Thrombotic microangiopathy (TMA) in adult patients with solid tumors: a challenging complication in the era of emerging anticancer therapies

Abstract

Thrombotic microangiopathy (TMA) is a syndrome that encompasses a group of disorders defined by the presence of endothelial damage leading to abnormal activation of coagulation, microangiopathic hemolytic anemia and thrombocytopenia, occlusive (micro)vascular dysfunction, and organ damage. TMA may occur in patients with malignancy as a manifestation of cancer-related coagulopathy itself or tumor-induced TMA (Ti-TMA) as a paraneoplastic uncommon manifestation of Trousseau syndrome. TMA can also be triggered by other overlapping conditions such as infections or more frequently as an adverse effect of anticancer drugs (drug-induced TMA or Di-TMA) due to direct dose-dependent toxicity or a drug-dependent antibody reaction. The clinical spectrum of TMA may vary widely from asymptomatic abnormal laboratory tests to acute severe potentially life-threatening forms due to massive microvascular occlusion. While TMA is a rare condition, its incidence may progressively increase within the context of the great development of anticancer drugs and the emerging scenarios in supportive care in cancer. The objective of the present narrative review is to provide a general perspective of the main causes, the key work-up clues that allow clinicians to diagnose and manage TMA in patients with solid tumors who develop anemia and thrombocytopenia due to frequent overlapping causes.

Bevacizumab-induced immune thrombocytopenia in an ovarian cancer patient with mixed connective tissue disease: case report and literature review

“…Possible causes of thrombocytopenia in the present patient included cancer-therapy-related thrombocytopenia, exacerbation of MCTD, primary immune thrombocytopenia (ITP), and PTCP. Thrombocytopenia maybe caused by cancer directly with tumor involvement of bone marrow and spleen, which occurred most often in patients with known metastatic cancer and exacerbation of the disease ( 6 , 7 ). It was ruled out that the thrombocytopenia was directly caused by the ovarian cancer or cancer-associated factors with unremarkable biomarkers and MRI results.…”

Thrombotic microangiopathy associated with anticancer and immune system targeting drugs: New insights from real‐world data using the WHO pharmacovigilance database

“…As it is classically accepted that the development of secondary TMA results from the encounter of multiple triggers (“hits”) [6], it may be difficult to determine whether a drug can be considered causal, except in rare situations with strong chronological arguments (recurrence on rechallenge) or serological documentation of the pathogenic role of the drug. This is particularly the case for immune system targeting drugs/anticancer drugs, where the indication (i.e., solid cancer and autoimmune diseases) may be intrinsically associated with a risk of TMA [7], and in situations of co‐prescription of several potentially inducing drugs (e.g., calcineurin inhibitors with mammalian target of rapamycin inhibitors). For these drugs, the use of population‐based approaches may be particularly important to assess the potential association between drug exposure and TMA.…”

“…A recent study indicated that 27% of patients with TMA were treated with drugs known to be able to trigger TMA development [6]. Drug‐associated TMA is becoming a real concern in the field of oncology [7]. Indeed, the worldwide development of new biotherapies has revolutionized many fields, including oncology, immunology, hematology, and transplantation.…”

Surufatinib-induced renal thrombotic microangiopathy: first case report and review of literature

“…TMAs are a group of disorders characterized by microangiopathic haemolytic anaemia and thrombocytopenia leading to microvascular occlusion and different levels of end-organ injury [ 21 ]. During the last few decades, the incidence of cancer drug-induced TMA has been reported to account for >15% of all TMAs, primarily due to the introduction of VEGF inhibitors [ 22 ].…”