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Biomedical subjects

W Tatewaki

Publications and source records attributed to W Tatewaki.

At least 37 records · Page 2Linked to original sources
PubMed1990

Thrombin vs. plasmin generation in disseminated intravascular coagulation associated with various underlying disorders.

In order to assess the thrombin and plasmin generation in vivo in disseminated intravascular coagulation (DIC), plasma levels of thrombin-antithrombin III (ATIII) complex (TAT) and plasmin-alpha 2-antiplasmin (a2AP) complex (PAP) were measured together with standard coagulation and fibrinolytic parameters in 80 patients with DIC. Both TAT and PAP were markedly elevated in patients with DIC. When plotted by the underlying disease categories, differences in the magnitude of the elevations of these complexes were recognized among groups. Patients with acute promyelocytic leukemia (APL) had the highest PAP, the lowest TAT/PAP ratio, low a2AP, and low fibrinogen, indicating that the most excessive fibrinolysis can occur in APL. Similar profiles, although less marked, were observed in patients with other leukemias and vascular diseases. Patients with sepsis showed the highest TAT/PAP ratio and the lowest PAP with no decrease in a2AP or fibrinogen, demonstrating a relatively impaired fibrinolysis. Patients with cancer had a relatively high TAT and high TAT/PAP ratio. In addition, both TAT and PAP were markedly elevated in patients with shock. From these, it was suggested that, although laboratory manifestations in DIC are extremely variable from patient to patient, underlying disorders are, at least in part, responsible for the observed variations. Recognition of this variable activation of coagulation and fibrinolysis would be helpful for the proper management of patients with DIC.

Adolescent↗
PubMed1990

Fibrinolysis and fibrinogenolysis in liver disease.

Patients with liver disease frequently have hemostatic abnormalities which include accelerated fibrinolysis. In order to assess the fibrinolytic state in liver disease, plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP), and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 36 patients with liver disease (six patients with acute hepatitis, seven with chronic hepatitis, ten with liver cirrhosis, 11 with hepatocellular carcinoma, and two with intrahepatic cholestasis). As compared with healthy subjects, mean plasma levels of FbDP (1,083 +/- SD 1,254 vs. 236 +/- 100 ng/ml, P = 0.005) and TDP (1,773 +/- 1,814 vs. 669 +/- 212 ng/ml, P = 0.001) were significantly elevated in patients with liver disease, whereas FgDP was normal (389 +/- 202 vs. 396 +/- 132 ng/ml, P = 0.87). Plasma FbDP correlated very well with TDP (r = 0.986, P less than 0.00001) in liver disease. In addition, FbDP and TDP but not FgDP correlated with plasma concentrations of thrombin-antithrombin III complex. When plotted by the disease categories, the magnitude of elevations of FbDP and TDP was the most prominent in acute hepatitis followed by hepatocellular carcinoma. These findings indicate that activation of fibrinolysis occurs following thrombin generation, but increased primary fibrinogenolysis is rare in liver disease.

Antithrombin III↗
PubMed1990

[Effect of splenectomy for management of thrombocytopenia associated with systemic lupus erythematosus: a case report].

A 51-year-old female with systemic lupus erythematosus (SLE) was admitted in November 1987 because of general fatigue and muscular weakness. She was treated with prednisolone (PSL) 30 mg and azathioprine (AZP) 50 mg after failure in the management of thrombocytopenia by PSL 15 mg. She exhibited no splenomegaly. Muscular atrophy and weakness were seen in the proximal muscles. Her platelet count was 44,000/microliters. A bone marrow aspiration revealed an increase in megakaryocytes. The blood chemistry revealed a normal CPK level and an elevated LDH level, indicating a presence of steroid myopathy. A splenectomy was performed after an increase of platelet count by giving gamma-globulin 400 mg/kg for 5 days. The platelet count rose to 368,000/microliters on the 46th postoperative day. She was treated with PSL 5 mg and AZP 50 mg as postsplenectomy therapy. The splenectomy did not adversely affect other aspects of SLE, in particular, renal function. She had no major complications in the postoperative period. Her platelet count reached a plateau 4 months later and revealed 115,000/microliters 18 months postoperatively.

Female↗
PubMed1989

Plasmin-a2-plasmin inhibitor complex in plasma of patients with thromboembolic diseases.

