Off-label drug use refers to drug use beyond the specifications authorized for marketing [J Med Case Rep. 2014 Dec;8(1):303]. Eltrombopag is a thrombopoietin receptor agonist that has been used in treating thrombocytopenia due to chronic liver disease (CLD) as an off-label medication. Treatment of thrombocytopenia in patients with CLD constitute a real dilemma as the options are limited and some of them are invasive. However, thrombopoietin receptor agonist has been increasingly used for this purpose. Here we report a 34-year-old woman who has been diagnosed with CLD due to autoimmune hepatitis 20 years ago. Her condition was complicated with portal vein thrombosis, chronic thrombocytopenia, and variceal hemorrhage, and she has been listed as a candidate for liver transplantation. Given her high risk of bleeding, we started her on low dose of eltrombopag (25 mg daily) in order to maintain a platelet level of ≥50 × 10 3 /µL. However, 1 year after initiation of the therapy, she developed left lower limb deep vein thrombosis.

Thrombolysis is an established therapeutic modality for patients with high-risk (and some selected intermediate-risk) pulmonary embolism (PE) with hemodynamic instability. Physicians sometimes experience cases where both a high-risk PE and thrombocytopenia coexist. Although thrombocytopenia of <  100 × 10 3 /mm 3 is considered a contraindication in patients with ischemic stroke, the safety and outcomes of thrombolysis in patients with acute PE and thrombocytopenia are unknown. This systemic review aimed to pool data on the safety and outcomes of thrombolysis use in patients with PE and platelet count less than 150 × 10 3 /mm 3 . Patients’ demographics, clinical characteristics, management, type of thrombolytic therapy, and outcomes were extracted and analyzed. Of 283 articles identified through the systematic search, 11 case reports fulfilled the inclusion criteria. The mean age of the patients was 52.27 years, and 54.5% were women. The median platelet level before thrombolysis was 65.50 × 10 3 /mm 3 . Before thrombolysis was initiated, the lowest and highest platelet levels were 29 × 10 3 /mm 3 and 105 × 10 3 /mm 3 , respectively. Alteplase was used in 10 patients and urokinase in one patient. One patient who had a massive PE died of aspiration pneumonia. Interestingly, no thrombocytopenia-related complications were reported. This systematic review highlights the potential benefits and safety of thrombolysis in patients with acute PE in the context of thrombocytopenia. Nevertheless, data available in the literature concerning this topic are scarce and limited to case reports. More extensive studies on the use of thrombolysis in patients with PE and thrombocytopenia are desperately needed. Systematic review registration: The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42021286415.