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1.
Semin Thromb Hemost ; 26(1): 17-21, 2000.
Article in English | MEDLINE | ID: mdl-10805276

ABSTRACT

In the present study, the positive rate of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (sFM), and D-dimer for the diagnosis of disseminated intravascular coagulation (DIC) was evaluated. The study comprised 307 patients with DIC, 123 with pre-DIC, and 121 with non-DIC. Plasma levels of TAT, PPIC, sFM, and D-dimer were significantly higher in DIC and pre-DIC patients than in non-DIC patients. In DIC patients, the positive rate of sFM was high and that of D-dimer was low; the positive rate of PPIC was higher in patients with hematopoietic malignancy than in those without this disease. In pre-DIC patients, the positive rate of all markers was low (<0.16), and the positive rate of PPIC was relatively high. In non-DIC patients, the positive rate of all hemostatic markers was low (<0.16), that of sFM being the lowest. Scoring the positive rate of TAT, PPIC, and sFM disclosed the following results: 72% of DIC patients had three or more points, 17.6% of pre-DIC patients had three or more points, and almost all (96.6%) non-DIC patients had two or less points. Scoring the positive rate of TAT, PPIC, and D-dimer disclosed the following results: 52.9% of DIC patients and 27.4% of pre-DIC patients had three or more points and almost all (96.7%) non-DIC patients had 2 or less points. These data suggest that the combination of TAT, PPIC, and sFM is useful for making the diagnosis of DIC.


Subject(s)
Antifibrinolytic Agents/analysis , Disseminated Intravascular Coagulation/diagnosis , Fibrinolysin/analysis , alpha-2-Antiplasmin , Antithrombin III/analysis , Biomarkers , Disseminated Intravascular Coagulation/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Partial Thromboplastin Time , Peptide Hydrolases/analysis , Thrombophilia/blood , Thrombophilia/diagnosis
2.
Semin Thromb Hemost ; 26(1): 113-8, 2000.
Article in English | MEDLINE | ID: mdl-10805292

ABSTRACT

We evaluated several molecular markers of hemostasis in 92 patients with hypercoagulable states treated with anticoagulant therapy. In all patients, the average values of the international normalized ratio (INR) were 1.70 +/- 0.50; this increase in INR was not, however, significant in patients under thrombotest (TT) monitoring. There were no thrombotic or severe bleeding complications in these patients during a period of 27 months. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were slightly increased, suggesting that anticoagulant therapy was not completely effective in our Japanese patients based on the values of the TT. The INR was negatively correlated with TT, protein C, and protein S and particularly with TT between 10 and 80%. The range of TT was not correlated with the plasma level of TAT, PPIC, D-dimer, or sFM, but the range of INR was correlated with the plasma level of TAT, D-dimer, and sFM. The percentage of TAT, D-dimer, and sFM within normal range was significantly lower in patients with high INR. These findings show that INR is better than TT for the monitoring of warfarin therapy and that the therapeutic values of INR during the anticoagulant therapy should be > 1.7 in Japanese patients.


Subject(s)
Anticoagulants/pharmacology , Antifibrinolytic Agents , Antithrombin III/analysis , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysin/analysis , Hemostasis/drug effects , Peptide Hydrolases/analysis , Warfarin/pharmacology , alpha-2-Antiplasmin/analysis , Adult , Aged , Anticoagulants/therapeutic use , Arterial Occlusive Diseases/blood , Biomarkers , Female , Heart Valve Prosthesis , Humans , International Normalized Ratio , Male , Middle Aged , Protein C/analysis , Protein S/analysis , Pulmonary Embolism/blood , Thrombin Time , Thromboembolism/blood , Venous Thrombosis/blood , Warfarin/therapeutic use
3.
Clin Appl Thromb Hemost ; 6(2): 100-3, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10775031

ABSTRACT

Before hemodialysis (HD), plasma levels of tissue factor (TF), free-TF pathway inhibitor (TFPI) and thrombomodulin (TM) were significantly higher in patients with HD than in healthy volunteers. Plasma levels of (T-F) TFPI and plasmin plasmin inhibitor complex (PPIC) were significantly higher in patients with HD than in healthy volunteers. During HD, plasma levels of TF and (T-F) TFPI were not significantly increased, but plasma levels of total TFPI and free TFPI at 1 hour after and at the end of HD were significantly increased, compared with levels before start of HD. Plasma level of PPIC 1 hour after start of HD was significantly higher than before start of HD, and plasma levels of thrombin antithrombin complex (TAT), PPIC, D-dimer, TM, and protein C (PC) at the end of HD were significantly higher than before start of HD. In patients with thrombosis complications, plasma TF levels were significantly higher than in patients without thrombotic complications during HD. Plasma levels of PC were significantly lower in patients with thrombotic complications than in patients without thrombotic complications. There was no significant difference between both groups during HD in hemostatic parameters, with the exception of TF and PC. Hemostatic abnormalities existed in patients with HD; especially, increased TF and decreased PC might cause thrombotic complications.


