Increase in the <i>D</i>-Dimer Levels during Treatment in Patients with Acute Myelogenous Leukemia

Abstract

Plasma concentration of thrombin-antithrombin III complex (TAT), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-2, D-dimer complex and urokinase-plasminogen activator (u-PA) activity were studied in 30 patients with acute nonlymphoblastic leukemia (ANLL), before and during antileukemic therapy. Fifteen patients showed signs of disseminated intravascular coagulation (DIC), 10 of them classified as M3, 2 as M2 and 3 as M5 subtypes. The initial levels of TAT complex were elevated in all ANLL patients. This increase was more pronounced in patients with DIC (p < 0.05). TAT increased significantly during the treatment period in all cases. u-PA and PAI-1 levels were elevated but there were no statistically significant differences between patients with and without DIC. PAI-2 levels were below the limit of detection in controls and in patients. However, the initially elevated D-dimer complex levels were significantly higher in DIC cases (p < 0.01) and they increased during the treatment period. A significant and positive correlation between D-dimer and TAT complex values was found in DIC patients (r = 0.68, p < 0.001). The high TAT complex and D-dimer levels further increased during chemotherapy treatment strongly suggest a hypercoagulable state with secondary activation of fibrinolysis not severe enough to manifest itself as clinically evident DIC in the majority of cases.

Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia

“…The increased D-dimer levels during CR following chemotherapy treatment suggest a hypercoagulable state with secondary activation of fibrinolysis. Velasco et al (46). Observed an increase in the D-dimer level during treatment in patients with AML.…”

Tissue Factor (TF) and Urokinase Plasminogen Activator Receptor (uPAR) and Bleeding Complications in Leukemic Patients

“…Eight patients with acute lymphoblastic leukemia (ALL) according to cytological, cytochemical, cytogenetic and cell surface marker criteria were also studied (16). In these patients, the diagnosis of DIC was established when four of five previously established criteria were met: 1) less than 40% prothrombin activity; 2) prolonged activated partial thromboplastin time (APTT); 3) less than 1.5 g of fibrinogen per 1; 4) increased D-Dimer levels (>5 yglml of plasma); 5) more than 20 kglml of fibrinlfibrinogen degradation products (23). Enhanced fibrinolysis or hyperfibrinolysis, was established by an increase in fibrinlfibrinogen degradation products and reduced antiplasmin activity as described previously (23).…”

“…Routine hemostatic tests were carried out in our laboratory according to published methods (38). Assays for measuring plasmin inhibitory activity and D-Dimer levels were performed as previously described by us (23).…”

“…In ANLL patients, it has been suggested that TF released from leukemic cells is responsible for triggering acute DIC, especially in patients with APL (15)(16)(17)(18)(19)(20)(21)(22). In addition, enhanced fibrinolytic activity also has been found in patients with ANLL (15,23). Although the role of leukemic cells in inducing excessive fibrinolysis is not fully understood (15), the overexpression of the urinary-type plasminogen activator, urokinase (uPA), by these cells has been demonstrated in excessive fibrinolysis (24)(25)(26).…”

The Influence of Low Molecular Weight Heparin on the Intravascular Activation of the Coagulation System in Patients With Acute Leukemia During Induction Chemotherapy--Report of a Prospective Randomized Study

“…Most commonly they appear in laboratory tests and correspond with chronic activation of the coagulation system, manifested in the elevation of such activation markers as F1 þ 2, TAT, DD and PAP [1,12]. The results of basic coagulation tests are usually within the reference range.…”