PubMed Health⌕ Search

Biomedical subjects

T Lecompte

Publications and source records attributed to T Lecompte.

At least 19 recordsLinked to original sources
PubMed1992

In vitro effect of plasmin on human platelet function in plasma. Inhibition of aggregation caused by fibrinogenolysis.

BACKGROUND: Plasmin has been reported both to activate platelets and to inhibit platelet functions. The latter effect was thought to be caused by proteolysis of the main membrane glycoproteins. METHODS AND RESULTS: We found that incubation of citrated human platelet-rich plasma with streptokinase (SK) (300 IU/ml) does not produce any detectable activation but leads to a time-dependent inhibition of ADP-induced aggregation accompanied by substantial fibrinogenolysis. These effects were abrogated by previous addition of a plasmin inhibitor, aprotinin. Crossover experiments (SK-treated or control platelets mixed with SK-treated or control plasma) demonstrated that the platelets remained functional and that the aggregation defect was caused by fibrinogenolysis. Further experiments (addition of purified fibrinogen to fibrinogen-depleted plasma with either SK or thrombin) suggested that in addition to the low residual level of fibrinogen, fibrinogen degradation products had an inhibitory effect. Under the same conditions, tissue-type plasminogen activator (t-PA) (3,000 ng/ml) had no effect on platelet aggregation, and plasma fibrinogen was not significantly lowered. The effects on glycoproteins IIb-IIIa of incubation with SK, t-PA, or plasmin were assessed with immunoblots with murine monoclonal antibodies directed against either part of the complex, which is the receptor for fibrinogen. Proteolysis was detected only in the presence of EDTA, a potent chelator of divalent cations. CONCLUSIONS: The incubation of human platelets in citrated plasma with SK concentrations obtained during therapy leads to an aggregation defect that is related to the decrease in fibrinogen, the adhesive protein involved in this function, and to the impeding effect of fibrinogen degradation products on its binding onto platelets but not to an alteration of the corresponding platelet receptor, the heterodimer glycoproteins IIb-IIIa.

Blood Platelets↗
PubMed1992

[Nitrate derivatives and hemostasis: fundamental concepts and clinical implications].

The nitrate derivatives in clinical usage have in vitro platelet inhibitor and therefore antiaggregant properties. As with EDRF, this effect is mediated, at least partially, by increased intraplatelet cGMP concentrations. There is a probable synergistic action with prostacyclin and its clinically stable analogues which exert their inhibitor effect via cGMP. The reality of an ex vivo inhibitor effect (after clinical administration) is more difficult to demonstrate. Some groups have reported prolonged bleeding times after administration of trinitrin. The interactions of nitrate derivatives with molecules used as platelet inhibitors, such as aspirin, require further study as do interactions with heparin (possible induction of resistance by a qualitative anti-thrombin III deficiency) and thrombolytics (increased clearance of tissue type plasminogen activator).

Bleeding Time↗
PubMed1991

Rapid aequorin loading into platelets in the presence of DMSO--characteristics of the responses (changes in light transmission and in calcium) to various agonists.

We have looked at different parameters which could modify platelet behaviour during and after aequorin loading in the presence of DMSO. There is a decreased platelet reactivity in response to ADP, PAF and A-23,187 which appears to be mainly due to the exposure to EGTA during washing and loading and the 1 ml volume of the test suspension. All the studied agonists (including PMA) which elicit aggregation are able to induce an intracellular Ca2+ change detected with the aequorin probe. By contrast, epinephrine alone induces neither aggregation nor Ca2+ rise, but potentiates the responses to ADP. Different consecutive phases in Ca2+ changes after stimulation with ADP, PMA and A-23,187 can be evidenced. In the presence of external Ca2+, the second component of the Ca2+ change evoked with ADP is dependent on aggregation and the subsequent TXA2 synthesis. When the external medium is Ca2+ depleted, the two Ca2+ peaks induced by ADP disappear whereas a Ca2+ rise persists (endogenous mobilization) with the other agonists, being independent of TXA2 and ADP release. Ca2+ mobilization parallels activation with A-23,187 but not with low concentrations of thrombin.

Aequorin↗
PubMed1991

Osteonectin is an alpha-granule component involved with thrombospondin in platelet aggregation.

