Biomedical subjects

A Ordinas

Publications and source records attributed to A Ordinas.

At least 19 recordsLinked to original sources

PubMed1992

Recombinant human erythropoietin treatment improves platelet function in uremic patients.

The effect of recombinant human erythropoietin (rHuEPO) on primary hemostasis was tested in 19 hemodialyzed patients. Bleeding time, platelet aggregation and platelet interaction with vessel subendothelium (SE) under flow conditions were determined before treatment and after patients reached hematocrits greater than or equal to 30%. Two thrombotic events (an acute myocardial infarction and an AV fistula clotting) were recorded during the early stages of treatment. A shortening of average bleeding times (P less than 0.01), an increase in platelet count (P less than 0.01) and an improvement of platelet aggregation (P less than 0.01) and of platelet-SE interaction (P less than 0.01) were observed. A low correlation index was found between hematocrit and bleeding time (r = -0.351, P less than 0.05). To assess a possible effect of rHuEPO on platelet function, the same parameters were evaluated before and after receiving three doses of rHuEPO (40 U/kg i.v. post-hemodialysis) in 14 of the patients. No changes in platelet or erythrocyte counts were observed, the mean bleeding time remained unchanged, but platelet aggregation induced by arachidonic acid (P less than 0.05), ADP (P less than 0.01) and ristocetin (P less than 0.05) improved. Perfusion studies confirmed moderate but significant increases in the parameters that quantify platelet-SE interaction (P less than 0.05). Improvement of ADP-induced aggregation correlated with the increase of platelet adhesion to SE (r = 0.675, P less than 0.05). We conclude that rHuEPO treatment improves primary hemostasis in uremia through an increase of red cell mass but also through a beneficial effect on platelet function, which is independent of the hematocrit rise.

Adult↗

PubMed1992

A variant of Glanzmann's thrombasthenia which fails to express a GPIIb-IIIa related epitope that is recognized by a specific monoclonal antibody (C17).

Binding of different antibodies to the GPIIb-IIIa complex in resting (AP2, EDU3, C17) or activated platelets (PAC1) was studied by flow cytometry in a patient with a platelet defect involving GPIIb-IIIa related functions. The patient has a mild history of bleeding. Aggregation induced by ADP and collagen were absent but normal response was obtained with ristocetin. Platelets from the patient do not bind fibrinogen. Perfusion studies with flowing blood showed that patient's platelets have a marked impairment in the process of spreading and aggregate formation on vascular subendothelium. Electrophoretic studies in SDS-polyacrylamide gels demonstrated the presence of normal amounts and normal mobility of GPIIb-IIIa. Fibrinogen was present in the patient's platelets (68-74% of controls). The binding of AP2 and EDU3 to patient's resting platelets was normal as assessed by flow cytometry. In contrast, a decreased presence of the C17 antigen (10 fold lower than control platelets) was detected in resting platelets and a markedly reduced binding of PAC1 was found in thrombin activated platelets. These studies suggest that C17 recognizes an epitope of the GPIIb-IIIa in resting platelets that is implicated in the regulation of adhesive and cohesive properties of GPIIb-IIIa. Studies on this patient might be helpful for the understanding of GPIIb-IIIa functions.

Adenosine Diphosphate↗

PubMed1992

Hemostatic effect of platelet von Willebrand factor.

In type III von Willebrand disease (vWD) patients, the bleeding time was only partially corrected or not modified after cryoprecipitate infusion, although the levels and the multimeric structure of plasma von Willebrand factor (vWF) were normal. However, the adhesion of normal platelets on the vessel wall subendothelium in the presence of postinfusion patient plasma improved more significantly than the bleeding time. These results suggest a role of the vWF released from normal platelets which is absent in type III vWD platelets. In 5 patients transfusion of normal platelet concentrates performed 1 h after cryoprecipitate infusion without modification of the bleeding time (> 30 min) normalized this parameter, and platelet adhesion to the subendothelium elicited a marked improvement. These last results confirm the suggestion that platelet vWF plays an important 'in vivo' role in the hemostatic process, particularly in patients suffering from severe vWD.

Animals↗

PubMed1992

Plasma from systemic lupus erythematosus patients with antiphospholipid antibodies promotes platelet aggregation. Studies in a perfusion system.

