Hemostatic function in hyperfibrinolytic disseminated intravascular coagulation

Abstract

Background Global hemostatic mechanism(s) in patients with disseminated intravascular coagulation (DIC) are poorly understood. There are few diagnostic criteria of DIC based on overall or global hemostatic mechanisms. Methods We have assessed in detailed the dynamic global hemostatic changes using thrombin and plasmin generation assay (T/P‐GA), clot fibrinolytic waveform analysis (CFWA) and not‐activated rotational thromboelastometry (NATEM), in a young girl with DIC associated with acute myeloid leukemia (AML). The ratios of endogenous thrombin potential (T‐EP) and plasmin lag time (P‐LT) relative to normal plasma was sourced from pooled normal plasma from healthy volunteers on T/P‐GA. Results The inverse P‐LT ratio prior to tranexamic acid (TXA) treatment was greater than the T‐EP ratio (1.1–2.8 and 0.83–1.2, respectively). Significant reduction in inverse P‐LT ratio (0.084–1.3) was observed after TXA treatment. The interval from clotting to the initiation of fibrinolysis (fibrinolysis lag time: FLT) in CFWA was significantly shorter than the control at onset (74.2–91.6 s vs 109 s), indicating enhanced fibrinolysis. Data from an adult with acute promyelocytic leukemia‐associated DIC also supportively showed a high inverse P‐LT ratio (2.1) and shortened FLT (83.7 s). The clotting time in patient whole blood using NATEM‐mode during an episode of severe epistaxis markedly shortened beyond control, but returned to normal after the addition of an anti‐tissue factor (TF) monoclonal antibody. Conclusion The release of intravascular TF contributed to sustained activation of coagulation and subsequent fibrinolytic activity in this patient with AML‐associated DIC, and T/P‐GA could provide better quantitative data than conventional assays in these circumstances.

Disordered hemostasis associated with severely depressed fibrinolysis demonstrated using a simultaneous thrombin and plasmin generation assay during L‐asparaginase induction therapy in pediatric acute lymphoblastic leukemia

“…The T/P‐GA technique has recently been described by our research group . Briefly, blood coagulation and fibrinolytic reactions were initiated by the addition of a mixture of optimized final concentrations of tissue factor (1 pM), phospholipid vesicles (4 µM), and tissue‐type plasminogen activator (3.2 nM).…”

“…The T/P-GA technique has recently been described by our research group. [8][9][10][11][12][13] Briefly, blood coagulation and fibrinolytic reactions were initiated by the addition of a mixture of optimized final concentrations of tissue factor (1 pM), phospholipid vesicles (4 µM), and tissue-type plasminogen activator (3.2 nM). Thrombin and plasmin generation were monitored simultaneously using individual fluorescent substrates in separate 96-well microtiter plates.…”

“…9,10 Plasmin generation was delayed in these circumstances, and plasmin generation curves were unreliable at intersections on the time axes (ie, horizontal axes). 9 Following the several recent reports on T/P-GA, [9][10][11][12][13] ratios of T-EP and P-Peak to PNP (as control normal plasma) were calculated to estimate the balance of coagulation and fibrinolytic potential in patients' plasmas. A ratio >1.0 was defined as high coagulation or fibrinolytic potential relative to normal.…”

“…In this context, therefore, we focused on the dynamic hemostatic balance between coagulation and fibrinolysis likely to be associated with the clinical thromboembolisms mediated by induction therapy in pediatric ALL. Recently, a novel assay designed to assess the interplay between coagulation and fibrinolysis with the simultaneous measurement of thrombin and plasmin generation has been established and utilized in several hemostatic disorder reports . In the present study, we have extended these investigations to assess the balance of coagulation and fibrinolytic potential using the thrombin and plasmin generation assay (T/P‐GA) during induction chemotherapy in 72 children newly diagnosed with ALL.…”

“…Recently, a novel assay designed to assess the interplay between coagulation and fibrinolysis with the simultaneous measurement of thrombin and plasmin generation has been established and utilized in several hemostatic disorder reports. [8][9][10][11][12][13] In the present study, we have extended these investigations to assess the balance of coagulation and fibrinolytic potential using the thrombin and plasmin generation assay (T/P-GA) during induction chemotherapy in 72 children newly diagnosed with ALL.…”