Iloprost (ZK36374), a stable analogue of prostacyclin, preserves platelets during simulated extracorporeal circulation

Addonizio, V. Paul; Fisher, Carol A.; Jenkin, Brenda K.; Strauss, Jerome F.; Musiał, Jacek; Edmunds, L. Henry

doi:10.1016/s0022-5223(19)38702-1

Cited by 57 publications

(12 citation statements)

References 14 publications

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“…19 At appropriate infusion rates, iloprost allows safe heparin administration in patients with HITT antibodies provided there is close monitoring of hemodynamics and careful use of alpha agonists (norepinephrine and phenylephrine) to prevent or treat hypotension. [9][10][11][12][13] Our data support the hypothesis that heparin may be used with impunity in patients with HITT when their platelets are completely inhibited with iloprost and their hemodynamics are closely monitored. The main side effect of iloprost is hypotension secondary to vasodilation.…”

Section: Discussionsupporting

confidence: 72%

“…2,4,14,15 Patients with HITT antibodies were subsequently tested with a HIPA assay using increasing micromolar concentrations of iloprost (Ilomedin, Berlex Laboratories, Edison, NJ) to determine the dose that completely inhibited platelet aggregation to heparin. [9][10][11][12] During surgery, patients with anti-heparin-PF4 antibodies were treated with iloprost to achieve complete inhibition of HIPA before heparinization (group A or treated group). Ten additional patients with normal platelet counts and without history of prolonged exposure to heparin or thrombosis were matched for age, gender, and procedure, and were included in the study as controls (group C).…”

Section: Patientsmentioning

confidence: 99%

“…Our management protocol was based on reports by Addonizio and associates, 9,10 Kappa and collaborators, 11,12 and Palatianos and colleagues (on the use of the prostacyclin analog iloprost [ZK 36374]). 13 Addonizio and associates 9,10 and Kappa and associates 11,12 reported platelet preservation with iloprost during cardiopulmonary bypass (CPB) and showed that temporary platelet inhibition with iloprost allowed safe heparin administration in patients with HITT undergoing cardiac or vascular operations.…”

mentioning

confidence: 99%

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Preoperative detection and management of immune heparin-induced thrombocytopenia in patients undergoing heart surgery with iloprost

Palatianos

Foroulis

Vassili

et al. 2004

The Journal of Thoracic and Cardiovascular Surgery

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Section: Discussionsupporting

confidence: 72%

Section: Patientsmentioning

confidence: 99%

mentioning

confidence: 99%

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Preoperative detection and management of immune heparin-induced thrombocytopenia in patients undergoing heart surgery with iloprost

Palatianos

Foroulis

Vassili

et al. 2004

The Journal of Thoracic and Cardiovascular Surgery

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“…However, in vitro results do not always correlate with in vivo results. For example, desmopressin and prostaglandin E 1 prevented platelet consumption in vitro but failed to preserve platelets in vivo ( 29, 30). The definitive assessment of efficacy and safety will need to await further in vitro and in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

Platelet Protective Effect of TAK‐029, A Novel Glycoprotein IIb/IIIa Antagonist: An In Vitro Study

et al. 1998

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Previous studies have indicated that exposure of fibrinogen receptors associated with the glycoprotein IIb/IIIa complex contributes to platelet loss during cardiopulmonary bypass. TAK-029 is a newly developed reversible, nonpeptide inhibitor of platelet glycoprotein IIb/IIIa receptors. In this study, we tested the platelet preserving effect of TAK-029 in an in vitro model. The methods included the comparison of the release of beta-thromboglobulin (beta-TG) between a TAK-029 group (n = 5) and a control group (n = 5) in a mock circulation under a shear force generated by a centrifugal pump. To evaluate the degree of beta-TG release, deltabeta-TG/deltaT was calculated where deltabeta-TG is the increase in beta-TG and deltaT is the time. The results showed that the value of deltabeta-TG/deltaT in the TAK-029 group was significantly lower than it was in the control group (4.22 +/- 0.27 x 10(2) ng/ml vs. 7.33 +/- 0.66 x 10(2) ng/ml, respectively). In conclusion, TAK-029 reduced the platelet activation under the shear forces of an in vitro model, suggesting that TAK-029 is a potential candidate for platelet protection during cardiopulmonary bypass.

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“…As a consequence, the platelet count was dramatically altered in our control group. Experimental ECC is usually performed either using in-vivo models with larger species, such as dogs (23)(24)(25), pigs (26)(27)(28), sheeps (29 , 30), or simply in-vitro models using anticoagulated human blood (10,15,19). When smaller species such as rabbits and rats were studied for ECC, the latter were mainly used for studying the thrombus formation in extracorporeal shunts (31), or for performing a locally controlled perfusion (32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Ro 44-9883, a New Non-Peptidic GPIIb-GPIIIa Antagonist Prevents Platelet Loss in a Guinea Pig Model of Extracorporeal Circulation

1993

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SummaryExtensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with bubble oxygenation. In 15 guinea pigs, an arterio-arterial shunt was created and perfused for 1 h from the aortic arch to the descending aorta. The guinea pigs were divided into three groups: A control group receiving only heparin as an i.v. bolus, a low dose-treated group and a high dose-treated group receiving in addition to heparin and before starting ECC, 1 or 7 mg/kg Ro 449883 as an i.v. bolus, respectively. In the control group, the platelet count at 30 and 60 min of ECC was dramatically decreased (35 ± 4% and 25 ± 3% of initial value). In the low dose-treated group, Ro 44-9883 partially prevented the drop in platelet count (69 ± 8% and 54 ± 9%; p <0.05) whereas in the high dose-treated group, the platelet count was normal at 30 min (97 ± 8%) and only slightly decreased at 60 min (80 ± 7%). Mean arterial pressure and hematocrit were not significantly different between groups during the experiment. We conclude that i) ECC in guinea pigs provides an interesting in-vivo model for studying platelet loss by contact activation and ii) Ro 44-9883 prevents platelet loss during ECC in a dose dependent manner.

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Iloprost (ZK36374), a stable analogue of prostacyclin, preserves platelets during simulated extracorporeal circulation

Cited by 57 publications

References 14 publications

Preoperative detection and management of immune heparin-induced thrombocytopenia in patients undergoing heart surgery with iloprost

Preoperative detection and management of immune heparin-induced thrombocytopenia in patients undergoing heart surgery with iloprost

Platelet Protective Effect of TAK‐029, A Novel Glycoprotein IIb/IIIa Antagonist: An In Vitro Study

Ro 44-9883, a New Non-Peptidic GPIIb-GPIIIa Antagonist Prevents Platelet Loss in a Guinea Pig Model of Extracorporeal Circulation

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