Tyrosine Kinase Inhibitor–Induced Pulmonary Arterial Hypertension

The treatment of the malignant hematological diseases has been revolutionized by the use of tyrosine kinase inhibitors (TKI): for example, imatinib in patients with chronic myeloid leukemia. Dasatinib, a second-generation TKI, has been reported to induce severe pulmonary arterial hypertension (PAH). The mechanism of PAH development is presumed to be endothelial cell toxicity through the production of mitochondrial reactive oxygen species. There are other TKIs that are reported to cause PAH, such as: ponatinib, bosutinib, lapatinib, and lorlatinib. The management of PAH due to TKIs primarily involves stopping the TKI treatment, which can lead to clinical and hemodynamic normalization. A third of the patients who develop PAH can have persistent symptoms of dyspnea and right heart failure even after the interruption of the TKIs. For these patients, use of specific PAH treatment is indicated along with close follow-up. In rare cases, TKI-induced PAH can be fatal. Thus, early screening for PAH diagnosis and pr...