scholarly journals The role of the spleen in regulating the plasma levels of factor VIII-- von Willebrand's factor after DDAVP

Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1402-1406 ◽  
Author(s):  
VV Garcia ◽  
R Coppola ◽  
PM Mannucci
Keyword(s):  
Factor Viii ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Storage Site ◽  
Inactive Form ◽  
Coagulant Activity ◽  
High Concentrations ◽  
Von Willebrand’S Factor ◽  
Normal Controls

Abstract Organ transplantation and perfusion studied indicate that the spleen plays an important role in the regulation of plasma levels of factor VIII-von Willebrand's factor (FVIII-vWF). To better understand the mechanisms that regulate the FVIII-vWF increases after infusion of 1- deamino-8-D-arginine vasopressin (DDAVP), we have measured factor VIII coagulant activity (FVIII:C) and antigen (FVIII:CAg) and von Willebrand's factor antigen (vWF:Ag) and ristocetin cofactor (vWF:RCof) in 9 asplenic subjects with normal baseline concentrations, in 7 asplenic subjects with high concentrations, and in 14 normal controls with intact spleens. In “normal” aasplenics, all the FVIII-vWF-related measurements increased significantly over baseline values, indicating that responsiveness to DDAVP is not abolished by splenectomy. The maximal vWF:Ag and vWF:RCof responses were no different from those of normal controls, suggesting that DDAVP releases vWF from storage sites other than the spleen. The FVIII:C response was significantly lower than in normal controls, but FVIII:CAg did not differ, making FVIII:CAg higher than FVIII:CAg in “normal” asplenics. These findings suggest that the spleen, rather than being a storage site for FVIII, is the organ in which a partially inactive form of FVIII acquires full coagulant activity. In “high” asplenics, all the FVIII-vWF-related measurements increased less than in “normal” splenics, indicating that long-term elevations of plasma concentrations of FVIII-vWF are accompanied by decreased release from those storage pool(s) mobilized by DDAVP.

scholarly journals The role of the spleen in regulating the plasma levels of factor VIII-- von Willebrand's factor after DDAVP

Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1402-1406 ◽  
Author(s):  
VV Garcia ◽  
R Coppola ◽  
PM Mannucci
Keyword(s):  
Factor Viii ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Storage Site ◽  
Inactive Form ◽  
Coagulant Activity ◽  
High Concentrations ◽  
Von Willebrand’S Factor ◽  
Normal Controls

Organ transplantation and perfusion studied indicate that the spleen plays an important role in the regulation of plasma levels of factor VIII-von Willebrand's factor (FVIII-vWF). To better understand the mechanisms that regulate the FVIII-vWF increases after infusion of 1- deamino-8-D-arginine vasopressin (DDAVP), we have measured factor VIII coagulant activity (FVIII:C) and antigen (FVIII:CAg) and von Willebrand's factor antigen (vWF:Ag) and ristocetin cofactor (vWF:RCof) in 9 asplenic subjects with normal baseline concentrations, in 7 asplenic subjects with high concentrations, and in 14 normal controls with intact spleens. In “normal” aasplenics, all the FVIII-vWF-related measurements increased significantly over baseline values, indicating that responsiveness to DDAVP is not abolished by splenectomy. The maximal vWF:Ag and vWF:RCof responses were no different from those of normal controls, suggesting that DDAVP releases vWF from storage sites other than the spleen. The FVIII:C response was significantly lower than in normal controls, but FVIII:CAg did not differ, making FVIII:CAg higher than FVIII:CAg in “normal” asplenics. These findings suggest that the spleen, rather than being a storage site for FVIII, is the organ in which a partially inactive form of FVIII acquires full coagulant activity. In “high” asplenics, all the FVIII-vWF-related measurements increased less than in “normal” splenics, indicating that long-term elevations of plasma concentrations of FVIII-vWF are accompanied by decreased release from those storage pool(s) mobilized by DDAVP.

