Tumour cell u‐PA as a cause of fibrinolytic bleeding in metastatic disease

Bennett, Bruce; Croll, A.; Robbie, Linda A.; Herriot, Richard

doi:10.1046/j.1365-2141.1997.4303242.x

Cited by 9 publications

(19 citation statements)

References 12 publications

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“…All involve basement membrane digestion ( Liotta et al , 1981 ; O'Grady et al , 1981 ; Jones & DeClerk, 1982; Salo et al , 1982 ; Sheela & Barrett, 1982) to which u‐PA may contribute directly by digestion of laminin or indirectly by activation of the proenzyme form of type IV collagenase. Malignant cell transformation has been associated with the expression of two‐chain u‐PA activity in leukaemic and single‐chain u‐PA in other cell lines ( Stump et al , 1986 ; Stephens et al , 1987 , 1988) and there are numerous reports of enhanced local u‐PA in a variety of malignancies in vivo ( Gralnick & Abrell, 1973; Nielsen et al , 1982 ; Wun et al , 1982 ; Camiolo et al , 1984 ; Gurewich et al , 1984 ; Skriver et al , 1984 , Stephens et al , 1987 ; Sappino et al , 1987 ; Bennett et al , 1989 , 1997; Janicke et al , 1990 ). Differentiation stimuli also modify u‐PA expression by cells ( Prokopowicz & Stormorken, 1968; Granelli‐Piperno et al , 1977 ; Wilson & Francis, 1987).…”

Section: Discussionmentioning

confidence: 99%

Plasminogen activator in acute myeloid leukaemic marrows: u‐PA in contrast to t‐PA in normal marrow

et al. 1998

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Leukaemic and normal bone marrow samples were compared in terms of their content of the fibrinolytic agents, tissue plasminogen activator (t‐PA) and urokinase‐type plasminogen activator (u‐PA) and their inhibitors, plasminogen activator inhibitors 1 and 2 (PAI‐1 and PAI‐2). Normal marrow contained t‐PA as the principal plasminogen activator, whereas in leukaemic marrow samples u‐PA was the predominant activator. Both normal and leukaemic marrows contained PAI‐1 in similar amounts, but whereas normal marrow contained significant amounts of PAI‐2 the leukaemic marrows contained very little. Plasminogen activators were present in uncomplexed, active forms and plasmin–α2‐antiplasmin complexes were generated locally more prominently in leukaemic marrows. u‐PA associated with blast cells may contribute to the severe forms of haemorrhage sometimes occurring in myeloid types of leukaemia.

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Section: Discussionmentioning

confidence: 99%

Plasminogen activator in acute myeloid leukaemic marrows: u‐PA in contrast to t‐PA in normal marrow

et al. 1998

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“…34 Even though disseminated malignancy is only rarely complicated by a sustained bleeding tendency, free active u-PA and u-PA antigen were found on malignant cells in two cancer patients with a hemorrhagic syndrome, which improved after tranexamic acid therapy. 35…”

Section: Fibrinolysismentioning

confidence: 99%

Laboratory Diagnosis of the Thrombophilic State in Cancer Patients

Gouin‐Thibault¹,

Samama²

1999

Semin Thromb Hemost

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Perturbations of coagulation in cancer patients have been described for a long time. In up to 90% of cancer patients "routine" blood tests are abnormal leading to a hypercoagulable state in these patients. Among these tests are an increase in clotting factors, fibrinogen, fibrinogen/fibrin degradation products, and thrombocytosis. Markers of the activation of coagulation have been developed, and levels of FPA, F1+2, TAT, and D-Dimer have been found higher in cancer patients. More specific procoagulant activities in cancer (CP and TF) have also been described and can be measured but none of them have any predictive value for the occurrence of venous thromboembolism in these patients. Consistent with this hypercoagulable state in cancer is the finding that most cancer patients have reduced plasma levels of inhibitors of coagulation. These complex abnormalities are clinically expressed as thrombosis, low-grade or fulminant DIC which can be assessed by different laboratory tests, and as hemorrhage when the fibrinolysis system is impaired. However, no studies have shown to date a relationship between these abnormalities of the coagulation tests and the clinical expression in any single individual. Because these patients are at high risk for thrombosis in special conditions such as surgery or during chemotherapy, prophylaxis with various forms of heparin are recommended.

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“…This increased expression of an activator of fibrinolysis in cancer would shift the fibrinolysis balance towards hyperfibrinolysis and play an important role in the pathogenesis of bleeding symptoms in some patients with leukemia [13, 36]. However the balance between activation and inhibition of fibrinolysis is delicate since, in addition to uPA expression, tumor cells produce the plasminogen activator inhibitor 1 (PAI-1).…”

Section: The Fibrinolytic Systemmentioning

confidence: 99%

The Thrombophilic State in Cancer Patients

2001

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Thrombosis and disseminated intravascular coagulation are common complications of cancer. Specific conditions associated with cancer such as stasis due to immobilization or blood flow obstruction, surgery, infections, endothelium damage due to chemotherapeutic agents and abnormalities of blood coagulation contribute to the hypercoagulable and thrombophilic state of cancer patients. This procoagulant state in cancer arises mostly from the capacity of tumor cells to express and release procoagulant activities (cancer procoagulant and tissue factor). Decreased levels of inhibitors of coagulation, impaired fibrinolysis, the presence of antiphospholipid antibodies and an acquired activated protein C resistance contribute to the hypercoagulable state. The activation of coagulation is also implicated in tumor proliferation through interactions of coagulation with inflammation and increased tissue factor pathway inhibitor. Laboratory diagnosis of the thrombophilic state include (1) elevation of clotting factors, fibrinogen/fibrin degradation products, hyperfibrinogenemia and thrombocytosis and (2) elevation of specific markers of activation of coagulation: fibrinopeptide A, fragment 1 + 2, thrombin-antithrombin complexes and D-dimers. However, none of the tests has any predictive value for the occurrence of thrombotic events in one individual patient. In patients with venous thromboembolism a noninvasive screening for occult cancer is able to detect a relatively high incidence of hidden cancer and the search for thrombophilia seems important in patients without known cancer.

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Tumour cell u‐PA as a cause of fibrinolytic bleeding in metastatic disease

Cited by 9 publications

References 12 publications

Plasminogen activator in acute myeloid leukaemic marrows: u‐PA in contrast to t‐PA in normal marrow

Plasminogen activator in acute myeloid leukaemic marrows: u‐PA in contrast to t‐PA in normal marrow

Laboratory Diagnosis of the Thrombophilic State in Cancer Patients

The Thrombophilic State in Cancer Patients

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