New thrombopoietin receptor agonists (TPO-RA) eltrombopag and romiplostin were initially used for refractory immune thrombocytopaenic purpura, but more recently reported experience shows that they may also be applied to patients with thrombocytopaenia secondary to hepatitis C virus (HCV)-related chronic liver disease (CLD) in certain clinical situations; in haemophilic patients these drugs are always part of a therapeutic approach involving other haemostatic resources required to cover the joint congenital and acquired bleeding diathesis found in these patients. Platelet count elevation before invasive procedures or surgery or prior to and during antiviral therapy involving interferon are the main clinical applications of these drugs; they might also be useful in cases with advanced CLD and severe thrombocytopaenia in order to prevent recurrent bleeding episodes (namely articular and muscular in haemophilic individuals) or reduce bleeding risk in patients with multiple haemorrhagic risk factors. Long-term prophylactic treatment with factor concentrates in such cases is mandatory. There have been some reports of portal or splanchnic thromboses in patients on TPO-RA with CLD, especially in cases undergoing invasive procedures who reach platelet counts at least 200 × 109/l and often with additional risk factors for thrombosis. For this reason, and although haemophilic patients have an important protection against thrombosis, platelet counts should ideally be maintained between 50 and 100 × 109/l with dose adjustments carried out as required and initial doses of eltrombopag in patients with moderate or severe CLD, especially in prolonged treatments, should be reduced to 25 mg once daily. These new drugs can be a useful adjuvant tool in patients with thrombocytopaenia secondary to CLD.