Drug-induced thrombotic microangiopathy: a systematic review of published reports.

Many patients with syndromes of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, have been reported to have a drug-induced etiology, and many different drugs have been suspected as a cause of TMA. We established criteria to assess the strength of evidence for a causal association of a drug with TMA and systematically searched for all published reports of drug-induced TMA. We identified 1569 articles: 604 were retrieved for review, 344 reported evaluable data for 586 individual patients, 43 reported evaluable data on 46 patient groups. Seventy-eight drugs were described; 22 had evidence supporting a definite causal association with TMA. Three drugs accounted for 61 of the 104 patient reports with definite evidence (quinine, 34; cyclosporine, 15; tacrolimus, 12). Twenty additional drugs had evidence supporting a probable association with TMA. These criteria and data can provide support for clinicians evaluating patients with suspected TMA.

Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes.

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.