In both cases, the patients were brought to the emergency room because of a history of syncope associated with increasing abdominal pain. The syncopal attacks could be attributed to the decrease in blood pressure present in both, to a low of 70 mm Hg in the second case. Blood tests done for each of them revealed low hemoglobin with a normal WBC count. Fortunately, CT scans were ordered, and the presence of splenic rupture was recognized early in each case. Emergency splenectomy proved to be life saving for both of them.
The difference between the two is the postsplenectomy clinical course. After the procedure, the first case developed progressive decrease in hemoglobin associated with fever and was diagnosed with Babesia in postoperative peripheral blood smear and spleen sections, shedding light on the cause of the continuous hemolysis. The necessary antibiotics were administered then. In contrast in the second case, the babesial forms were identified in a perioperative peripheral blood smear, confirmed by diagnostic intraerythrocytic babesial forms present in the ruptured spleen, and the patient was treated early without developing hemolysis. Both patients did well with antibiotic treatment and recovered completely.
The following additional illustrative case demonstrates importance of maintaining a high index of suspicion regarding babesial infection in the asplenic patient.
A 66-year-old white woman, with no recent travel history and with history of an accident-related splenectomy, presented with a temperature of 101°F, feeling generalized sickness of severe degree and loosing mental abilities according to a friend's observation. Her blood count showed mild reactive leukocytosis (WBC count, 16,700/μL) with left neutrophilic shift and toxic granulation, and mild monocytosis. There was moderate normocytic anemia (8 g/dL) with polychromasia, Howell-Jolly bodies, and nucleated RBCs. Platelets were normal in number, with occasional macroplatelets noted. Her attending physician planned to rule out chronic loss of blood in the gastrointestinal and genitourinary systems, with subsequently occult blood in stool negative. Sedimentation rate was 129 mm/h (reference range, 0-20 mm/h). Total bilirubin was 1.6 mg/dL (reference range, 0.2-1.0 mg/dL), with direct 0.3 mg/dL (reference range, 0-0.5 mg/dL). Serum iron of 89 μg/dL (reference range, 35-175 μg/dL) with ferritin 5846 ng/mL (reference range, 10-291 ng/mL) as well as haptoglobin less than 8.0 mg/dL (43-212 mg/dL), lactate dehydrogenase 1191 U/L (reference range, 91-180 U/L), and reticulocyte count of 7.7% (reference range, 0.6%-2.7%) confirmed significant hemolysis. Urine morphology showed "large amount of hemolyzed blood on slide." Direct Coombs was negative. The review of the peripheral blood smear revealed numerous erythrocytes that contained small ring-form parasites, single or multiple (including tetrads). Some parasites were found outside the erythrocytes, forming aggregates that probably embolized capillaries and impaired tissue oxygenation. The patient had Po2 of 70.0 mm Hg (reference range, 75-100 mm Hg) in radial artery on 5 L by nasal cannula. Double blood cultures and urine culture were negative.
The peripheral blood smear was reviewed by a pathologist, and the above findings were reported. It was directly brought to the attention of an infectious disease specialist consulting this case that the patient was infested by Babesia parasites. Despite early skepticism, the infectious disease consultant was convinced to begin treatment. The treatment included quinine sulfate 520 mg orally TID and clindamycin phosphate 600 mg IV QID. High temperature persisted for more than a week with parasites slowly decreasing in number. However, the patient began recovering mentally quickly and reported improvement subjectively soon after the beginning of treatment.
Splenopathies of various etiologies may render the spleen susceptible to spontaneous rupture after relatively minor trauma. Spontaneous rupture of the spleen has been seen in association with several infectious diseases including cytomegalovirus, Schistosoma, dengue, Bartonella henselae, salmonellosis, Plasmodium vivax, Q fever, hydatid cysts, and Epstein-Barr virus.1-8 Splenitis with rupture may also serve as a sentinel for other pathophysiologic processes such as bacterial endocarditis.9-11 Spontaneous splenic rupture has also been seen in association with various autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and polyarteritis nodosa.12
Human babesiosis or "Nantucket fever" is an illness transmitted by ticks of the genus Ixodes and caused by an intraerythrocytic protozoan of the genus Babesia.13 The life cycle of Babesia has no known exoerythrocytic stage. The fertilized gametes migrate from the tick gut to the tick salivary gland. Sporozoites from the tick bite infect the erythrocytes directly. Trophozoites reproduce within the RBCs by binary fission. Transmitted by the Ixodes tick, Babesia may use virtually any mammal as a host for the infection.
