Acute promyelocytic leukaemia and acquired alpha-2-plasmin inhibitor deficiency: a retrospective look at the use of epsilon-aminocaproic acid (Amicar) in 30 patients.
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 alpha-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 alpha-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 alpha-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. alpha-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.
Wassenaar
T
T
University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. tr.wassenaar@hosp.wisc.edu
Black
J
J
Kahl
B
B
Schwartz
B
B
Longo
W
W
Mosher
D
D
Williams
E
E
D015119:Aminocaproic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000979:alpha-2-Antiplasmin / Q000172:deficiency*
D000933:Antifibrinolytic Agents; D000979:alpha-2-Antiplasmin; D006493:Heparin; D015119:Aminocaproic Acid