Acute promyelocytic leukaemia and acquired α‐2‐plasmin inhibitor deficiency: a retrospective look at the use of epsilon‐aminocaproic acid (Amicar) in 30 patients

Abstract

Bleeding diathesis and a hyper-fibrinolytic state often accompany a diagnosis of Acute Promyelocytic Leukaemia (APML). This complication can have grave effects if not successfully treated, with a 10–20% incidence of haemorrhagic death. We hypothesized that α-2-antiplasmin levels would correlate with the risk for bleeding, and that administration of epsilon-aminocaproic acid (EACA) would attenuate that risk. To assess this, we conducted a retrospective chart review analyzing 30 APML patients, 17 of whom were treated with EACA. Thirty patients were treated, 21 with primary induction therapy. Patients with low α-2-antiplasmin levels were treated with a coagulopathy protocol consisting of low-dose heparin, EACA and blood product support. Seventeen patients (57%) developed haemorrhagic complications during their treatment. The presence and grade of haemorrhage appeared to be associated with the α-2-antiplasmin level. There were no grade IV haemorrhages or episodes of haemorrhagic death. One episode of central venous catheter associated thromboembolism and three deaths from infection during chemotherapy were observed. α-2-Antiplasmin levels are a reliable surrogate for fibrinolysis and haemorrhagic risk in patients with APML. Treatment with EACA is a rational way to pharmacologically inhibit fibrinolysis, is associated with a low incidence of severe haemorrhagic events, and appears to be safe with a low risk of thrombosis. Randomized clinical trials further assessing the efficacy and potential toxicity of EACA in inhibiting fibrinolysis in patients with APML are needed.

Inactivation of ADAMTS13 by plasmin as a potential cause of thrombotic thrombocytopenic purpura

“…However, the deficiency in our patient is not congenital but acquired, as it resolved during remission and the patient never presented with bleeding problems [41] prior to this. Acquired α 2 ‐antiplasmin deficiency is usually associated with primary illnesses such as nephrotic syndrome [42], acute promyelocytic leukemia [43] and amyloidosis [44]. These diseases mainly cause α 2 ‐antiplasmin antigen depletion, and were not diagnosed in our patient.…”

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

“…45 In fact, this low level has been shown to be a marker for bleeding events. 72 Many components of the fibrinolytic system have also been found to be increased in microparticles/microvesicles derived from APL promyelocytes as well as NB4 cells. 52,[73][74][75] These are subcellular particles, 0.1 to 1.0 μ in size, consisting of cell membrane vesicles, with increased amounts of tPA, uPA, annexin A2, and PAI-1 as well as tPA-PAI-1 complex and uPA-PAI-1 complex.…”

Characteristics of fibrinolytic disorders in acute promyelocytic leukemia

“…Hemorrhagic events were classified as described in the literature [17]: grade 0 (no hemorrhage), grade I (minor bleeding), grade II (moderate bleeding not requiring a transfusion), grade III (bleeding requiring transfusion), grade IV (catastrophic bleeding requiring major non-elective intervention), and grade V (death).…”