1,721,020 research outputs found
Patients with congenital abnormality of platelet aggregation induced by Ca2+ ionophores may have a defect of the platelet P2Y(12) receptor for ADP
No full textInhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin
No full textBackground: Activation of two receptors for adenosine diphosphate (ADP), P2Y1 and P2Y12, is necessary for ADP-induced platelet aggregation (PA). It is generally believed that the antithrombotic effects of drugs inhibiting P2Y12, such as clopidogrel, are uniquely mediated by inhibition of P2Y12 -dependent PA. However, as P2Y12 is negatively coupled to adenylyl cyclase (AC), its inhibition may also exert antithrombotic effects through the potentiation of prostacyclin (PGI2), which inhibit PA by stimulating AC. Objectives: To test whether inhibition of P2Y12 potentiates the antiplatelet effects of PGI2. Methods: We measured the effects of PGI2 (0.01-10 μ m) on PA of washed human platelets induced by thrombin (0.5 U mL-1) in the presence or absence of ARC69931MX (anti-P2Y2) or MRS2500 (anti-P2Y1). Results: PGI2 inhibited PA in the presence of anti-P2Y12, but not in the presence of anti-P2Y1 or in the absence of inhibitors. In contrast, dibutyryl-cyclicAMP inhibited PA both in the presence and absence of anti-P2Y1 or anti-P2Y12. PGI2 increased platelet cyclicAMP levels only in the absence of thrombin or in the presence of thrombin plus anti-P2Y12. Conclusions: PGI2 did not inhibit PA induced by thrombin, because its effect on AC was prevented by released ADP interacting with P2Y12. Anti-P2Y12 drugs, by rescuing AC activity, potentiate the antiplatelet effect of PGI2, which may contribute to their antithrombotic effect
INVITRO AND EXVIVO EFFECTS OF INDOBUFEN ON HUMAN-PLATELET AGGREGATION, THE RELEASE REACTION AND THROMBOXANE-B2 PRODUCTION
No full textWe have done a comprehensive study in normal volunteers of the in vitro and ex vivo effects of the antiplatlet agent indobufen on platelet aggregation, the release reaction and thromboxane B2 (TxB2) production as induced by different concentrations of aggregating agents. At low concentrations (10 μM), indobufen completely inhibited secondary platelet aggregation, the release reaction and TxB2 production stimulated by ADP, epinephrine and low concentrations of platelet-activating factor (PAF acether). Higher concentrations of indobufen (100 μM) completely inhibited TxB2 production, platelet aggregation and ATP release induced by arachidonic acid (1 mM) or collagen (2 μg/ml) . The inhibitory effect was partially overcome by higher concentrations of arachidonic acid (2 mM). Data obtained ex vivo 2 h after the oral administration of 200 mg indobufen to 8 normal volunteers were in keeping with those of the in vitro study. We concluce that indobufen inhibits platelet aggregation and the release reaction by inhibiting the platelet arachidonate pathway
Usefulness of PFA-100 (R) testing in the diagnostic screening of patients with suspected abnormalities of hemostasis: comparison with the bleeding time
No full textBackground: Global tests of hemostasis that are used to screen patients with clinical suspicion of bleeding disorders should help the physician to identify the phase of the hemostatic system that is abnormal and guide further diagnostic workup.Patients and methods: We compared the performance of Platelet Function Analyzer-100 (PFA-100((R))) closure time (CT) with bleeding time (BT), both of which are screening tests for primary hemostasis, in the diagnostic workup of 128 consecutive patients who were screened for bleeding disorders. The sensitivities of BT and PFA-100 CT for known defects of hemostasis were evaluated; in addition, we calculated their correlation with the levels of severity of the bleeding symptoms, which were recorded using a standardized questionnaire.Results: The sensitivity of PFA-100 testing was 71% for von Willebrand disease (VWD) [with both collagen-adenosine diphosphate (C-ADP) and collagen-epinephrine (C-EPI) cartridges]; 58% (C-EPI) and 8% (C-ADP) for platelet function disorders (PFDs); and the sensitivity of BT was 29% (VWD) and 33% (PFD). C-EPI CT was also prolonged in about 20% of patients with abnormalities of coagulation or fibrinolysis. Only the C-EPI CT was significantly associated with the levels of severity of the patients' bleeding scores.Conclusions: BT and C-EPI are insufficiently sensitive to be recommended as hemostasis screening tests. The C-ADP cartridge, which is sensitive to VWD only, might prove useful in further diagnostic workup of defects of primary hemostasis. The association of C-EPI CT with the severity of bleeding symptoms as a useful predictor of risk of bleeding in clinical practise should be tested in properly designed studies
Platelets from a patient heterozygous for the defect of P2(CYC) receptors for ADP have a secretion defect despite normal thromboxane A(2) production and normal granule stores - Further evidence that some cases of platelet 'primary secretion defect' are heterozygous for a defect of P2(CYC) receptors
No full textPlatelet aggregation studies : autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count
No full textAdjusting platelet count (PC) in platelet-rich plasma (PRP) using platelet-poor plasma
(PPP) is recommended for platelet aggregation (PA) studies, but it could also affect
PA independently of the decrease in PC. Analysis of aggregation tracings from healthy
controls showed that PC correlated with PA in 47 diluted-PRPs, but not in 104 undiluted-
PRPs. Dilution of 9 PRPs with PPP progressively decreased PA, while dilution of
washed platelets with buffer hardly affected PA. Apyrase partially prevented the
inhibitory effect of PPP. Therefore, the practice of diluting PRP with PPP to adjust