Subject(s)
Antifibrinolytic Agents/blood , Antifibrinolytic Agents/metabolism , Fibrinolysin/metabolism , Lipoproteins/blood , Renal Dialysis/adverse effects , Thrombomodulin/blood , Thromboplastin/analysis , Thrombosis/blood , Thrombosis/etiology , alpha-2-Antiplasmin , Antithrombin III/analysis , Biomarkers/blood , Female , Fibrin Fibrinogen Degradation Products/analysis , Hemostasis , Humans , Male , Middle Aged , Peptide Hydrolases/analysis , Reference Values
4.
Am J Hematol ; 61(4): 238-42, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10440909

ABSTRACT

Changes of hemostatic parameters during percutaneous transluminal coronary angioplasty (PTCA) in 75 patients with chronic coronary artery disease were evaluated. Plasma levels of D-dimer, soluble fibrin monomer, plasmin-alpha2 antiplasmin inhibitor complex, and tissue factor (TF) were significantly increased in all patients with chronic coronary artery disease. The activity of antithrombin and protein C and the levels of protein C antigen were significantly decreased 1 hr after PTCA, but they returned to normal range 1 day after PTCA. There was no significant difference in the level of plasma APC-PCI complex before and 1 hr after PTCA. The plasma levels of D-dimer, soluble fibrin monomer, thrombomodulin, TF and PPIC were significantly decreased 1 hr, and the plasma levels of plasmin-alpha2 antiplasmin inhibitor complex 1 day after PTCA. These findings suggest that the decrease of protein C and antithrombin resulted in activation of the coagulation system. One hour after PTCA, the plasma levels of (total-free) TF pathway inhibitor (TFPI) were significantly decreased, but the plasma levels of total and free-TFPI were significantly increased, suggesting that consumption of (total-free) TFPI occurs during PTCA. Overall, these findings suggest that the hypercoagulable state improves during PTCA and that transient decrease of antithrombin, protein C, (total-free) TFPI or plasmin-alpha2 antiplasmin inhibitor complex may cause restenosis of coronary artery.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Disease/blood , Coronary Disease/therapy , Lipoproteins/blood , Pyrimidine Dimers/blood , Serine Proteinase Inhibitors/blood , Thromboplastin/metabolism , alpha-2-Antiplasmin/metabolism , Biomarkers/blood , Blood Coagulation Factors/metabolism , Chronic Disease , Female , Humans , Male , Middle Aged , Protein C/metabolism
5.
Am J Hematol ; 61(1): 21-5, 1999 May.
Article in English | MEDLINE | ID: mdl-10331507

ABSTRACT

Fas, a member of the tumor necrosis receptor superfamily, is 36 kD surface protein containing a single transmembrane region and induces apoptosis by Fas-Fas ligand binding. Soluble Fas (sFas) is produced as the form lacking 21 amino acid residues containing the transmembrane domain by alternative splicing. We found that the plasma sFas levels of 33 patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), 19 patients with disseminated intravascular coagulation (DIC), and 10 non-DIC patients with multiple organ failure (MOF) were significantly higher than those of 21 non-DIC patients without organ failure and those of 25 healthy volunteers. The plasma sFas ligand levels of the TTP/HUS patients, the DIC patients, and the non-DIC patients with MOF were significantly higher than those of the non-DIC patients without organ failure and those of the healthy volunteers. The plasma sFas levels were significantly correlated with the plasma sFas ligand levels in all subjects. The plasma thrombomodulin (TM) levels were increased significantly in the TTP/HUS patients, the DIC patients, and the non-DIC patients with MOF compared with the levels of the non-DIC patients without organ failure and the healthy volunteers. The plasma sFas antigen levels were correlated significantly with the plasma TM levels in all subjects. These findings suggest that the increases of sFas and sFas ligand that cause apoptosis might be related to the vascular endothelial cell injuries in TTP and DIC with organ failure.


