrombomodulin inhibited fibrin-enhanced factor XIII activation. Based upon these and prior published results, we propose that the polymerization process forms a fibrin cofactor that acts to approximate thrombin and factor XIII bound to separate and complementary domains of fibrinogen. This enables enhanced factor XIII activation to be localized around the fibrin clot. We also conclude that proximity to and competition for cofactor interaction sites primarily directs the fate of thrombin.