Einfluß von Zytostatik auf das Gerinnungssystem

F. M. Fellin; C. Barsigian; J. Martinez; W. Base

doi:10.1055/s-0038-1659944

Hämostaseologie, Table of Contents

Hamostaseologie 1988; 08(01): 18-26
DOI: 10.1055/s-0038-1659944

Originalarbeiten

Schattauer GmbH

Einfluß von Zytostatik auf das Gerinnungssystem

F. M. Fellin

¹Cardeza Foundation for Hematologic Research, Department of Medicine, The Jefferson Medical College of Thomas Jefferson University, Philadelphia, USA

,

C. Barsigian

¹Cardeza Foundation for Hematologic Research, Department of Medicine, The Jefferson Medical College of Thomas Jefferson University, Philadelphia, USA

,

J. Martinez

¹Cardeza Foundation for Hematologic Research, Department of Medicine, The Jefferson Medical College of Thomas Jefferson University, Philadelphia, USA

,

W. Base

^*I. Medizinische Universitätsklinik, Wien

› Author Affiliations

Abstract

Zusammenfassung

Zytostatika werden sehr viel in der Behandlung von Malignomen verwendet. Blutungskomplikationen und thrombotische Ereignisse treten bei Patienten mit Karzinomen entweder durch die Krebserkrankung selbst oder aufgrund der Behandlung der Krebserkrankung auf. Die Mechanismen für die thrombotischen und hämorrhagischen Syndrome sind bisher noch unzureichend untersucht. Diese Arbeit gibt eine Übersicht der wesentlichen thrombotischen und hämorrhagischen Zustände, die sich aus der Anwendung antineoplastischer Substanzen ergeben, und versucht eine Darstellung des gegenwärtigen Wissensstandes der Pathophysiologie dieser Zustände.