Subject(s)
Disseminated Intravascular Coagulation/blood , Membrane Glycoproteins/blood , Purpura, Thrombotic Thrombocytopenic/blood , fas Receptor/blood , Adult , Aged , Alternative Splicing , Disseminated Intravascular Coagulation/complications , Fas Ligand Protein , Female , Humans , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Purpura, Thrombotic Thrombocytopenic/complications , Solubility , Thrombomodulin/blood , fas Receptor/genetics
6.
Am J Hematol ; 60(4): 273-8, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10203100

ABSTRACT

We retrospectively measured various hemostatic markers in 240 patients with disseminated intravascular coagulation (DIC) before the onset of DIC and in 110 non-DIC patients, and examined their usefulness for the diagnosis of pre-DIC. Changes in prothrombin time ratio and fibrinogen levels were not significant before the onset of DIC. The plasma levels of fibrinogen and fibrin degradation products before the onset of DIC were increased and the platelet count was gradually reduced in nonleukemic patients; these changes were already significant in the non-DIC state. The plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were increased before the onset of DIC. In leukemic patients, the plasma levels of sFM on day 5, those of TAT on day 3, and D-dimer on day 1, were significantly increased before the onset of DIC. The levels of most hemostatic markers 7 days before the onset of DIC were not different from those observed in the non-DIC state. In nonleukemic patients, only D-dimer, sFM, and TAT levels were significantly increased 7 days before the onset of DIC compared with values in the non-DIC state. The positive rate of hemostatic markers for the diagnosis of DIC, TAT, and PPIC were high during the pre-DIC and non-DIC groups. The plasma levels of sFM and D-dimer were low in non-DIC and increased gradually during the pre-DIC state. These findings suggest that hemostatic molecular markers such as sFM, D-dimer, and TAT are useful for the diagnosis of pre-DIC, although their cutoff values were different among various diseases.


Subject(s)
Biomarkers/blood , Disseminated Intravascular Coagulation/blood , Hemostasis , alpha-2-Antiplasmin , Antifibrinolytic Agents/blood , Antifibrinolytic Agents/metabolism , Antithrombin III/analysis , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/diagnosis , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/metabolism , Fibrinolysin/metabolism , Humans , Infections/complications , Leukemia/complications , Neoplasms/complications , Peptide Hydrolases/analysis , Platelet Count , Prothrombin Time , Retrospective Studies
7.
Am J Hematol ; 60(2): 94-8, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9929099

ABSTRACT

To evaluate that the relationship between the truncated form of tissue factor pathway inhibitor (TFPI) and the stage of disseminated intravascular coagulation (DIC), we measured the plasma levels of tissue factor (TF) antigen and the intact and truncated forms of TFPI antigens in 41 patients with DIC, 12 with pre-DIC, and 20 with non-DIC. The plasma TF and total TFPI antigen levels were significantly higher in patients with DIC than in non-DIC patients. Plasma levels of intact TFPI antigen in the pre-DIC groups were significantly lower than in the non-DIC and DIC groups. The truncated form of TFPI antigen levels in DIC patients were significantly increased compared with those in non-DIC and pre-DIC patients. The fact that the intact form of TFPI was decreased in pre-DIC patients compared with that in non-DIC patients, suggests that it is consumed in the pre-DIC state and that hypercoagulability occurs in pre-DIC patients. The increased level of the truncated form of TFPI in DIC patients may be attributed to proteolysis of the intact form of TFPI in these patients. The increased level of the truncated form of TFPI may be a useful index for the diagnosis of DIC.


Subject(s)
Disseminated Intravascular Coagulation/blood , Lipoproteins/blood , Peptide Fragments/blood , Endopeptidases/metabolism , Humans , Serine Proteinase Inhibitors
8.
Clin Appl Thromb Hemost ; 5(1): 10-5, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10725976

