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Biomedical subjects

N Ellison

Publications and source records attributed to N Ellison.

At least 19 recordsLinked to original sources
PubMed1990

Direct detection of activated platelets and platelet-derived microparticles in humans.

Flow cytometry was used to determine whether activated platelets and platelet-derived microparticles can be detected directly in whole blood after a hemostatic insult. Two different in vivo models of platelet activation were examined: (1) a standardized bleeding time, and (2) cardiopulmonary bypass. Platelets and microplatelets were identified with a biotinylated anti-glycoprotein (GP)lb antibody and a fluorophore, phycoerythrin-streptavidin. Microparticles were distinguished from platelets by light scatter. Activated platelets were detected with three fluorescein-labeled monoclonal antibodies (MoAbs): (1) PAC1, which binds to the activated form of GPIIb-IIIa; (2) 9F9, a newly developed antibody that is specific for fibrinogen bound to the surface of activated platelets; and (3) S12, which binds to an alpha-granule membrane protein expressed on the platelet surface after granule secretion. In nine normal subjects, bleeding times ranged from 4.5 to 7.5 minutes. Over this time, there was a progressive increase in the amount of PAC1, 9F9, and S12 bound to platelets in blood emerging from the bleeding time wound. With all three antibodies, platelet activation was apparent as early as 30 seconds after the incision (P less than .03). Activation was accompanied by a progressive decrease in the concentration of platelets in blood from the wound, while the concentration of microparticles increased slightly. In nine patients undergoing open heart surgery, 1 hour of cardiopulmonary bypass caused a 2.2-fold increase in the relative proportion of microparticles in circulating blood (P less than .001). Moreover, bypass caused platelet activation as evidenced by a mean two- to threefold increase in PAC1 binding to platelets. Although this increase was significant (P less than .02), PAC1 binding exceeded the normal range for unstimulated control platelets in only 5 of 9 patients, and 9F9 and S12 binding exceeded the normal range in only two patients. Taken together, these studies demonstrate that it is now feasible using flow cytometry to evaluate the extent of platelet activation and the presence of platelet-derived microparticles in the circulation of humans.

Adenosine Diphosphate↗
PubMed1990

Intraoperative management of patients with heparin-induced thrombocytopenia.

For 11 patients with confirmed heparin-induced thrombocytopenia, we used reversible platelet inhibition with iloprost, a stable prostacyclin analogue, to permit safe heparin administration for cardiac (n = 9) or vascular (n = 2) operations. In vitro, iloprost (0.01 mumol/L) prevented both heparin-induced platelet aggregation and 14C-serotonin release in all patients. Therefore, intraoperatively, a continuous infusion of iloprost was started before administration of heparin and was continued until 15 minutes after administration of protamine. For cardiac patients, after heparin administration, the whole blood platelet count did not change (171,000 +/- 29,000/microL versus 174,000 +/- 29,000/microL, mean +/- standard error of the mean); no spontaneous platelet aggregation was observed, and plasma levels of the alpha-granule constituents platelet factor 4 and beta-thromboglobulin increased from 38 +/- 14 and 140 +/- 18 ng/mL to 591 +/- 135 and 235 +/- 48 ng/mL, respectively. Fibrinopeptide A levels actually decreased from 287 +/- 150 to 27 +/- 6 ng/mL. Furthermore, adenosine diphosphate-induced platelet activation was preserved, postoperative bleeding times were unchanged, and no heparin-related deaths occurred. Similar results were obtained in both vascular patients. We conclude that temporary platelet inhibition with iloprost now permits safe heparin administration in all patients with heparin-induced thrombocytopenia who require a cardiac or vascular operation.

Adult↗
PubMed1987

Carotid endarterectomy in patients with heparin-induced platelet activation: comparative efficacy of aspirin and iloprost (ZK36374).

Patients with heparin-induced platelet activation who are reexposed to heparin may have recurrent thrombocytopenia, intravascular thrombosis, arterial emboli, or sudden death. To permit carotid endarterectomy in two patients with confirmed heparin-induced platelet activation, we compared the efficacies of aspirin and iloprost, a stable analogue of prostacyclin, in preventing heparin-induced platelet activation. In the first patient, although aspirin prevented both in vitro heparin-induced platelet aggregation (70% without and 7.5% with aspirin) and 14C serotonin release (48% without and 0% with aspirin), intraoperative administration of heparin resulted in an increase in plasma levels of platelet factor 4 from 8 to 260 ng/ml and beta-thromboglobulin levels from 29 to 39 ng/ml. In addition, the circulating platelet count decreased from 221,000 to 174,000 microliters, and 15% spontaneous platelet aggregation was observed. Fortunately, fibrinopeptide A levels remained less than 10 ng/ml intraoperatively, and no thrombotic complications occurred. In the second patient, aspirin did not prevent heparin-induced platelet aggregation in vitro (65% without and 41% with aspirin); however, iloprost (0.01 mumol/L) prevented both in vitro heparin-induced platelet aggregation (59.5% without and 0.0% with iloprost) and 14C serotonin release (56.7% without and 0.0% with iloprost). Therefore, a continuous infusion of iloprost was begun before administration of heparin and was continued until 20 minutes after reversal of heparin with protamine. After intraoperative administration of heparin, plasma levels of platelet factor 4 increased from 19 to 200 ng/ml, and beta-thromboglobulin levels increased from 56 to 76 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Efficacy of iloprost (ZK36374) versus aspirin in preventing heparin-induced platelet activation during cardiac operations.