Plasmin generation in vivo was assessed by measuring plasma levels of plasmin-a2-plasmin inhibitor complex (PAP) with an ELISA in 42 patients with arterial or venous thromboembolic diseases. Plasma concentration of PAP was markedly elevated in patients with venous thromboembolic diseases during acute illness (3.32 +/- 3.71 ug/ml, mean +/- SD) as compared to healthy subjects (0.24 +/- 0.13 ug/ml, n = 14), while it was nearly normal (0.30 +/- 0.13 ug/ml) in patients with venous thromboembolic diseases in chronic stage. Patients with arterial thromboembolism had modestly elevated PAP; 1.05 +/- 0.77 ug/ml during acute episode, and 0.84 +/- 0.40 ug/ml in chronic stage. These results indicate that excessive activation of fibrinolytic system (plasmin generation in vivo) occurs actually in many patients with thrombotic diseases, especially in venous thromboembolic diseases during acute illness.

Acute Disease↗
PubMed1989

Plasma von Willebrand factor proteolysis in patients with chronic myeloproliferative disorders: no possibility of ex vivo degradation by calcium-dependent proteases.

Patients with chronic myeloproliferative disorders (CMPD) frequently have abnormalities of plasma von Willebrand factor (vWf) multimers. The pathogenesis of this phenomenon is still unknown. In order to evaluate the possibility of ex vivo degradation of vWf during blood processing, we compared vWf antigen, ristocetin cofactor and the multimeric composition of vWf in plasmas obtained in the presence of trisodium citrate with or without calcium-dependent protease inhibitors (leupeptin, N-ethylmaleimide and Na2EDTA). The subjects included 20 patients with CMPD, 11 with other diseases and 8 normal subjects. In patients with CMPD and normal subjects, the values of vWf antigen, ristocetin cofactor, ristocetin cofactor/vWf antigen ratio and the relative amount of large multimers of vWf did not significantly differ from each other in plasma samples with and without protease inhibitors. In other diseases, especially in a patient with disseminated intravascular coagulation, a somewhat higher amount of large multimers were found in plasma with protease inhibitors than without inhibitors. These findings indicate that the ex vivo proteolysis during blood processing is negligible in patients with CMPD, and that the observed abnormalities in vWf is an in vivo phenomenon.

Calcium↗
PubMed1989

Activation of blood coagulation and fibrinolysis in diabetes mellitus: evaluation by plasma levels of thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex.

Diabetes mellitus (DM) is associated with an increased incidence of vascular complications. Abnormalities in the hemostatic system contribute at least in part to the development of vascular disease or atherosclerosis. In order to assess the actual degree of activation of the coagulation and fibrinolytic systems in diabetics, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP) were measured together with tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 18 patients with DM (three patients with type I DM and 15 with type II DM). Mean plasma levels of TAT (2.5 +/- SD 1.2 ng/mL) and PAP (0.9 +/- 1.2 micrograms/mL) were significantly elevated in diabetics as compared with healthy subjects (1.7 +/- 0.3 ng TAT and 0.2 +/- 0.1 micrograms PAP per mL of plasma; p = 0.009 and 0.02, respectively). Plasma antigen concentration of t-PA but not of PAI-1 was also elevated. No difference was found in the levels of these variables between type I and type II diabetics or between patients with and without retinopathy or nephropathy. These findings indicate that continuous activation of coagulation and fibrinolysis actually occurs in the majority of the patients with DM.

Adult↗
PubMed1989

Plasma protein S in disseminated intravascular coagulation, liver disease, collagen disease, diabetes mellitus, and under oral anticoagulant therapy.

Plasma levels of protein S (PS) antigen, both total and free fractions, were measured together with C4b-binding protein (C4bp) and protein C (PC) antigen in 39 patients with disseminated intravascular coagulation (DIC), 34 with liver disease, 17 with collagen disease, 17 with diabetes mellitus, and 51 under stabilized warfarin treatment. In patients with DIC, mean concentrations of total PS and free PS were normal, while PC was reduced and C4bp were elevated. Total PS, free PS, C4bp and PC were all decreased in liver disease, elevated in diabetes mellitus, and normal in collagen disease. In warfarin-treated patients, total PS, free PS and PC were moderately decreased, but the decrease in C4bp was minimal. The concentration of PS correlated positively with PC in liver disease, diabetes mellitus, and during oral anticoagulation, but did not in DIC. These results indicate that PS and PC behave similarly when liver synthetic function is principally affected, but in contrast to PC, PS is hardly consumed during intravascular coagulation.