ABSTRACT

To evaluate the relationship between the tissue factor (TF) pathway and lupus anticoagulant (LA), in the present study, we measured the plasma levels of TF antigen and TF pathway inhibitor (TFPI) antigen in patients positive for LA. Plasma TF and TFPI levels in LA-positive patients were significantly higher than levels in healthy volunteers (p < 0.01). In LA-positive patients, there were no significant differences in plasma TF and TFPI levels between patients with and without thrombosis. In patients with thrombosis, there was no significant difference in the plasma TF level between LA-positive and LA-negative patients; however, the plasma TFPI level in LA-positive patients was significantly lower than that in LA-negative patients (p < 0.01). We also examined the TF pathway in human umbilical venous endothelial cells (HUVEC) incubated with plasma of LA-positive patients, LA-negative patients, and healthy volunteers. TF activity was significantly higher (p < .05) in HUVECs incubated with the plasma of LA-positive patients than in cells incubated with the plasma of the other two groups (p < .01). However, there was no significant difference in TFPI antigen levels among the media of HUVECs incubated with the plasma of all groups. The viability of HUVEC incubated with the plasma of LA-positive patients with thromboses, LA-positive patients without thromboses, and LA-negative patients with thromboses were significantly lower than that of HUVECs incubated with the plasma of healthy volunteers (p < .01). These findings suggest that abnormalities of the TF pathway plays an important role in the mechanism of hypercoagulability in LA-positive patients. LA may affect vascular endothelial cells causing thrombogenesis.


Subject(s)
Lupus Coagulation Inhibitor/blood , Thromboplastin/biosynthesis , Thromboplastin/metabolism , alpha-2-Antiplasmin , Adult , Anticoagulants/blood , Anticoagulants/immunology , Antifibrinolytic Agents/metabolism , Antigens/blood , Antithrombin III/metabolism , Cell Culture Techniques , Cell Survival , Cohort Studies , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Factor Xa Inhibitors , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinolysin/metabolism , Fibrinolytic Agents/blood , Fibrinolytic Agents/immunology , Hemostatics , Humans , Lipoproteins/blood , Lipoproteins/immunology , Lupus Erythematosus, Systemic/blood , Male , Middle Aged , Peptide Hydrolases/metabolism , Serine Proteinase Inhibitors/blood , Serine Proteinase Inhibitors/immunology , Thromboplastin/immunology , Thrombosis/blood , Thrombosis/metabolism , Umbilical Veins/pathology
9.
Blood Coagul Fibrinolysis ; 10(7): 429-34, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10695769

ABSTRACT

The objective of this study was to evaluate several molecular markers of hemostasis in 84 patients with hypercoagulable state, treated with warfarin under thrombo-test (TT) monitoring; TT was expressed as percent of control (TT%). In all patients, the average values of international normalized ratio (INR) of prothrombin time (PT;PT-INR) was 1.68+/-0.49; this increase in PT-INR was not, however, significant in patients under TT% monitoring. There were no thrombotic or severe bleeding complications in these patients during a period of 2 years. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were slightly increased, suggesting that anticoagulant therapy was not completely effective in our Japanese patients based on the values of TT%. Activated partial thromboplastin time, PT-INR, TT% and protein C activity were significantly correlated with the dose of warfarin; fibrinogen, activated thromboplastin, TAT, PPIC, D-dimer, sFM, protein S and thrombomodulin were not significantly correlated with the dose of warfarin. The PT-INR was negatively correlated with TT%, protein C and protein S, and the correlation between PT-INR and TT-INR was better than that between PT-INR and TT%. The range of TT% was not correlated with the plasma levels of TAT, PPIC, D-dimer or sFM, but the range of PT-INR was correlated with the plasma level of TAT, D-dimer and sFM. The percentage of TAT, D-dimer and sFM within normal range was significantly low in patients with high PT-INR. These finding showed that PT-INR is better than TT% for monitoring the anticoagulant therapy with warfarin, and that TT should be expressed as INR. The values of PT-INR should be more than 1.7 during the anticoagulant therapy with warfarin in Japanese patients with high risk of thrombosis.


Subject(s)
Anticoagulants/pharmacology , Hemostasis , Thrombophlebitis/blood , Thrombophlebitis/drug therapy , Adult , Anticoagulants/therapeutic use , Biomarkers , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , International Normalized Ratio , Japan , Male , Middle Aged
10.
Blood Coagul Fibrinolysis ; 9(6): 491-7, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9818999

