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Biomedical subjects

G Escolar

Publications and source records attributed to G Escolar.

At least 19 recordsLinked to original sources
PubMed1999

Influence of thrombin in suspension, surface activation, and high shear on platelet surface GPIb/IX distribution.

Studies in our laboratory have shown that glycoprotein Ib/IX (GPIb/IX), the receptor for von Willebrand factor (vWf), is not decreased in number or cleared from exposed surfaces to the internal membranes of platelets activated in suspension by thrombin alone, by interaction with formvar surfaces alone, or by a combination of the two modes of stimulation. The present study has examined the influence of three different types of stimulation including activation by thrombin in suspension followed by surface activation on formvar, then exposure to high shear stress in a flat chamber. Samples were fixed for study in the electron microscope after each single stimulus, after the combination of two modes of activation, and after the combination of suspension, surface, and shear activation and were stained by an immunogold procedure using monoclonal antibodies to localize GPIb/IX on singly, doubly, or multiply activated cells. The results demonstrate that GPIb/IX receptors remain on activated platelets from edge to edge and that there is no difference in the number or distribution of receptor complexes on thrombin-activated platelets, surface-activated cells, or platelets exposed to the combination of suspension, surface, and shear activation. The findings add additional support to the concept that GPIb/IX is not a mobile receptor and is not cleared from exposed surfaces to internal membranes under physiologic conditions.

Blood Platelets↗
PubMed1999

von Willebrand factor contained in a high purity FVIII concentrate (Fanhdi) binds to platelet glycoproteins and supports platelet adhesion to subendothelium under flow conditions.

BACKGROUND AND OBJECTIVE: There is evidence suggesting that von Willebrand factor (VWF) from high purity factor VIII concentrates could be of clinical use in the management of patients suffering from VWD. We analyzed structural and functional characteristics of VWF present in a high purity factor VIII concentrate VWFHPC (Fanhdi). The multimeric structure, the ability to bind to platelet GP Ib/IX or GP IIb/IIIa, and the capacity of VWFHPC to promote platelet adhesion on injured vessels were investigated and compared with that present in standard plasma cryoprecipitates [VWFCRYO]. DESIGN AND METHODS: Binding studies were carried out by incubating radiolabeled VWF and washed platelets, which were activated with either ristocetin (1 mg/mL; for GP Ib/IX), or thrombin (2.5 U/mL; for GP IIb/IIIa). Platelet adhesion was assessed in a perfusion system (shear rate = 800 s-1, 10 min) in which the source of VWF was added (at 0.4 or 0.8 U/mL VWF:Ag) to washed platelets and red cells suspended in a human albumin solution. The deposition of platelets onto the perfused subendothelial surface was morphometrically evaluated and expressed as percentage of surface coverage (%SC). RESULTS: The VWFHPC (152 Units VWF:RCof/mg protein; VWF:RCof/VWF:Ag = 0.97), lacked only a small proportion of high-molecular-weight multimers present in VWFCRYO. Binding affinities (Kd values, nM) of VWFHPC were similar to those of VWFCRYO (5.3 +/- 0.86 vs 5.2 +/- 0.95, for GP Ib/IX; and 11.6 +/- 2.7 vs 15.4 +/- 1.7 for GPIIb-IIIa). A slightly, though not significantly, higher binding capacity for these receptors (Bmax values, molecules/pit) was obtained for VWFHPC. The %SC in perfusions in the presence of albumin was < 10%. Addition of VWFHPC or VWFCRYO significantly increased the %SC, with values of 27.1 +/- 4.9 and 17.5 +/- 2.8%, respectively with 0.4 U/mL (p < 0.004 and p < 0.02 vs albumin); and 30.8 +/- 4.9% and 20.03 +/- 4.1%, respectively, at 0.8 U/mL (p < 0.001 and p < 0.02 vs albumin). INTERPRETATION AND CONCLUSIONS: Our data show that VWF present in the high purity FVIII concentrate Fanhdi retains the functional capacity to bind to GPs Ib/IX and IIb/IIIa and to promote platelet adhesion onto exposed subendothelium.

