We present a patient with PC who had a bleeding tendency of which the first sign was purpura. DIC is initiated by TF
 with factor VIIa that activates the extrinsic coagulation pathway. TF is positive in more than 70% of human PCs and increase of TF in patients’ plasma is associated with patient poor prognosis
. The TF expression in the PC cells of this patient (Figure
3) suggests DIC induction by the cancer-derived TF. Coagulation activation results in fibrinogen consumption to some extent but the severe hypofibrinogenemia seen in the present case is unusual in DIC
. This was supported by no correlation between fibrinogen and TAT levels (Figure
2). By LMWH administration, levels of FDP, D-dimer and TAT decreased but the fibrinogen level was not improved (Figure
1). These results indicated that hypofibrinogenemia was not induced by DIC alone. Under normal conditions, plasmin degrades only stable fibrin (cross-linked fibrin) and is immediately inhibited by α2-AP in circulation. If the plasma α2-AP level is below 60% of the normal level, α2-AP is unable to control plasmin sufficiently, thus plasmin also degrades fibrinogen, fibrin monomers and unstable fibrin in addition to stable fibrin
. The high PAP and low α2-AP levels at the hospitalization day 1 (Figure
1) indicated consumption of α2-AP by forming complexes with increased plasmin. Plasmin generates D-dimers only from stable fibrin, whereas FDP derives from either fibrinogen or any forms of fibrin. Accordingly, the decrease in D-dimers/FDP ratio indicated a relative increase in fibrinogenolysis that could lead to hypofibrinogenemia. By the treatment with tranexamic acid, the low fibrinogen level elevated in correlation to the increase in D-dimers/FDP ratio and α2-AP level and to the decrease in PAP level. It is probable that the severe hypofibrinogenemia in this patient was caused by fibrinogenolysis due to excess plasmin production. The low plasma α2-AP level and high plasma PAP level agreed with the fibrinogenolysis observed in a patient with metastatic PC
. Bleeding diathesis of this patient was improved by administration of tranexamic acid in relation to elevation of α2-AP level, suggesting that excessive fibrinolysis induced bleeding diathesis. Platelet and coagulation factors, such as factor VIII and IX, are important in normal hemostasis. From data that the platelet count was within the normal range and clotting time was slightly prolonged, it is unlikely that bleeding diathesis was caused by thrombocytopenia or consumption of coagulation factors. The result that fibrinolysis activation was not improved by anticoagulation therapy alone, suggests an involvement of the primary fibrinolysis, at least partially, in the bleeding diathesis. The plasma uPA level was not measured, but uPA expressed in PC cells probably contributed to excessive fibrinolysis.
Unfractioned heparin has been used for treating patients with DIC complicated with cancer and shown to prolong their survival. Tranexamic acid inhibits plasminogen activation, thereby causing thrombotic tendency in typical DIC cases
, therefore, this agent is usually contraindicative for DIC patients. However, in this case, together with LMWH for DIC, we administered tranexamic acid to the patient who manifested excessive fibrinolysis, and successfully controlled the complicated coagulation disorder. In such a case, tranexamic acid is potentially available for treatment of excessive fibrinolysis.