We previously showed that thrombospondin, a major alpha-granule glycoprotein of human platelets, forms a specific complex with osteonectin, a phosphoglycoprotein originally described in bone that is also present in human platelets. The storage organelles and the function of osteonectin in platelets are still unknown. In this study, using electron microscopy in combination with immunogold staining, the major storage organelle for platelet-secreted proteins, the alpha-granules. Furthermore, osteonectin was qualitatively and quantitatively assessed by studying normal platelets and the platelets from a patient with gray platelet syndrome. Gray platelet syndrome is a rare congenital bleeding disorder characterized by a selective deficiency in morphologically recognizable platelet alpha-granules and in the alpha-granule secretory proteins. Binding of an iodinated antiosteonectin monoclonal antibody to gray platelet proteins transferred to nitrocellulose from SDS-polyacrylamide gels showed no band corresponding to osteonectin compared to control platelets. Using a polyclonal antiosteonectin antibody-based radioimmunoassay, gray platelets contained 0.2 +/- 0.03 ng osteonectin per 10(6) platelets, which is only 20% of the normal platelet content of osteonectin (0.93 +/- 0.16 ng per 10(6) platelets). Study of the localization of osteonectin to the surface of human platelets demonstrated that a radioiodinated antiosteonectin polyclonal antibody bound specifically to thrombin-stimulated platelets but not to resting platelets. Binding was concentration-dependent, saturable (1710 +/- 453 binding sites per platelet, Kd = 1 microM), and inhibited by an excess of cold antiosteonectin polyclonal antibody. No binding was observed on the surface of thrombin-stimulated gray platelets. To gain further insights into the role of osteonectin released from activated platelets, the effect of an antiosteonectin polyclonal antibody was tested on the aggregation of washed platelets. F(ab')2 fragments from the antiosteonectin polyclonal antibody inhibited in a dose-dependent manner the aggregation of collagen-stimulated, washed human platelets without affecting collagen-induced platelet serotonin release. To characterize the mechanism through which antiosteonectin F(ab')2 fragments inhibit platelet aggregation, the expression of endogenous thrombospondin (TSP) on the surface of thrombin-activated platelets was studied using 125I-labeled anti-TSP monoclonal antibody P10. The endogenous surface expression of TSP to thrombin-stimulated platelets was significantly inhibited in the presence of antiosteonectin F(ab')2 fragments (6286 +/- 2065 molecules of P10 per platelet) compared to 11,230 +/- 766 molecules of P10 per platelet in the presence of nonimmune F(ab')2 fragments.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

X-linked thrombocytopenia and Wiskott-Aldrich syndrome: similar regional assignment but distinct X-inactivation pattern in carriers.

While inherited X-linked (XL) isolated thrombocytopenia is a mild condition, the Wiskott-Aldrich syndrome (WAS) associates severe thrombocytopenia with an immunodeficiency component and has a poor prognosis. Whether these conditions correspond to separate genetic entities or to different mutations of the same gene(s) remains unresolved. The Wiskott-Aldrich syndrome locus has been assigned to Xp 11.2 by means of RFLP studies. The X-inactivation pattern in female carriers has been found to follow a skewed pattern in the hematopoietic cells, thus allowing carrier detection. We studied a family with four members affected by XL thrombocytopenia and report the results of genetic segregation analysis, together with the X-inactivation pattern of hematopoietic cells from an obligate female carrier. Although the affected locus mapped to the same region as that of WAS, lymphocytes presented a skewed pattern of X-inactivation, whereas polymorphonuclear lymphocytes (PMN) did not. These results provide further evidence that the Wiskott-Aldrich syndrome and XL thrombocytopenia are different expressions of mutations within a single locus and that the severity of the disease corresponds to distinct hematopoietic cell selections in obligate carriers.

Adult↗
PubMed1990

Aequorin-detected calcium changes in stimulated thrombasthenic platelets. Aggregation-dependent calcium movement in response to ADP.

Calcium changes in normal and thrombasthenic platelets were recorded using the PICA-apparatus. Aequorin was loaded in the presence of DMSO, EGTA and PGE1. Platelets of three patients with type I thrombasthenia stimulated with A-23, 187, thrombin, PMA in the presence 1 mM Ca++ and 1 mM Mg++ were able to normally raise their calcium concentrations. The maximal values could be found below the normal range with collagen, ADP and PAF-acether. Calcium mobilization from internal stores in response to thrombin was normal. There were two calcium peaks in normal platelets stimulated with ADP. The second one was suppressed by omitting fibrinogen, stirring, or by adding aspirin, and was absent in thrombasthenic platelets. Thus the GP IIb-IIIa complex is not a prerequisite for calcium fluxes but is involved, when weak agonists such ADP are used, through an aggregation-dependent reinforcement of platelet activation.

Adenosine Diphosphate↗
PubMed1990

Genetic thrombocytopenia with autosomal dominant transmission: a review of 54 cases.

On the basis of a retrospective study of 3600 platelet kinetic studies, we have isolated 54 cases with chronic thrombocytopenia, a normal autologous and homologous platelet lifespan, and increased mean platelet volume without Döhle bodies, the absence of any functional platelet abnormalities, and a normal megakaryocyte count. These cases were either discovered during the first few years of life (i.e. constitutional) and/or were proven to be familial (autosomal dominant transmission). Previous treatments (corticosteroids, immunoglobulins, androgens, immunosuppressor agents, splenectomy) were not effective in any of these cases or in their relatives. A new syndrome can therefore be proposed which can easily be suspected on the basis of platelet kinetic studies performed in cases of early onset, increased platelet volume, failure of corticosteroids or evidence of a familial blood disorder. It can be proved when the autologous platelet life span is demonstrated to be normal in spite of a chronic thrombocytopenia and a normal megakaryocytic count. The recognition of this syndrome will avoid neonatal complications (cephal-haematomas), surgical complications, and the use of expensive and possibly harmful ineffective treatments, both in the propositus and in other abnormal family members. The syndrome is certainly frequent (54 cases are presented here), but the diagnosis is often missed or delayed due to the low risk of haemorrhage. However, it is associated with a certain risk of leukaemia (four cases in three families).

