Biomedical subjects

G Escolar

Publications and source records attributed to G Escolar.

At least 19 recordsLinked to original sources

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↗

PubMed1996

Activated protein C inhibits thrombus formation in a system with flowing blood.

We studied the effect of increasing concentrations of protein C (PC) and activated protein C (APC) on haemostasis in an in vitro thrombosis model. Blood from healthy donors was anticoagulated with citrate-phosphate-dextrose (final citrate concentration 19 mM) or a low molecular weight heparin (LMWH, 20 IU/ml). Enzymatically denuded rabbit aorta segments were exposed to flowing blood for 10 min in an annular perfusion chamber. PC and APC were added to the perfusate immediately prior to exposure. In citrated blood at a shear rate of 800/s, PC and APC induced a statistically significant decrease in platelet deposit at 16 micrograms/ml and 32 micrograms/ml. In perfusions performed with blood anticoagulated with LMWH, there was no effect on platelet deposition at 16 and 32 micrograms/ml either at shear rates of 300/s or 800/s. Addition of PC showed no effect on fibrin deposition at a shear rate of 300/s; in contrast, a nonstatistically significant 40% reduction was seen at a shear rate of 800/s, compared to controls. Addition of APC caused a 100% reduction in fibrin formation at 16 and 32 micrograms/ml at both shear rates studied. PC and APC inhibited platelet deposition on the exposed subendothelial surface, in a dose-dependent manner. Effects of PC and APC on platelet function might be mediated through inhibition of thrombin generation at the platelet microenvironment.

Animals↗

PubMed1996

Procoagulant effect of incompatible platelet transfusions in alloimmunized refractory patients.

The clinical effectiveness of platelet transfusion in refractory patients is still a subject of debate. We have evaluated the possible hemostatic effect of platelet transfusion in 16 alloimmunized thrombocytopenic patients whose platelet counts were less than 20,000/microliters. Platelet concentrates were always obtained by apheresis procedures from incompatible donors. The posttransfusion platelet recovery was greater than 15% only in 3 cases. In the first 6 patients, measurements of bleeding time performed immediately before transfusion were in all cases longer than 30 min and did not change significantly 10 and 60 min after platelet transfusions. In all patients, ex vivo perfusion experiments with Baumgartner's platelet adhesion model, using native nonanticoagulated blood, were performed immediately before and 10 and 60 min after transfusion. No difference in platelet deposition onto the subendothelial surface was observed after platelet transfusion. Unexpectedly, the deposition of fibrin on the subendothelial surface was statistically augmented in the posttransfusion studies. Quantification of thrombin-antithrombin complexes (TAT) in plasma showed statistically significant elevations (p < 0.01) in the posttransfusion samples (31.9 +/- 12.6 vs. baseline 5.8 +/- 1.7 ng/ml), not justified by TAT levels in the transfused material (2.3 +/- 0.17 ng/ml). Transfusion of incompatible platelets to refractory patients may activate coagulation mechanisms in the absence of an increase in peripheral platelet count.

Blood Group Incompatibility↗

PubMed1996

Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: studies under flow conditions.

A defect in hemostasis has been repeatedly reported in patients with cirrhosis. However, the nature of this defect has not been fully characterized. We explored adhesive and cohesive functions of platelets from cirrhotic patients at different stages of disease development. The response of platelets to standard activating agents was tested by aggregometric procedures. The interaction of platelets with subendothelial components was explored in a perfusion system in which blood was exposed (shear rate, 800/s; 10 minutes) to denuded segments of rabbit aorta. Platelet interactions in these perfusions were analyzed morphometrically. Results were always compared with those obtained in similar studies using blood obtained from healthy subjects. Aggregation studies showed abnormal responses for single or several agonists. Abnormalities in aggregation were more evident in patients with severe disease (Child-Pugh class C), although they occasionally were abnormal for single agonists (ADP or U46619) in patients with less severe disease (Child-Pugh classes A or B). All the patient classes showed impaired platelet-subendothelial interactions (P < .01 vs. healthy subjects) that were not justified by the relative thrombocytopenia present in the more severely affected patients. Experimental increases in hematocrit in patients at stages B and C did not improve platelet-subendothelial interactions. Platelets from cirrhotic patients interact defectively with subendothelial components under flow conditions. The adhesion defect is more evident and consistent than the aggregation defects and may already be present in patients with mild liver failure. This adhesion defect may contribute to the defective hemostasis observed in cirrhotic patients.