Albumins↗
PubMed1998

Effect of recombinant human erythropoietin treatment on circulating reticulated platelets in uremic patients: association with early improvement in platelet function.

Recombinant human erythropoietin improves platelet function in uremia through the correction of anemia, but this effect can be seen also before the hematocrit rise. We studied 12 hemodialyzed patients (seven men, five women) who received recombinant human erythropoietin (40 IU kg(-1)i.v., three times weekly) and were evaluated before treatment and after three doses; 24 control subjects were used. Platelet aggregation induced by adenosine 5'-diphosphate (ADP), epinephrine, collagen, arachidonic acid, and ristocetin, and reticulated platelets determined by flow cytometry after staining with thiazole orange were measured. Platelet aggregation induced by all the agonists were impaired in uremic patients (P < 0.01), but ADP and ristocetin-induced aggregations improved after treatment (P < 0.01). Hemodialyzed patients had less reticulated platelets than controls (P < 0.01). Reticulated platelets increased after three doses of treatment (P < 0.01). In conclusion, improvement of platelet function at early stages of recombinant human erythropoietin treatment may be attributed to the increase in young platelets detected as reticulated platelets.

Adenosine Diphosphate↗
PubMed1998

Effects of human monoclonal anticardiolipin antibodies on platelet function and on tissue factor expression on monocytes.

OBJECTIVE: To investigate the effect of human monoclonal anticardiolipin antibodies (aCL) on platelet interaction with the subendothelium under flow conditions and on tissue factor (TF) expression on normal monocytes. METHODS: Three monoclonal IgM aCL (TM1B3, GR1D5, and EY2C9) and 2 affinity-purified IgM aCL were studied. Immunoglobulins were added to normal blood and perfused through chambers containing denuded vascular segments. Platelet interactions were morphometrically evaluated by determining the percentage of total surface covered by platelets (PCS) or by large aggregates of thrombi platelets (TP). Expression of TF on monocytes was measured after immunoglobulin incubation with normal mononuclear cells. RESULTS: Significant increases in the total PCS and expression of TF were observed using all aCL. Increased levels of TP were induced by all aCL except EY2C9 (obtained from a patient without thrombosis). Previous incubations of these aCL with subendothelial surfaces did not increase platelet interaction. CONCLUSION: The effects of aCL on platelet function may help to explain the pathophysiology of thrombosis in the antiphospholipid syndrome.

Adult↗
PubMed1998

Inhibition of platelet-vessel wall interactions by thromboxane receptor antagonism in a human in vitro system: potentiation of antiplatelet effects of aspirin.

BACKGROUND: Pharmacological inhibition of arachidonic acid metabolism has proven therapeutically useful in the prevention of cardiovascular events. METHODS: We have investigated the ability of Bay u 3405, a synthetic thromboxane antagonist, to interfere with platelet aggregation and arachidonic acid metabolism. The antiplatelet action was also analysed in a perfusion system in which vascular subendothelium was exposed to circulating human blood (10 min; shear rate = 800 s-1). Platelet interactions were morphometrically analysed and results compared with those obtained in studies with blood from donors taking aspirin (acetylsalicylic acid, ASA) (500 mg day-1). The additional effect of Bay u 3405 on the antiplatelet action of ASA was also evaluated. RESULTS: Bay u 3405 caused a dose-dependent inhibition of platelet aggregation induced by U46619 with a maximal effect at concentrations > or = 0.01 microgram mL-1. Higher concentrations (> or = 0.05 micrograms mL-1) also inhibited aggregations induced by ADP or collagen. Bay u 3405 did not interfere with platelet arachidonic acid metabolism. In perfusion studies, Bay u 3405 (0.01 microgram mL-1) significantly decreased the total surface of the vessel covered by platelets (%CS = 18.7 +/- 1.09 vs. 24.4 +/- 1.94; P < 0.05) and the formation of large aggregates %T = 7.5 +/- 0.87 vs. 19.3 +/- 1.61; P < 0.01). ASA treatment reduced platelet aggregate formation (%T = 13.7 +/- 2.06; P < 0.05) but did not affect the total surface covered by platelets. The in vitro addition of Bay u 3405 to blood from ASA-treated donors further reduced the formation of large aggregates (%T = 2.7 +/- 0.79; P < 0.01 vs. ASA). CONCLUSIONS: In vitro effect of Bay u 3405 on platelet function were superior to those observed with ASA. The thromboxane antagonism antagonism provided by Bay u 3405 further enhanced the inhibition of platelet aggregate formation found after ASA treatment.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Platelet-leukocyte activation during hemodialysis detected with a monoclonal antibody to leukocyte integrin CD11b.

