Case Presentation: We describe a case of TTP that developed subsequent to diagnosis and empiric treatment of AML. The patient was a 71 year old male with a past medical history of hypertension, hyperlipidemia, and stage III CKD who presented with a three-week history of fatigue, fevers, chills, and dyspnea. He was found to have a hemoglobin of 6.8, platelets of 18,000 and white blood cell count of 27,200 with 33% peripheral blasts. A bone marrow biopsy was obtained, revealing 78% myeloblasts. Routine cytogenetics revealed aneuploidy with very complex karyotype, and a somatic TP53 mutation was detected on next generation sequencing confirming a diagnosis of AML.On hospital day 9, the patient developed worsening acute kidney injury and pancytopenia. Peripheral smear showed 3-4 schistocytes per high power field. Lactate dehydrogenase (LDH) and haptoglobin levels were elevated. The patient’s ADAMTS13 activity resulted three days after collection at 10%. ADAMTS13 inhibitor was present with Bethesda unit of 1.3, consistent with a diagnosis of TTP. Plasma exchange pheresis (PLEX) was begun immediately. ADAMTS13 levels were checked every other day for a goal of greater than 15% activity. The patient received a total of 15 days of PLEX.The patient’s mental status subsequently worsened, and he developed candidemia complicated by acute liver failure from treatment with systemic antifungals. Given poor prognosis, the patient was transitioned to comfort measures and was pronounced deceased a day later.
Discussion: The natural clinical course of TTP varies widely, but should be suspected in all patients who present with hemolysis and thrombocytopenia. The classic triad of fever, altered mental status, and kidney injury is present in only 7% of patients by some estimates.An ADAMTS13 level less than 10% is the most conclusive diagnostic test for TTP. However, at many institutions it can take several days to weeks to result. The PLASMIC score helps stratify patients into low, intermediate, or high risk of TTP. It takes into account kidney function, evidence ofhemolysis and platelet count, among other factors. Despite our patient’s low PLASMIC score, his final diagnosis was still consistent with TTP.After PLEX is begun in the treatment of TTP, daily PLEX is continued until a platelet count of 150,000 has been reached for two consecutive days. However, because of malignancy, this could not be used as a reliable marker of response. A study of 57 patients by George et. al found that the relative risk of relapse in patients who had ADAMTS13 activity less than 15% was 4.01(p=.031), when compared with relapse rates of patients who had ADAMTS13 activity greater than 15%. Although relapses of TTP may occur with normal ADAMTS13 activity, we used this marker to guide PLEX duration.
Conclusions: Our case demonstrates the difficulty in diagnosing TTP in patients with hematologic malignancies. A high index of suspicion must be maintained in these patients, and PLASMIC score interpreted with caution. Early ADAMTS13 activity collection can help make a timely diagnosis and should not be delayed. ADAMTS13 activity can be monitored for response to PLEX in patients who are persistently thrombocytopenic, however, activity does not always correlate with TTP remission. Finally, we describe, to our knowledge, the first case of acquired immune TTP diagnosis in the setting of newly diagnosed AML. While the trigger for our patient’s episode of TTP remains unclear, outcomes for patients with multiple hematologic aberrancies is demonstrated to be poor.
