title: Relationship of thrombin generation to peripheral blast cell count in patients with acute myeloblastic leukemia (AML).
abstract: Disseminated intravascular coagulation (DIC) commonly occurs in patients with acute promyelocytic leukemia (APL, FAB-M3) but may also be seen in other subtypes of AML. DIC in patients with AML has been attributed to procoagulants released from granular fractions of leukemic blast cells. The present study was designed (i) to evaluate thrombin activity in patients with AML by measuring plasma levels of fibrinopeptide A (FPA) prior to chemotherapy, and (ii) to examine whether a relationship between FPA levels and the number of peripheral blast cells exists. Plasma levels of FPA were determined using a commercially available RIA kit. To remove fibrinogen and the majority of elastase-induced fibrinopeptides (A alpha 1-21) known to crossreact with the FPA (A alpha 1-16) antiserum used in this assay, plasma samples were treated with bentonite prior to further processing. The study was conducted on 5 patients with APL and on 22 patients with other subtypes of AML. Peripheral blast cell counts at initial diagnosis ranged from 2100 to 56,000/microliters in patients with APL and from 1900 to 151,000/microliters in patients with other AML subtypes. The mean (+/- 1 SEM) pretreatment plasma level of FPA was significantly higher (p = 0.021) in the 5 patients with APL (38.2 +/- 8.3 ng/ml) than in patients with other AML subtypes (8.1 +/- 0.7 ng/ml). No relationship was found between peripheral blast cell counts and the corresponding FPA levels in the total group of 27 patients. However, when considering the 5 patients with APL separately, a significant correlation was observed between peripheral blast cell number and FPA plasma levels (r = 0.88, p = 0.050). This study confirms that thrombin generation is considerably greater in patients with acute promyelocytic leukemia than in other subtypes of AML. We conclude that type and number of circulating blast cells and their related capacity to express procoagulant activities appear to be major determinants of excessive fibrinogen degradation in AML.
authors.affiliation: Department of Internal Medicine, Heinrich Heine University, Düsseldorf, F.R.G.
authors.forename: R E
authors.initials: RE
authors.lastname: Scharf
authors.forename: W
authors.initials: W
authors.lastname: Schneider
mesh_terms: D001773:Blood Cells; D002452:Cell Count; D005344:Fibrinopeptide A / Q000032:analysis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D005344:Fibrinopeptide A; D013917:Thrombin