Platelet activation is commonly monitored with a battery of monoclonal antibodies against different platelet epitopes with controversial results. The transient expression of platelet markers and their role mediating interactions with other cells could easily explain these discrepancies. The present study has evaluated whether the analysis of a leukocyte activation antigen (CD11b) could provide more reliable results than detection of platelet activation markers. Cytometric techniques with specific monoclonal antibodies were used to compare the reliability of platelet and leukocyte markers to detect activation. Modifications in the presence of platelet glycoproteins GPIb (CD42b), GPIIIa (CD41) and GPIV (CD36), expression of specific platelet markers (P-selectin (CD62P) and lysosomal protein (CD63)) and leukocyte integrin (CD11b) were assessed during hemodialysis. Platelet antigens remained in uremic patients at levels similar or slightly above those detected in a group of healthy subjects. Modifications of platelet antigens during hemodialysis produced inconclusive results. However, numbers of leukocytes expressing CD11b increased progressively during hemodialysis (17.2 +/- 5.1% at 15 min and 21.3 +/- 6.6% at 2 h, p < 0.05, vs. baseline 6.9 +/- 0.2%). The hemodialysis procedure caused an increased formation of leukocyte-platelet aggregates. Detection of leukocyte CD11b may be a useful marker of overall cellular activation during the hemodialysis procedure.

Aged↗
PubMed1998

Cytoskeletal reorganization after preparation of platelet concentrates, using the buffy coat method, and during their storage.

BACKGROUND AND OBJECTIVE: The use of platelet transfusions has risen considerably in the last years. Changes occur in platelet biochemical and membrane properties during storage. We have analyzed the effect of platelet preparation and storage of platelet function through the evaluation of platelet cytoskeletal reorganization. METHODS: A blood sample was obtained from the donor and platelets were separated as standard platelet-rich plasma (PRP) (120 g, 20 min) (PRE sample). Aliquots were also collected immediately after preparation using buffy coat procedure of platelet concentrates (day 0) and after 1, 3 and 5 days of storage. Cytoskeleton composition in both low- and high-speed cytoskeletal fractions of detergent-lysed platelets was analyzed by gradient SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Presence of each contractile protein was quantified by densitometry. RESULTS: The method used to prepare platelet concentrates induced actin polymerization (actin increased to 163.5 +/- 4.8%, mean +/- SEM, n = 8, p < 0.001, considering actin values in PRE sample as 100%) with a concurrent increase in the association of actin-binding protein (ABP), myosin and alpha-actinin to the low-speed cytoskeletal fraction. During the first 24 hours of storage, cytoskeletal assembly was partially reversed (134.8 +/- 2.6% of actin, p < 0.001) and actin polymerization increased gradually to 144.3 +/- 5.8% and 153.2 +/- 5.1% at days 3 and 5, respectively (p < 0.001 for both days). ABP, myosin and alpha-actinin showed similar tendencies to those referred for actin. Conversely, during platelet preparation and storage, the contractile proteins associated with the high-speed cytoskeletal fraction decreased, due to reorganization of the contractile proteins to the low speed fraction. INTERPRETATION AND CONCLUSIONS: The method used to prepare platelet concentrates (buffy coat procedure) induced cytoskeletal polymerization. This activating effect was partially reversed after 1 day of storage, although it increased progressively after 3 days of storage. The storage lesion may lead to defective cytoskeletal assembly in response to further stimulus. Analysis of cytoskeletal assembly is a sensitive method for detecting platelet activation caused by the concentrate preparation method and the storage conditions.