Full Text

References

Literatur
1 Ahr D.J, Schalia S.J, Kimball D.B. Acquired platelet dysfunction following mithramycin therapy. Cancer 1978; 41: 448-54.
2 Almondhiry H. Disseminated intravascular coagulation. Thrombos Diathes Haemorrh 1975; 34: 181-93.
3 Asbury R.F, Rosenthal S.N, Descalzi M.E. et al. Hepatic venoocclusive disease due to DTIC. Cancer 1980; 45: 2670-4.
4 Ashby M, Lazarchick J. Case Report: Acquired dysfibrinogenemia secondary to mithramycin toxicity. Am J Med Sci 1986; 292: 53-5.
5 Barbui T, Finazzi G. et al. L-asparaginase lowers Protein C antigen. Thromb Haemost 1984; 52: 216.
6 Barbui T, Rooeghiero F. et al. Fatal pulmonary embolism and antithrombin III deficiency in adult lymphoblastic leukemia during L-asparaginase therapy. Acta Haemat 1983; 69: 188-91.
7 Bauer K.A, Teitel J.M, Rosenberg R.D. L-asparaginase induced antithrombin III deficiency: Evidence against the production of a hypercoagulable state. Thromb Res 1983; 29: 437-42.
8 Bauer K, Rosenberg R.D. Thrombin generation in acute promyelocytic leukemia. Blood 1984; 64: 791-6.
9 Bennet J.M, Reich S.D. Bleomycin. Ann Intern Med 1979; 90: 945-8.
10 Bennett M, Ludlam C.A. Platelet and fibrinogen survival in acute promyelocytic leukemia. Br Med J 1976; 2: 565.
11 Bernard J, Weil M. et al. Acute promyelocytic leukemia: Results of treatment by daunorubicin. Blood 1973; 41: 489-96.
12 Bezeaud A, Drouet L. et al. Effect of L-asparaginase therapy for acute lymphoblastic leukemia on plasma vitamin Independent coagulation factors and inhibitors. J Pediatr 1986; 108: 698-701.
13 Booth B.W, Weiss R.B. Venous thrombosis during adjuvant chemotherapy. N Engl J Med 1981; 305: 168 (letter)
14 Booth N.A, Bennett B. Plasmin-α₂-anti-plasmin complexes in bleeding disorders characterized by primary or secondary fibrinolysis. Br J Haematol 1984; 56: 545-56.
15 Bras G, Berry D.M, Gyorgy P. Plants as a etiological factor in veno-occlusive disease of the liver. Lancet 1957; I: 960-2.
16 Bras G, Jalliffe D.B, Stuart K.L. Veno-occlusive disease of liver with nonportal type of cirrhosis, occurring in Jamaica. Arch Pathol Lab Med 1954; 57: 285-300.
17 Buchanon G.R, Holtkamp C.A. Reduced antithrombin III levels during L-aspara-ginase therapy. Med Ped Oncol 1980; 8: 7-14.
18 Burke P.J, Serpick A.A. et al. A clinical evaluation of dose and schedule of administration of cytosine arabinoside (NSC 63878). Cancer Research 1968; 28: 274-9.
19 Cairo M.S, Lazarus K. et al. Intracranial hemorrhage and focal seizures secondary to use of L-asparaginase during induction therapy of acute lymphocytic leukemia. J Pediatr 1980; 97: 829-33.
20 Cantrell J.E, Phillips T.M, Schein P.S. Carcinoma-associated hemolytic-uremic syndrome : A complication of mitomycin C chemotherapy. J Clin Oncol 1985; 3: 723-34.
21 Cantrell J, Schein P, Winokur S. et al. A cancer-related thrombotic microangiopathy: Natural history and therapy. Proc ASCO 1983; 2: 12.
22 Chan T.K, Chan G.T.C, Chan V. Hyprofi-brinogenemia due to increased fibrinolysis in two patients with acute promyelocytic leukemia. Aust NZ J Med 1984; 14: 245-9.
23 Choi S. Vincristine induced thrombocytosis. In: Platelets: Production, Function, Transfusion, and Storage. Baldini M.G, Ebbe S. (eds) New York: Grune and Stratton; 1974: 57-71.
24 Chow S, Roscoe J, Cattran D.C. Plasmapheresis and antineoplastic agents in the treatment of the hemolytic uremic syndrome secondary to mitomycin. Am J Kidney Dis 1986; 7: 407-12.
25 Collins A.J, Bloomfield C.D. et al. Acute promyelocytic leukemia. Arch Intern Med 1978; 138: 1677-80.
26 Conard J, Horellow M.H. et al. Decrease in Protein C in L-asparaginase treated patients. Br J Haematol 1985; 59: 725-7.
