Platelet dysfunction after normothermic cardiopulmonary bypass in children: Effect of high-dose aprotinin

2007 ◽  
Vol 98 (08) ◽  
pp. 385-391 ◽  
Author(s):  
Claire Flaujac ◽  
Philippe Pouard ◽  
Pierre Boutouyrie ◽  
Joseph Emmerich ◽  
Christilla Bachelot-Loza ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Protective Effect ◽  
Platelet Activation ◽  
Platelet Function ◽  
Pediatric Patients ◽  
High Dose ◽  
Platelet Dysfunction ◽  
High Dose Aprotinin ◽  
Marker Expression ◽  
Heparin Neutralization

SummaryPlatelet dysfunction after cardiopulmonary bypass (CPB) can contribute to excessive post-operative bleeding. Most trials of the protective effect of aprotinin in this setting have involved hypothermic CPB, which is more deleterious for platelets than normothermic CPB.Here we investigated the effect of aprotinin on platelet function during normothermic CPB in pediatric patients. Twenty patients (9 newborns [<1 month old] and 11 infants [<36 month old]),weighting less than 15 kg and undergoing normothermic CPB (35–36°C) were randomly assigned to two equal groups,one of which received high-dose aprotinin.Platelet function was assessed by flow cytometry just before CPB and 5 minutes after heparin neutralization. F1+2 fragments were measured by ELISA before and 5 minutes after CPB. Platelet activation marker expression (CD62P and activated αIIbβ3) induced by ADP or TRAP was lower after CPB than before CPB, suggesting a deleterious effect of normothermic CPB on platelet function. Prothrombin fragment F1+2 levels increased after CPB. Aprotinin administration did not influence the level of prothrombin fragments or platelet marker expression measured in basal condition. However, after CPB, the capacity for platelet activation was higher in the aprotinin group, as shown by measuring CD62P expression afterTRAP activation (p=0.05).This study suggests that pediatric normothermic CPB causes platelet dysfunction, and that high-dose aprotinin has a protective effect.

Clot Impedence As An Indicator Of Platelet Dysfunction Following Cardiopulmonary Bypass

1981 ◽  
Author(s):  
A Saleem ◽  
D H Yawn ◽  
S A Saleh ◽  
E S Crawford
Keyword(s):  
Cardiopulmonary Bypass ◽  
Blood Sample ◽  
Platelet Function ◽  
Postoperative Bleeding ◽  
Coagulation Factors ◽  
Initial Slope ◽  
Platelet Dysfunction ◽  
Number Of Patients ◽  
Precision Evaluation ◽  
Surgical Bleeding

Post-operative bleeding following cardiopulmonary bypass remains a serious problem. Recent studies have indicated platelet dysfunction may be responsible for altered hemostasis in a significant number of patients. Although evaluation of coagulation factors can usually be done with speed and precision, evaluation of platelet function is time-consuming. We have evaluated a clot impedence device (Sonoclot®, Sieneo Inc., Colorado) to measure platelet function. The device measures and records the clot impedence to a vibrating probe as the blood sample clots and retracts. In our evaluation of healthy subjects, we found the initial slope of the impedence curve and the entire retraction phase are influenced by the number of platelets. Extrapolating this information to the patients undergoing cardiovascular bypass, we found 7 out of 11 patients with postoperative bleeding had poor retraction phase in spite of an adequate platelet count. This suggested platelet dysfunction. All seven patients achieved satisfactory hemostasis after platelet transfusion. This was correlated with a normal clot impedence study. Four patients with normal clot impedence were found to have surgical bleeding. The test is easy to perform and the result is available within fifteen minutes of drawing the blood sample. In our hands, the measurement of clot impedence appears to be a reliable adjunct in the etiological diagnosis of post-operative bleeding.

scholarly journals In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation

Blood ◽  
2012 ◽  
Vol 119 (17) ◽  
pp. 4066-4072 ◽  
Author(s):  
Bethan Psaila ◽  
James B. Bussel ◽  
Matthew D. Linden ◽  
Bracken Babula ◽  
Youfu Li ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Platelet Function ◽  
Whole Blood ◽  
Immune Thrombocytopenia ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
High Dose ◽  
Platelet Surface

