Circulating platelet/polymorphonuclear leukocyte mixed-cell aggregates in patients with mechanical heart valve replacement

Maugeri, Norma; Santarelli, María Teresa; Lazzari, M.A.

doi:10.1002/1096-8652(200010)65:2<93::aid-ajh1>3.0.co;2-4

Cited by 11 publications

(11 citation statements)

References 29 publications

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“…Blood samples were immediately treated with a cocktail of antiproteases [11] to prevent in vitro cellular activation, labelled with appropriate monoclonal antibodies and fixed with thrombofix. After 4 h, cells were washed twice and analyzed by double or three color flow cytometry, as described previously [1,11,12].…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?

Maugeri¹,

Giordano²,

Petrilli³

et al. 2006

Journal of Thrombosis and Haemostasis

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Summary. Background: Polymorphonuclear leukocytes (PMN) from healthy subjects can produce and store tissue factor (TF), which is expressed on PMN surface upon in vitro stimulation with P-selectin. Results: We report here that platelets and PMN from 12 patients with myeloproliferative disorders (MPD) (six with polycythemia vera, six with essential thrombocythemia) show up regulation of P-selectin and TF, respectively, in the absence of any in vitro challenge. The number of circulating mixed platelet-PMN aggregates was also increased. PMN TF expression as well as mixed platelet-PMN aggregates, but not platelet P-selectin, were significantly reduced in six MPD patients after treatment with hydroxyurea (HU). In vitro studies performed on PMN separated from healthy donors confirmed HU effects (0-1400 lM). HU prevented both P-selectin-induced TF expression and mixed cell aggregate formation. The inhibitory effect of HU was specific for P-selectin-induced PMN activation, as it did not affect formyl-methionyl-leucylphenylalanine-induced PMN TF expression. Conclusions: In MPD patients, platelet P-selectin-mediated TF expression on circulating PMN may play a role in thrombus formation and represents a novel target for the antithrombotic activity of HU.

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Section: Patients Materials and Methodsmentioning

confidence: 99%

Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?

Maugeri¹,

Giordano²,

Petrilli³

et al. 2006

Journal of Thrombosis and Haemostasis

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“…Circulating activated platelets have been measured in patients with stents, mechanical heart valves, and VADs as well as in patients suffering from acute myocardial infarction and ischemic stroke [7][8][9][10][11][12][13]. The presence of circulating activated platelets has been suggested as a marker for increased risk of thrombotic complications (10).…”

Section: Introductionmentioning

confidence: 99%

Flow Cytometric Assays for Quantifying Activated Ovine Platelets

et al. 2007

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Ovines are a common animal model for preclinical evaluation of cardiovascular devices including heart valves, endovascular grafts, and ventricular assist devices. Biocompatibility is essential to the success of these devices; however, tools to assess biocompatibility in ovines are limited. To address this need, antibodies that bind to activated human and bovine platelets and annexin V protein were evaluated for potential cross-reactivity to activated ovine platelets. These candidate markers were incubated with stimulated and quiescent ovine whole blood, and binding to platelets was quantified by flow cytometry. Several antihuman CD62P antibodies including one polyclonal antibody, three monoclonal antibodies, and annexin V selectively bound to activated ovine platelets. An assay to quantify platelet microaggregates was also developed. The availability of assays to quantify ovine platelet activation can increase the quality of biocompatibility data obtainable during preclinical development of artificial organs in the ovine model, potentially aiding in the evaluation of design refinements to enhance device biocompatibility. KeywordsBiocompatibility; Flow cytometry; Ovine platelets; Cardiovascular devices; Platelet activation Ovines are a common animal model for preclinical testing of blood-contacting cardiovascular devices including mechanical heart valves, endovascular grafts, and ventricular assist devices (VADs) (1-4). A critical aspect in the design of these devices is the evaluation of their blood biocompatibility. Yet, the biocompatibility data that can be obtained in ovine studies is limited due to a paucity of available assays for evaluating circulating blood elements during the implant period. In particular, there has only been one report on the use of flow cytometry to evaluate ovine platelet activation in platelet-rich plasma, and there have been no reports in the literature using such techniques to assess temporal platelet activation in ovines implanted with cardiovascular devices (5).Flow cytometry permits surface expression of platelet activation-dependent epitopes to be quantified, providing insight on circulating platelets not obtainable with platelet aggregometry and plasma assays for β-thromboglobulin and platelet factor 4 (6). Circulating activated platelets have been measured in patients with stents, mechanical heart valves, and VADs as well as in patients suffering from acute myocardial infarction and ischemic stroke [7][8][9][10][11][12][13]. The presence of circulating activated platelets has been suggested as a marker for increased risk of thrombotic complications (10). Previously, we have described several flow cytometric assays to quantify circulating activated bovine platelets and platelet microaggregates (14). These assays have been applied to assess circulating activated platelets in calves implanted with rotary VADs (14,15). The results demonstrate the ongoing presence of circulating activated platelets after the effects of surgery (without extracorporeal circulation) have di...

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“…No significant increase in platelet-leukocyte complex levels occurred after aspirin reintroduction. Such complexes have been described as a sensitive marker of platelet activation in acute coronary syndromes and after cardiac surgery [26], and correlate strongly with the risk of clinical thrombosis [27], [28], [29].…”

Section: Discussionmentioning

confidence: 97%

Impact of Aspirin and Clopidogrel Interruption on Platelet Function in Patients Undergoing Major Vascular Surgery

et al. 2014

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AimsTo investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption.Methods/ResultsWe conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group). The antiplatelet drugs were withdrawn five days before surgery (baseline) and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin) and ADP (clopidogrel) and by VASP assay (clopidogrel). Platelet-leukocyte complex (PLC) level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4±10%; p = 0.16), in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10±15%; p = 0.02), compared to baseline.ConclusionsAspirin withdrawal 5 days before high-bleeding-risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management.

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Circulating platelet/polymorphonuclear leukocyte mixed-cell aggregates in patients with mechanical heart valve replacement

Cited by 11 publications

References 29 publications

Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?

Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?

Flow Cytometric Assays for Quantifying Activated Ovine Platelets

Impact of Aspirin and Clopidogrel Interruption on Platelet Function in Patients Undergoing Major Vascular Surgery

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