ABSTRACT

In healthy volunteers, the plasma total tissue factor pathway inhibitor (TFPI) level was 68.7+/-14.1 ng/ml; the plasma free TFPI level, 17.7+/-5.4 ng/ml; the lipoprotein-associated TFPI (LP-TFPI), 51.1+/-12.0 ng/ml; the free TFPI/total TFPI ratio 0.26+/-0.07; and the plasma tissue factor levels were 149+/-46 pg/ml. Plasma tissue factor levels in patients with disseminated intravascular coagulation (DIC) were significantly higher than those in pre-DIC patients or in non-DIC patients. Plasma total-TFPI, free-TFPI and LP-TFPI levels were significantly higher in DIC patients than those in pre-DIC patients or in non-DIC patients. Before the onset of DIC, the plasma levels of tissue factor gradually increased, and 3 days before the onset of DIC they were significantly higher than those in non-DIC patients. The plasma levels of tissue factor reached their highest level 1 day before the onset of DIC and gradually decreased after the onset of DIC. Plasma levels of total-TFPI, free-TFPI, and LP-TFPI gradually increased before the onset of DIC, and the total-TFPI and LP-TFPI reached their highest levels at the onset of DIC. Plasma free-TFPI reached highest level one day after the onset of DIC. During the clinical course of DIC, the plasma level of tissue factor was the first to increase, then that of LP-TFPI and finally the free-TFPI plasma levels. These differences in the peak plasma levels of tissue factor, free-TFPI, and LP-TFPI might be related to the clinical course of DIC.


Subject(s)
Disseminated Intravascular Coagulation/blood , Lipoproteins/blood , Serine Proteinase Inhibitors/blood , Disseminated Intravascular Coagulation/diagnosis , Female , Humans , Male , Reference Values , Retrospective Studies , Thromboplastin/analysis
11.
Am J Hematol ; 58(3): 189-94, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9662269

ABSTRACT

Various hemostatic and vascular endothelial cell markers were measured in patients with disseminated intravascular coagulation (DIC), non-DIC, or thrombotic thrombocytopenic purpura (TTP) and in healthy volunteers to examine the relationships between the hemostatic abnormalities or vascular endothelial cell injuries and the patients' outcomes. Although the plasma levels of soluble fibrin monomer, thrombin-antithrombin complex, plasmin-plasmin inhibitor complex, and D-dimer were significantly increased in the DIC patients, there were no significant differences in these markers between the DIC patients who survived and those who died, suggesting that these markers might not be directly related to the patient outcome. The plasma thrombomodulin (TM) levels in the DIC and TTP patients were significantly higher than those in the healthy volunteers, and the plasma TM levels in the patients who died were significantly higher than those in the patients who survived. These findings showed that the TM level reflected the outcome, and that the outcome of the diseases underlying DIC and TTP might depend on vascular endothelial cell injuries. The plasma protein C and antithrombin activities were markedly reduced in the DIC, non-DIC, and TTP patients who died compared to those who survived. These findings suggest that reduced plasma antithrombin and protein C activities are useful markers of systemic vascular endothelial injuries. Although the plasma tissue factor (TF) levels were significantly increased in the DIC patients, there was no significant difference in the plasma TF levels between the DIC patients who died and those who survived. In conclusion, we found that the outcome of the diseases underlying DIC and TTP is related to vascular endothelial cells, and that plasma TM, antithrombin, and protein C are useful markers for systemic vascular endothelial cell injury.


Subject(s)
Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/physiopathology , Endothelium, Vascular/pathology , Purpura, Thrombotic Thrombocytopenic/mortality , Purpura, Thrombotic Thrombocytopenic/physiopathology , alpha-2-Antiplasmin , Antifibrinolytic Agents/analysis , Antifibrinolytic Agents/blood , Antithrombin III/analysis , Antithrombins/analysis , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysin/analysis , Fibrinolytic Agents/analysis , Hemolytic-Uremic Syndrome/blood , Humans , Partial Thromboplastin Time , Peptide Hydrolases/analysis , Protein C/analysis , Prothrombin Time , Survival Rate , Thrombomodulin/blood
12.
Blood Coagul Fibrinolysis ; 8(6): 345-9, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9351524

ABSTRACT

The serum levels of thrombopoietin (TPO) were measured in 16 patients with thrombotic thrombocytopenic purpura (TTP), 12 with hemolytic uremic syndrome (HUS), 10 with aplastic anemia (AA), 10 with disseminated intravascular coagulation (DIC), and 71 with idiopathic thrombocytopenic purpura (ITP). The serum TPO levels were measured with a sensitive sandwich enzyme-linked immunosorbent assay. The serum TPO level in the ITP group (1.68 +/- 0.85 fmol/ml) were not significantly increased compared with those of the normal subjects. The TPO levels in the TTP (2.77 +/- 1.38 fmol/ml) and HUS groups (5.77 +/- 4.41 fmol/ml) were higher than those of the normal subjects. The patients with AA (12.7 +/- 8.0 fmol/ml) and those with DIC (13.3 +/- 5.7 mol/ml) had significantly higher serum TPO levels than did the normal subjects and ITP patients. The TPO levels were well correlated with the platelet counts in the TTP patients, and were negatively correlated with the platelet counts in the ITP patients. These results suggest that the serum TPO levels in some thrombocytopenic diseases are regulated not only by the platelet count and the megakaryocyte mass, but also by other factors.


