fibrinopeptide-b and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Proteolysis of coagulation factors and inhibitors resulting in haemorrhage can be mediated by elastase. Indirect signs of this are elevated levels of elastase complexed to its inhibitor in plasma, alpha 1-antitrypsin (E alpha 1-AT). We have measured intracellular elastase activity in leukaemic cells from 60 patients with acute leukaemia. Elastase activity was detected in 92% of the patients with acute nonlymphoblastic leukaemia (ANL), no activity was found in the patients with acute lymphoblastic leukaemia (ALL). High levels were found in cells from patients with promyelocytic leukaemia. Moderate to high total circulating blast elastase activity was measured in 70% of the ANL patients with haemorrhage compared with 36% of the patients without bleeding complications (p < 0.05). The available intracellular elastase activity was correlated to the level of E alpha 1-AT (rs = 0.42, p < 0.01) but not to the elastase specific split product of fibrinogen, B beta 30-43. In complete remission the levels of E alpha 1-AT were normalized. Intracellular elastase activity might be a useful supplement to differentiate ANL and ALL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Biomarkers, Tumor; DNA; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide B; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Pancreatic Elastase; Peptide Fragments; Peptides; Platelet Count; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sepsis; Tissue Polypeptide Antigen

Little information is available on the prevalence and etiology of the coagulopathy present in some children with acute leukemia at disease presentation. We studied 102 children with newly diagnosed acute leukemia (50 retrospective: Group A; and 52 prospective: Group B) with prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), fibrinogen (FIB), and fibrin degradation products (FDP). All patients in Group B also had assessment of thrombin activation by measurement of the crosslinked fibrin fragment, D-dimer, and of primary fibrinolysis with the B beta 1-42 peptide. Additionally, ten patients from Group B had Factors II, V, VII, and X measured, and eight of these patients had measurement of tissue factor from sonicated bone marrow cells. Thirty-two percent of Group A and 40% of Group B had totally normal coagulation studies, whereas 20% of Group A and 10% of Group B had a severe coagulopathy on disease presentation. A high percentage of both groups had elevated PT (Group A, 52%; Group B, 27%) and increased FDP (Group A, 39%; Group B, 25%). In Group B, 38% of the patients had a positive D-dimer, whereas only 4% of this prospective group had an elevated B beta 1-42 peptide (P less than 0.00001). Nine of ten patients with a positive D-dimer had low levels of one or more of the extrinsic pathway factors. Three of four patients with the highest tissue factor levels were of monocytoid leukemia cell type. These data indicate that the coagulopathy associated with acute leukemia of childhood is usually mediated by thrombin activation.

Topics: Adolescent; Blood Coagulation Disorders; Child; Child, Preschool; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide B; Humans; Infant; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prevalence; Prospective Studies; Prothrombin Time; Retrospective Studies; Thrombin