Adult↗

PubMed1996

Antibodies to endothelial cells and to beta 2-glycoprotein I in the antiphospholipid syndrome: prevalence and isotype distribution.

The aim of this study was to analyse the prevalence and isotype distribution of antibodies to endothelial cells (aEC) and to beta 2-glycoprotein I (a beta 2GPI) in the antiphospholipid syndrome (APS). Fifteen patients with an APS [nine associated with systemic lupus erythematosus (SLE) and six "primary'] and 15 with SLE without an APS were prospectively studied. The aEC were determined by an enzyme-linked immunosorbent assay (ELISA) using endothelial cells derived from human umbilical vein and the a beta 2GPI by ELISA using highly purified beta 2GPI. A positive titre of aEC was detected in 20 out of 30 patients (67%), but in none of the control group. Ten patients had both IgG and IgM isotypes, five had IgG only and five had only IgM. Thirteen patients with the APS (87%) were found to have a positive titre of aEC, while only seven with SLE but without a history of APS (47%) had aEC (P < 0.05). Nine patients with the APS (60%) had a positive titre of a beta 2GPI (four had both IgG and IgM isotypes, one had IgG only and four had only IgM), while none of the patients without an APS (0%) had these antibodies (P < 0.001). A significant association was also found between the presence of aPL and aEC (P < 0.05), as well as between aPL and a beta 2GPI (P < 0.001). Both aEC and a beta 2GPI can be found in the APS. This reinforces the theory that APS represents a complex autoimmune disorder in which several autoantibodies co-exist with aPL.

Adult↗

PubMed1996

Redistribution of membrane glycoproteins in platelets activated under flow conditions.

A reduction in the ability of GPIb to bind specific MoAbs or ligands (vWF) has been reported in platelets exposed to thrombin in suspension. We have analyzed modifications in the presence of glycoproteins (GPs) on platelets activated under flow conditions in a system which allows limited thrombin and fibrin generation. Normal blood anticoagulated with low molecular weight heparin (LMWH, Dalteparin 20 IU/ml) was recirculated for up to 10 min at 800 s-1 through annular chambers containing denuded arterial segments. Aliquots of blood were removed from the reservoir at 0, 1, 5 and 10 min and immediately mixed with paraformaldehyde. Membrane glycoproteins: GPIb (CD42b), GPIIb-IIIa (CD41a), GPIV (CD36); and activation dependent antigens: P-selectin (CD62P) and lysosomal glycoprortein (CD63), were detected in whole blood by dual color flow cytometry. Circulation of through the perfusion system resulted in platelet activated as demonstrated by the increased percentage of platelets positive for antigens CD62P and CD63. A gradual increase in the binding of MoAbs directed against GPIb, GPIIb-IIIa, and GPIV epitopes was noted during the entire perfusion period. Observed differences in mean fluorescence intensities at all the observation times were statistically significant (P < 0.001). Our results obtained on platelets in an experimental thrombosis system indicate that GPIb, GPIIb-IIIa and GPIV remain on the surface of activated platelets and actually increase their expression. Alterations detected at the level of GPIb in platelets activated by thrombin in suspension may not take place under in vivo situations.

Antibodies, Monoclonal↗

PubMed1996

Fate of the GPIb/IX receptor complex following activation of human platelets.

Many excellent workers have concluded that platelet glycoprotein Ib/IX complex, the receptor for von Willebrand factor (vWF) is down-regulated in its ability to bind vWF or monoclonal antibodies and virtually cleared from the exterior surface to internal membranes following exposure of the cells to thrombin in suspension. Studies carried out in our laboratory, however, have not supported the concept of down-regulation or clearance. Experiments employing aggregation-disaggregation-reaggregation, agglutination and flow cytometry have demonstrated that physiologic levels of calcium ions prevent or reverse the phenomenon of down-regulation. GPIb/IX receptors remain edge to edge on surface-activated platelets, whether or not the cells are also exposed to thrombin before or after spreading. Addition of two ligands, fibrinogen labeled gold to mark GPIIb/IIIa and vWF to identify GPIb/IX, to discoid platelets before surface activation demonstrates that GPIIb/IIIa is a mobile receptor that concentrates with its ligand in cell centers while vWF bound to GPIb/IX moves with the membrane as it expands to the lateral edges of spread cell margins. Immunogold studies of thrombin-activated platelets in suspension reveal no clearance of GPIb/IX receptors, bound or not to vWF, from exposed surfaces to internal membranes. The clearance to the OCS reported by others may be due to difficulties encountered in staining GPIb/IX lining OCS channels in resting discoid platelets.