Parallel Reduction of Plasma Levels of High and Low Molecular Weight Kininogen in Patients with Cirrhosis

1999 ◽  
Vol 82 (11) ◽  
pp. 1428-1432 ◽  
Author(s):  
Cheryl Scott ◽  
Francesco Salerno ◽  
Elettra Lorenzano ◽  
Werner Müller-Esterl ◽  
Angelo Agostoni ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Liver Disease ◽  
Liver Function ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Low Molecular Weight ◽  
Major Band ◽  
Sds Page ◽  
Normal Controls

SummaryLittle is known about the regulation of high-molecular-weight-kininogen (HK) and low-molecular-weight-kininogen (LK) or the relationship of each to the degree of liver function impairment in patients with cirrhosis. In this study, we evaluated HK and LK quantitatively by a recently described particle concentration fluorescence immunoassay (PCFIA) and qualitatively by SDS PAGE and immunoblotting analyses in plasma from 33 patients with cirrhosis presenting various degrees of impairment of liver function. Thirty-three healthy subjects served as normal controls. Patients with cirrhosis had significantly lower plasma levels of HK (median 49 μg/ml [range 22-99 μg/ml]) and LK (58 μg/ml [15-100 μg/ml]) than normal subjects (HK 83 μg/ml [65-115 μg/ml]; LK 80 μg/ml [45-120 μg/ml]) (p < 0.0001). The plasma concentrations of HK and LK were directly related to plasma levels of cholinesterase (P < 0.0001) and albumin (P < 0.0001 and P < 0.001) and inversely to the Child-Pugh score (P < 0.0001) and to prothrombin time ratio (P < 0.0001) (reflecting the clinical and laboratory abnormalities in liver disease). Similar to normal individuals, in patients with cirrhosis, plasma HK and LK levels paralleled one another, suggesting that a coordinate regulation of those proteins persists in liver disease. SDS PAGE and immunoblotting analyses of kininogens in cirrhotic plasma showed a pattern similar to that observed in normal controls for LK (a single band at 66 kDa) with some lower molecular weight forms noted in cirrhotic plasma. A slight increase of cleavage of HK (a major band at 130 kDa and a faint but increased band at 107 kDa) was evident. The increased cleavage of HK was confirmed by the lower cleaved kininogen index (CKI), as compared to normal controls. These data suggest a defect in hepatic synthesis as well as increased destructive cleavage of both kininogens in plasma from patients with cirrhosis. The decrease of important regulatory proteins like kininogens may contribute to the imbalance in coagulation and fibrinolytic systems, which frequently occurs in cirrhotic patients.

scholarly journals Hemostasis Studies in Patients with Colon Cancer

1977 ◽  
Author(s):  
S.J. Scialla ◽  
D.B. Kimball
Keyword(s):  
Colon Cancer ◽  
Platelet Aggregation ◽  
Factor Viii ◽  
Coagulation Factor ◽  
Factor Analyses ◽  
Fibrin Monomer ◽  
Coagulant Activity ◽  
Spontaneous Platelet Aggregation ◽  
Extent Of Disease ◽  
Normal Controls

Coagulation and platelet function studies were evaluated in eighteen patients with colon cancer (all clinical stages) prior to treatment with chemotherapy. All patients were asymptomatic from bleeding or thrombosis and were not taking aspirin. The tests included general coagulation screening, coagulation factor analyses, platelet aggregation, fibrin split product concentration and a serial dilution protamine sulfate test for the presence of fibrin monomer. Average values compared to normal controls showed an elevated fibrinogen 400.5 mg.% (normal 300.0 mg.%), shorter activated partial thromboplastin time 29.4 seconds (normal 36.0), increased factor VIII coagulant activity 127-2% (normal 100%), and elevated fibrin split products 28.8 ug/ml.(normal less than l6 ug/ml.). Seven patients showed the presence of fibrin monomer. Eight patients showed enhanced aggregation reacting at or below 0.16 micromolar epinephrine. Six patients in the study showed more advanced cancer (five requiring intrahepatic artery infusion for extensive liver metastasis). Of this subgroup four patients demonstrated fibrin monomer and three patients showed spontaneous platelet aggregation. In this group, the fibrinogen was 484.22 mg.%, fibrin split products were 28.8 ug/ml., and factor VIII was 176%. A state of hypercoagulation with signs of a chronic process of intravascular coagulation was demonstrated in a group of colon cancer patients which corresponded to their extent of disease.

