From the Research
Definition and Causes of Drug-induced Thrombotic Microangiopathy (TMA)
- Drug-induced TMA is a condition characterized by microangiopathic haemolytic anaemia, thrombocytopenia, and variable signs of organ damage due to platelet thrombi in the microcirculation 1.
- Many drugs have been reported to cause TMA, including quinine, cyclosporine, tacrolimus, mitomycin-C, and ticlopidine 2, 3, 4, 1.
- The pathophysiological mechanisms of DITMA are heterogeneous and can be classified as immune-mediated (idiosyncratic) and dose-related/toxic 5.
Clinical Features and Diagnosis of DITMA
- The clinical features of DITMA can range from systemic to kidney-limited forms, and may include malignant hypertension, thrombocytopenia, and other signs of organ damage 5.
- Early diagnosis of DITMA is vital, and strict monitoring of renal function, urine and blood abnormalities, and arterial pressure is necessary in patients undergoing therapy with potentially toxic drugs 1.
- The diagnosis of DITMA can be supported by the presence of drug-dependent antibodies reactive with platelets and neutrophils, as well as by renal biopsy and genetic analysis for complement genes 2, 5.
Treatment and Management of DITMA
- The treatment of DITMA typically involves the immediate discontinuation of the offending drug, as well as supportive care and management of any resulting organ damage 2, 1.
- Therapeutic plasma-exchange (TPE), rituximab, and anti-complementary therapy may also be effective in the treatment of DITMA, although the effectiveness of these approaches has yet to be proven in multicentre, randomised clinical studies 5, 1.
- The importance of drug withdrawal and the role of TPE, rituximab, and anti-complementary therapy in the treatment of DITMA have been highlighted in recent literature 5.
Drugs Associated with DITMA
- Quinine is the most commonly implicated drug in DITMA, accounting for 92% of cases in one study 2 and 34 of 104 patient reports with definite evidence in another study 3.
- Other drugs associated with DITMA include cyclosporine, tacrolimus, mitomycin-C, ticlopidine, and gemcitabine, among others 2, 3, 4, 5, 1.
- The list of drugs potentially involved as causative for TMA is rapidly increasing, and physicians should be familiar with the full spectrum of clinical manifestations and pathophysiological mechanisms of DITMA 5.