The possible platelet-aggregating effect of plasma from systemic lupus erythematosus (SLE) patients (n = 19) was investigated under flow conditions. Aliquots of the SLE plasmas with (n = 10) or without (n = 9) anticardiolipin antibodies (ACAs) were added to anticoagulated blood (1:20, vol/vol). Plasma from normal donors was used as a control. Blood was incubated for 15 minutes at 37 degrees C and then perfused through annular chambers containing denuded arterial segments. Perfusions were performed for 10 minutes at a shear rate of 800 sec-1. The interaction of platelets with vessel subendothelium (SE) was morphometrically evaluated in thin sections. In control experiments, the percentage of the SE covered with platelets was 23.6 +/- 4.3% (mean +/- SD). Large aggregates (more than 5 microns in height) covering 11.8 +/- 5.7% of the exposed SE were noted. The deposition of platelets was statistically increased (38.5 +/- 7.6%, p less than 0.01 versus control) in the presence of SLE plasmas with demonstrated antiphospholipid antibodies (APAs). The formation of large aggregates was also augmented (30.3 +/- 5.9%, p less than 0.01 versus control). A similar response was obtained after addition of affinity-purified immunoglobulin G and immunoglobulin M fractions from two patients with ACAs. SLE plasmas with no detectable APAs did not influence the morphometric parameters studied. Results of the present study indicate that the presence of APAs in SLE plasma promotes platelet aggregation under flow conditions. These observations may help to explain the pathophysiology of the thrombotic events occurring in patients with APAs.

Adolescent↗

PubMed1992

Contribution of perfusion techniques to the evaluation of the hemostatic effectiveness of platelet concentrates.

Perfusion systems allowing the morphometric analysis of platelet interactions with vessel subendothelium under flow conditions have been applied to evaluate the quality and function of stored platelets. Studies performed in vitro indicate that despite the existence of storage lesions, platelets in concentrates stored for up to 5 days retain their ability to interact with the subendothelium. Perfusion studies ex vivo with nonanticoagulated blood from anemic-thrombocytopenic patients have shown the critical hemorrheological role of red blood cells facilitating platelet interactions with subendothelium. Similar studies performed on severely thrombocytopenic patients who received transfusions of platelets stored at 4 degrees C indicate that incompletely viable platelets can contribute to primary hemostasis through procoagulant mechanisms. The latter results suggest that storage lesions which contribute to impairment of platelet function may result in enhancement of platelet procoagulant activities. Perfusion techniques have contributed to the evaluation of the hemostatic effectiveness of platelet concentrates. These techniques will provide a useful model to test the impact of new storage technologies on platelet hemostatic function.

Animals↗

PubMed1992

The role of subendothelial laminin and platelet laminin receptors in haemostasis.

Laminin (LM) is a basement membrane glyco-protein which exhibits a number of biological activities, including the promotion of cell attachment and migration. In a static system, platelets attach to LM without spreading. In order to elucidate the mechanisms mediating platelet-LM interactions under flow conditions, we studied the effects of blocking subendothelial LM and its platelet receptor. We measured the extent of platelet adhesion to the endothelial cell extracellular matrix (ECM) using a parallel plate perfusion chamber. To do this, we performed the following experiments: i) blockade of subendothelial LM by incubation of ECM with an anti-LM antibody (Ab); ii) blockade of the platelet receptor for LM with: a) an anti-67 KDa receptor Ab; and b) three different LM-derived peptides (CFALRGDNP, IKVAV and CDPGYIGSR). In i) perfusates consisted of whole blood, whereas in ii) perfusates were prepared with washed platelets pre-incubated with Ab or peptides and reconstituted with plasma and washed red blood cells. Perfusions were carried out at 800 s-1 shear rate. Platelet deposition was morphometrically evaluated by a computerized system. Our results indicated that when ECM was pre-incubated with an anti-LM Ab (100 micrograms/ml, 30 min, 37 degrees C) a reduction of the surface coverage (SC) of 23.3 +/- 2.3% (p less than 0.01) was observed. When washed platelets were pre-incubated with an anti-67 KDa receptor Ab (40 micrograms/ml, 30 min, 37 degrees C) their interaction with ECM was decreased by 22.3 +/- 2.1% of SC (p less than 0.005). In other experiments platelets were pre-incubated with CFALRGDNP, IKVAV and CDPGYIGSR (200 micrograms/ml, 30 min, 37 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1992

[The effect of low-dose acetylsalicylic acid on platelet aggregation parameters in vitro].