Effects of physiological concentrations of vasopressin on haemostatic function in man

1985 ◽  
Vol 69 (4) ◽  
pp. 471-476 ◽  
Author(s):  
P. J. Grant ◽  
J. A. Davies ◽  
G. M. Tate ◽  
M. Boothby ◽  
C. R. M. Prentice
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Generation Time ◽  
Plasma Concentrations ◽  
Plasminogen Activator Activity ◽  
Lysis Time ◽  
Coagulation Mechanism ◽  
Coagulant Activity ◽  
Euglobulin Lysis Time ◽  
Ristocetin Cofactor

1. Plasma concentrations of vasopressin (aVP) attained under conditions of stress were simulated by infusing four volunteers with 0.25, 0.5, 1.0 and 2.0 pressor units of aVP over 1 h (units/h). Three subjects had all four infusions and one received only 1.0 unit/h. 2. Blood samples were taken for assay of factor VIII coagulant activity (FVIIIC), factor VIII related antigen (FVIIIRAg), the ristocetin cofactor (FVIIIRiCof), euglobulin lysis time (ELT) and aVP concentrations before infusion (time 0) and every 20 min for 80 min. Fibrinopeptide A (FPA) generation time was measured at time 0, 60 and 80 min. 3. At infusion rates of 0.25 unit/h median aVP levels peaked at 6.5 pg/ml and there was no change in haemostatic function. At 0.5 unit/h aVP levels peaked at 16.0 pg/ml, there was no change in FVIII or FPA generation time, and plasminogen activator activity (106/ELT2) rose from 100 to 400 units. At 1.0 unit/h, aVP levels rose to 25.4 pg/ml, FVIIIC rose by 160% and activator activity from 87 to 360 units. At 2.0 units/h, aVP concentrations reached 83 pg/ml, there was an increase in all modalities of FVIII and activator activity rose from 251 to 452 units. FPA generation time shortened and circulating plasma levels of FPA were increased. 4. There was a highly significant correlation between the percentage increases in all three components of FVIII and plasma aVP levels (FVIIIC: r = 0.87, P < 0.0001; FVIIIRAg: r = 0.61, P < 0.0001; FVIIIRiCof: r = 0.80, P < 0.0001) and between the increase in plasminogen activator activity and aVP levels (r = 0.56, P < 0.0001). 5. The results indicate that plasma concentrations of aVP comparable with those attained during stress cause a rise in FVIII, an increase in plasma activator activity and effects on FPA generation consistent with low-level activation of the coagulation mechanism. Endogenous vasopressin could mediate alterations in haemostatic function known to accompany events such as surgical operations.

scholarly journals Long-term effects of partial ileal bypass on the health status of rabbits

1986 ◽  
Vol 20 (2) ◽  
pp. 148-154
Author(s):  
J. A. Schouten ◽  
A. C. Beynen ◽  
P. D. de Rooy ◽  
H. F. W. Hoitsma ◽  
A. Bosma
Keyword(s):  
Health Status ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Experimental Studies ◽  
Liver Cholesterol ◽  
Plasma Vitamin ◽  
Long Term Effects ◽  
Glutamyl Transferase ◽  
Ileal Bypass

Partial ileal bypass (PIB) surgery is a method for the treatment of familial hypercholesterolaemia in man. Since the rabbit is frequently used as an animal model in experimental studies on PIB, we have investigated the long-term effects of this surgical procedure on the health status of rabbits. Forty-eight weeks after surgery plasma and liver cholesterol levels were decreased by about 40%. The inner diameter of the bypassed ileum was drastically reduced, unlike its length. The bypassed segment did not show clear histological abnormalities. The microflora of the caecum was similar in control and PIB rabbits. PIB did not influence liver histology. The bile of the rabbits with PIB was less lithogenic than that of control animals. Blood haemoglobin levels, haematocrit values and plasma concentrations of alkaline phosphatase, alanine aminotransferase, γ-glutamyl transferase and lactate dehydrogenase were not changed after PIB. Plasma levels of albumin, creatinine, calcium, phosphorus, vitamin B12 and folic acid were not significantly affected by PIB. Rabbits with PIB had significantly higher plasma levels of bilirubin and zinc than control rabbits, but plasma vitamin E concentrations were significantly lower. These results may be of importance for further studies on the effects of PIB in rabbits.

