PDF herunterladen
Thromb Haemost 1984; 52(01): 081-084
DOI: 10.1055/s-0038-1661142
Original Article
Schattauer GmbH Stuttgart

Changes in Plasma Levels of Protease and Fibrinolytic Inhibitors Induced by Treatment in Acute Myeloid Leukemia

F Velasco
The Department of Haematology, “Reina Sofia” Hospital, Cordoba, Spain
,
A Torres
The Department of Haematology, “Reina Sofia” Hospital, Cordoba, Spain
,
P Andres
The Department of Haematology, “Reina Sofia” Hospital, Cordoba, Spain
,
F Martinez
The Department of Haematology, “Reina Sofia” Hospital, Cordoba, Spain
,
P Gomez
The Department of Haematology, “Reina Sofia” Hospital, Cordoba, Spain
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 02. Februar 1984

Accepted 05. Mai 1984

Publikationsdatum:
19. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

We have studied the main protease inhibitors of leukocytes, alpha-1-protease (α1-PI), alpha- 1-antichymotrypsin (α1-Achy) and alpha-2-macroglobulin (α2-M), as well as different parameters of coagulation and fibrinolysis in 21 cases of acute nonlymphoblastic leukemia (ANLL) before, during and after therapy.

Nine of the patients presented signs of DIC, 8 of whom belonged to subtype M3 and to subtype 1 M1.

The initial α1-PI and α1-Achy levels, which were elevated, increased during the treatment period. There was no significant difference between patients with and without DIC. However, those leukemic patients with DIC showed a significant decrease in plasminogen (p <0.005) and fast antiplasmin (p <0.01) only during the treatment compared with DIC free patients. All DIC cases demonstrated circulating plasmin-antiplasmin complex (P-AP) both before and during treatment.

Independent of a possible proteolytic action of leukocyte enzymes on clotting factors in the clinical course of ANLL (mainly M3 subtype), our results suggest an activation of plasminmediated fibrinolysis related to the activation of plasminogen by leukocytes, reactive DIC or both.

