How I treat microangiopathic hemolytic anemia in patients with cancer

Abstract

Microangiopathic hemolytic anemia (MAHA) in patients with cancer requires urgent diagnosis and treatment. MAHA associated with thrombocytopenia, suggests a thrombotic microangiopathy (TMA), where there is thrombus formation affecting small or larger vessels. It may be directly related to the underlying malignancy (either the initial presentation or with progressive disease); to its treatment or it may be a separate incidental diagnosis. Although less common, it is vital to differentiate incidental thrombotic thrombocytopenia purpura (TTP) or atypical haemolytic uraemic syndrome (aHUS) in cancer patients presenting with a TMA as quickly as possible, as they have different treatment strategies, and prompt initiation of treatment has a critical impact on outcome. In the oncology patient, widespread microvascular metastases or extensive bone marrow involvement can cause MAHA and thrombocytopenia. A disseminated intravascular coagulation (DIC) picture may be precipitated by sepsis or driven by the cancer itself. Cancer therapies may cause a TMA either by dose-dependent toxicity, or an idiosyncratic immune-mediated reaction after development of drug-dependent antibodies. Many of the causes of TMA seen in the oncology patient do not respond to plasma exchange and, where feasible, treatment of the underlying malignancy is important in controlling both cancer-TMA and DIC driven by the disease. The potential for drug-induced TMA should be considered and any putative causal agent stopped. We will discuss the differential diagnosis and treatment of MAHA in patients with cancer using clinical cases to highlight management principles.

Immune Checkpoint Inhibitor-Associated Thrombotic Thrombocytopenic Purpura in a Patient With Metastatic Non-Small-Cell Lung Cancer

“…Thrombotic microangiopathy (TMA) is defined as microangiopathic hemolytic anemia (MAHA) with thrombocytopenia and end-organ damage due to the formation of microvascular thrombi. TMA subtypes include disseminated intravascular coagulation, atypical hemolytic uremic syndrome, cancer-related TMA (CR-TMA), and TTP [ 11 , 12 ]. In this case, a 61-year-old male receiving treatment with chemoimmunotherapy followed by pembrolizumab maintenance therapy for advanced NSCLC with metastasis to the rib and spine presented with bleeding symptoms, anemia, and thrombocytopenia.…”

“…Thrombotic thrombocytopenic purpura is often diagnosed by severe thrombocytopenia, reticulocytosis, elevated LDH levels, elevated indirect bilirubin, low or absent haptoglobin levels, and very low ADAMTS13 activity [ 13 ]. One validated scoring tool to aid in clinical judgment, particularly at sites with available ADAMTS13 testing, is the PLASMIC score, which gives a point for each of the following: platelet count <30 × 109/L, hemolysis, no active cancer within the past year, no history of solid organ transplant (SOT) or blood and marrow stem cell transplant (BMT), MCV < 90 fL, INR < 1.5, and serum creatinine < 2.0 mg/dL [ 11 ]. Therefore, PLASMIC scoring and specialized testing with ADAMTS13 activity and inhibitor can be used to differentiate a diagnosis of TTP, from CR-TMA clinically.…”

“…Frontline therapy for aTTP in the acute setting involves urgent total plasma exchange (TPE) repeated over multiple sessions combined with glucocorticoids, often starting with intravenous methylprednisolone before transitioning to oral prednisone. Drug-induced TTP is managed by immediate cessation of the causative agent along with the standard of care therapy for aTTP [ 11 ]. However, in the case of ICIs, which tend to have delayed onset of effect and irAEs, it is unclear how long the effect could continue after cessation of the drug.…”

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

“…TMA has been associated with many drugs, although definitive causality has only been established in relatively few [ 23 – 25 ]. Drug-mediated TMA with endothelial damage leading to platelet aggregation and microthrombi predominantly in glomerular capillaries and arterioles occurs with cumulative renal damage by two main mechanisms:…”

Challenges and Advances in Managing Thrombocytopenic Cancer Patients

“…For example, patients with hematological malignancies and those receiving carboplatin or oxaliplatin based chemotherapy regimens, have a higher risk of severe thrombocytopenia. Anticancer drugs can cause thrombocytopenia via various mechanisms [2][3][4][5][6][7][8][9][10][11][12][13][14][15], as previously reviewed [1] and as shown in Figure 1. While pancytopenia due to general bone marrow suppression is most common, some antineoplastic drugs, such as proteosome inhibitors used primarily in multiple myeloma, can cause isolated thrombocytopenia.…”