Administration, Oral↗
PubMed1989

Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von Willebrand factor and protein S.

The profile of blood coagulation and fibrinolysis was studied in detail in eight patients with acute thrombotic thrombocytopenic purpura (TTP). In the majority of the patients, fibrinogen, factor XIII, antithrombin III, alpha 2-plasmin inhibitor, plasminogen, and alpha 2-macroglobulin were normal, whereas FDP, plasmin-alpha 2-plasmin inhibitor complex, and tissue-type plasminogen activator antigen were marginally or moderately elevated. Low fibronectin values were observed in four patients. Protein C and C4b-binding protein were nearly normal, whereas total protein S and free protein S were reduced in five and six patients, respectively. A positive correlation was found between total protein S and C4 and between free protein S and C3. von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCof) were either normal or elevated, but RCof/vWf:Ag ratio was decreased in seven patients. Crossed immunoelectrophoresis and sodium dodecyl sulfate (SDS)-agarose gel electrophoresis revealed that the large vWf multimers were either absent from or relatively decreased in all patients except one. In addition, one patient had unusually large vWf multimers, and a low-molecular-weight vWf fragment was apparently observed in three patients. These findings indicate that the intravascular generation of thrombin and plasmin was minimal in TTP and suggest that the alterations of the vWf molecule were caused not only by consumption through its participation in platelet thrombus formation but also by accelerated proteolysis. Low protein S values would be related to the immunological abnormalities underlying TTP.

Adolescent↗
PubMed1989

Thrombin and plasmin generation in patients with liver disease.

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.

Antithrombin III↗
PubMed1989

Thrombin generation in patients with thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is thought to be caused primarily by endothelial cell injury or primary platelet agglutination. A coagulation screen usually shows normal or minimal changes, but a modest elevation of fibrinogen/fibrin degradation products (FDP) is observed in many patients with TTP. To assess the thrombin generation in vivo in TTP, plasma levels of thrombin-antithrombin III complex (TAT) were measured together with plasmin-alpha 2-antiplasmin complex (PAP) in ten patients with acute TTP. Plasma TAT [mean 6.7 +/- (SD) 3.7 micrograms/liter] as well as PAP (2.1 +/- 1.2 mg/liter) were elevated in patients with TTP as compared with healthy subjects (TAT of 1.7 +/- 0.3 microgram/liter and PAP of 0.2 +/- 0.1 mg/liter; n = 10). These findings indicate that considerable amounts of thrombin and plasmin are actually generated in TTP, although the majority of patients do not show signs of consumption coagulopathy.

Adult↗
PubMed1988

Multimeric composition of plasma von Willebrand factor in chronic myelocytic leukaemia.

We studied the multimeric composition of plasma von Willebrand factor (vWf) in 26 patients with chronic myelocytic leukaemia (CML); 13 in chronic phase, 8 in blast crisis, 5 in both chronic phase and blast crisis. The relative amount of large (multimer band greater than or equal to 11) multimers calculated by densitometer scan following SDS-agarose gel electrophoresis was 14.6 +/- 2.9% (mean +/- SD) in normal controls, 8.7 +/- 4.7% in chronic phase and 15.0 +/- 5.2% in blast crisis. CML patients in chronic phase (but not in blast crisis) had a significantly lower percentage of large multimers than normal controls (p less than 0.001). The relative amount of large multimers was positively correlated with a ratio of ristocetin cofactor/vWf antigen (p less than 0.005), and was negatively correlated with platelet count (p less than 0.001), WBC count (p less than 0.05) and granulocyte count (p less than 0.05). We conclude that some patients with CML, especially in chronic phase, lack large multimers. The negative correlation of the relative amount of large multimers with platelet and granulocyte count suggests that large multimers may be consumed in high platelet count states or degraded by protease(s) from increased blood cells.

Adult↗
PubMed1988

Behavior of protein S during long-term oral anticoagulant therapy.