Keywords

Leukocyte proteases - ANLL - DIC - Fibrinolytic inhibitors - P-AP complex
 

  • References

  • 1 Rosenthal RL. Acute promyelocytic leukemia associated with hypofibrinogenemia. Blood 1963; 21: 495-508
    PubMedSuche in Google Scholar
  • 2 Didisheim P, Thrombold JS, Vandervoort LE, Mibashan RS. Acute promyelocytic leukemia with fibrinogen and factor V deficiencies. Blood 1964; 23: 717-728
    CrossrefPubMedSuche in Google Scholar
  • 3 Gralnick HR, Tan KH. Acute promyelocytic leukemia. Hum Pathol 1974; 5: 661-673
    CrossrefPubMedSuche in Google Scholar
  • 4 Gralnick HR, Sultan C. Acute promyelocytic leukemia: haemorrhagic manifestation and morphologic criteria. Br J Haematol 1975; 29: 373-376
    CrossrefPubMedSuche in Google Scholar
  • 5 Plow EF, Edgington TS. An alternative pathway for fibrinolysis. The cleavage of fibrinogen by leukocytes proteases at physiologic pH J Clin Invest 1975; 58: 30-38
    PubMedSuche in Google Scholar
  • 6 Egbring R, Schmidt W, Fuchs G, Havemann K. Demonstration of granulocytic proteases in plasma of patients with acute leukemia and septicemia with coagulation defects. Blood 1977; 49: 219-231
    PubMedSuche in Google Scholar
  • 7 Bennett JM, Catosvky D, Daniel MT, Flandrin G, Galton DA G, Gralnick HR, Sultan C. Proposals classification of the acute leukemias. Br J Haematol 1976; 33: 451-458
    CrossrefPubMedSuche in Google Scholar
  • 8 Gamba G, Fornasari P, Montanini N, Biancardi M, Grignani G, Ascari E. Plasma levels of protease inhibitors in acute myeloid leukemia at the onset of the disease and during antiblastic therapy. Thromb Res 1980; 17: 41-53
    CrossrefPubMedSuche in Google Scholar
  • 9 Miralles J, Felez J, Ramirez de Arellano R, Velasco F, Fontcuberta J, Borrell M, Rutilant ML. Metodo rapido y simple de extraction de heparina y sulfato de protamina del plasma humano. Metodologia Biol Clin Hematol 1980; 2: 19-23
    PubMedSuche in Google Scholar
  • 10 Caen J, Larrieu M, Samama M. L’Hémostase. Méthodes d’exploration et diagnostic practique. L’Expansion Scientifique 1975
    PubMedSuche in Google Scholar
  • 11 Laurell CM. Quantitative estimation of protein by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
    CrossrefPubMedSuche in Google Scholar
  • 12 ødegård OR, Lie M, Abildgaard U. Heparin cofactor activity measured with an amidolytic methods. Thromb Res 1975; 6: 287-294
    CrossrefPubMedSuche in Google Scholar
  • 13 Friberger P, Knös M, Gustavsson S, Aurell L, Claeson G. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis 1978; 7: 138-145
    PubMedSuche in Google Scholar
  • 14 Teger-Nilsson AC, Friberger P, Gyzander E. Determination of a new rapid plasma inhibitor in human blood by means of plasma specific tripeptide substrate. Scand J Clin Lab Invest 1977; 37: 403-404
    CrossrefPubMedSuche in Google Scholar
  • 15 Ganrot PO. Crossed Immunoelectrophoresis. Scand J Clin Lab Invest 1972; (Suppl. 29) Suppl 124-139
    PubMedSuche in Google Scholar
  • 16 Collen D. On the regulation and control of fibrinolysis. Thromb Haemostas 1980; 43: 77-89
    PubMedSuche in Google Scholar
  • 17 Felez J, Borrell M, Fontcuberta J, Rutllant ML. Determinacion del complejo plasmina-antiplasmina en sujetos normales y en el curso del tratamiento fibrinolitico. Biol Clin Hematol 1979; 2: 153-158
    PubMedSuche in Google Scholar
  • 18 Velasco F, Torres A, Andres P, Duran M. Functional activities and concentrations of plasmin inhibitors in normal subjects and DIC patients. Thromb Haemostas 1982; 47: 275-277
    PubMedSuche in Google Scholar
  • 19 Shipper HG, Kalhe LH, Jenkins CS P, Ten Cate JW. Antithrombin III transfusion in disseminated intravascular coagulation. Lancet 1978; 2: 854
    PubMedSuche in Google Scholar
  • 20 Vellenga E, Mulder NH. Normal levels of antithrombin III in acute leukemia complicated by coagulopathy. Acta Haematol 1980; 63: 336-338
    CrossrefPubMedSuche in Google Scholar
  • 21 Trobisch H. Hämostatische. Dt Med Wschr 1976; 101: 1420-1433
    PubMedSuche in Google Scholar
  • 22 Denson KW E. The ratio of factor VIII-related antigen and factor VIII biological activity as an index of hypercoagulability and intravascular clotting. Thromb Res 1977; 10: 107-119
    CrossrefPubMedSuche in Google Scholar
  • 23 Kopec M, Bykowska K, Lopaciuk S, Jelenska M, Kaczanowska J, Sopata I, Wojtecka E. Effects of neutral proteases from leukocytes on structure and biological properties of human factor VIII. Thromb Haemostas 1980; 43: 211-217
    PubMedSuche in Google Scholar
  • 24 Kopec M, Kaczanowska J, Stachurska J, Tomczak Z, Wojteckalukasik E, Bykowska K, Lopaciuk S. Effects of granulocytic neutral protease on some clotting factors. In: Progress in fibrinolysis. Davidson JF, Nilsson IM, Asted B. (eds) Churchill Livingstone; New York: 1981. 5 75-77
    Suche in Google Scholar
  • 25 Moroz LA. Nonplasmin-mediated fibrinolysis. Semin Thromb Haemostas 1984; 10: 80-86
    Thieme ConnectPubMedSuche in Google Scholar
  • 26 Graeff H, Hafter R. Subunit structure of circulating fibrin. In: Progress in fibrinolysis. Davidson JF, Nilsson IM, Asted B. (eds) Churchill Livingstone; New York: 1981. 5 393-398
    Suche in Google Scholar
  • 27 Pizzo SV, Schwartz ML, Hill RL, Mckee PA. The effect of plasmin on the subunic structure of human fibrinogen. J Biol Chem 1972; 247: 636-645
    PubMedSuche in Google Scholar
  • 28 McDonald JA, Braun BJ, Rosenberg DM, Kelman JA, Brin SC, Crystal RG. Destruction of major extracellular adhesive glycoprotein (fibronectin) of human fibroblast by neutral protease from polymorphonuclear leukocyte granules. Lab Invest 1979; 40: 350-357
    PubMedSuche in Google Scholar
  • 29 Gramse M, Bingenheimer C, Schmidt W. Degradation products of fibrinogen by elastase-like neutral protease from human granulocytes. Characterization and effects on blood coagulation in vitro J Clin Invest 1978; 61: 1027-1033
    CrossrefPubMedSuche in Google Scholar
  • 30 Ohlsson K, Akersson V. α1-Antichymotrypsin interaction with cationic proteins from granulocytes. Clin Chim Acta 1976; 73: 285
    CrossrefPubMedSuche in Google Scholar
  • 31 Venge P, Ohlsson I, Odebery H. Cationic proteins of human granulocytes. Interaction with plasma protease inhibitors Scand J Clin Lab Invest 1975; 35: 737-744
    CrossrefPubMedSuche in Google Scholar
  • 32 Morse JO. Alpha-1-antitrypsin deficiency. N Eng J Med 1978; 299: 1045-1048
    CrossrefPubMedSuche in Google Scholar
  • 33 Brower MS, Harper PC. Alpha-l-antitrypsin-human leukocyte elastase complexes in blood: quantification by an enzyme-linked differential antibody immunosorbent assay and comparison with alpha-2-plasmin inhibitor-plasmin complexes. Blood 1983; 61: 841-849
    PubMedSuche in Google Scholar
  • 34 Plow EF, Edgington TS. Comparative immunochemical characterization of products of plasmin and leukocyte protease cleavage of human fibrinogen. Thromb Res 1978; 12: 653-665
    CrossrefPubMedSuche in Google Scholar