Adolescent↗
PubMed1990

Inhibition of platelet activation by the nitrate Sin-1: studies with human aequorin-loaded platelets.

The effects of the nitrovasodilator Sin-1, which is thought to work through cyclic-GMP, were studied using human, aequorin-loaded, washed platelets. Changes in light transmission (shape change, aggregation), and in intracellular calcium were simultaneously recorded. Evidence was obtained for an inhibitory effect distal to calcium changes, in a similar way than a prostacyclin analogue, Iloprost. By contrast the response to an activator of protein kinase C was unaffected. There was a partial, parallel decrease in calcium changes and aggregation induced with thrombin, and a total inhibition of the responses to ADP (linked to a calcium influx).

Aequorin↗
PubMed1990

[Pure genetic thrombocytopenia. A new clinical entity].

From a retrospective study of 3,500 platelet kinetic studies, we isolated 51 cases with chronic thrombocytopenia, excessive platelet volume without Döhle bodies and no functional platelet anomalies, normal megakaryocyte count and normal autologous and homologous platelet life-span. These cases were either discovered during the first year of life (i.e. constitutional) or proved as familial (with autosomal dominant transmission). Previous therapies (corticosteroids, immune globulins, androgens, immuno-suppressive agents, splenectomy) were unefficient in all cases as in their relatives.

Adolescent↗
PubMed1990

Genetic thrombocytopenia with an autosomal dominant transmission: a study of 54 cases.

On the basis of a retrospective study of 3,600 platelet kinetic studies, we have isolated 54 cases with chronic thrombocytopenia, a normal autologous and homologous platelet lifespan, and increased mean platelet volume without Döhle bodies, the absence of any functional platelet abnormalities, and a normal megakaryocyte count. These cases were either discovered during the first few years of life (i.e. constitutional) and/or were proven to be familial (autosomal dominant transmission). Previous treatments (corticosteroids, immunoglobulins, androgens, immunosuppressor agents, splenectomy) were not effective in any of these cases or in their relatives. A new syndrome can therefore be proposed which can be easily suspected in cases of early onset in life, increased platelet volume, failure of corticosteroids or evidence of a familial blood disorder. It can be proved when the autologous platelet life span is demonstrated to be normal in spite of a chronic thrombocytopenia and a normal megakaryocytic count. The recognition of this syndrome will avoid neonatal complications (cephal-hematomas), surgical complications, and the use of expensive and possibility harmful ineffective treatments, both in the propositus and in other abnormal family members. The syndrome is certainly frequent (54 families are presented here), but the diagnosis is often missed or delayed due to the low risk of hemorrhage. However, it is associated with a certain risk of leukemia (4 cases in 3 families).

Blood Platelets↗
PubMed1989

Chronic pure thrombocytopenia in elderly patients. An aspect of the myelodysplastic syndrome.

From a group of 276 elderly patients studied in the last 12 years in a department of nuclear medicine for investigating a chronic thrombocytopenia, 36 patients have an acquired disorder, with normal platelet life span, a normal megakaryocytic bone marrow count, and absence of any evident cause at the time of clinical evaluation. During the 2 to 10 subsequent years, 16 patients developed symptoms of the myelodysplastic syndrome, i.e., chronic aregenerative anemia, granulocytopenia, dysmyelopoiesis, and appearance of circulating blast cells; three of them died from acute myeloblastic leukemia. So a pure thrombocytopenia due to a platelet production defect, without any demonstrated functional platelet defect or morphologic dysmegakaryocytosis, may be a preleukemic syndrome. In the other 20 patients, with the same pure chronic thrombocytopenia, no malignant evolution has been seen with long follow-up delays, which is often also the case in pure refractory anemias. In the absence of objective criteria of a possible premalignant disorder, the classification of these cases is difficult, which it is also the case for the so-called refractory anemias. We suggest to individualize, in the classification of the myelodysplastic syndromes, a group of pure refractory thrombocytopenias. From a practical point of view such a diagnosis may be useful, at least to avoid inefficient and possibly harmful treatments.

Aged↗
PubMed1989

Calcium rise in human platelets elicited by anti-CD9 and -CD41 murine monoclonal antibodies.

Three murine monoclonal antibodies (anti-CD9: ALB6, anti-CD41: VI-PL3 and PL2-49/GPIIb - final concentration: 7.5 micrograms/mL) are shown to elicit after a lag time aggregation of washed platelets and a calcium signal (as detected by light emitted by loaded aequorin), which is only partially inhibited by aspirin. By comparison the rise induced by thrombin is greater and almost instantaneous. In the presence of EGTA a calcium mobilization from internal stores can be detected with thrombin and with ALB6, but neither with PL2-49 nor with VI-PL3, whereas platelets still change their shape and release ATP. It is tempting to speculate that although all the antibodies induce a calcium change, they activate platelets by different pathways: calcium may be not primarily involved in the activation induced by the anti-CD41 antibodies.

Adenosine Triphosphate↗