Case Presentation:

A 48‐year‐old man was hospitalized with fatigue, dyspnea, mild confusion, and faint lower extremity petechiae that followed an upper respiratory infection. At admission, his blood pressure was normal, and his temperature was 100.8°F. Laboratory data were notable for a platelet count of 7000/μL, hemoglobin of 6.8 g %, reticulocytes of 17%, D‐dimer < 40, creatinine of 1.8 mg/dL, and lactate dehydrogenase of 1800 U/L. Fibrin split products were within normal range. A peripheral smear revealed significant (3+) schistocytosis. Direct Coombs was repeatedly positive for both IgG and C3d. The eluate test was reactive in all cell lines. Prothrombin time (PT) and partial thromboplastin time (PTT) were 12 and 24 seconds, respectively. HIV antibody and antinuclear antibodies (ANA) were negative. Blood and urine cultures were repeatedly negative. TTP was diagnosed, and the patient was started on plasmapheresis. In view of a positive direct Coombs test, corticosteroid therapy was also started. However, he deteriorated with worsening renal function, delirium, and respiratory distress. Unfortunately, the patient then succumbed to acute respiratory distress syndrome despite aggressive treatment. The autopsy revealed numerous microthrombi in the heart and kidneys, consistent with TTP There was no evidence of large‐vessel occlusion.


Microangiopathic hemolysis with a negative Coombs test is the hallmark of thrombotic thrombocytopenic purpura (TTP). TTP associated with a positive direct Coombs test is a rare entity. Very few cases of TTP with a positive Coombs test have been reported, but most of them were associated with systemic lupus erythematosus. TTP with a positive direct Coombs in the absence of collagen vascular disease is extremely rare, A false‐positive direct Coombs test is possible with drugs such as penicillin, cephalosporins, methyldopa, and intravenous gamma globulin. Our patient was not on any of these drugs. A positive direct Coombs can also occur with alloimmunization. However, the fact that our patient has no history of blood transfusion in the past 3 months and that the elution was reactive in all cell lines strongly indicate the presence of an autoantibody. In our patient, the diagnosis of TTP was confirmed by numerous schistocytes on the peripheral smear as well as by autopsy findings of widespread microthrombi. Although a strongly positive Coombs may suggest immune hemolysis, one should also look for and exclude other causes of hemolysis because there is a possibility of coexisting TTP, as was true in our patient. Early diagnosis of TTP by demonstration of schistocytes and aggressive treatment by plasmapheresis are of paramount importance to improve outcome.


We report this case to illustrate that a positive direct Coombs test should not deter hospitalists from pursuing a further workup for TTP. Such a delay in diagnosis of TTP can lead to increased mortality

Author Disclosure:

K. Koduru, none; T. Hamieh, none; P. Koduru, none; N.Abd‐Alnoor, none; M. Maroules, none.