27 Cordonnier C, Vernant J.P. et al. Acute promyelocytic leukemia in 57 previously untreated patients. Cancer 1985; 55: 18-25.
28 Daly P.A, Schiffer C.A, Wiernik P.H. Acute promyelocytic leukemia - Clinical management of 15 patients. Am J Hema-tol 1980; 8: 347-59.
29 Deutsch E, Fischer M. et al. Blood coagulation changes under L-asparaginase therapy. In: Experimental and Clinical Effects of L-Asparaginase. Grundmann E, Oettgen H.F. (eds) New York: Springer; 1970: 331-41.
30 Doli D.C, List A.F, Greco F.A. et al. Acute arterial ischemie events following cisplatin-based combination chemotherapy for germ cell tumors of the testis. Ann Intern Med 1986; 105: 48-51.
31 Doll D.C, Ringenberg Q.S, Yarbro J.W. Vascular toxicity associated with antineoplastic agents. J Clin Oncol 1986; 4: 1405-17.
32 Doll D.C, Weiss R.B. Hemolytic anemia associated with antineoplastic agents. Can Treat Rep 1985; 69: 777-82.
33 Doll D.C, Weiss R.B, Issell B.F. Mitomycin: Ten years after approval for marketing. J Clin Oncol 1985; 3: 276-86.
34 Drapkin R.L, Gee T.E. et al. Prophylactic heparin therapy in acute promyelocytic leukemia. Cancer 1978; 41: 2484-90.
35 Egbring R, Schmidt W. et al. Demonstration of granulocytic proteases in plasma of patients with acute leukemia and septicemia with coagulation defects. Blood 1977; 49: 219-31.
36 Erichsen C, Jonsson P. Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma. J Surg One 1984; 27: 268-70.
37 Fielding J.W.L, Fagg S.L, Jones B.G. et al. An interim report of a prospective, randomized, controlled study of adjuvant chemotherapy in operable gastric cancer. British Stomach Cancer Group. World J Surg 1983; 7: 390-9.
38 Garnick M.B, Larson P.R. Acute deficiency of thyroxine-binding globulin during L-asparaginase therapy. N Eng J Med 1979; 301: 252-3.
39 Gill R.A, Onstad G.R, Cardamone J.M. et al. Hepatic venoocclusive disease caused by 6-thioguanine. Ann Intern Med 1982; 96: 58-60.
40 Goldberg M.A, Ginsberg D. et al. Is heparin administration necessary during induction chemotherapy for patients with acute promyelocytic leukemia?. Blood 1987; 69: 187-91.
41 Goodnight S.H. Bleeding and intravascular coagulation in malignancy: A review. Ann N Y Acad Sci 1974; 230: 271-88.
42 Goodnough L.T, Saito H, Manni A. et al. Increased incidence of thromboembolism in stage IV breast cancer patients treated with a five-drug chemotherapy regimen: A study of 159 patients. Cancer 1984; 54: 1264-8.
43 Gottfried M.R, Sudilovsky O. Hepatic veno-occlusive disease after high-dose mitomycin C and autologous bone marrow transplantation therapy. Hum Path 1982; 13: 646-50.
44 Gralnick H.R, Abrell E. Studies of the procoagulant and fibrinolytic activity of promyelocytes in acute promyelocytic leukemia. Br J Haematol 1973; 24: 89-99.
45 Gralnick H.R, Bagley J, Abrell E. Heparin treatment for the hemorrhagic diathesis of acute promyelocytic leukemia. Am J Med 1972; 52: 167-74.
46 Gralnick H.R, Henderson E. Hypofibrino-genemia and coagulation factor deficiencies with L-asparaginase treatment. Cancer 1971; 27: 1313-20.
47 Gralnick H.R, Sultan C. Acute promyelocytic leukemia: Haemorrhagic manifestation and morphologic criteria. Br J Haematol 1975; 29: 373-5.
48 Gralnick H.R, Tan H.K. Acute promyelocytic leukemia. A model for understanding the role of the malignant cell in hemostasis. Hum Pathol 1974; 5: 661-73.
49 Granelli-Piperno A, Vassalli J.D, Reich E. Secretion of plasminogen activator by human polymorphonuclear leukocytes. J Exp Med 1977; 146: 1693-706.
50 Greenstone M.A, Dowd P.M, Mikhailidis D.P. et al. Hepatic vascular lesions associated with dacarbazine treatment. Br Med J 1981; 282: 1744-5.
51 Grcm J.L, Merritt J.A, Carbone P.P. Treatment of mitomycin-associated microangiopathic hemolytic anemia with vincristine. Arch Intern Med 1986; 146: 566-8.