Actins↗
PubMed1998

von Willebrand factor contained in factor VIII concentrates of different purities supports platelet adhesion in blood samples from a heterogeneous group of patients with von Willebrand disease.

BACKGROUND AND OBJECTIVE: Plasma derived FVIII-VWF concentrates in which the VWF structure is reasonably maintained are recommended as substitutive therapy in VWD. Our aim was to assess platelet deposition and binding to subendothelial structures of VWF present in FVIII concentrates. DESIGN AND METHODS: Cryoprecipitate (CRY), intermediate-purity (IPC), or high-purity (HPC) FVIII concentrates were added in vitro to citrated blood samples from 11 patients affected by different subtypes of VWD, with the aim of normalizing VWF levels. Measurements of VWF:Ag, ristocetin cofactor (RiCof) activities, FVIII coagulant activity (FVIII:C), and platelet interaction with subendothelium under flow conditions (Baumgartner's perfusion method, computer-assisted morphometry, shear rate 1000 s-1, 10 min, 37 degrees C) were determined. Binding of VWF to the luminal surface of the perfused vessels was assessed by immunofluorescence microscopy. Paired t-test statistics were performed. RESULTS: Addition of FVIII-VWF preparations raised VWF:Ag from baseline (BSL) values of 0.3 (SD 0.2) to averages of 1.4 (SD 0.5, p < 0.001), 1.2 (SD 0.6, p < 0.001), and 0.4 (SD 0.3) IU mL-1 after CRY, IPC, and HPC, respectively. A positive labeling for VWF was observed by immunofluorescence in vessels perfused with blood containing any of the concentrates. Platelet adhesion of 13.2 (SD 7.6), 22.4 (SD 10.8), 24.8 (SD 7.8, p < 0.03), or 22.5 (SD 4.8)% was measured in BSL, CRY, IPC, or HPC tests, respectively. INTERPRETATION AND CONCLUSIONS: Our observations support the hypothesis above the mechanisms involved in the beneficial effects of commercial concentrates in von Willebrand disease: the VWF in these concentrates has functional capacity to bind to subendothelium and to support platelet adhesion.

Adult↗
PubMed1997

Differential effect of a low-molecular-weight heparin (dalteparin) and unfractionated heparin on platelet interaction with the subendothelium under flow conditions.

Effects of heparins on platelet function are controversial, but perfusion studies, that simulate physiological conditions, might help to explain their clinical behaviour. We used a perfusion system to test the effect unfractionated heparin and a low-molecular-weight heparin (dalteparin, Fragmin) on platelet adhesion promoted by a damaged vascular surface. Normal blood samples containing increasing concentrations of unfractionated heparin and dalteparin were perfused through annular chambers containing enzymatically denuded rabbit aorta segments (5 min at 800 sec-1). Segments were evaluated morphometrically measuring the total surface covered by platelets and by large aggregates (thrombi). Unfractionated heparin inhibited platelet interaction with subendothelium in a lesser extent than dalteparin in both covered surface and thrombi (p < 0.01). At heparin doses that caused maximal inhibition covered surface was 10.0% +/- 3.1% with dalteparin and 18.3% +/- 4.2% with unfractionated heparin, and thrombi were 5.6% +/- 3.2% and 12.3% +/- 3.0%, respectively. These results may collaborate to explain some differences observed in the clinical results obtained with unfractionated heparin and with dalteparin.

Animals↗
PubMed1997

Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: a prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus.

