A Case of Severe Thrombotic Thrombocytopenic Purpura With Concomitant Legionella Pneumonia: Review of Pathogenesis and Treatment

Abstract

Thrombotic thrombocytopenia purpura (TTP) is a severe multisystem disorder characterized by fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, and impaired renal function. Platelet counts are usually diminished, whereas the bone marrow shows a large number of megakaryocytes indicating peripheral destruction and consumption of platelets. Coagulation studies in patients with TTP are normal or slightly elevated, which helps differentiate this entity from disseminated intravascular coagulation. The peripheral smear shows an abundance of schistocytes, reticulocytes, and, at times, nucleated red blood cells. Serum lactate dehydrogenase and indirect bilirubin are elevated as a result of mechanical destruction of red blood cells. Legionella pneumophila has been identified as a relatively common cause of both community-acquired and hospital-acquired pneumonia. An association between Legionella and TTP has only been cited once in the literature. Here we present a case of severe TTP with concurrent Legionella infection. Our patient presented with the classic clinical findings of TTP and an ADAMTS13 level of less than 5% associated with an inhibitor. After a 3-week treatment course with plasma exchange, steroids, and antibiotics, he had complete clinical recovery and his ADAMTS13 level increased to greater than 75%.

Humoral immune response to ADAMTS13 in acquired thrombotic thrombocytopenic purpura

“…3) [57]. A large number of case reports have suggested a role of viral and bacterial infections in acquired TTP, which developed following or during infections with influenza A [61], HIV [62], parvovirus [63], Helicobacter pylori [64], hepatitis C [65], brucella [66] or legionella [67]. The large variety of microbial agents implicated in the onset of autoimmune TTP suggests that triggering of the innate immune system plays a role at the onset and perhaps also in the recurrence of acquired TTP by lowering the threshold for activation of ADAMTS13‐specific T cells that have escaped negative selection in the thymus (see Fig.…”

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation:an Update

“…Cases of TMA associated with severe ADAMTS13 deficiency and inhibitory anti-ADAMTS13 IgG have been reported with influenza A,79 legionella pneumonia80 and brucellosis 81…”

“…ADAMTS13 levels are not generally decreased with infections such as HIV, suggesting an alternative mechanism for TMA in these patients. 77 , 78 Cases of TMA associated with severe ADAMTS13 deficiency and inhibitory anti-ADAMTS13 IgG have been reported with influenza A, 79 legionella pneumonia 80 and brucellosis. 81 …”

Pulmonary involvement in patients with thrombotic thrombocytopenic purpura

“…Our literature search criteria identified 144 articles; 21 met our selection criteria of presenting individual patient data ; Following review, 14 of the 21 articles were excluded from our analysis. One article was excluded because TMA was attributed to HIV‐associated nephropathy and malignant hypertension .…”

“…Five articles were excluded because the pulmonary abnormalities were attributed to adverse reactions to plasma ; three were reports of transfusion‐related acute lung injury (TRALI) . Two articles were excluded because pulmonary abnormalities were attributed to aspiration pneumonia and Legionella pneumonia . Four articles were excluded because no lung involvement was described .…”