fibrin and Leukemia--Monocytic--Acute

We report two cases of atypical defibrination syndromes in patients with respectively acute monoblastic leukemia (chronic myeloid leukemia initially) and acute lymphoblastic leukemia. Hemostasis studies show low fibrinogen level, elevated D-dimers, decreased alpha 2 antiplasmin and factor V, normal antithrombin III values. Plasminogen is below the normal range in one patient. Soluble complexes, which are an important argument for diagnosis of intravascular coagulation disease, are not detected in both patients. Primary or secondary hyperfibrinolysis seems also excluded since euglobulin clot lysis time was normal. Enzymatic proteolysis of fibrinogen (or fibrin) by the blast cells has been reported by some authors; this mechanism could account for the hemostasis abnormalities observed in these two patients.

Topics: Adult; alpha-2-Antiplasmin; Antithrombin III; Diagnosis, Differential; Disseminated Intravascular Coagulation; Factor V Deficiency; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Leukemia, Monocytic, Acute; Male; Neoplastic Stem Cells; Plasminogen; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Syndrome

The leukocyte integrin Mac-1 (CD11b/CD18) and the urokinase receptor (uPAR, CD87) mediate complementary functions in myelomonocytic cells. Both receptors promote degradation of fibrin(ogen) and also confer adhesive properties on cells because Mac-1 and uPAR bind fibrin and vitronectin, respectively. Staining of lung biopsy specimens from patients with acute lung injury indicated that fibrin and vitronectin colocalize at exudative sites in which macrophages bearing these receptors accumulate. Because of the parallel roles and physical proximity of Mac-1 and uPAR, the capacity of these receptors to functionally interact was explored. Induction of Mac-1 and uPAR expression on monocytic cell lines by transforming growth factor- beta 1 and 1.25-(OH)2 vitamin D3 conferred urokinase and uPAR-dependent adhesion to vitronectin, which was further promoted by engagement of Mac-1. Vitronectin attachment promoted subsequent Mac-1-mediated fibrinogen degradation threefold to fourfold. In contrast, enhancement of uPAR occupancy by exogenous urokinase or receptor binding fragments thereof inhibited Mac-1 function. Addition of urokinase progressively inhibited Mac-1-mediated fibrinogen binding and degradation (maximal inhibition, 91% +/- 14% and 72% +/- 15%, respectively). Saturation of uPAR with urokinase also inhibited binding of the procoagulant Mac-1 ligand, Factor X. These inhibitory effects of uPAR were reproduced in fresh monocytes, cultured monocytic cells, and in Chinese hamster ovary (CHO) cells transfected with both human Mac-1 and human uPAR. These data show that the procoagulant and fibrinolytic potential of monocytic cells is co-ordinately regulated by ligand binding to both Mac-1 and uPAR and identify uPAR as a regulator of integrin function. Vitronectin-enhanced fibrin(ogen) turnover by Mac-1 may operate as a salvage pathway in the setting of urokinase and plasmin inhibitors to promote clearance of the provisional matrix and subsequent healing.

Topics: Animals; Blood Coagulation; Calcitriol; CD18 Antigens; Cell Adhesion; CHO Cells; Cricetinae; Factor X; Fibrin; Fibrinogen; Fibrinolysis; Humans; Leukemia, Monocytic, Acute; Lung; Lung Injury; Lymphoma, Large B-Cell, Diffuse; Macromolecular Substances; Macrophage-1 Antigen; Macrophages; Monocytes; Neoplasm Proteins; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Recombinant Proteins; Transfection; Transforming Growth Factor beta; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator; Vitronectin

Topics: Acute Disease; Antithrombins; Blood Cell Count; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Liver Cirrhosis; Lymphatic Diseases; Platelet Adhesiveness; Prothrombin Time; Retinal Detachment; Thrombin; Thrombophlebitis

Topics: Acute Disease; Adenine Nucleotides; Adenosine Diphosphate; Adult; Aged; Blood Platelets; Collagen; Epinephrine; Female; Fibrin; Humans; Kaolin; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Middle Aged; Muramidase; Platelet Adhesiveness; Remission, Spontaneous; Thrombin