Activation of Blood Coagulation and Anomalous Behaviour of Fibrinpeptide a to Heparin Treatment in Patients with Malignancy

1979 ◽  
Author(s):  
F.W. Peuscher ◽  
W.G. van Aken ◽  
A.L. Armstrong ◽  
E. A. Stoepman-van Dalen ◽  
J.A. van Mourik
Keyword(s):  
Venous Thromboembolism ◽  
Blood Coagulation ◽  
Tumor Cells ◽  
Malignant Disease ◽  
Clinical Signs ◽  
Anomalous Behaviour ◽  
Fibrinopeptide A ◽  
Heparin Treatment ◽  
Sensitive Marker

Hypercoagulability, known to complicate malignant disease, can be detected by the measurement of fibrinopeptide A (FPA). The aim of the present study was to establish the significance of FPA production in. patients (n = 113) with various types of malignancy, without clinical signs of DIC, venous thromboembolism, not receiving cytostatic, anticoagulant or radiotherapy or bedrest. 8 patients presented laboratory abnormalities compatible with DIC; In this group mean FPA was 9.8 ng/ml (normal 1.4±0.9.2SD) and FPA generation In vitro (ΔFPA) was 15 ng/ml/10 min (normal 0.4±0.8, 230). In the remaining 105 patients, mean FPA was 5.2 ng/ml andFPA was 1.8 ng/ml/10 min. Of the 20 patients with both normal FPA and ΔFPA, 13 were clinically in remission, 5 had malignancies without detectable metastases and only 2 showed metastases. In 2 patients FPA was normal but ΔFPA was slIghtLy accelerated. 50 patients had elevated ΔFPA but normal FPA and in 33 cases both FPA and ΔFPA were increased; in these groups the majority of patients had a metastatic malignancy In 22 patients mean FPA before (4.9 ng/ml) and 20 mln after(4.2 ng/ml) receiving heparin (7500 U, i.v.) was not significantly different. These results suggest that apart from DIC tumor cells or the adjacent inflammatory area of tumors may trigger FPA generation, not being affected by heparin. It Is postulated that “heparin resistant” FPA generation Is potentially a sensitive marker of tumor activity.

scholarly journals Successful in vitro graft-versus-tumor effect against an Ia-bearing tumor using cyclosporine-induced syngeneic graft-versus-host disease in the rat

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1165-1171 ◽  
Author(s):  
RB Geller ◽  
AH Esa ◽  
WE Beschorner ◽  
CG Frondoza ◽  
GW Santos ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Clinical Signs ◽  
Class Ii ◽  
Target Cells ◽  
Tumor Target ◽  
Host Disease ◽  
Class Ii Mhc ◽  
Mhc Antigen ◽  
Nylon Wool

Abstract Lethally irradiated LouM rats reconstituted with syngeneic bone marrow and then treated with cyclosporine (CsA) for 40 consecutive days following transplant developed a graft-v-host disease (GVHD)-like syndrome after CsA cessation. This model of GVHD was used to define and characterize a graft-v-tumor (GVT) effect against a syngeneic plasmacytoma CRL1662 cell line which expresses class II major histocompatibility (MHC) antigen (Ia). Nylon wool-nonadherent spleen cells from animals who developed syngeneic GVHD were capable of significant lysis against chromium-labeled tumor target cells in a four- hour chromium released cell mediated lympholysis assay; maximum lysis occurred five days following cessation of CsA when clinical signs first appeared. Cytolytic activity declined to baseline as GVHD symptoms resolved. Fractionation of splenocytes into lymphocyte subsets demonstrated that cytolytic lymphocytes (CTLs) of the OX8 phenotype (non-helper T) were capable of significant lysis against tumor target cells. Lysis of tumor cells was blocked by preincubation with monoclonal antibodies (MoAb) specific for the rat anti-class II MHC antigen but not with MoAb against class I. Incubation of tumor cells with gamma-interferon increased expression of tumor class II MHC antigens and significantly increased their susceptibility to lysis by nylon wool-nonadherent splenocytes from animals with syngeneic GVHD. These studies have demonstrated an in vitro GVT of syngeneic GVHD against an Ia-bearing tumor; the effector cell is a CTL of the OX8 phenotype specific for the class II MHC antigen.

