title: Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes.
abstract: Evaluation and management of patients with suspected thrombotic thrombocytopenic purpura (TTP) continue to be a critical challenge for hematologists. The diagnostic criteria are not precise, often causing uncertainty about whether it is appropriate to initiate plasma exchange (PEX), the essential treatment for TTP. Initiation of PEX remains a clinical decision; severe ADAMTS13 (< 10% activity) deficiency alone is neither sufficiently sensitive nor specific for the diagnosis of TTP. However, patients who do have severe acquired ADAMTS13 deficiency define the characteristic clinical features of TTP, the response to treatment, and the long-term outcomes. Patients with severe acquired ADAMTS13 deficiency are predominantly young women and the relative frequency of blacks is increased. Patients may present with only microangiopathic hemolytic anemia and thrombocytopenia, neurologic and renal abnormalities are often not present, fever rarely occurs; the complete "pentad" of these clinical features almost never occurs in current practice. Response to PEX is typically rapid but may not be sustained when PEX is stopped. Use of corticosteroids and rituximab has decreased the number of PEX treatments required to achieve a remission and has resulted in fewer PEX-related major complications. Relapse (in approximately 40% of patients) may be the most apparent risk after recovery, but long-term health outcomes are also very important. Minor cognitive abnormalities are common, the frequency of depression is increased, and the frequency of hypertension is increased. Careful long-term follow-up of TTP patients is essential.
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, Department of Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126-0901, USA. james-george@ouhsc.edu
authors.forename: James N
authors.initials: JN
authors.lastname: George
authors.forename: Zayd L
authors.initials: ZL
authors.lastname: Al-Nouri
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006405:Hematology / Q000379:methods*; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis* / Q000628:therapy*; D006801:Humans; D006973:Hypertension / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009825:Oklahoma; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis* / Q000628:therapy*; D012008:Recurrence; D012042:Registries; D012306:Risk; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human