52 Griner P.F, Elbadawi A, Packham C.H. Veno-occlusive disease of the liver after chemotherapy of acute leukemia. Ann Intern Med 1976; 85: 578-82.
53 Groopman J, Ellman L. Acute promyelocytic leukemia. Am J Hematol 1979; 7: 395-408.
54 Hamner R.W, Verani R, Weinman E. Mitomycin-associated renal failure. Case report and review. Arch Intern Med 1983; 143: 803-7.
55 Hanna W.T, Krauss S, Regester R.F. et al. Renal disease after mitomycin C therapy. Cancer 1981; 48: 2583-8.
56 Henderson E.S. The granulocytopenic effects of cancer chemotherapeutic agents. In: Drugs and Hemotologic Reactions. The Twenty-Ninth Hahnemann Symposium. Dimitrov N.V, Nodine J.H. (eds) New York : Grune and Stratton; 1974: 207-21.
57 Hillstad L.K. Acute promyelocytic leukemia. Acta Med Scand 1957; 159: 189-94.
58 Hoagland H.C. Hematologic complications of cancer chemotherapy. In: Toxicity of Chemotherapy. Perry M.C, Yarbro J.W. (eds) Orlando: Grune and Stratton, Ine; 1984: 443-8.
59 Hohnsen H, Weiss H.J. Further evidence for a deficient storage pool of adenine nucleotides in platelets from some patients with thrombocytopathia - “Storage Pool Disease”. Blood 1972; 39: 197-209.
60 Homans A.C, Rybak M.E. et al. Effect of L-asparaginase administration, coagulation and platelet function in children with leukemia. J Clin Oncol 1987; 5: 811-7.
61 Houghton A.N, Shafin N, Rickles F.R. Acute hepatic vein thrombosis occurring during therapy for Hodgkin’s disease. A case report. Cancer 1979; 44: 2324-9.
62 Hug V, Burgess A, Blumenschein G, Hortobagyi G, Cohen A.G. Effect of cyclophosphamide on the mitomycin-in-duced syndrome of thrombotic thrombocytopenic purpura. Can Treat Rep 1985; 69: 565-6.
63 Jackson A.M, Rose B.D. et al. Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy. Ann Inter Med 1984; 101: 41-4.
64 Jackson C.W, Edwards C.C. Evidence that stimulation of megakaryocytopoiesis low dose vincristine results from an effect on platelets. Br H Haematol 1977; 36: 97-105.
65 Jao W, Manaligod J.R. Renal disease associated with mitomycin therapy. Ultra-struct Pathol 1983; 5: 83-8.
66 Jedrzejczak W.W, Siekierzynski M. et al. Modified megathrombocyte index in the diagnosis of thrombopoiesis injury produced by cancer chemotherapy. Neoplasma 1982; 29: 493-6.
67 Jerushalmy L.Z, Patya M. et al. Alteration of rat bone marrow megakaryocytes following administration of cytosine arabino-side, daunomycin and hydroxyurea. Haemostasis 1977; 6: 110-7.
68 Kantarjlan H.M, Keating M.J. et al. Acute promyelocytic leukemia. Am J Med 1986; 80: 789-97.
69 Kasimis B.S, Spiers A.S.D. Thrombotic complications in patients with advanced prostatic cancer treated with chemotherapy. Lancet 1979; I: 159 (letter)
70 Keane T.J, Gorman A.M. et al. ε-aminoca-proic acid in the management of acute promyelocytic leukemia. Acta Haemat 1976; 56: 202-4.
71 Kennedy B.J. Metabolic and toxic effects of mithramycin during tumor therapy. Am J Med 1970; 49: 494-503.
72 Klener P, Kubisz P, Suranova J. Influence of cytotoxic drugs on platelet functions and coagulation in vitro. IV. Melphalan. Thromb Haemost 1977; 37: 53-61.
73 Komp D.M, Lyles R.L. et al. The effect of cancer chemotherapeutic agents on fibrin formation and stabilization in vitro. Pediat Res 1974; 8: 75-81.
74 Krivoy N, Raz R, Carter A. et al. Reversible hepatic venoocclusive disease and 6-thioguanine. Ann Intern Med 1982; 96: 788 (letter)
75 Lazarus H.M, Gottfried M.R, Herzig R.H. et al. Veno-occlusive disease of the liver after high dose mitomycin C therapy and autologous bone marrow transplantation. Cancer 1982; 49: 1789-95.