Effect of Heparin on Antithrombin III Activity During Delivery and Early Puerperium

1975 ◽  
Author(s):  
I. Rákóczi ◽  
B. Garadnay ◽  
L. Arnold ◽  
I. Gáti
Keyword(s):  
Pregnant Women ◽  
Blood Coagulation ◽  
Antithrombin Iii ◽  
Modified Method ◽  
Heparin Treatment ◽  
At Iii ◽  
Antithrombin Iii Activity

It is known that antithrombin III (AT III) is the main inhibitor of blood coagulation. It inactivates thrombin and activated × factor. Heparin increases the AT III activity in vitro as well as in vivo. The authors have studied the AT III activity in sera of 30 pregnant women, at term, before labour started (2–24 hrs) and 30 as well as 60 min after the birth of placenta and daily for five days after delivery. The AT III activity was determined using the modified method of Gerendas. Out of the 30 women 15 were given 5000 IU heparin subcutaneously 1½—2 hours before delivery. In the 15 women with no heparin treatment AT III activity of serum significantly decreased after birth of placenta compared with the predelivery value and became normal on the fifth postpartum day. Heparin given subcutaneously prevented development of this decrease.

scholarly journals Successful in vitro graft-versus-tumor effect against an Ia-bearing tumor using cyclosporine-induced syngeneic graft-versus-host disease in the rat

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1165-1171 ◽  
Author(s):  
RB Geller ◽  
AH Esa ◽  
WE Beschorner ◽  
CG Frondoza ◽  
GW Santos ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Clinical Signs ◽  
Class Ii ◽  
Target Cells ◽  
Tumor Target ◽  
Host Disease ◽  
Class Ii Mhc ◽  
Mhc Antigen ◽  
Nylon Wool

Lethally irradiated LouM rats reconstituted with syngeneic bone marrow and then treated with cyclosporine (CsA) for 40 consecutive days following transplant developed a graft-v-host disease (GVHD)-like syndrome after CsA cessation. This model of GVHD was used to define and characterize a graft-v-tumor (GVT) effect against a syngeneic plasmacytoma CRL1662 cell line which expresses class II major histocompatibility (MHC) antigen (Ia). Nylon wool-nonadherent spleen cells from animals who developed syngeneic GVHD were capable of significant lysis against chromium-labeled tumor target cells in a four- hour chromium released cell mediated lympholysis assay; maximum lysis occurred five days following cessation of CsA when clinical signs first appeared. Cytolytic activity declined to baseline as GVHD symptoms resolved. Fractionation of splenocytes into lymphocyte subsets demonstrated that cytolytic lymphocytes (CTLs) of the OX8 phenotype (non-helper T) were capable of significant lysis against tumor target cells. Lysis of tumor cells was blocked by preincubation with monoclonal antibodies (MoAb) specific for the rat anti-class II MHC antigen but not with MoAb against class I. Incubation of tumor cells with gamma-interferon increased expression of tumor class II MHC antigens and significantly increased their susceptibility to lysis by nylon wool-nonadherent splenocytes from animals with syngeneic GVHD. These studies have demonstrated an in vitro GVT of syngeneic GVHD against an Ia-bearing tumor; the effector cell is a CTL of the OX8 phenotype specific for the class II MHC antigen.

