None of the above: thrombotic microangiopathy beyond TTP and HUS

Abstract

Acquired thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are appropriately at the top of a clinician’s differential when a patient presents with a clinical picture consistent with an acute thrombotic microangiopathy (TMA). However, there are several additional diagnoses that should be considered in patients presenting with an acute TMA, especially in patients with nondeficient ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity (>10%). An increased awareness of drug-induced TMA is also essential because the key to their diagnosis more often is an appropriately detailed medical history to inquire about potential exposures. Widespread inflammation and endothelial damage are central in the pathogenesis of the TMA, with the treatment directed at the underlying disease if possible. TMA presentations in the critically ill, drug-induced TMA, cancer-associated TMA, and hematopoietic transplant–associated TMA (TA-TMA) and their specific treatment, where applicable, will be discussed in this manuscript. A complete assessment of all the potential etiologies for the TMA findings including acquired TTP will allow for a more accurate diagnosis and prevent prolonged or inappropriate treatment with plasma exchange therapy when it is less likely to be successful.

Sudden elevation of plasma D‐dimer levels induced by the combination therapy of dabrafenib and trametinib: Report of two cases

“…For patients with toxic-mediated DI-TMA, it is possible to re-challenge with a lower dose. 10 In our cases, although patients were treated with CombiDT only for a few weeks, both mechanisms are possible. Although hemolytic anemia was not evident, the laboratory test revealed thrombocytopenia with elevation of D-dimer, which improved within several days after the cessation of combination therapy.…”

“…Although the mechanism is not fully understood, decreased expression of vascular endothelial growth factor seems to play a role . Toxicity‐mediated DI‐TMA may occur acutely or after weeks or months of drug administration . The drugs that can cause dose‐dependent toxic‐mediated DI‐TMA primarily represent three classes of drugs: (i) chemotherapeutic agents (e.g.…”

“…After stopping the drug, hematological improvement could usually be seen within the next several days, whereas improvement of renal function may take longer and patients may not completely recover. For patients with toxic‐mediated DI‐TMA, it is possible to re‐challenge with a lower dose . In our cases, although patients were treated with CombiDT only for a few weeks, both mechanisms are possible.…”

“…9 Toxicity-mediated DI-TMA may occur acutely or after weeks or months of drug administration. 10 The drugs that can cause dose-dependent toxicmediated DI-TMA primarily represent three classes of drugs: (i) chemotherapeutic agents (e.g. gemcitabine and mitomycin); (ii) immunosuppressive agents (e.g.…”

Drug Induced Thrombotic Microangiopathy Caused by Levofloxacin

“…By day 9 of levofl oxacin, haemoglobin was 72 g/L and platelet count was 52 x 10 9 /L. Coagulation profi le was normal 1 Specialty Trainee, 2 (Table 1).…”