Coagulation Activation in Extracorporeal Hemodialysis

1997 ◽  
Vol 20 (3) ◽  
pp. 163-165 ◽  
Author(s):  
M. Camici ◽  
L. Evangelisti ◽  
P. Balestri ◽  
L. Cioni ◽  
P. Fundi ◽  
...  
Keyword(s):  
Protein C ◽  
Serum Lipoprotein ◽  
Factor Vii ◽  
Maintenance Hemodialysis ◽  
Factor X ◽  
Lipoprotein A ◽  
Activity Factor ◽  
Before And After ◽  
Protein C Activity

The Authors evaluated the behavior of protein C activity, factor X and factor VII coagulant activity and serum lipoprotein(a) before and after dialytic treatment in patients on maintenance hemodialysis. They observed depressed protein C activity that significantly (p<0.005) increased and became normal immediately after hemodialysis while factor X and factor VII increased (p<0.01; p<0.05) despite heparinization together with amount of serum lipoprotein(a). In vitro incubation (30 'at 37°C) of uremic and healthy blood showed a decrease in serum lipoprotein(a) concentration. After heparin addition (final concentration 0.5 U/ml) lipoprotein(a) increased in the uremic blood only. The clinical and physiopathological implications of these results are discussed.

HAEMOSTATIC CHANGES INDUCED BY TWO LOW DOSE TRIPHASIC ORAL CONTRACEPTIVES

1987 ◽  
Author(s):  
S J Machin ◽  
I J Mackie ◽  
K Walshe ◽  
M D Gillmer
Keyword(s):  
Oral Contraceptives ◽  
Protein C ◽  
Low Dose ◽  
Factor Vii ◽  
Cycle Period ◽  
Factor Xii ◽  
Factor X ◽  
Combined Oral Contraceptives ◽  
First Time ◽  
Protein C Activity

The haemostatic system was investigated in 26 women taking cyclically administered triphasic combined oral contraceptives for the first time during their first six cycles. Fourteen women received Logynon (mean dose 32.4μg ethinyloestradiol, 92pg progestagen) and 12 received SHD 415G (Schering) which contains a mean dosage of 32.4μg ethinyloestradiol and 78pg gestodene, a recently developed progesterone. The Logynon group showed a significant increase (p<0.005) in fibrinogen (pre-mean 284.4 g/1; after 1 cycle 347.3 g/1, after 6 cycles 318.6 g/1) , factor VII (65.8 u/1 to 73.9 u/1 to 83.2 u/1), factor XII (1.74 u/1 to 2.41 u/1, to 2.25 u/1), plasminogen (100.9 u/1 to 135.1 u/1 to 126.3 u/1); decrease in ATIII (115.9 u/1 to 103.1 u/1 to 93.4 u/1) but no significant change in factor X (98.4 u/1 to 108.9 u/1 to 102.4) or protein C (0.85 u/1 to 0.88 u/1 to 0.94 u/1) activity. The SHD 415G group showed similar changes with an increase in fibrinogen (247.9 g/1 to 330.8 g/1 to 373 .1 g/1), factor VII (63.1 u/1 to 73.1 u/1 to 90.3 u/1, factor X (98.3 u/1 to 112.0 u/1 to 124.4 u/1), factor XII (1.46 u/1, to 1.93 u/1, to 2.03 u/1), plasminogen (110.8 u/1 to 125.4 u/1 to 136.7 u/1); decrease in ATIII (113.1 u/1 to 96.3 u/1 to 89.7 u/1), but no change in protein C (0.84 u/1 to - 0.78 u/1 to 0.85 u/1) activity. These changes were apparent after the first cycle of therapy and the differences were maintained over the six cycle period. There was no increase in protein C activity despite changes in the other vitamin K dependent proteins factors VII and X. Both low oestrogen dose triphasic pills caused similar prothrombotic changes which were not modified by the new progesterone, gestodene.