Fibrinopeptide A in Urine from Patients with Venous Thromboembolism, Disseminated Intravascular Coagulation and Rheumatoid Arthritis - Evidence for Dephosphorylation and Carboxyterminal Degradation of the Peptide by the Kidney

1985 ◽  
Vol 54 (04) ◽  
pp. 792-798 ◽  
Author(s):  
O C Leeksma ◽  
F Meijer-Huizinga ◽  
E A Stoepman-van Dalen ◽  
W G van Aken ◽  
J A van Mourik
Keyword(s):  
Rheumatoid Arthritis ◽  
Venous Thromboembolism ◽  
Disseminated Intravascular Coagulation ◽  
High Performance ◽  
Active Role ◽  
Study Data ◽  
Fibrinopeptide A ◽  
Intravascular Coagulation

SummaryUrinary fibrinopeptide A immunoreactivity was determined by radioimmunoassay using two anti-fibrinopeptide A sera with a different specificity in patients with venous thromboembolism, disseminated intravascular coagulation and rheumatoid arthritis. Elevated levels were frequently observed with both sera, and intravenous administration of heparin in patients with a thromboembolic disorder resulted in a decline of urinary fibrinopeptide A (FPA) concentrations to normal or nearly normal values. For both sera significant correlations with plasma levels were found although one of the sera reacted significantly better with the material in urine samples from these patients than the other (p <0.0001, n = 73). Analysis of urinary fibrinopeptide A immunoreactivity by high performance liquid chromatography (HPLC) provided evidence that A peptide material present in this body fluid was heterogeneous. In view of the characteristics of the antisera used in this study, data suggest that urinary FPA immunoreactivity consists to a large extent of carboxyterminally degraded FPA. Excretion of circulating FPA immunoreactive material through the kidneys apparently involves dephosphorylation and carboxyterminal breakdown of the A peptide. Since both synthetic and native phosphorylated or unphosphorylated fibrinopeptide A appeared to be stable in urine in vitro, an active role of the kidney in degrading the A peptide is likely.

CHANGES IN THE COAGULATION AND FIBRINOLYTIC SYSTEM DURING PREGNANCY

1987 ◽  
Author(s):  
B J Woodhams ◽  
G Candotti ◽  
P B A Kernoff
Keyword(s):  
Oral Contraceptives ◽  
Fibrinolytic Activity ◽  
Degradation Products ◽  
Clinical Signs ◽  
Normal Pregnancy ◽  
Fibrinopeptide A ◽  
Blood Samples ◽  
D Dimer ◽  
Control Samples

Blood samples were collected from 17 volunteers between 8-14, 26-28 and 32-34 weeks of pregnancy. Control samples were collected from 12 non-pregnant female volunteers not using oral contraceptives. All samples were assayed for fibrinopeptide A (FPA), B beta 15-42 and for cross linked D-dimer fragments. A sample was collected for measurement of the in vitro rate of generation of fibrinopeptide A from whole blood (FPA-R).These results are consistent with an increased activation of coagulation (increased FPA and shortened FPA-R) during normal pregnancy, which is compensated for by a concomitant rise in fibrinolytic activity (increased D-dimer and B beta 15-42). In 2 patients who miscarried and 2 patients who developed hypertension during pregnancy changes indicative of a non compensated hypercoagulable state could be seen. The study shows that the progress of pregnancy is associated with increased activation of coagulation and a concomitant rise in fibrin(ogen) degradation products. This data shows that a combination of these tests may be capable of detecting changes in the haemostatic balance that occur before the onset of clinical signs of gynaecological problems.

The Natural Course of Defibrination Syndrome Caused by Echis Colorata Venom in Man

1974 ◽  
Vol 31 (03) ◽  
pp. 420-428 ◽  
Author(s):  
M Fainaru ◽  
S Eisenberg ◽  
N Manny ◽  
C Hershko
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Major Bleeding ◽  
Renal Damage ◽  
Specific Treatment ◽  
Natural Course ◽  
Factor V ◽  
Thrombocyte Count

SummaryThe natural course of defibrination syndrome caused by Echis colorata venom (ECV) in five patients is reported. All patients developed afibrinogenemia within six hours after the bite. Concomitantly a depression in factor V was recorded. Factor VIII and thrombocyte count in blood were normal in most patients. In the light of the known effects of ECV on blood coagulation in vivo and in vitro it is concluded that the afibrinogenemia is due to intravascular clotting.Four patients had transient renal damage, manifested by oliguria, azotemia, albuminuria and cylindruria, ascribed to microthrombi in the renal glomeruli.After the bite, the natural course was benign, no major bleeding was observed, and all signs of coagulopathy reverted to normal within 7 days. Therefore we recommend no specific treatment for this condition. In the case of heavily bleeding patients, administration of antiserum against ECV and/or heparin should be considered.

