Fibrinolysis in patients with acute promyelocytic leukemia and disseminated intravascular coagulation during heparin therapy

Abstract

Two patients diagnosed as having acute promyelocytic leukemia (APL) and disseminated intravascular coagulation (DIC) were closely followed by serial fibrinolysis and coagulation studies from the day of admission until completion of the first course of chemotherapy. One patient was treated with intravenous heparin and Trasylol (Bayer AG, West Germany) and the other received heparin therapy without Trasylol. In Patient 1, hyperfibrinolytic activity, not observed during the administration of Trasylol, developed with its discontinuance. In Patient 2, hyperfibrinolysis was observed coincidentally with a decrease in APL cells due to chemotherapy. These results indicate that hyperfibrinolysis in APL is not associated with DIC. Deaths from intracerebral hemorrhage are frequently described, and account for a significant number of early deaths. Therapy with intravenous heparin has been attempted to control intravascular coagulation in APL patients, and recent reports suggest that it may be beneficial. Indeed, deaths due to intracerebral hemorrhage appeared to be less frequent in patients given However, the role of heparin in controlling the coagulopathy of APL remains controversial.In this article, we report on fibrinolysis which persisted in two patients with APL and DIC despite treatment with heparin. Our studies support the clinical impression that antifibrinolytic therapy may be the treatment of choice in addition to heparin therapy. Case Reports Case 1A 26-year-old woman was admitted with a 10-day history of anemia and subfebrile condition and was given a blood transfusion. On admission, there were symptoms of nausea and vomFrom the Departments of *Surgery and ?Internal Medicine, The Center for Adult Diseases, Osaka, Japan.Address for reprints: Shingi Imaoka, MD, Department of Surgery, The Center for Adult Diseases, Osaka 1-3-3 Nakamichi, Higashinariku, Osaka, Japan.Accepted for publication February 14, 1986. iting. Results of the physical examination were essentially normal. Her hemoglobin level was 9.3 g/dl, leucocyte count was 1800/mm3 with 55.8% promyelocytes, and platelet count was 79,000/mm3. A bone marrow aspiration showed acute promyelocytic leukemia; 57% promyelocytes/35,000 nucleic cells/mm3. She was diagnosed as having DIC on the basis of coagulation studies: 30% (21 seconds) prothrombin time (PT) (normal, 12 seconds), 40 seconds activated partial thromboplastin time (AFTT) (normal, 27-33 seconds), 80 mg/dl fibrinogen (Fbg), 98% antithrombin I11 (AT 111), 80 pg/ml fibrin/fibrinogen degradation products (FDP), 28.3 mm2 lysis area of fibrin plate, but a negative protamine sulfate test.The patient received heparin by constant infusion (400-800 U/hr), from the beginning of the treatment on the first hospital day (day I), and Trasylol (Bayer AG, West Germany) (500,000 U/day) intravenously (Fig. 1). Combination chemotherapy with daunomycin was begun on day 1, and predonisolone, cytosine arabinoside, and 6 mercaptopurine were added on day 9 and discontinued on day 13. Trasylol therapy was begun on day 1 and on...

Disseminated intravascular coagulation in acute lymphoblastic leukemia at presentation and in early phase of remission induction therapy

“…Less severe fibrinolysis, together with its subacute nature, may contribute to the milder hemorrhagic complications of DIC in ALL. Accordingly, it appears that, while all our ALL patients received anti-DIC therapy, anti-fibrinolytic agents do not play as large a role in ALL as in APL [4,13,23].…”

“…Follow-up coagulation study was performed in 40 patients -37 of 54 patients without DIC at presentation and three in whom the initial coagulation study had not been performed -within 7 days after the initiation of induction chemotherapy, and 14 developed DIC (35% All 24 patients with DIC were treated immediately following diagnosis of DIC either with heparin (seven patients), gabexate mesilate (seven patients), or both (ten patients). The median duration of treatment was 11 days (range, [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] for heparin, 12 days (range, 6-50) for gabexate mesilate, and 15 days (range, 7-22) for both agents. Twenty-one patients received platelet transfusions.…”

Annexin II and Bleeding in Acute Promyelocytic Leukemia

“…Because plasmin formed on cell surfaces appears to be protected from its primary inhibitor, a 2 -plasmin inhibitor, 49 the total fibrinolytic effect of overexpression of annexin II may be clinically significant. Furthermore, because a 2 -plasmin inhibitor may become depleted in patients with APL, 12,13,18,22,24,25 circulating plasmin may go unchecked, further increasing the potential for hemorrhage.…”

“…Evidence in support of this possibility includes low plasma levels of plasminogen, a 2 -plasmin inhibitor (the primary plasmin inhibitor), plasminogen-activator inhibitor 1 (an inhibitor of both t-PA and u-PA), and other abnormalities in patients with APL that are consistent with excessive fibrinolysis. 12,13,18,[22][23][24][25][26][27][28][29][30][31][32] Annexin II is a calcium-regulated, phospholipidbinding protein on endothelial cells, macrophages, and some tumor cells. 33 It is a cell-surface receptor for both plasminogen (the inactive precursor of plasmin), and its activator, t-PA. 34 Soluble annexin II acts as a t-PA cofactor, increasing the efficiency of plasmin formation by a factor of 60.…”

Pancreatic cancer complicated by disseminated intravascular coagulation associated with production of tissue factor

“…[1][2][3][4][5][6] The recent literature emphasizes that tissue factor (TF) is a key initiator of the DIC associated with malignant diseases. [7][8][9][10] In this article, we report a patient with pancreatic cancer with associated DIC.…”