The first case report describes a man who fractured his arm three times, then found out his entire humerus had disappeared.

Firstly, why examine the role of thromboembolic disease in APL when serious bleeding is essentially universal? Thromboembolic episodes are more common than may be appreciated in this setting. The 16% incidence of thromboembolic events observed by Rodriguez-Viega and co-workers is higher than the 12% found in patients with acute myeloid leukemia.⁵ Furthermore, the major cause of treatment failure in APL is early death and the development of clotting is associated with early death. Early death in APL occurs most frequently during the first 24–48 hours after presentation. Understandably, very few, if any, of such patients are enrolled on clinical trials. Enrollment on a trial would facilitate further insights into thromboembolic events and may pave the way for prevention and therapeutic intervention.

Secondly, why are patients with APL predisposed to develop thrombosis? After all, the disease is infamous for its life-threatening and potentially catastrophic bleeding. This prominent characteristic was recognized by Dr. Leif Hillstad, who is credited with the first description of APL as a distinct clinical entity in 1957.⁶ Acute promyelocytic leukemia cells are associated with the release of plasminogen activator inhibitor-1, tissue factor, and TNFα. These proteins, together with a decrease in thrombomodulin which functions as an anticoagulant by binding to thrombin, favor the balance towards thromboembolic events⁷ (Figure 1). Alternatively, with the generation of annexin II, plasminogen activators, and podoplanin, a transmembrane protein which interacts with cell lectin superfamily 2 (CLEC-2) on platelets to induce platelet aggregation and adhesion to lymphatic vessels,⁸ bleeding is much more commonly present. Furthermore, direct proteolysis of fibrinogen and von Willebrand factor contributes to bleeding. This compilation of processes explains why some patients with APL have bleeding while others have thromboembolic episodes and some have both depending on the balance of procoagulant and anticoagulant proteins. However, bleeding, usually clinically manifested by large ecchymoses on the trunk and extremities, is the major hallmark of the disease.

Finally, how can thromboembolic events in APL be prevented? The most important thing is to maintain a high level of suspicion. The report by Rodriguez-Veiga and co-workers reminds us to be vigilant for the possibility of thromboembolic events in patients with APL. The risk of thrombosis was 1.4% among low-risk patients (presenting WBC 40×10⁹/L), 4.9% for intermediate-risk patients (WBC 10×10⁹/L and platelet count 10×10⁹/L). In contemporary practice, low-and intermediate-risk groups are combined since outcomes among these patients proved to be similar.

An early clinical study shows that a new oral drug is safe and well tolerated in patients with chronic heart failure. The study, led by researchers at Karolinska Institutet, has been published in The Lancet.

Heart failure with reduced pumping capacity means that the heart struggles to pump blood effectively around the body. Despite current treatments, many patients’ conditions worsen over time, and existing drugs that strengthen the heart’s contractions can cause serious side effects, such as heart rhythm disturbances and effects on blood pressure.

In the study, researchers investigated a new drug, AC01, which targets the body’s ghrelin receptor. Ghrelin is a hormone that influences metabolism and growth hormone release, and its receptor is also found in heart muscle. AC01 is intended to strengthen the heart’s pumping ability through a different biological mechanism from traditional heart-stimulating drugs, thereby reducing the risk of side effects.

Research led by the University of Cambridge Loke Center for Trophoblast Research has shown that a genome-editing technique can be used to alter a single gene in human embryonic cells, enabling the study of very early human development in unparalleled detail. The study is published in the journal Nature.