Members of the Mayo Clinic in Rochester, MN, have provided guidelines for the creation of evidence-based clinical pathways for thrombotic microangiopathies (TMAs).
TMAs are a diverse set of disorders sharing a similar presentation, typically microangiopathic hemolytic anemia and thrombocytopenia. In some cases, these conditions can also lead to end-organ damage, such as renal abnormalities and neurologic symptoms. Additionally, difficulties associated with the identification of TMAs can cause problems among treating physicians, impatience with therapeutic plans, and the inappropriate use of treatment, all of which cause significant cost problems for patients and systems.
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To assist practicing physicians, the Mayo Clinic formed the Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) group to develop rational, evidence-based pathways for TMA. They published their recommendations for the treatment of different TMA presentations and follow-up in Mayo Clinic Proceedings.
The CAP-TMA, a multidisciplinary team of physicians and scientists with expertise in the fields of hematology, immunology, laboratory medicine, nephrology, pathology, transfusion medicine, and transplantation, began meeting monthly in September 2014. Their goal was to provide a uniform and practical approach to the diagnosis and management of TMA on the basis of consensus recommendations backed by evidence in literature.
In January 2015, their pathways were distributed to hematology and nephrology clinicians at the Mayo Clinic for use and to provide feedback. Nine chronological pathways were created in all, each addressing a different facet or presentation of TMA. In the first pathway, the authors recommend that, once a diagnosis of TMA is considered probable on the basis of clinical grounds and laboratory findings, level 1 tests should be used in all cases during this early stage of evaluation. In particular, they state that Shiga toxin-induced TMA should be treated with the best supportive care. Pathway 2 focuses on thrombotic thrombocytopenic purpura (TTP), which recent studies have shown results from an immune inhibitor of ADAMTS13. Plasma infusion can assist in managing TTP, although clinicians should also be aware that many patients who receive this treatment develop volume overload.
For hyperhomocysteinemia, recommendations in Pathway 3 advise that a combination of hydroxocobalamin, betaine, and folic acid be used. Pathway 4 addresses cases in which TTP and Shiga toxin-induced TMA have both been ruled out. In such instances, clinicians should begin evaluating for precipitating factors of TMA. Because drug-induced TMA is the most common and best-studied secondary cause, offending drugs should be discontinued. When TTP and Shiga toxin-induced TMA are excluded and there are no obvious precipitating factors, level 2 tests for complement functional assay and mutational analysis are recommended in Pathway 5. In the case of renal transplantation, which can present without any systemic manifestations in 40% of patients, Pathway 6 calls for immediate evaluation for antibody-mediated graft rejection and the investigation of any contributing causes.
Pathway 7 for stem-cell transplantation has different recommendations depending on whether pediatric or adult patients are being treated, but both call for the management of secondary causes and the use of therapeutic plasma exchange if there is no evidence of secondary causes. In patients with complement mutations (Pathway 8), developers advise that patients discontinue therapeutic plasma exchange in those with CD46 mutation but continue it in patients with other mutations, unless the disease becomes refractory or dependency to the treatment develops. Finally, though information regarding the treatment of patients with plasminogen- or DGKE-associated TMA (Pathway 9) is limited, the best available data support the use of plasma infusion or therapeutic plasma exchange if volume cannot be tolerated.
Authors of the report, led by Ronald S Go, MD, Mayo Clinic, hope that the pathways will provide guidance for clinicians treating patients with the possibility of TMAs. However, they also note that the development of new diagnostic tools and treatment options could change best treatment tactics. For this reason, their recommendations will be subject to modification as new information and experience with the pathways in clinical use become available.—Sean McGuire
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