Comparison of the Actions of Thrombin and the Thrombin-Like Venom Enzymes Ancrod and Batroxobin

1976 ◽  
Vol 36 (01) ◽  
pp. 009-013 ◽  
Author(s):  
D. L Aronson
Keyword(s):  
Factor Viii ◽  
Fibrinopeptide A ◽  
Enzymic Reaction

SummaryThrombin acts on several coagulant proteins to produce products with physiologic, pharmacologic and pathologic potential. The most sensitive thrombin substrate seems to be factor VIII. Some thrombin dependent reactions studied in vitro and proposed as control reactions seem too insensitive to the action of thrombin to be of in vivo significance.The only enzymic reaction the thrombin-like venom enzymes, Ancrod and Batroxobin, have in common with thrombin is the removal of fibrinopeptide A.

Fibrinopeptide A (FPA) Level and Fibrinogen Kinetics in Patients with Malignant Disease

1981 ◽  
Vol 46 (04) ◽  
pp. 706-709 ◽  
Author(s):  
Yasuhiro Yoda ◽  
Tsukasa Abe
Keyword(s):  
Fibrinolytic Activity ◽  
Turnover Rate ◽  
Malignant Disease ◽  
Major Determinant ◽  
Fibrinopeptide A

SummaryFPA level, fibrinogen turnover rate, and fibrinolytic activity were studied on 18 patients with malignant disease. It was found that the FPA levels were significantly elevated and were correlated with fibrinogen turnover rate (r=0.74, p<0.001) and FDP (r = 0.58, p<0.02). Estimated FPA turnover rate was also correlated with fibrinogen turnover rate (r = 0.70, p<0.001). These results suggest that fibrinogen catabolism in patients with malignant disease is related with thrombin proteolysis. However, ratios of 1/2 FPA turnover rate to fibrinogen turnover rate suggest that intravascular thrombin proteolysis is not the major determinant of fibrinogen catabolism. It is suspected that extravascular thrombin proteolysis is responsible for the elevation of plasma FPA level which is correlated with acceleration of fibrinogen catabolism.

Effect of Temperature, Velocity Gradient and I.V. Heparin on in Vitro Blood Coagulation and Platelet Aggregation

1967 ◽  
Vol 17 (01/02) ◽  
pp. 112-119 ◽  
Author(s):  
L Dintenfass ◽  
M. C Rozenberg
Keyword(s):  
Blood Coagulation ◽  
Velocity Gradient ◽  
Elevated Temperatures ◽  
Morphological Changes ◽  
Effect Of Temperature ◽  
Clotting Time ◽  
Progressive Change ◽  
Aggregation Of Platelets ◽  
Microscopic Techniques

SummaryA study of blood coagulation was carried out by observing changes in the blood viscosity of blood coagulating in the cone-in-cone viscometer. The clots were investigated by microscopic techniques.Immediately after blood is obtained by venepuncture, viscosity of blood remains constant for a certain “latent” period. The duration of this period depends not only on the intrinsic properties of the blood sample, but also on temperature and rate of shear used during blood storage. An increase of temperature decreases the clotting time ; also, an increase in the rate of shear decreases the clotting time.It is confirmed that morphological changes take place in blood coagula as a function of the velocity gradient at which such coagulation takes place. There is a progressive change from the red clot to white thrombus as the rates of shear increase. Aggregation of platelets increases as the rate of shear increases.This pattern is maintained with changes of temperature, although aggregation of platelets appears to be increased at elevated temperatures.Intravenously added heparin affects the clotting time and the aggregation of platelets in in vitro coagulation.

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