76 Lehrner I.M, Enck R.E. Hepatic vein thrombosis after chemotherapy for histiocytoma. Ann Intern Med 1978; 88: 575-6 (letter)
77 Levin J. Pathophysiology of drug induced thrombocytopenia. In: Drugs and Hematologic Reactions. The Twenty-Ninth Hahnemann Symposium. Dimitrov N.V, Nodine J.H. (eds) New York: Grune and Stratton; 1974: 87-99.
78 Levin J. Thrombopoiesis. In: Hemostasis and Thrombosis. Colman R.W, Hirsh J, Marder V.J, Salzman E.W. (eds) Philadelphia: J B Lippincott; 1987: 418-30.
79 Lewis J.H, Tice H, Zimmerman H.J. Budd-Chiari syndrome associated with oral contraceptive steroids. Review of treatment of 47 cases. Dig Dis Sci 1983; 38: 673-83.
80 Licciardello J, Moake J, Rudy C. et al. Elevated plasma von Willebrand factor levels and arterial occlusive complications associated with cisplatin-based chemotherapy. Oncology 1985; 42: 296-300.
81 Lichtman M.A, Brennan J.K. Platelet production and destruction. In: Hemostasis and Thrombosis. Colman R.W, Hirsh J, Marder V.J, Salzman E.W. (eds) Philadelphia: Lippincott; 1987: 395-417.
82 Lisiewicz J. Mechanisms of hemorrhage in leukemias. Semin Thromb Hemost 1978; 4: 241-67.
83 Liu K.M, Mittelman A, Sproul E.E. et al. Renal toxicity in man treated with mitomy-cin-C. Cancer 1971; 28: 1314-20.
84 Manni A, Trujillo J.E, Pearson O.H. Sequential use of endocrine therapy and chemotherapy for metastatic breast cancer. Effects on survival. Cancer Treat Rep 1980; 64: 111-6.
85 Marubbio A.T, Danielson B. Hepatic veno-occlusive disease in a renal transplantation patient receiving azothioprine. Gastroenterology 1975; 69: 739-43.
86 Monto R.W, Talley R.W. et al. Observations on the mechanism of hemorrhagic toxicity in mithramycin (NSC 24559) therapy. Cancer Research 1969; 29: 697-704.
87 Morley A, Trainor K. et al. A primary stem cell lesion in experimental chronic hypoplastic marrow failure. Blood 1975; 45: 681-8.
88 Ogston D, Dawson A.A. Thrombocytosis following thrombocytopenia in man. Postgrad Med J 1969; 45: 754-6.
89 Ogston D, Dawson A.A, Philip J.F. Methotrexate and the platelet count. Br J Cancer 1968; 22: 244-9.
90 Palascak J.E, Martinez J. Dysfibrinogene-mia associated with liver disease. J Clin Invest 1977; 60: 89-95.
91 Petursson S.R, Chervenick P.A. Megakaryocytopoiesis and granulopoiesis following cyclophosphamide. J Clin Lab Invest 1982; 100: 682-94.
92 Plow E.F, Edgington T.S. An alternative pathway for fibrinolysis. J Clin Invest 1975; 56: 30-8.
93 Polliack A. Acute promyelocytic leukemia with disseminated intravascular coagulation. Am J Clin Pathol 1971; 56: 155-61.
94 Priest J.R, Ramsey N.K.C. et al. A syndrome of thrombosis and hemorrhage complicating L-asparaginase therapy for childhood acute lymphoblastic leukemia. J Pediatr 1982; 100: 984-9.
95 Priest J.R, Ramsey N.K.C. et al. The effect of L-asparaginase on antithrombin, plasminogen and plasma coagulation during therapy for acute lymphoblastic leukemia. J Pediatr 1982; 100: 990-5.
96 Pui C.H, Chesney C.M, Weed J. et al. Altered von Willebrand factor molecule in children with thrombosis following asparaginase-prednisone-vincristine therapy for leukemia. J Clin Oncol 1985; 3: 1266-72.
97 Pui C.H, Chesney C.M. et al. Lack of pathogenetic role of proteins C and S in thrombosis associated with asparaginase-prednisone-vincristine therapy for leukemia. Br J Haematol 1986; 64: 283-90.
98 Pui C, Jackson C.W. et al. Sequential changes in platelet function and coagulation in leukemic children treated with 1-asparaginase, prednisone and vincristine. J Clin Oncol 1983; 1: 380-5.
99 Ramsey N.K.C, Coccia P.F. et al. The effect of L-asparaginase on plasma coagulation factors in acute lymphoblastic leukemia. Cancer 1977; 40: 1398-407.
100 Rand J.J, Moloney W.C, Sise H.S. Coagulation defects in acute promyelocytic leukemia. Arch Inter Med 1969; 123: 39-47.