Subject(s)
Disseminated Intravascular Coagulation/blood , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombotic Thrombocytopenic/blood , Thrombopoietin/blood , Adult , Anemia, Aplastic/blood , Female , Hemolytic-Uremic Syndrome/blood , Humans , Iodide Peroxidase/blood , Male , Middle Aged , Platelet Count
13.
Am J Hematol ; 55(4): 169-74, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9257875

ABSTRACT

We measured the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. Plasma TF (273 +/- 90 pg/ml) and TFPI (252 +/- 125 ng/ml) levels were significantly increased in patients with DIC compared with non-DIC patients. Plasma TF antigen level was significantly increased in pre-DIC patients (285 +/- 85 pg/ml), while the plasma TFPI level (152 +/- 54 ng/ml) was not markedly increased in such a state. The plasma TF/TFPI ratio was high in the pre-DIC patients (2.10 +/- 0.90), and low in the DIC patients (1.40 +/- 0.87) and healthy volunteers (0.84 +/- 0.26). There was no significant difference between the DIC patients with a good outcome and those with a poor outcome in terms of plasma TF levels, although the plasma TFPI level in the DIC patients with a good outcome (289 +/- 133 ng/ml) was significantly higher than those with a poor outcome (187 +/- 75 ng/ml). During the clinical course of DIC, plasma TF antigen was increased first, and an increase of the plasma TFPI level followed the increase in plasma TF level. These findings suggest that plasma TFPI is released from vascular endothelial cells and it may reflect vascular endothelial cell injury. It is conceivable that TF and TFPI may play an important role in the onset of DIC.


Subject(s)
Anticoagulants/blood , Disseminated Intravascular Coagulation/blood , Lipoproteins/blood , Thromboplastin/analysis , Endothelium, Vascular/physiology , Humans , Prognosis
14.
Am J Hematol ; 55(4): 183-7, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9257877

ABSTRACT

We examined hemostatic abnormalities in 23 patients with acute myocardial infarction (AMI), 10 with pulmonary embolism (PE), and 10 with deep vein thrombosis (DVT). At the onset of AMI, plasma levels of tissue-type plasminogen activator (t-PA), PA inhibitor-I (PAI-I), fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PPIC) were significantly increased. Both the plasma total TFPI and free-TFPI levels in the AMI patients were significantly higher than those in the healthy volunteers, PE patients, and DVT patients. There was no significant difference in total TFPI or free-TFPI among patients with PE, those with DVT, and healthy volunteers. One hour after percutaneous transluminal coronary angioplasty (PTCA) in the AMI group, the total TFPI level was further increased, and it was significantly reduced 24 hr after PTCA, to a level similar to that in healthy volunteers. Free-TFPI showed a pattern similar to that of total TFPI. The ratio of free-TFPI/total TFPI was highest 1 hr after PTCA. Increased TFPI in AMI patients might be released from ischemic tissues.


Subject(s)
Lipoproteins/blood , Myocardial Infarction/blood , alpha-2-Antiplasmin , Adult , Angioplasty, Balloon, Coronary , Antifibrinolytic Agents/analysis , Antifibrinolytic Agents/blood , Antithrombin III/analysis , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysin/analysis , Humans , Male , Middle Aged , Peptide Hydrolases/analysis , Plasminogen Activator Inhibitor 1/blood , Pulmonary Embolism/blood , Thrombosis/blood , Tissue Plasminogen Activator/blood
15.
Blood Coagul Fibrinolysis ; 8(5): 303-7, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9282795

