Plasma coagulation factor XIII (pFXIII) strengthens and stabilizes thrombus mainly by linking fibrin molecules and recruiting α2 antiplasminase. Deficiency of this factor causes bleeding characterized by "late onset" and spontaneous abortion. According to the pathogenesis, it can be divided into two types: congenital and acquired. Acquired FXIII deficiency, which is rare and not easy to identify early, can be caused by an acquired factor inhibitor or by a disease that results in reduced FXIII synthesis or increased consumption. The most common clinical manifestation is soft tissue hematoma, which occurs in more than 70% of patients, and central nervous system bleeding is also relatively common. With the increasing number of patients with acquired FXIII deficiency reported, attention has been gradually drawn, but it is still easy to miss and delay diagnosis. This paper reviews the research progress on the mechanism, diagnosis and treatment of acquired FXIII deficiency.