In order to elucidate whether a single dose of 150 mg acetylsalicylic acid three times a day, provokes significant changes into platelet aggregation, we analyzed a group of 50 patients who underwent coronary revascularization. During 48 hours before surgery, all patients received 100 mg dipyridamole orally every 6 hours and 1 hour after the end of the operation 100 mg dipyridamole via nasogastric tube. Patients were then randomized into three groups to receive 3 times a day a capsule containing: 50 mg acetylsalicylic acid, 50 mg acetylsalicylic acid plus 75 mg dipyridamole or placebo. Before the antiplatelet therapy was started, the day of the operation and 5 days after the onset of the treatment, blood samples were taken to determine platelet aggregation (turbidimetric technique) and the thromboxane A2 liberation. The three groups were comparable for all the studied clinical and angiographic variables. Preoperative dipyridamole did not provoke significant changes in platelet aggregation (acetylsalicylic acid group 86.5 +/- 10% vs 71 +/- 28.8%; acetylsalicylic acid + dipyridamole group 81.5 +/- 7.8% vs 75.3 +/- 22.7%; placebo group 83.7 +/- 8.9% vs 70 +/- 21.5%). After 5 days of treatment with acetylsalicylic acid, both groups under active treatment showed a significant (p less than 0.001) decrease of aggregability (acetylsalicylic acid 12.8 +/- 4.4%; acetylsalicylic acid + dipyridamole 20.5 +/- 17%; placebo 72 +/- 21.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

PubMed1991

Dipyridamole induces changes in the thrombogenic properties of extracellular matrix generated by endothelial cells in culture.

Dipyridamole (DIP) is a drug widely used as an antiplatelet agent, which also has effects on endothelial cells. In this study, the effects of treating confluent endothelial cell monolayers (EC) with DIP on EC viability (trypan blue exclusion test) and metabolic activity (3H-thymidine incorporation) were examined. Platelet reactivity of the extracellular matrix (ECM) produced by untreated and DIP-treated ECs was determined morphometrically by a perfusion technique. Levels of ECM-associated von Willebrand factor (vWF) and fibronectin (FN) were also quantified (ELISA). The present results indicate that treatment of EC with 10 microM DIP did not reduce EC viability but that the incorporation of labelled nucleotides was significantly decreased (p less than 0.01). Platelet deposition onto the ECM generated by DIP-treated cells, perfused at a shear rate of 1300 sec-1, differed significantly with respect to controls (p less than 0.05), and platelet adhesion was also reduced (25% less, p less than 0.05). This effect was shear rate dependent, as no differences were noted when the ECMs were perfused at 300 sec-1 shear rate. Levels of VWF and FN associated with ECM remained unchanged with respect to controls. These results suggest that treatment with DIP alters EC metabolic activity, which in turn, influences the reactivity of the ECM generated by treated cells.

Cell Count↗

PubMed1991

Thrombin generation and fibrinolysis in the thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.

Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT), as well as other coagulation and fibrinolysis parameters, were studied in a series of 13 patients affected by thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS). Fragment F1 + 2 was found to be increased in all patients at diagnosis (patients' range, 1.21-19.03 nmol/l; normal limits, 0.28-1.08 nmol/l), and remained also higher than normal after treatment with plasma exchange (patients' range, 1.5-4.01 nmol/l). Even though the analysis of fibrinolysis markers did not show a definite state of hypo or hyperfibrinolysis in the systemic circulation, enhanced circulating D-dimer levels (0.53-12.6 micrograms/ml, normal levels of 0.03-0.29 micrograms/ml) indicated that a certain grade of fibrin lysis was present at previously formed thrombi. Plasma PAI-1 activities either on admission (9.2-38.2 U/ml) and after plasma exchange therapy (2.6-38.6 U/ml) showed a behavior irrespective of t-PA:Ag changes, and post-plasmapheresis values remained high only in patients with fatal neurological outcome. Nevertheless, no correlations between clinical and laboratory data could be established useful for the TTP/HUS prognosis. We conclude that increased thrombin generation occurring in damaged areas is appropriately inhibited by antithrombin III in the systemic circulation, avoiding consumption coagulopathy to develop in uncomplicated patients. In addition, fibrinolysis data suggest that elevated PAI-1 may decisively favor the development of microvascular thrombi.