It has recently been reported that a natural anticoagulant, protein S (PS), is depressed during oral anticoagulation. Since more detailed information is required from the clinical standpoint, we measured plasma levels of PS [both total and free (not complexed) PS antigen], C4b-binding protein (C4bp) and other vitamin K-dependent proteins (factors II, VII, IX, X and protein C) in 60 plasma samples from patients on long-term oral anticoagulant therapy with warfarin. Together with the reduction of other vitamin K-dependent plasma proteins, PS decreased during warfarin treatment, being dependent on the intensity of the therapy. A considerable variation in plasma PS levels was also observed among individuals with a similar intensity of anticoagulation. Plasma concentration of C4bp was closely correlated with total PS level, and free PS/total PS ratio was independent of thrombotest values. These findings indicate that long-term oral anticoagulant therapy results in the suppression of the synthesis of PS, and that its reduction is on the whole balanced with C4bp and vitamin K-dependent coagulation factors. It was suggested that the metabolism of C4bp might be regulated by the plasma PS level, although this hypothesis needs further exploration.

Administration, Oral↗
PubMed1988

Fast functional assay of protein C in whole plasma using a snake venom activator: evaluation in patients with congenital and acquired protein C deficiencies.

Both anticoagulant and amidolytic activities of protein C (PC) were measured using a snake venom activator in 4 patients with hereditary PC deficiency, 37 with disseminated intravascular coagulation (DIC), and 30 under stabilized warfarin therapy. The results were compared with those obtained by an immunological assay (ELISA). PC levels measured by different functional and immunological assays were very close in patients with hereditary PC deficiency and DIC. In patients under stable oral anticoagulant therapy, there was no detectable difference between amidolytic activity and antigen levels of PC in each patient plasma, whereas a decrease in anticoagulant activity was much more pronounced. These results indicate that the present activity assays measure PC specifically, and that the snake venom activator is capable of activating both carboxylated and hypocarboxylated forms of PC, but only anticoagulant assay can evaluate the physiological PC function in vitamin K-deficient states.

Biological Assay↗
PubMed1988

Plasmin-alpha 2-plasmin inhibitor complex in plasma of patients with disseminated intravascular coagulation.

Plasmin-alpha 2-plasmin inhibitor (alpha 2PI) complex, an indicator of in vivo plasmin generation, was measured in the plasma of 48 patients with disseminated intravascular coagulation (DIC), by enzyme-linked immunosorbent assay (ELISA). Plasmin-alpha 2PI complex was markedly elevated to 7.9 +/- 4.26 mg/liter (mean +/- SD) in DIC at presentation, with normal values at less than 0.8 mg/liter. The concentration of plasmin-alpha 2PI complex changed in parallel with the course of DIC and decreased to 1.9 +/- 1.49 mg/liter (n = 28) in remission. Among various underlying disorders, DIC, in patients with acute promyelocytic leukemia, had the highest complex levels (mean 10.8 mg/liter), and septic patients had the lowest levels (mean 3.4 mg/liter). No significant correlation was found between FDP and plasmin-alpha 2PI complex. These results indicate that the quantitative assay of plasmin-alpha 2PI complex in plasma would be valuable in the assessment of hyperfibrinolysis in DIC.

Acute Disease↗
PubMed1988

Multimeric composition of plasma von Willebrand factor in chronic myeloproliferative disorders.

In chronic myeloproliferative disorders (CMPD) thrombohaemorrhagic complications occur occasionally in association with thrombocytosis. We studied the multimeric composition of plasma von Willebrand factor (vWf) in 15 patients with polycythaemia vera (PV), 12 with essential thrombocythaemia (ET) and eight with primary myelofibrosis (PMF). The relative content of large (multimer band greater than or equal to 11) multimers calculated by densitometer scan following SDS-agarose gel electrophoresis was 18.5 +/- 4.4% (mean +/- SD) in normal controls, 8.3 +/- 7.9% in PV, 8.1 +/- 4.6% in ET and 19.6 +/- 6.7% in PMF. The patients with PV and ET but not PMF had a significantly lower percentage of large multimers than normal controls (P less than 0.001). The relative content of large multimers was negatively correlated with WBC and platelet count (P less than 0.02 each) in PV. It was negatively correlated with platelet count (P less than 0.005) and was positively correlated with a ratio of ristocetin cofactor/vWf antigen (RCof/vWf:Ag) (P less than 0.01) in ET. These results indicate that acquired defects of vWf are quite common in PV and ET but not in PMF. In addition, some CMPD patients with high platelet counts completely lacked large multimers. The negative correlation of the relative content of large multimers with platelet count suggests that large multimers may be preferentially consumed during thrombocytosis or degraded by protease(s) from increased blood cells.

Aged↗