Vascular complications are the main cause of morbidity in diabetes mellitus. To evaluate lipoprotein and hemostatic parameters and their relationship with clinically detectable microangiopathy, we studied 58 insulin-dependent diabetes mellitus patients and 60 controls matched for age, sex, and body mass index. Thirteen patients presented clinically detectable microangiopathy (8 retinopathy and 5 both retinopathy and microalbuminuria). A cross-sectional study of lipid profile, coagulation parameters, and a flow-cytometric evaluation of tissue factor expression in normal monocytes induced by patient plasma were performed. Patients were re-evaluated for microangiopathy in a 3-year median follow-up. Patients showed triglyceride enrichment in low (P = 0.00002) and high density lipoproteins (P = 0.004) and increased levels of D-dimer (P < 0.00001), prothrombin fragment 1 + 2 (P < 0.00001), and thrombin-antithrombin III complex (P = 0.0001). Patients with clinically detectable microangiopathy had increased type 1 plasminogen activator inhibitor (P = 0.00001), thrombomodulin (P = 0.02), and induced monocyte tissue factor expression (P < 0.00001). Nine patients developed clinically detectable microangiopathy in the follow-up and the only predictive variable was increased induced tissue factor expression. In conclusion, in these patients elevated thrombin and fibrin generation reflects a hypercoagulable state but clinically detectable microangiopathy seems related to endothelial cell injury markers and to increased induced tissue factor expression on monocytes.

Adolescent↗
PubMed1997

Cocaine administration enhances platelet reactivity to subendothelial components: studies in a pig model.

Myocardial infarction in cocaine abusers may be related to a direct platelet-activating effect. We analysed this possibility in an experimental model. Studies were carried out in eight normal, anaesthetized pigs with a weight of 30.7 +/- 3.7 kg. Blood samples were withdrawn before and 20 min after i.v. administration of cocaine (10 mg kg-1; at 1 mg kg-1 every 2 min). Modifications in platelet responses to arachidonic acid (AA; 1.4 mmol L-1), ADP (1-4 microM), synthetic thromboxane endoperoxide analogue (U46619; 1 microM), collagen (2.5-5 micrograms mL-1), adrenaline (10 microM) and ristocetin (0.8-1 mg mL-1) were tested by conventional aggregometry. Changes in the capacity of platelets to form aggregates on damaged subendothelium were assessed by means of an ex vivo perfusion system in which blood was circulated for 10 min at 800 s-1, a shear rate similar to that found in normal coronary arteries. The interaction of platelets with perfused denuded arterial segments was morphometrically quantified and expressed as a percentage of damaged vessel surface covered by platelets (%CS). Cocaine administration did not influence platelet aggregation patterns in pigs. However, there was a significant increase in the interaction of pig platelets with subendothelial structures after cocaine infusion (%CS = 40 +/- 17% vs. 27 +/- 16% baseline; mean +/- SD; P < 0.01). Cocaine administration in this animal model increases the reactivity of platelets exposed to subendothelium. These results support the concept that the administration of cocaine to pigs has a prothrombotic effect by facilitating the interaction of platelets with damaged arteries.

Animals↗
PubMed1997

In vitro evaluation of the hemostatic effectiveness of non viable platelet preparations: studies with frozen-thawed, sonicated or lyophilized platelets.

OBJECTIVES: Because of the limited life span of platelets in regular storage systems, we were interested in investigating the effects on hemostasis of nonliving platelet derivatives. METHODS: We evaluated the effects of different platelet preparations on primary hemostasis in a well-established perfusion model. Studies were carried out with blood anticoagulated with low molecular weight heparin. Similar amounts of frozen-thawed, sonicated or lyophilized platelets were added to normal blood or to blood which had been experimentally depleted of platelets. Platelet interaction with the subendothelium and fibrin deposition were morphometrically evaluated. RESULTS: Addition of nonviable platelet preparations to thrombocytopenic blood always promoted a statistically significant increase in the deposition of fibrin on the subendothelium, but only lyophilized platelets retained some ability to interact with the subendothelium. Flow cytometry studies demonstrated the presence of GPIb, GPIIIa and P-selectin on lyophilized platelets. CONCLUSIONS: Preparations containing nonviable platelets may still retain some hemostatic properties.