Antithrombin III↗

PubMed1991

Hemostatic effect of normal platelet transfusion in severe von Willebrand disease patients.

Platelet von Willebrand factor (vWF) has been suggested to play an important role in the hemostatic process. Clinical and experimental data indicate that bleeding time (BT) and platelet-vessel wall interaction cannot be normalized unless the defect of platelet vWF is also corrected. We have examined the effect of normal platelet concentrate transfusion 1 hour after cryoprecipitate infusion in five type III von Willebrand disease (vWD) patients. The cryoprecipitate infusion attained normal circulating levels of ristocetin cofactor, vWF antigen, and factor VIII activity. In two patients, cryoprecipitate infusion did not modify the BT (greater than 30 minutes), whereas in the remaining three patients BT was only partially corrected (from greater than 30 to 12, 18, and 21 minutes). However, the immediate platelet transfusion completely corrected the BT in four cases, and in one case it shortened the BT to 8.30 minutes (n = 3 to 8 minutes). In the perfusion study, cryoprecipitate infusion only resulted in a slight increase in platelet deposition (surface coverage range: 2.4% to 11.3%), whereas the platelet concentrate transfusion elicited a more marked improvement (range: 8.2% to 26.4%; P less than .02 v post-cryoprecipitate). These results suggest an important in vivo role of the platelet vWF in supporting platelet-vessel wall interaction. They also give support to the occasional addition of normal platelet transfusion to the cryoprecipitate infusion for the control of serious bleeding episodes resistant to cryoprecipitate in severe vWD patients.

Bleeding Time↗

PubMed1991

Platelet antiaggregate activity.

Calcium ions act as a second messenger to platelet agonists, with increases in intracellular calcium bringing about changes in shape, aggregation, and release reactions. Changes in platelet function have been reported previously in migraine sufferers and there is evidence that hyperaggregability occurs during a migraine attack. It was decided to assess platelet aggregation with platelet-rich plasma (PRP) from nicardipine-treated migraine sufferers because dihydropyridine derivatives are known to inhibit adenosine diphosphate (ADP)- and epinephrine-induced aggregation. Aggregation induced by 1.4 mumol/L arachidonic acid was similar in PRP from control subjects and untreated migraine sufferers, whereas 1 or 2 mumol/L ADP-induced aggregation was lower in PRP from migraine sufferers. Treatment with 20 mg of nicardipine three times daily for 2 months significantly (p less than 0.05) increased 2 mumol/L ADP-induced aggregation. It is concluded that nicardipine was acting either on migraine pathogenic mechanisms or directly on the platelets.

Adenosine Diphosphate↗

PubMed1991

Evaluation of the transfusion effectiveness of various platelet concentrates by means of an in vitro perfusion technique.

An in vitro perfusion technique was used for the assessment of the effectiveness of platelet concentrates (PCs) administered to patients with bone marrow failure. Denuded rabbit arterial segments mounted in annular chambers were exposed to nonanticoagulated blood drawn directly from the antecubital vein. This perfusion system allows the direct visualization of platelet-subendothelium interactions. The deposition of platelets on exposed subendothelium and the presence of fibrin were evaluated morphometrically. Perfusions were performed before and 10 and 120 minutes after the transfusion of PCs that had been obtained by apheresis and administered immediately after collection (A) or separated by centrifugation of blood units and transfused 24 hours after storage at 22 degrees C (B) or 4 degrees C (C). Bleeding times were also determined systematically. The deposition of platelets on the subendothelium increased significantly (p less than 0.01) 10 minutes after transfusions of A and B PCs, but the presence of fibrin did not differ from pretransfusion values. Two hours after the administration of A or B PCs, the improvement of platelet deposition persisted. By then, the presence of fibrin increased markedly (p less than 0.01). The deposition of platelets was not modified after the transfusion of C PCs, but the presence of fibrin was augmented significantly at both posttransfusion times. Comparisons between bleeding times and morphometric results pointed to a possible role of fibrin formation in contributing to primary hemostasis.