Haemostatic responses and vasopressin release during colonoscopy in man

1991 ◽  
Vol 81 (2) ◽  
pp. 257-260 ◽  
Author(s):  
K. K. Hampton ◽  
P. J. Grant ◽  
J. Primrose ◽  
H. G. Dean ◽  
J. A. Davies ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Plasma Vasopressin ◽  
Type Plasminogen Activator ◽  
Coagulant Activity ◽  
Von Willebrand

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VIII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.

Idiopathic venous thrombosis

2006 ◽  
Vol 26 (01) ◽  
pp. 52-54 ◽  
Author(s):  
P. A. Kyrle
Keyword(s):  
Chronic Disease ◽  
Venous Thrombosis ◽  
Vitamin K ◽  
Clinical Benefit ◽  
Plasma Levels ◽  
Vitamin K Antagonists ◽  
Antithrombin Deficiency ◽  
Optimal Duration ◽  
Risk Of Treatment

SummaryVenous thrombosis is a chronic disease with a recurrence rate of approximately 30% within 5-8 years. The optimal duration of secondary thromboprophylaxis in these patients entails balancing the risk of recurrence against the risk of treatment-associated bleeding. There is agreement that patients with a first idiopathic venous thrombosis should receive vitamin K antagonists for at least 3-6 months. Convincing trials showing a clinical benefit in terms of morbidity or mortality with respect to expansion of anticoagulation beyond 6 months are lacking. Nevertheless, some subgroups of patients with venous thrombosis may benefit from indefinite anticoagulation. Thus, patients with antithrombin deficiency, combined or homozygous defects, more than one unprovoked episode of thrombosis, the lupus anticoagulant or high factor VIII plasma levels are good candidates for long-term prevention.

The Endothelial Cell and the Factor VIII Bypassing Activity of Prothrombin Complex Concentrate

1988 ◽  
Vol 60 (02) ◽  
pp. 226-229 ◽  
Author(s):  
Jerome M Teitel ◽  
Hong-Yu Ni ◽  
John J Freedman ◽  
M Bernadette Garvey
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Factor Viii ◽  
Prothrombin Complex Concentrate ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Monolayer Cultures ◽  
Coagulant Activity ◽  
Time Courses ◽  
Privileged Site

SummarySome classical hemophiliacs have a paradoxical hemostatic response to prothrombin complex concentrate (PCC). We hypothesized that vascular endothelial cells (EC) may contribute to this “factor VIII bypassing activity”. When PCC were incubated with suspensions or monolayer cultures of EC, they acquired the ability to partially bypass the defect of factor VIII deficient plasma. This factor VIII bypassing activity distributed with EC and not with the supernatant PCC, and was not a general property of intravascular cells. The effect of PCC was even more dramatic on fixed EC monolayers, which became procoagulant after incubation with PCC. The time courses of association and dissociation of the PCC-derived factor VIII bypassing activity of fixed and viable EC monolayers were both rapid. We conclude that EC may provide a privileged site for sequestration of constituents of PCC which express coagulant activity and which bypass the abnormality of factor VIII deficient plasma.

Plasma Thrombospondin as an Indicator of Intravascular Platelet Activation in Patients with Vasculitis

1987 ◽  
Vol 58 (03) ◽  
pp. 850-852 ◽  
Author(s):  
M B McCrohan ◽  
S W Huang ◽  
J W Sleasman ◽  
P A Klein ◽  
K J Kao
Keyword(s):  
Platelet Activation ◽  
Plasma Levels ◽  
Half Life ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Primary Source ◽  
Positive Correlation ◽  
Activation Marker ◽  
Fibrin Degradation Products ◽  
The Mean

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.

Elevated Circulating P-Selectin in Insulin Dependent Diabetes Mellitus

1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Insulin Dependent Diabetes Mellitus ◽  
Interquartile Range ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Intergroup Comparison ◽  
Median Plasma ◽  
Insulin Dependent

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.

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