platelet count should be avoided because it artefactually inhibits P
Effect of platelet count on platelet aggregation measured by impedance aggregometry (Multiplate(TM) analyser) and by light transmission aggregometry
No full textThe in vitro evaluation of platelet aggregation is useful to diagnose platelet function disorders [1, 2]; in some laboratories, the test is also used to monitor antiplatelet treatment [3]. Traditionally, platelet aggregation is measured by light transmission aggregometry (LTA), which measures the changes in transmission of a beam of light through a sample of platelet-rich plasma (PRP) or platelet suspensions in buffer, which occur when platelets change shape and aggregate upon stimulation. As this technique has some disadvantages [2], novel methods were introduced to measure platelet aggregation in vitro
Low plasma levels of vitamin B-6 are independently associated with a heightened risk of deep-vein thrombosis
No full textBackground - Elevated plasma levels of total homocysteine (tHcy) before and after an oral methionine load (PML) are associated with an elevated risk of deep-vein thrombosis (DVT). We investigated whether plasma levels of B vitamins that are involved in Hcy metabolism are associated with an elevated risk of DVT. Methods and Results - We compared 397 cases with previous DVT with 585 matched healthy controls. The plasma levels of folate, vitamin B12, vitamin B6, and fasting and PML tHcy were measured. The ORs for DVT associated with high (>95th percentile) fasting levels and PML increases of tHcy were 2.1 (95% CI, 1.2 to 3.4) and 2.4 (95% CI, 1.5 to 3.9) after adjustment for established risk factors for DVT. Fasting plasma levels and PML increases in tHcy correlated negatively with vitamin levels. The crude OR for folate levels in the lowest quartile compared with the highest was 1.5 (95% CI, 1.1 to 2.1), and that for B6 levels in the lowest and second quartiles compared with the highest was 1.5 (95% CI, 1.0 to 2.1). However, after adjustment for established risk factors and fasting and PML tHcy, the ORs for B6 levels in the lowest and second quartiles only remained statistically significant (lowest quartile: OR, 1.8; 95% CI, 1.2 to 2.8; second quartile, OR, 1.9; 95% CI, 1.3 to 2.9). Conclusions - High fasting and PML tHcy and low vitamin B6 plasma levels are associated with an elevated risk for DVT independently of established risk factors for DVT. The association of low vitamin B6 levels with the risk for DVT is independent of fasting and PML tHcy levels
IDENTIFICATION OF A NEW CONGENITAL DEFECT OF PLATELET-FUNCTION CHARACTERIZED BY SEVERE IMPAIRMENT OF PLATELET RESPONSES TO ADENOSINE-DIPHOSPHATE
No full textThis study characterizes a congenital hemorrhagic disorder caused by a platelet function defect with the following features: (1) severely impaired platelet aggregation and fibrinogen or von Willebrand factor (vWF) binding induced by adenosine diphosphate (ADP); (2) defective aggregation, release reaction, and fibrinogen or vWF binding induced by other agonists; (3) normal aggregation and release reaction induced by high concentrations of thrombin or collagen; (4) no further inhibition by ADP scavengers of aggregation, release reaction, and fibrinogen or vWF binding, comparable with those observed for normal platelets in the presence of ADP scavengers; (5) normal membrane glycoprotein (GP) composition and normal binding of the anti-GP IIb/IIIa monoclonal antibody 10E5; (6) no acceleration by ADP of binding of the anti-GP IIb/IIIa monoclonal antibody 7E3; (7) normal platelet-fibrin clot retraction if induced by thrombin or reptilase plus epinephrine, absent if induced by reptilase plus ADP; (8) no inhibition by ADP of the prostaglandin E1-induced increase in platelet cyclic adenosine monophosphate, but normal inhibition by epinephrine; (9) defective mobilization of cytoplasmic Ca2+ by ADP; (10) normal binding of 14C-ADP to fresh platelets, but defective binding of [2-3H]-ADP to formalin-fixed platelets. This congenital platelet function defect is characterized by selective impairment of platelet responses to ADP, caused by either decreased number of platelet ADP receptors or abnormalities of the signal-transduction pathway of platelet activation by ADP
INVITRO EFFECTS OF PICOTAMIDE ON HUMAN PLATELET-AGGREGATION, THE RELEASE REACTION AND THROMBOXANE-B2 PRODUCTION
No full textWe studied the in vitro effects of picotamide (N,N′ bis 3 picolyl-4-methoxy-isophthalamide) on human platelet aggregation, the release reaction and the production of thromboxane B2 (TxB2) induced by several platelet agonists. The effects of picotamide were compared to those of acetylsalicylic acid (ASA). Picotamide (0.5 mmol/1) inhibited platelet aggregation, the release of ATP and TxB2 production induced by ADP, arachidonic acid (AA), collagen or the prostaglandin endoperoxide (PE) analogue U46619. ASA (0.5 mmol/1) did not affect platelet aggregation and the release of ATP induced by U46619. Picotamide and ASA inhibited the AA-induced platelet TxB2 production both under stirring and non-stirring conditions, whereas the pure thromboxane A2 receptor antagonist BM13177 (0.5 mmol/1) was inhibitory only under stirring conditions. Since under non-stirring conditions platelet aggregation does not occur, picotamide directly inhibits TxB2 production, whereas BM13177 inhibits the potentiation of TxB2 production due to TxA2/PE-dependent platelet aggregation. Malondialdehyde (MDA) production by unstirred platelets stimulated with AA was not significantly inhibited by picotamide. In conclusion, picotamide inhibits the TxA2/PE-dependent platelet responses to agonists by a double mechanism: (i), TxA2/PE antagonism; (ii) inhibition of thromboxane synthase
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