The clinical presentation of babesiosis is characterized by fever, arthralgia, and hemolytic anemia. Risk factors for clinically severe infection include increasing age, immunosuppression, and postsplenectomy or asplenic state.14,15 Transfusion-transmitted Babesiosis has been described, and it is interesting to note that 1 study showed 3% to 8% seropositivity for Babesia in the general population of blood donors.16-19 Although Romanowsky-stained peripheral blood can identify ring forms in parasitized erythrocytes, a babesial infection may also be identified by polymerase chain reaction.20 Because the spleen removes RBCs containing Babesia parasites from the blood, asplenic patients may be at higher risk for severe infection.13 Therefore, splenectomized individuals may be at increased risk for infection presenting as overwhelming sepsis by Babesia.21 Septic shock in asplenic patients and renal failure caused by babesiosis have been documented.22
Therefore, patients who have experienced spontaneous splenic rupture or who are asplenic may suffer life-threatening infections associated with Babesia and may require exchange transfusion and antibiotic therapy.23-25
Although resolution of imaged splenic disruption may obviate the need for splenectomy, this may still represent a prudent course of action in avoiding spontaneous rupture of the spleen.26 The most common indications for a splenectomy include symptomatic splenic abscess, infarct, splenomegaly, severe hypersplenism, prophylaxis for splenic rupture, and neoplastic exclusion.27,28
Clinically, babesiosis varies from mild and self-limiting to life-threatening sepsis with fever, myalgia, anemia, and hepatosplenomegaly. Parasitized erythrocytes lack the deformability needed to transit the splenic sinusoids and are therefore sequestered within the spleen. As a result, the development of subclinical splenomegaly may render the spleen susceptible to spontaneous rupture with relatively minor trauma.
Splenic rupture or asplenic state can be associated with overwhelming babesial sepsis and may be life threatening. Importantly, relative thrombocythemia in postsplenectomy (or asplenic) patients can obscure intraerythrocytic ring forms in peripheral smear, possibly delaying identification of the infection.
The diagnosis of babesiosis is supported identifying trophozoites of Babesia within erythrocytes either in peripheral blood or within erythrocytes in splenic sinusoids. There is no documented extraerythrocytic form except when associated with lysed RBCs. Diagnosis is best accomplished by evaluating Romanowsky-stained peripheral blood smears. Although similar to the intraerythrocytic ring forms of Plasmodium falciparum, those of Babesia are generally smaller and more variable in size with rare extracellular trophozoites and multiple infected erythrocytes. Clinical samples of Babesia may rarely present a tetrad or "Maltese cross" within a single erythrocyte. Definitive diagnosis may require serologic testing, hamster inoculation, or polymerase chain reaction amplification.
A review of the literature failed to show other reported cases of splenic rupture specifically because of a Babesia infection. However, a similar case study reported in 1982 by the Harvard Public School of Health documented a 60-year-old man who was hospitalized with a splenic rupture, given 4 transfusions, and splenectomized a day after admission. Two weeks after the patient's discharge, he was readmitted with shaking, chills, and a temperature of 39°C. Blood films were positive for Babesia microti. However, the Babesia infection had not been identified as the etiological agent of the splenomegaly.
Infections with Babesia may be overwhelming and life threatening in asplenic, elderly, or immunocompromised patients, as these cases also demonstrate and may require prompt antibiotic treatment with atovaquone and azithromycin or with an alternative regimen of clindamycin and quinine. The dosages should be adjusted to the severity of the infection on the presentation. Postsplenectomy patients may generally need higher doses. In addition, a supplemental exchange transfusion may also be considered in severe cases. However, an infectious disease consultation is recommended in all the clinically advanced cases.
In summary, we believe that the relative hypersplenism and associated splenomegaly seen with babesiosis may render the spleen susceptible to spontaneous rupture, possibly after relatively minor trauma. The postsplenectomy thrombocytosis may mask a life-threatening, overwhelming infection. The first 2 cases presented in this article suggest that babesiosis may be included in the differential diagnosis for a patient with fever, arthralgia, and anemia who presents with spontaneous rupture of the spleen. During the peak season of infection, May through September, Babesia should be considered in the differential diagnosis of patients (inparticular, those from areas endemic for Lyme disease, babesiosis, and human granulocytic ehrlichiosis) who exhibit hemolyticanemia, fatigue, thrombocytopenia, and fever.29,30 In the event of spontaneous splenic rupture in a patient with continued fever, anemia, and arthralgia, the postsplenectomy babesial infection should be maintained in the differential diagnosis, especially in light of partially obscuring postsplenectomy thrombocythemia.
The authors thank the editors for their suggestions and guidance in the presentation of this paper.
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