Animals↗
PubMed1997

Hemostasis in patients with severe von Willebrand disease improves after normal platelet transfusion and normalizes with further correction of the plasma defect.

BACKGROUND: A defective hemostatic effect of plasma concentrate infusion in patients with severe von Willebrand disease (vWD) has been ascribed to the absence of platelet von Willebrand factor (vWF) STUDY DESIGN AND METHODS: The role of platelet vWF in hemostasis of severe vWD was investigated. A plateletpheresis unit (4-5 x 10(11) platelets) from a normal compatible donor was transfused before any cryoprecipitate infusion to three type 3 vWD patients and to one patient with severe type 1 vWD with low levels of platelet vWF who required replacement therapy for bleeding episodes. Autologous platelets were transfused to one of the patients with type 3 vWD. RESULTS: Partial corrections of bleeding times (14-17 min vs. baseline >30 min) were observed in all patients after the transfusion of normal platelets. During cryoprecipitate infusion, bleeding times were normalized (<6 min), and bleeding episodes stopped when plasma levels of vWF activity ranged from 14 to 18 U per dL. Platelet interactions with the subendothelium increased in parallel with the correction of bleeding times. These results indicate that if approximately 20 percent of the total number of platelets have normal vWF antigen and if plasma vWF levels are at least 14 U per dL, then bleeding times will normalize and mucosal hemorrhages will stop. Transfusion of autologous platelets in one patient with type 3 vWD did not modify bleeding times or platelet adhesion on the subendothelium. CONCLUSION: The hemostatic effect of normal platelets in type 3 vWD seems to be related to the platelet vWF in the transfused platelets.

Bleeding Time↗
PubMed1997

Anti-beta 2-glycoprotein I antibodies: a useful marker for the antiphospholipid syndrome.

We studied anti-beta 2-glycoprotein I antibodies (a beta 2GPI) in autoimmune disease patients to evaluate their relationship to clinical findings. Seventy-nine systemic lupus erythematosus (SLE) patients [44 with antiphospholipid antibodies (aPL)], 21 with primary antiphospholipid syndrome (APS), eight asymptomatic individuals with aPL and 60 controls were studied. Sixteen SLE patients (14 with aPL and two without aPL) and six with primary APS had a beta 2GPI. A significant relationship was found between a beta 2GPI and aPL (P < 0.01). In SLE, a significant correlation was found between previous thrombosis or thrombocytopenia and a beta 2GPI or a beta 2GPI + aPL, but not between fetal losses and a beta 2GPI. These data suggest that a beta 2GPI may be useful in the study of APS.

Adult↗
PubMed1997

In vivo evaluation of platelet activation by different cellulosic membranes.

This study was undertaken to evaluate platelet activation in vivo induced by different cellulosic membranes by measuring the expression of P-selectin on the platelet surface during hemodialysis in 9 uremic patients. Hollow fiber dialyzers of similar surface with different cellulosic membranes (Cuprophan, cellulose acetate, cellulose triacetate, and Hemophan) were evaluated and compared to a synthetic membrane (polysulfone). Blood samples were obtained before hemodialysis and from the efferent and afferent limbs 5 min after the beginning of dialysis. P-selectin exposure was evaluated by flow cytometry (FACScan) using a monoclonal antibody (RUU 2.17). The percentage of platelets expressing P-selectin before hemodialysis and the percentage from the arterial line during hemodialysis were similar. All membranes evaluated induced platelet activation (estimated as the increase in percentage of platelets expressing P-selectin in samples obtained from the venous line with respect to the arterial line). Cuprophan induced more platelet activation than any other membrane (p < 0.05). The activation induced by cellulose acetate and cellulose triacetate membranes was also higher than that observed with Hemophan (p < 0.05). Hemophan-induced platelet activation was similar to that of polysulfone. These results indicate that all cellulosic membranes induce platelet activation during hemodialysis although there are quantitative differences among them. While Cuprophan induced the highest degree of platelet activation, Hemophan was the only cellulosic membrane that showed a degree of platelet activation similar to the biocompatible membrane polysulfone.