COAGULATION, FIBRINOLYSIS AND PLATELET FUNCTION DURING COUMARIN THERAPY

1987 ◽  
Author(s):  
D A Taberner ◽  
J M Thomson ◽  
L Poller
Keyword(s):  
Factor Viii ◽  
Protein C ◽  
T Test ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Complex Activity ◽  
Oral Anticoagulant Treatment ◽  
Protein C Activity ◽  
Paired T Test

The inactivation of factors VIII:C, V:C and fast acting TPA inhibitor by activated Protein C indicates that oral anticoagulation is more than simple reduction of prothrombin complex activity. To investigate these changes, six patients were studied after stopping oral anticoagulant treatment. Protein C activity and C antigen, Factors VIII:C, VIII:vWFAg, V:C, V:Ag, X:C, VII:C, fibrinogen and TPA activity were measured during long-term nicoumalone therapy (duration of therapy 8-96 months, mean 28 months), and after discontinuation on days 2, 4, 8, 10, 15, 30 and 42.The INR on the last day of therapy ranged between 2.0 - 3.3, (mean 2.6). Protein C activity and antigen and factor X became normal by day 8; factor II by day 10. Factor VII activity peaked on day 8, falling to resting levels by day 30. Factor VIII parameters remained high throughout, whereas Factor V antigen showed no significant change. Factor V activity was not quantifiable untill day 8 because of non-parallelism (? PIVKA effect), but was higher on day 8 than day 42 (p < 0.002 paired “t” test) . The higher levels of factor V activity could be protein C dependent, but the high factor VIII appears unrelated. Fibrinogen levels were higher on coumarin treatment (p < 0.05 paired “t” test) and took 30 days to fall to resting level. The effect of Protein C on TPA inhibitor would be expected to increase the activity of TPA, but this activity remained unchanged. Raised fibrinogen levels did not, therefore, appear to be mediated by the effect of protein C on fibrinolysis. Fibrinogen levels in plasma influence ADP induced platelet aggregation which is known to be increased in patients receiving coumarin drugs. In conclusion, patients on coumarin treatment, in addition to showing a reduction in protein C activity, also have higher fibrinogen levels and increased platelet aggregability all of which may be undesirable.

STUDY ON THE EFFECT OF UNFRACTIONATED (UFH) AND LOW MOLECULAR WEIGHT (LMWH) HEPARINS ON THE DETERMINATION OF PROTEIN C ACTIVITY

1987 ◽  
Author(s):  
N Sala ◽  
J Fontcuberta
Keyword(s):  
Protein C ◽  
Plasma Samples ◽  
Protamine Sulphate ◽  
Vein Thrombosis ◽  
Antigen Elisa ◽  
Before And After ◽  
Control Plasma ◽  
Protein C Activity

In an attempt to see whether the presence of different heparins affected the determination of protein C activity (APC),this parameter was measured before and during treatment in 23 deep vein thrombosis patients that had been randomly treated with 3 different LMWH (Choay CY-216 and CY-222 and Kabi-2165) and UFH,for 10 days, Very low levels of APC (amidolytic assay that uses thrombin-thrombomodulin to activate the barium citrate eluted PC) were found in those patients receiving UFH and having an APTT more than 3 times that of control, as well as in those patients receiving LMWH CY-216 and having an APTT of only 8 to 10 seconds higher than that of control plasma, In patients receiving CY-222 and Kabi-2165, no significant differences were observed between APC levels before and during treatment, PC antigen (ELISA assay) was normal in all cases, In order to see if these low APC levels were due to interference of heparin with the assay and at which doses, control plasma pool was supplemented "in vitro" with 0 to 2.5 IU/ml (0 to 0,00252) of UFH and with 0 to 3 anti-Xa U/ml of LMWH CY-216, APTT, PCAg, APC and presence of ATI 11 in the barium citrate eluates (immunodiffusion), were determined in all plasma samples before and after treatment with protamine sulphate (PS) at 0,0032, The results showed that UFH, when not neutralized with PS, resulted in low APC values only at doses higher than 0,8 IU/ml, corresponding to an APTT of more than 3 times that of control plasma, LMWH CY-216 at doses above 1 anti-XaU/ml, corresponding to an APTT of only 10 seconds higher than that of control, also produced a gradual decrease in APC values, ATI 11 was clearly visualized in the barium citrate eluates of all those plasma samples having a low APC value, The addition of PS to all samples containing UFH resulted in a complete normalization of APC values, with almost normal AFTT values and disappearance of ATI 11 from the barium citrate eluates, On the contrary, addition of PS to plasma containing CY-216 resulted in low APC values and presence of ATI 11 in the eluates of those samples containing more than 4 antiXaU/ml, whose APTT still was about 10 seconds above that of control.It is concluded that at therapeutic doses not only UFH but also LMWH CY-216 interfere with the APC assay, probably through binding of hepar in-ATI 11 complexes to barium citrate and neutralization of the thrombin used to activate the barium citrate eluted PC, LMWH CY-222 and Kabi-2165, although increasing the APTT similarly to CY-216, do not seem to interfere with the APC assay, Protamine sulphate, at 0,0032 in plasma, completely abolishes the effect of UFH on APC assay but not that of LMWH CY-216, More studies are being performed to see if higher doses of PS can be used to neutralize the effect of this LMWH.