ABSTRACT

We measured the plasma levels of fibrinogen, D-dimer, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (SFM), tissue-type plasminogen activator (t-PA) and thrombomodulin (TM) in patients with non-insulin-dependent diabetes mellitus (NIDDM). There were no significant differences in the hemostatic parameters between the 77 patients with NIDDM and healthy control subjects, although the plasma levels of fibrinogen, D-dimer, TAT, and PPIC in the NIDDM patients were slightly higher than those in the healthy controls. Among the NIDDM patients divided into three groups by the urinary albumin excretion (UAE) level, there was no significant difference in age or sex among the normo-, micro-, and macroalbuminuria groups, and the HbA1C level in the micro- and macroalbuminuria groups were slightly higher than those in the normoalbuminuria group. There was no significant difference in activated partial thromboplastin time, prothrombin time, fibrinogen, TAT, PPIC, D-dimer, or t-PA among these three groups. The plasma SFM and TM levels in the macroalbuminuria group were significantly higher than those in the normo- and microalbuminuria groups. The relationships between HbA1C and the hemostatic parameters were poor, but the plasma TM and SFM levels were significantly correlated with the urine albumin index.


Subject(s)
Albuminuria/blood , Diabetes Mellitus, Type 2/blood , Fibrin/analysis , Thrombomodulin/blood , Adult , Aged , Female , Humans , Male , Middle Aged , Prothrombin Time
16.
Am J Hematol ; 55(1): 9-14, 1997 May.
Article in English | MEDLINE | ID: mdl-9136911

ABSTRACT

We examined plasma levels of activated factor VII (F VIla) in 50 patients positive for lupus anticoagulant (LA), in 83 patients negative for LA, and in 10 healthy volunteers as controls. Plasma F VIIa was present in healthy volunteers; its level was significantly increased, compared to the level in the controls, in patients with thrombosis, collagen diseases, and disseminated intravascular coagulation (DIC), suggesting that it reflected a thrombotic state. Plasma F VIIa was correlated with thrombin-antithrombin complex (TAT) in patients negative for LA but showed no such correlation in those positive for LA. Plasma F VIIa was negatively correlated with activated partial thromboplastin time (APTT) in patients positive for LA, but not in those negative for LA, suggesting that LA could inhibit the F VIIa assay system. Plasma F VIIa level was significantly increased in patients with thrombotic diseases; however, in patients positive for LA, it is possible that increased plasma F VIIa level may not be correlated with thrombogenicity.


Subject(s)
Factor VIIa/metabolism , Lupus Coagulation Inhibitor/blood , Collagen Diseases/blood , Disseminated Intravascular Coagulation/blood , Hemostasis , Humans , Partial Thromboplastin Time , Thrombosis/blood
17.
Blood Coagul Fibrinolysis ; 7(8): 794-8, 1996 Nov.
Article in English | MEDLINE | ID: mdl-9034561

ABSTRACT

Plasma activated factor VIIa (FVIIa) levels were measured in various diseases using mutant tissue factor (TF). FVIIa levels in thrombotic patients and patients with idiopathic thrombocytopenic purpura were significantly higher than those in healthy control subjects. The plasma FVIIa levels in thrombotic patients treated with warfarin were similar to those of control subjects. The plasma FVIIa levels in pregnant women and patients with systemic lupus erythematosus, infection or malignancies were high. However, the levels in patients with disseminated intravascular coagulation (DIC) were not significantly increased. DIC patients are in a severe hypercoagulable state, and exhibit severe consumption of coagulation factors. The slightly increased FVIIa level in the DIC patients observed is probably considered to be caused by consumption of coagulation factors. The plasma FVIIa level was poorly correlated with other hemostatic parameters except for protein C in our analysis of all cases. In the analysis of DIC and thrombotic patients treated without warfarin, the plasma FVIIa level was negatively correlated with TF antigen. Plasma FVIIa levels might reflect hypercoagulability in thrombotic diseases, and a normalized FVIIa level in patients with thrombotic diseases should be considered to be associated with DIC.