Adult↗
PubMed1997

Anti-endothelial cell antibodies in systemic autoimmune diseases: prevalence and clinical significance.

OBJECTIVE: To investigate the prevalence and characteristics of anti-endothelial cell antibodies (AECA) in a large cohort of patients with several well defined systemic autoimmune diseases, in order to determine their relationship with the clinical and laboratory features of these diseases. METHODS: Clinical and laboratory features of 216 consecutive Caucasian patients were prospectively studied. One hundred and seven patients had been diagnosed as having a primary systemic vasculitis-specifically, 39 had temporal arteritis (TA), 25 polyarteritis nodosa (PAN), 9 Wegener's granulomatosis (WG), and 34 Behcet's disease (BD)-, 90 patients had systemic lupus erythematosus (SLE), and 19 had a primary Sjogren's syndrome (SS). The AECA were determined by ELISA. RESULTS: One hundred and four (48%) patients with systemic autoimmune diseases were found to have a positive titre of AECA. Specifically, AECA were detected in 41 (38%) patients with a primary systemic vasculitis (13 (33%) with TA, 14 (56%) with PAN, 5 (56%) with WG and 9 (26%) with BD), in 58 (63%) patients with SLE, and in 5 (26%) patients with a primary SS. In patients with a primary systemic vasculitis, those with AECA were found to have an increased prevalence of disease activity (P < 0.05). In SLE patients, those with AECA were found to have an increased prevalence of vascular lesions (P < 0.05), lupus nephropathy (P < 0.05), and anticardiolipin antibodies (aCL) (P < 0.001). CONCLUSIONS: Patients with systemic autoimmune diseases have a high prevalence of AECA and they are associated with the presence of vascular lesions, nephropathy, and aCL in SLE, as well as with disease activity in several primary systemic vasculitis (TA, PAN, WG and BD).

Adult↗
PubMed1997

Desmopressin (DDAVP) enhances platelet adhesion to the extracellular matrix of cultured human endothelial cells through increased expression of tissue factor.

The effect of desmopressin (DDAVP) on thrombogenicity, expression of tissue factor and procoagulant activity (PCA) of extracellular matrix (ECM) generated by human umbilical vein endothelial cells cultures (HUVEC), was studied under different experimental conditions. HUVEC were incubated with DDAVP (1, 5 and 30 ng/ml) and then detached from their ECM. The reactivity towards platelets of this ECM was tested in a perfusion system. Coverslips covered with DDAVP-treated ECMS were inserted in a parallel-plate chamber and exposed to normal blood anticoagulated with low molecular weight heparin (Fragmin, 20 U/ml). Perfusions with run for 5 min at a shear rate of 800 s-1. Deposition of platelets on ECMs was significantly increased with respect to control ECMs when DDAVP was used at 5 and 30 ng/ml (p < 0.05 and p. < 0.01 respectively). The increase in platelet deposition was prevented by incubation of ECMs with an antibody against human tissue factor prior to perfusion. Immunofluorescence studies positively detected tissue factor antigen on DDAVP derived ECMs. A chromogenic assay performed under standardized conditions revealed a statistically significant increase in the procoagulant activity of the ECMs produced by ECs incubated with 30 ng/ml DDAVP (p < 0.01 vs. control samples). Northern blot analysis revealed increased levels of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate that DDAVP in vitro enhances platelet adhesion to the ECMs through increased expression of tissue factor. A similar increase in the expression of tissue factor might contribute to the in vivo hemostatic effect of DDAVP.

Anticoagulants↗