101 Robertson J.H, Crozier E.H, Woodend B.E. The effect of vincristine on the platelet count in rats. Br J Haematol 1970; 19: 331-7.
102 Rozencweig M, Von Hoff D.D. et al. Cisdiaminedichloroplatinum (II). Ann Intern Med 1977; 86: 803-12.
103 Sack G.H, Levin J, Bell W.R. Trousseau’s syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: Clinical, pathophysiologic and therapeutic features. Medicine 1977; 56: 1-37.
104 Schafer A.I. The hypercoagulable states. Ann Intern Med 1985; 102: 814-28.
105 Schwartz B.S, Williams E.C. et al. Epsilon-aminocaproic acid in the treatment of patients with acute promyelocytic leukemia and acquired alpha-2 plasmin inhibitor deficiency. Ann Intern Med 1986; 105: 873-7.
106 Seifter E.J, Bell W.R. Coagulation disorders in the cancer patient. Mount Kisco, NY: Futura Pubi; 1984
107 Seifter E.J, Young R.C, Longo D.L. Deep venous thrombosis during therapy for Hodgkin’s disease. Cancer Treat Rep 1985; 69: 1011-3.
108 Sensenbrenner L.L, Owens A.H. The effects of mechlorethamine on bone marrow function and iron metabolism in man. Johns-Hopkins Med J 1967; 121: 162-74.
109 Shaw M.T, Spector M.H, Ladman A.J. Effects of cancer, radiotherapy and cytotoxic drugs on intestinal structure and function. Cancer Treat Rev 1979; 6: 141-51.
110 Sheldon R, Slaughter D. A syndrome of microangiopathic hemolytic anemia, renal impairment, and pulmonary edema in chemotherapy-treated patients with adenocarcinoma. Cancer 1986; 58: 1428-36.
111 Shulman H.M, McDonald G.B, Matthews D. et al. An analysis of hepatic veno-occlusive disease and centrilobular hepatic degeneration following bone marrow transplantation. Gastroenterology 1980; 79: 1178-91.
112 Sloane J.P, Farthing M.J.G, Powles P.L. Histopathological changes in the liver after allogeneic bone marrow transplantation. J Clin Pathol 1980; 33: 344-8.
113 Smith F.P, Kisner D, Schein P.S. Nutrition and cancer: Prospects for clinical research. Nutrition and Cancer 1980; 2: 34-9.
114 Smith F.P, Kisner D.L. et al. Chemothera-peutic alteration of small intestine morphology and function: A progress report. J Clin Gastroenterol 1979; 1: 203-7.
115 Steinhorz P.G, Miller L.P. et al. Dural sinus thrombosis in children with acute lymphoblastic leukemia. JAMA 1981; 246: 2837-41.
116 Tanum G. Megakaryocyte DNA content and platelet formation in rats after sublethal dose of thio-TEPA. Exp Hematol 1986; 14: 202-6.
117 Vellenga E, Broekmans A.W, Kluft C. Thrombotic complications during L-asparaginase related to protein C deficiency?. Thromb Haemost 1985; 53: 443.
118 Vellenga E, Kluft C. et al. The influence of L-asparaginase therapy on the fibrinolytic system. Br J Haematol 1984; 57: 247-54.
119 Wasser J.S, Coleman M. Leukemia chemotherapy and centrilobular hepatic necrosis. Ann Intern Med 1977; 86: 508-9 (letter)
120 Weiss R.B, Poster D.S. The renal toxicity of cancer chemotherapeutic agents. Cancer Treat Rev 1982; 9: 37-56.
121 Weiss R.B, Tormey D.C, Holland J.F. et al. Venous thrombosis during multimodal treatment of primary breast carcinoma. Cancer Treat Rep 1981; 65: 677-9.
122 Whitecar J.P, Bodey G.P. et al. L-asparaginase. N Engl J Med 1970; 282: 732-4.
123 Woods W.G, Dehner L.P, Nesbit M.E. et al. Fatal veno-occlusive disease of the liver following high dose chemotherapy, irradiation and bone marrow transplantation. Am J Med 1980; 68: 285-90.
124 Zafrani S, Pinaudeau Y, Dhumeaux D. Drug-induced vascular lesions of the liver. Arch Intern Med 1983; 143: 495-502.
125 Zimmerman S, Smith F.P, Phillips T.M. et al. Gastric carcinoma and thrombotic thrombocytopenic purpura: Association with plasma immune complex concentrations. Br Med J 1982; 284: 1432-4.