Subject(s)
Autoimmune Diseases/blood , Communicable Diseases/blood , Factor VIIa/analysis , Hematologic Diseases/blood , Neoplasms/blood , Pregnancy/blood , Biomarkers , Female , Humans , Male
18.
Am J Hematol ; 52(3): 165-70, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8756081

ABSTRACT

We measured the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. Plasma TF (273 +/- 90 pg/ml) and TFPI (252 +/- 125 ng/ml) levels were significantly increased in patients with DIC compared with non-DIC patients. Plasma TF antigen level was significantly increased in pre-DIC patients (285 +/- 85 pg/ml), while the plasma TFPI level (152 +/- 54 ng/ml) was not markedly increased in such a state. The plasma TF/TFPI ratio was high in the pre-DIC patients (2.10 +/- 0.90), and low in the DIC patients (1.40 +/- 0.87) and healthy volunteers (0.84 +/- 0.26). There was no significant difference between the DIC patients with a good outcome and those with a poor outcome in terms of plasma TF levels, although the plasma TFPI level in the DIC patients with a good outcome (289 +/- 133 ng/ml) was significantly higher than that in those with a poor outcome (187 +/- 75 ng/ml). During the clinical course of DIC, plasma TF antigen was increased first, and an increase of the plasma TFPI level followed the increase in plasma TF level. These findings suggest that plasma TFPI is released from vascular endothelial cells and it may reflect vascular endothelial cell injury. It is conceivable that TF and TFPI may play an important role in the onset of DIC.


Subject(s)
Disseminated Intravascular Coagulation/blood , Lipoproteins/blood , Thromboplastin/metabolism , Anticoagulants/blood , Disseminated Intravascular Coagulation/drug therapy , Humans , Reference Values , Treatment Outcome
19.
Am J Hematol ; 51(4): 255-60, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8602623

ABSTRACT

Plasma-soluble fibrin monomer (SFM) level in patients with disseminated intravascular coagulation (DIC) was significantly higher than the level in patients with pre-DIC or in non-DIC patients, and the level in patients with pre-DIC was significantly higher than that in non-DIC patients. There was no significant difference in plasma SFM levels among various diseases underlying DIC. Plasma SFM level in patients with good outcome was significantly decreased after treatment for DIC. The sensitivity of fibrin degradation products and platelet number was high for DIC, but not for pre-DIC. The sensitivity of thrombin-antithrombin III complex, plasmin-plasmin inhibitor complex, and SFM was high for both DIC and pre-DIC. The specificity of these markers was also high. Receiver operating characteristic analysis suggests that plasma SFM level could be the most useful marker for the diagnosis of both DIC and pre-DIC.


Subject(s)
Disseminated Intravascular Coagulation/blood , Enzyme-Linked Immunosorbent Assay , Fibrin Fibrinogen Degradation Products/analysis , Amino Acid Sequence , Animals , Antibodies, Monoclonal/immunology , Blood Coagulation Tests , Disseminated Intravascular Coagulation/mortality , Fibrin/immunology , Humans , Leukemia/blood , Molecular Sequence Data , Neoplasms/blood , Platelet Count , Prognosis , Retrospective Studies , Sensitivity and Specificity , Sepsis/blood
20.
Pol J Pharmacol ; 48(2): 225-8, 1996.
Article in English | MEDLINE | ID: mdl-9112656

ABSTRACT

We examined various hemostatic abnormalities in 395 patients with disseminated intravascular coagulation (DIC), in 177 patients in a Pre-DIC stage, and in 99 patients who did not exhibit DIC. Pre-DIC was defined as the condition at least one week before the onset of DIC. The differences in activated partial thromboplastin time (APTT), FDP, prothrombin time (PT) ratio, fibrinogen, and platelet count between DIC and Non-DIC patients were significant, but there were no significant differences in these parameters between Pre-DIC and Non-DIC patients. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (sFM), prothrombin activated peptide F1 + 2 (F1 + 2), thrombomodulin (TM), tissue type plasminogen activator (t-PA), and PA inhibitor (PAI-I) in DIC patients were significantly higher than levels in Non-DIC patients. However, only TAT, sFM and PAI-I values in the Pre-DIC patients were significantly higher than the values in the Non-DIC patients. Almost all the hemostatic molecular markers examined had high sensitivity for DIC, but only TAT and PPIC had high sensitivity for Pre-DIC. Specificity for DIC was also high with TAT, sFM, and F1 + 2. Early diagnosis and early treatment are important in DIC; we believe that it is possible to predict Pre-DIC by assessing values for the combination of hemostatic molecular markers.


Subject(s)
Biomarkers/blood , Disseminated Intravascular Coagulation/diagnosis , Antithrombin III/metabolism , Disseminated Intravascular Coagulation/blood , Fibrin/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Fibrinolysin/antagonists & inhibitors , Fibrinolysin/metabolism , Humans , Partial Thromboplastin Time , Peptide Hydrolases/metabolism , Platelet Count , Prothrombin Time
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