Bleeding Time↗

PubMed1991

Comparison between human umbilical artery and rabbit abdominal aorta as substrata for platelet adhesion and platelet thrombus formation under flow conditions.

Rabbit abdominal aortas and human umbilical arteries are currently used as substrata for the study of platelet adhesion and aggregate formation under flow conditions. Using immunohistochemical and ultrastructural methods, we have analyzed both vessel surfaces. The reactivity towards platelets of the subendothelium (SE) exposed on these vessels after mechanical or enzymatic digestion (alpha-chymotrypsin) was morphometrically quantified and the nature of the interaction studied in the electron microscope. After mechanical damage, the ultrastructural study of rabbit aortas showed a clearly defined internal elastic lamina (IEL). In contrast, umbilical vessels lacked a consistent IEL and masses of amorphous material often located deeper in the media were the main constitutents of the SE. Immunohistochemical labeling of the von Willebrand factor bound to both types of vessel differed considerably. Quantification of platelet interactions after perfusion of citrated blood showed qualitative differences between mechanically damaged rabbit or human vessels. Enzymatic digestion produced a more thrombogenic surface on rabbit aortas (p less than 0.01 vs. nondigested), but decreased their reactivity towards platelets on umbilical arteries (p less than 0.01 vs. nondigested). The ultrastructural study of the interacting platelets revealed that aggregates, when present, were found on the extracellular matrix underlying endothelial cells of rabbit aortas, but interacting with fibrillar structures probably derived from cell elements of the media in the case of umbilical arteries. These findings indicate that rabbit aortas and umbilical arteries possess structural characteristics that result in different thrombogenic properties with respect to circulating platelets.

Aorta, Abdominal↗

PubMed1991

Effects of endothelial cell treatment on 13-HODE and prostacyclin synthesis and its correlation with tumor cell-vascular endothelial cell adhesion.

Adhesion of tumor cells to vascular endothelial surfaces is one of the key steps in metastatic dissemination. Several factors are believed to be implicated in the regulation of the adhesive properties of tumor cells. We show that the adhesion of five different tumor cell lines, all of them of human origin, to human umbilical vascular endothelial cells (ECs) significantly increases following pretreatment of ECs with the cytokines interleukin-1 and tumor necrosis factor, whereas tumor cell/EC interactions remained unchanged after incubation with interferon-gamma. Significant augmentation in tumor cell adhesion was also observed when ECs were treated with the lipoxygenase inhibitors salicylate and the compound BW755C. In all cases, increased tumor cell adhesion was concomitant with significant decreases in the EC levels of linoleic acid, lipoxygenase-derived metabolite 13-hydroxy-octadecadienoic acid (13-HODE). On the contrary, pretreatment of the EC monolayers with aspirin did not result in any changes towards tumor cell adhesion. These results suggest that tumor cell/EC interaction is modulated, at least in part, by intracellular levels of 13-HODE and is independent of prostacyclin (PGI2) production by the ECs.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

[Effects of the treatment with human recombinant erythropoietin on primary hemostasis in uremic patients].

The effect of human recombinant erythropoietin (r-EPO) on primary hemostasia was studied in 9 patients undergoing hemodialysis. The analysis was performed before and after the hematocrit reached a value of 30%. The most important complications observed during the study period were a death for acute myocardial infarction in a patient with previous severe ischemic cardiopathy and a thrombosis of the venous line. The bleeding time shortened in four patients although the mean value did not change significantly. Platelet count showed a non significant increase. There was a significant improvement in in vitro platelet aggregability with ADP (p less than 0.05), arachidonic acid (p less than 0.05), adrenaline (p less than 0.05), and ristocetin (p less than 0.05) as well as in the parameters that quantify the interaction between platelets and subendothelium in in vitro experiments using perfused models (p less than 0.05). There were no significant changes in coagulation and fibrinolysis tests. The treatment with r-EPO improved primary hemostasia in uremic patients. This beneficial effect was due to the increased hematocrit and to the improvement of platelet function induced by r-EPO.

Adult↗

PubMed1990

Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa.