Blood Platelets↗

PubMed1996

Platelet sensitivity to prostaglandin E1 inhibition is reduced in pre-eclampsia but not in nonproteinuric gestational hypertension.

OBJECTIVE: Platelet aggregometry was used to discriminate platelet sensitivity to prostaglandin E1 (PGE1) inhibition, to evaluate whether platelet behaviour in pre-eclamptic women was different in this respect than from that in nonproteinuric hypertensive women. METHODS: The amount of PGE1 required to inhibit in vitro platelet aggregation induced by arachidonic acid was determined in samples from 60 women: 20 nonpregnant controls, 20 women with normal pregnancies, 10 women with gestational hypertension and 10 with pre-eclampsia. RESULTS: The response to arachidonic acid was similar among the four groups. Amounts of PGE1 necessary to inhibit platelet aggregation were significantly higher in normal pregnant women compared with nonpregnant controls (P<0.001). Platelets from pre-eclamptic women required significantly higher concentrations of PGE1 to inhibit aggregation than the other groups studied (P<0.001). However, there was no significant difference between normal and nonproteinuric hypertensive pregnant women. CONCLUSIONS: Our findings support the notion that increased platelet reactivity during late pregnancy is exacerbated in pre-eclamptic women but not in nonproteinuric hypertensive women. This is in agreement with the hypothesis that pre-eclampsia and gestational hypertension are different conditions. Prospective studies are required to confirm if this simple test may be useful in the early identification of pregnant women at risk for pre-eclampsia.

Adult↗

PubMed1996

Hypercoagulable state in patients with antiphospholipid syndrome is related to high induced tissue factor expression on monocytes and to low free protein s.

Antiphospholipid antibodies (aPLs) are associated with thrombosis, but the mechanisms of this thrombotic tendency are unknown. We studied 56 patients 612 with systemic lupus erythematosus [SLE] and aPLs and previous thrombosis, 12 with SLE and aPLs but no thrombosis, 15 with SLE without aPLs or thrombosis, 11 with primary antiphospholipid syndrome with thrombosis, and 6 asymptomatic subjects with aPLs) to investigate the ability of aPLs to induce tissue factor (TF) expression on human normal monocytes. A double direct immunofluorescence technique (anti-CD14 and anti-TF) was used, and procoagulant activity in viable and disrupted cells was measured after plasma incubation for 6 hours at 37 degrees C with normal mononuclear cells. Hemostasis regulatory proteins, prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels were determined. Increased TF expression and procoagulant activity were observed using plasma samples from SLE patients with aPLs and thrombosis (P < .01) and from primary antiphospholipid syndrome patients (P < .01) but not from patients with SLE and aPLs but no thrombosis, patients with SLE without aPLs, or asymptomatic patients with aPLs. Purified aPL immunoglobulins from one primary antiphospholipid syndrome and two SLE patients added to normal plasma showed a significant increase in both TF expression and procoagulant activity (P < .05) compared with purified aPL from two SLE patients without thrombosis. The addition of nonspecific IgG from three SLE patients without aPLs and from three control subjects did not increase TF expression. Low free protein S was seen in eight patients. Increased TF expression and low free protein S correlated with thrombosis (P < .01) and with higher prothrombin fragment 1 + 2 and thrombin-antithrombin III values (P < .01). These observations may contribute to a further understanding of the thrombotic risk in aPL patients.

Antiphospholipid Syndrome↗

PubMed1996

Uptake of vWF-anti-vWF complexes by platelets in suspension.

Efforts to identify the translocation of glycoprotein (GP) Ib/IX receptors, either bound to von Willebrand factor (vWF) or not, from exposed surfaces to interior membranes of thrombin-activated platelets in suspension have been unsuccessful. To observe vWF uptake by platelets, we added an anti-vWF antibody and staphylococcal protein A-gold (to act as a marker for the antibody) to an incubation medium containing washed platelets and bovine plasma vWF or ristocetin-activated human vWF. Thin sections of platelets incubated for 10, 20, or 30 minutes with vWF but without antibody revealed no internalization and minimal changes in the original discoid form. Over the same 30-minute period with anti-vWF, however, GPIb/IX-vWF-anti-vWF complexes were cleared from cell exteriors to channels of the open canalicular system. Engorgement of the open canalicular system with vWF multimers resulted in changes in shape, internal transformation, and degranulation. Physical changes associated with anti-vWF-induced uptake of vWF are not seen in platelets that are involved in hemostatic plug formation or clot retraction.

Animals↗