An Algorithmic Approach to the Diagnosis and Management of the Thrombotic Microangiopathies

No clinical consult raises the heart rate of a transfusion medicine specialist quite like that involving thrombotic microangiopathy (TMA) concerning for thrombotic thrombocytopenic purpura (TTP). The differential diagnosis is complex and challenging, the patients tend to be very ill, and effective treatment requires providing therapy directed at the underlying pathology as quickly as possible. Clinical pathologists are well positioned to provide guidance in these cases since they are usually alerted to all patients in the hospital with suspected TTP and therefore have considerable experience to offer. In contrast, the consulting physician may be somewhat less experienced in formulating a diagnostic and therapeutic plan of care for these patients and might opt for therapeutic plasma exchange (TPE) when in fact a more careful evaluation is merited and other therapies might be more effective. The article by Williams and Marques1 in this issue of the Journal highlights the key role played by the clinical pathologist in the care of patients with TMA, focusing on the important distinction between TTP, hemolytic uremic syndrome (HUS), and atypical uremic syndrome (aHUS) and providing a clear and logical approach to these disorders. TMA should be viewed as a manifestation of diverse pathologies involving either hemostasis (inappropriate platelet activation or thrombin generation) or the endothelium (exposure to Shiga toxin, uncontrolled complement deposition).2 Treatments differ depending on the underlying mechanism of disease. Whereas TPE is an effective treatment for TTP,3,4 eculizumab has emerged as an important new therapy for aHUS,5 providing superior renal survival in comparison to outcomes observed following treatment with TPE alone.6 The understanding that aHUS results from dysregulation of the alternative complement pathway and is associated with inherited mutations in complement regulatory proteins while TTP results from severe deficiency of the ADAMT13 enzyme caused by autoantibodies to this … Corresponding author: Robert S. Makar, MD, PhD, Massachusetts General Hospital Blood Transfusion Service, GRJ-148, 55 Fruit St, Boston, MA 02114; rmakar{at}mgh.harvard.edu.