Dietary Changes in Fasting Levels of Factor VII Coagulant Activity (FVII: C) Are Accompanied by Changes in Factor VII Protein and other Vitamin K-dependent Proteins

1995 ◽  
Vol 73 (02) ◽  
pp. 239-242 ◽  
Author(s):  
E M Bladbjerg ◽  
T Tholstrup ◽  
P Marckmann ◽  
B Sandström ◽  
J Jespersen
Keyword(s):  
Fatty Acids ◽  
Vitamin K ◽  
Protein C ◽  
Saturated Fatty Acids ◽  
Factor Vii ◽  
Dietary Regimen ◽  
Blood Samples ◽  
Dietary Changes ◽  
Coagulant Activity ◽  
Before And After

SummaryThe mechanisms behind dietary effects on fasting coagulant activity of factor VII (FVII: C) are not clarified. In the present study of 15 young volunteers, two experimental diets differing in composition of saturated fatty acids (C18:0 [diet S] or C12:0 + C14:0 [diet ML]) were served for 3 weeks each. Fasting blood samples were collected before and after the dietary regimen and analysed for triglycerides, FVII:C, and protein concentrations of FVII, FII, FX, protein C, CRP, albumin, fibrinogen, and F1+2. FVII:C was significantly reduced on diet S compared with diet ML. This was accompanied by a decrease in FVII protein, F1+2 and the vitamin K-dependent proteins FII, FX, and protein C. In contrast, no changes were observed in triglycerides, FVII:C/FVII: Ag, albumin and CRP. Fibrinogen was increased on diet S compared with diet ML. Our findings suggest that the change in fasting FVII:C was part of a general change in concentrations of vitamin K-dependent proteins.

scholarly journals Activation of human factor VII during clotting in vitro

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 218-226 ◽  
Author(s):  
LV Rao ◽  
SP Bajaj ◽  
SI Rapaport
Keyword(s):  
Tissue Factor ◽  
Glass Tube ◽  
Factor Vii ◽  
Clotting Factor ◽  
Activate Factor ◽  
Factor Xii ◽  
Factor X ◽  
Normal Plasma

Abstract We have studied factor VII activation by measuring the ratio of factor VII clotting to coupled amidolytic activity (VIIc/VIIam) and cleavage of 125I-factor VII. In purified systems, a low concentration of Xa or a higher concentration of IXa rapidly activated 125I-factor VII, yielding a VIIc/VIIam ratio of 25 and similar gel profiles of heavy and light chain peaks of VIIa. On further incubation, VIIa activity diminished and a third 125I-peak appeared. When normal blood containing added 125I- factor VII was clotted in a glass tube, the VIIc/VIIam ratio rose fivefold, and 20% of the 125I-factor VII was cleaved. Clotting normal plasma in an activated partial thromboplastin time (APTT) system yielded a VIIc/VIIam ratio of 25 and over 90% cleavage of 125I-factor VII. Clotting factor XII-deficient plasma preincubated with antibodies to factor X in an APTT system with added XIa yielded a VIIc/VIIam ratio of 19 and about 60% cleavage, which indicates that IXa, at a concentration achievable in plasma, can effectively activate factor VII. Clotting normal plasma with undiluted tissue factor yielded a VIIc/VIIam ratio of 15 to 20 and 60% cleavage of 125I-factor VII, whereas clotting plasma with diluted tissue factor activated factor VII only minimally. We conclude that both Xa and IXa can function as significant activators of factor VII in in vitro clotting mixtures but believe that only small amounts of factor VII may be activated in vivo during hemostasis.