Uremic patients have an impaired platelet function that has been related to membrane glycoprotein (GP) abnormalities. Using a perfusion system, we have studied the interaction of normal and uremic platelets with vessel subendothelium (SE) under flow conditions. Reconstituted blood containing washed platelets, purified von Willebrand factor (vWF) (1 U/mL), and normal washed red blood cells was exposed to de-endothelialized rabbit segments for 10 minutes at two different shear rates (800 and 1,600 seconds-1). In some experiments a monoclonal antibody to the GPIIb-IIIa complex (EDU3) was added to the perfusates. With normal platelets, the percentage of the vessel covered by platelets (%CS) was 23.1% +/- 3.7% at 800 seconds-1 and 30% +/- 4.3% at 1,600 seconds-1. Platelets were observed in contact or forming monolayers on vessel SE. EDU3 inhibited the spreading of normal platelets. The %CS (11.1% +/- 3.3%) was statistically decreased (P less than .01) and most of the platelets were observed in contact with the vessel surface. These data indicate that, under flow conditions, the interaction of vWF with GPIIb-IIIa can support the spreading of normal platelets in the absence of exogenous fibrinogen. Under the same experimental conditions, the interaction of uremic platelets with SE was markedly impaired at both shear rates studied (P less than .01 v normal platelets). The presence of EDU3 did not modify the interaction of uremic platelets. These results confirm the impairment of the platelet adhesion observed in uremic patients. Furthermore, they indicate the presence of a functional defect in the interaction of vWF with GPIIb-IIIa. The fact that perfusions with normal and uremic platelets in the presence of an antibody to the GPIIb-IIIa complex did not show any differences gives indirect evidence on a functionally normal interaction vWF/GPIb in uremic patients.

Blood Platelets↗

PubMed1990

Investigation of plasma von Willebrand factor and circulating platelet aggregating activity in mitomycin C-related hemolytic-uremic syndrome.

We have studied the ability of the plasma to induce aggregation of both homologous and heterologous platelets in four patients with hemolytic-uremic syndrome (HUS) associated with chemotherapy with mitomycin C (MMC). Neither platelet aggregation was elicited by patients' plasmas nor the in vitro addition of purified von Willebrand factor (vWF) had any effect on the aggregation pattern. In addition, ristocetin-induced binding of patients' vWF to formaldehyde-fixed platelets was normal, and multimeric vWF analysis revealed a normal structure of patients' plasmatic vWF whatever the clinical stage in which it was studied. These findings suggest that, in spite of the existence of common clinical and biological features in the various forms of HUS, the pathogenesis of MMC-related HUS may be, at least in part, different from that of the other forms of HUS in which both platelet-aggregating activity and alterations in the vWF are found.

Blood Platelets↗

PubMed1990

Differential localization of von Willebrand factor, fibronectin and 13-HODE in human endothelial cell cultures.

Von Willebrand factor (vWF), fibronectin (FN) and 13-hydroxy-octadecadienoic acid (13-HODE) are known to influence the regulation of the adhesive properties of vascular surfaces. In the present study vWF, FN and 13-HODE were comparatively localized in endothelial cells (EC) and in the extracellular matrix (ECM) produced by EC. An indirect immunofluorescent technique was applied to coverslips containing human EC cultures previously fixed and permeabilized following different procedures: A. Alcohol/acetone; B. Paraformaldehyde alone and C. Paraformaldehyde followed by Triton X-100. vWF was observed inside EC (A), on the ECM produced by EC (B) or in EC and ECM (C) depending on the fixation procedures used. FN was mainly localized in the ECM despite the fixation procedures employed. FN was only seen in relation to cell bodies after strong permeabilization (A). Under our experimental conditions 13-HODE was never found in ECM. This latter antigen was observed randomly dispersed in those preparations fixed with alcohol/acetone, indicating that it is probably extracted by this fixative. 13-HODE was detected in granular shaped structures in EC after permeabilization with detergent (C). These results suggest that the cellular localization of vWF and FN is compatible with an adhesive role related to the abluminal side of ECs. 13-HODE was readily observed after mild permeabilization. This finding would be morphologically consistent with its contribution to the regulation of the vessel wall thromboresistance.

Cells, Cultured↗