fibrinopeptide-a and Leukemia--Promyelocytic--Acute

DIC is an acquired disorder in which intravascular coagulation may lead to microvascular fibrin formation and a hemorrhagic diathesis. If DIC is acute and severe, fibrin formation may lead to microvascular thrombosis, and consumption of coagulation factors and platelets may result in a hemorrhagic diathesis. Secondary to or simultaneously with coagulation, the fibrinolytic system may be activated, accentuating the bleeding tendency. All the systems involved in DIC, such as coagulation, fibrinolysis, kallikrein-kinin, complement, and possibly other systems are regulated. Coagulation is the central event of DIC. The different coagulation factor derivatives may be generated that can be determined and used as markers for the degree of DIC and for effective control of therapy. Some of the procoagulant and anticoagulant factors are converted in the course of coagulation to their active forms and activation peptides. The active factor is subsequently neutralized by forming a complex with an inhibitor. Hemostatic molecular markers, D-dimer of cross-linked fibrin degradation products (D-dimer), thrombin-antithrombin III complex (TAT), and plasmin-alpha 2-plasmin inhibitor complex (PIC) have all been used for the diagnosis of DIC.

Topics: alpha-2-Antiplasmin; Antifibrinolytic Agents; Antithrombin III; Biomarkers; Diagnosis, Differential; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Humans; Leukemia, Promyelocytic, Acute; Peptide Hydrolases

Coagulation abnormalities occurring in patients with acute promyelocytic leukemia (APL) are partially corrected by heparin administration. This study was undertaken to verify if "supra-normal" levels of antithrombin III (AT-III) are similarly able to quench intravascular thrombin generation triggered by APL cells. Eight patients with APL were randomly assigned to receive either 50 U/kg (Group A) or 100 U/kg (Group B) of an AT-III concentrate, starting on the first day of chemotherapy and continuing for 7 days thereafter. Fibrinopeptide A (FPA), prothrombin fragment F1+2 and thrombin-AT III complexes, measured before and 15 minutes after each AT-III infusion, decreased significantly after each infusion, but the effect was minimal and short-lived, despite the achievement of post-infusion levels of AT-III activity well above 150% (Group A) or 200% (Group B). Small amounts of heparin were consistently detected in AT-III concentrates and post-infusion plasma samples. The short-lived quenching of thrombin generation after AT-III concentrate could be partially explained by the infusion of heparin, rather than by supranormal AT-III levels.

Topics: Adult; Aged; Antithrombin III; Blood Coagulation; Blood Transfusion; Female; Fibrinopeptide A; Heparin; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Peptide Fragments; Peptide Hydrolases; Platelet Transfusion; Prothrombin; Thrombin

We studied the pathogenesis of the bleeding disorder in acute promyelocytic leukemia by measuring procoagulant, profibrinolytic, and proinflammatory mediators in peripheral blood and bone marrow cells from 25 previously untreated patients. Patients were induced with either all-trans retinoic acid (ATRA) or chemotherapy. Plasma levels of fibrinopeptide A (FPA), fibrin d-dimer, thrombin antithrombin (TAT) complex, prothrombin fragment 1.2 (F1.2), urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor 1 (PAI-1) were measured before and after therapy, as was the cellular expression of the genes for tissue factor (TF) and interleukin-1 beta (IL-1 beta). The mean plasma levels of fibrin d-dimer, F1.2, TAT and FPA were markedly elevated prior to therapy and declined during the first 30 days of treatment with either ATRA or chemotherapy, but more rapidly and to a greater extent in patients treated with ATRA. ATRA treatment was associated with a significant decrease in TF gene expression in bone marrow cells during the first 30 days of treatment, whereas IL-1 beta gene expression, which decreased in the cells of six patients treated with either chemotherapy or ATRA, actually increased in the remaining six patients treated with either chemotherapy or ATRA. In patients with APL, treatment with either chemotherapy or ATRA rapidly ameliorates the coagulopathy, as indicated by an abrupt decline in markers of clotting activation. An increase in cytokine gene expression (e.g. IL-1 beta) may provide an explanation for the persistent hypercoagulability observed in some patients with APL, regardless of therapeutic approach. Our data confirms and extends earlier observations by others that ATRA is more effective than chemotherapy alone in rapidly reducing the procoagulant burden of APL tumor cells. However, our data also suggests that cytokine expression in some patients may be accelerated by either chemotherapy or ATRA. The implications of this observation for understanding the retinoic acid syndrome will require further studies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antithrombins; Blood Coagulation; Bone Marrow Cells; Cell Line, Tumor; Child; Child, Preschool; Cytokines; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Infant; Interleukin-1; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Ribonucleases; Thrombin; Thromboplastin; Time Factors; Tissue Plasminogen Activator; Tretinoin; Urokinase-Type Plasminogen Activator

Topics: Fibrinogen; Fibrinopeptide A; Hemorrhagic Disorders; Humans; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Leukocyte Count; Neoplastic Stem Cells; Thrombin