Neonatal Polycythemia: A Disorder Associated With Hyperviscosity, Normal Coagulation Findings And Thrombocytopenia

1981 ◽  
Author(s):  
J Katz ◽  
E Rodriguez ◽  
C Madani ◽  
D Hicks ◽  
H E Branson
Keyword(s):  
Plasma Exchange ◽  
Gestational Age ◽  
Degradation Products ◽  
Factor Ix ◽  
Factor Vii ◽  
Large For Gestational Age ◽  
Factor Xii ◽  
Factor X ◽  
Platelet Counts ◽  
Before And After

Thirty-two newborns with elevated capillary hematocrits >65% were studied. Twenty-two newborns required plasmaexchange transfusion. All had central (venous) hematocrits >65% and had symptoms referrable to complications associated with this syndrome. Of the 22, 15 were appropriate-for-gestational age, 5 were small-for-gestational age, and 2 were large-for-gestational age. Viscosity measurements in the 10 newborns who did not require plasma-exchanges showed increased viscosity in 2 in the slow shear rates associated with bloodflow in the smaller vessels. Coagulation data before and after plasma exchange did not show a hypercoagulable state: PT-14.2±0.7 and 12.9±1.2 secs, PTT 49.9±3.6 and 42.2±3.2 secs, factor VII 73±5 and 78±5%, factor VIII 103±10 and 94±10%, AT III levels were low 14±1.2 and 17±1.3 mg/dl, fibrin degradation products were <10μg/ml, fibrin monomer was not detected, plasminogen levels were 5±0.8 and 7±0.9mg/dl, fibrinogen levels were 203±9.8 and 200±11.8 mg%. Vitamin K dependent factors were reduced factor V 44±6 and 49±11%, factor VII 77±5 and 86±5%, factor IX 28±2 and 42±3%, factor X 35±4 and 62±6%, factor XI 55±5 and 84±9%, factor XII 47±5 and 63±5%. Statistical significant differences were found only with factors IX, X, XI and XII. Thrombocytopenia was present in 6 patients (20% incidence) and post plasma exchange the platelet counts rose significantly and in 2 patients within 3 days reached normal levels. No statistical difference in the platelet counts were noted before and after the plasma-exchange and were similar to the levels determined in 10 newborn controls. Neonatal polycythemia with thrombocytopenia may indicate a more severe disorder, with hematocrits in the 6 patients >70%. It is suggested that the mechanism of the thrombocytopenia may be aggregates of platelets that deaggregate following plasmaexchange. The complications associated with neonatal polycythemia appear related to hyperviscosity, erythrocyte and platelet “sludging” in the smaller vessels.

scholarly journals The endotoxin-induced procoagulant of mouse exudate macrophages: a factor-X activator

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 333-340 ◽  
Author(s):  
JW Jr Shands
Keyword(s):  
Tissue Factor ◽  
Culture Supernatant ◽  
Factor Vii ◽  
Mouse Tissue ◽  
Factor X ◽  
Macrophage Culture ◽  
Cellular Factor ◽  
Culture Supernatants ◽  
Bovine Factor

Abstract The properties of mouse macrophage procoagulant induced by endotoxin in vitro were studied by the acceleration of clotting and by chromogenic assays using as substrates human plasma and bovine components, which are not activated by mouse tissue factor. Maximal macrophage procoagulant activity occurred when activated cells were lysed in culture supernatant fluids, suggesting the interaction of cellular and supernatant factors. This procoagulant was clearly able to activate bovine factor X. The procoagulant also appeared to have prothrombinase activity. However, additional experiments suggested that the bulk of this activity was due to the activation of factor X contaminating the prothrombin. The production of the procoagulant was inhibited by warfarin (5 microM). Its activity was inhibited by 1 mM diisopropylfluorophosphate and unaffected by iodoacetamide, indicating that the procoagulant is a serine protease. Macrophage culture supernatants contained factor-VII-like activity. Neither mouse tissue factor nor macrophage culture supernatants alone activated bovine factor X. The two combined served as an efficient factor-X activator. Active supernatant factor (factor-VII-like) was not produced by macrophages cultured in the presence of warfarin, while the production of the macrophage cellular factor was unaffected by the presence of warfarin. I conclude that exudate macrophages cultured in vitro make and secrete factor VII or a factor-VII-like substance into the culture supernatant. When activated macrophages are lysed in this supernatant, the interaction of a cellular factor (? tissue factor) and factor VII gives rise to a factor-X activator.

Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production

1997 ◽  
Vol 272 (2) ◽  
pp. L197-L202 ◽  
Author(s):  
K. Murakami ◽  
K. Okajima ◽  
M. Uchiba ◽  
M. Johno ◽  
T. Nakagaki ◽  
...  
Keyword(s):  
Vascular Injury ◽  
Protein C ◽  
Cytokine Production ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Weight Ratio ◽  
Dry Weight ◽  
Endothelial Damage ◽  
Factor X

We investigated the effect of activated protein C (APC) on pulmonary vascular injury and the increase in tumor necrosis factor (TNF) levels in lipopolysaccharide (LPS)-treated rats to determine whether APC reduces LPS-induced endothelial damage by inhibiting cytokine production. Intravenously administered LPS (5 mg/kg) induced pulmonary vascular injury, as indicated by an increase in the lung wet-to-dry weight ratio. LPS-induced pulmonary vascular injury was prevented by APC but not by active site-blocked factor Xa [dansyl glutamyl-glycyl-arginyl chloromethyl detone-treated activated factor X (DEGR-Xa)], a selective inhibitor of thrombin generation, or inactivated APC [diisopropyl fluorophosphate-treated APC (DIP-APC)]. APC, but not DEGR-Xa or DIP-APC, significantly inhibited the LPS-induced increase in the plasma level of TNF. APC significantly inhibited the production of TNF by LPS-stimulated monocytes in a dose-dependent fashion in vitro, but DIP-APC did not. APC did not inhibit the functions of activated neutrophils in vitro. These findings suggest that APC prevented LPS-induced pulmonary vascular injury by inhibiting TNF production by monocytes and not via its anticoagulant activity. The serine protease activity of APC appears to be essential for inhibition of TNF production.

THE "LUPUS ANTICOAGULANT" INDUCES FUNCTIONAL CHANGES IN ENDOTHELIAL CELLS AND PLATELETS

1987 ◽  
Author(s):  
Anna E Schorer ◽  
Kathleen V Watson
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Lupus Anticoagulant ◽  
Inhibitory Effect ◽  
Clinical Syndrome ◽  
Factor Vii ◽  
Factor X ◽  
Functional Changes ◽  
Thrombin Activation

The presence of the "lupus anticoagulant" (LA) predicts a clinical syndrome of excessive arterial, venous and microvascu-lar thrombosis. LA is an antibody which reacts with negatively charged phospholipid (PL) species in vitro. Since PL is involved in many aspects of the regulation of thrombosis, we postulated that LA might modify one or more of the membrane-(PL-dependent reactions of platelets and endothelial cells (EC). Blood samples from 20 patients with a history of thrombosis were tested for the presence of LA (kaolin PTT) and titres determined. LA-positive (LA+) sera and plasma were compared to LA-negative (LA−) samples from normal donors (n=6) or patients who had lupus but no clinical thrombosis (n=4). These specimens were tested in a panel of assays. The thrombin-stimulated release of prostacyclin (PG12) from cultured human EC was markedly reduced (52%±12.5 s.e.) by preincubation of the EC with LA+ sera (30 minutes). Purified LA+ IgG from one patient reproduced this effect. Thrombin induction of EC synthesis of the procoagulant, tissue factor-which is dissociable from prostaglandin metabolism-was also inhibited by LA+ sera. Normal platelets incubated in LA+ plasma became refractory to thrombin (1 unit/ml) but retained their responsiveness to epinephrine and ADP. The reduced responsiveness to thrombin was not due to altered (specific or total) binding of thrombin. The cleavage of Factor X by Factor VII requires PL as a co-factor for the EC procoagulant, tissue factor (TF). Unlike the inhibitory effect of LA on thrombin activation of EC and platelets, this distinct membrane-(PL-) dependent function was variably enhanced by LA+ sera. Brief (20 min) exposure of EC to LA+ sera increased TF co-catalysis of Factor VII cleavage of Factor X (measured by chromogenic Xa substrate, S-2222) by up to 10 fold (p<0.05, unpaired t test). This effect was not the result of EC disruption or changes in whole-cell TF content. These data suggest multiple, complex and heterogenous effects of LA, including impaired production of PG12, impaired EC modulation, and heightened ability of endogenous EC tissue factor to initiate coagulation. These (and perhaps other) membrane-dependent effects may contribute to the tendency of LA+ patients to develop clots.

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