For patients with heparin-induced platelet activation, reexposure to heparin can result in profound thrombocytopenia, intravascular thrombosis, and hemorrhage. We compared the ability of aspirin to that of iloprost (ZK36374), an analogue of prostacyclin, in preventing heparin-induced platelet activation and thus permitting a cardiac operation in a patient with heparin-induced platelet activation. Despite abolishing thromboxane A2 synthesis, aspirin (4 mmol/L) failed to prevent either in vitro heparin-induced platelet aggregation (65.0% without versus 59% with aspirin) or carbon 14-serotonin release (81.8% without versus 59.7% with aspirin). In contrast, iloprost (0.01 mumol/L) prevented both in vitro heparin-induced platelet aggregation (65% without versus 5.0% with iloprost) and release (81.8% without versus 0% with iloprost). Consequently, a continuous infusion of iloprost was begun before administration of heparin, continued throughout cardiopulmonary bypass, and discontinued 15 minutes after administration of protamine. The whole blood platelet count (209,000/microliter) remained stable after intraoperative administration of heparin (238,000/microliter) and was 115,000/microliter after the operation. No spontaneous platelet aggregates were observed in samples of platelet-rich plasma after heparin administration, and no platelet transfusions were required. Plasma levels of platelet factor 4 rose from 27 to 725 ng/ml after heparin administration but then declined during bypass to 50 ng/ml. Beta thromboglobulin levels only rose from 92 to 496 ng/ml with administration of heparin. Fibrinopeptide A levels fell from 72 to 22 ng/ml after heparin and remained stable throughout bypass. The template bleeding time was 7.5 minutes preoperatively and 8.0 minutes postoperatively. The postoperative chest tube drainage (12 hours) was 475 ml, and platelets responded normally to adenosine diphosphate. In conclusion, iloprost but not aspirin completely prevented heparin-induced platelet activation in vitro. Furthermore, iloprost effectively prevented this syndrome clinically, which permitted a safe cardiac operation in this patient with heparin-induced platelet activation.

Aged↗
PubMed1987

Prevention of heparin-induced thrombocytopenia during open heart surgery with iloprost (ZK36374).

Recurrent thrombocytopenia, thrombosis, or sudden death may develop in patients with heparin-induced thrombocytopenia who are reexposed to heparin. Three patients came to us in whom a diagnosis of heparin-induced thrombocytopenia had been made on the basis of clinical and serologic evidence; these patients required reexposure to heparin because of urgent cardiac surgery. Therefore, we evaluated the ability of iloprost (ZK36374), a new analogue of prostacyclin, to prevent heparin-dependent activation of platelets and thereby permit obligatory heparinization for safe extracorporeal circulation. Before operation, we demonstrated that iloprost prevented both heparin-dependent platelet aggregation and tritiated (3H)-serotonin release in vitro. Therefore a continuous infusion of iloprost was begun 1 hour before heparinization and was continued throughout cardiopulmonary bypass and for an additional 15 minutes after protamine administration. The mean platelet count of 130,000/microliters before operation remained stable, and no spontaneous platelet aggregation was observed in samples of platelet-rich plasma obtained before cardiopulmonary bypass but after heparin administration. Similarly, after heparin administration but before bypass, platelet responsiveness to adenosine diphosphate remained unchanged when compared with preoperative values. Plasma levels of platelet factor 4 increased from 26 +/- 1 ng/ml (mean +/- standard error) to 843 +/- 383 ng/ml after heparin administration but actually decreased throughout cardiopulmonary bypass to 52 +/- 25 ng/ml. Beta-thromboglobulin levels increased from 103 +/- 16 to 244 +/- 94 ng/ml with heparinization. The mean bleeding time was 10.5 minutes preoperatively and 13.3 minutes postoperatively. The mean amount of postoperative chest tube drainage (duration: 12 hours) was 432 +/- 67 ml. Thus, despite the confirmed presence of heparin-dependent platelet-activating factor in the plasma of these three patients, iloprost prevented heparin-induced platelet activation during cardiopulmonary bypass while preserving platelet function, as would be desired for postoperative hemostasis.

Adult↗