Abstract The effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased.

scholarly journals Superoxide Dismutase 2 is dispensable for platelet function

2017 ◽  
Vol 117 (10) ◽  
pp. 1859-1867 ◽  
Author(s):  
Trevor P. Fidler ◽  
Jesse W. Rowley ◽  
Claudia Araujo ◽  
Luc H. Boudreau ◽  
Alex Marti ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Platelet Activation ◽  
Platelet Function ◽  
Mitochondrial Function ◽  
Oxygen Species ◽  
Platelet Dysfunction ◽  
Mitochondrial Ros ◽  
Superoxide Dismutase 2

SummaryIncreased intracellular reactive oxygen species (ROS) promote platelet activation. The sources of platelet-derived ROS are diverse and whether or not mitochondrial derived ROS, modulates platelet function is incompletely understood. Studies of platelets from patients with sickle cell disease, and diabetes suggest a correlation between mitochondrial ROS and platelet dysfunction. Therefore, we generated mice with a platelet specific knockout of superoxide dismutase 2 (SOD2-KO) to determine if increased mitochondrial ROS increases platelet activation. SOD2-KO platelets demonstrated decreased SOD2 activity and increased mitochondrial ROS, however total platelet ROS was unchanged. Mitochondrial function and content were maintained in non-stimulated platelets. However SOD2-KO platelets demonstrated decreased mitochondrial function following thrombin stimulation. In vitro platelet activation and spreading was normal and in vivo, deletion of SOD2 did not change tail-bleeding or arterial thrombosis indices. In pathophysiological models mediated by platelet-dependent immune mechanisms such as sepsis and autoimmune inflammatory arthritis, SOD2-KO mice were phenotypically identical to wildtype controls. These data demonstrate that increased mitochondrial ROS does not result in platelet dysfunction.

A Study of Platelet Activation during Human Cardiopulmonary Bypass and the Effect of S-Nitrosoglutathione

1997 ◽  
Vol 78 (06) ◽  
pp. 1516-1519 ◽  
Author(s):  
Edward J Langford ◽  
Andrew Parfitt ◽  
Adam J de Beider ◽  
Michael T Marrinan ◽  
John F Martin
Keyword(s):  
Nitric Oxide ◽  
Flow Cytometry ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Platelet Activation ◽  
Surface Expression ◽  
Platelet Inhibition ◽  
Nitric Oxide Donor ◽  
Platelet Dysfunction ◽  
Platelet Surface

SummaryCardiac surgery is complicated by the occurrence of post-operative bleeding due to platelet dysfunction. This is largely caused by platelet activation and consumption during cardiopulmonary bypass. Patients undergoing cardiac surgery requiring cardiopulmonary bypass were studied to determine whether early platelet changes due to bypass could be inhibited using the platelet-selective nitric oxide donor S-nitroso-glutathione (GSNO). Flow cytometry was used to measure platelet surface expression of P-selectin (an α-granule protein) and glycoproteins (GP) IIb/IIIa and Ib (mediators of aggregation and adhesion) before and 5 and 10 min after commencing cardiopulmonary bypass, in 6 controls and 6 patients receiving GSNO 50 μg/min. Platelet P-selectin expression increased during bypass both in controls and patients receiving GSNO. Glycoproteins IIb/IIIa and Ib fell during bypass in control and GSNO-treated patients. There was no difference between control and GSNO-treated groups. Thus no significant platelet inhibition by S-nitrosoglutathione was demonstrated under these conditions.

Protection of Single-chain Urokinase-type Plasminogen Activator (scu-PA) in Aprotinin Treated Cardiac Surgical Patients Undergoing Cardiopulmonary Bypass

1995 ◽  
Vol 73 (05) ◽  
pp. 825-828 ◽  
Author(s):  
M Spannagl ◽  
G Dooijewaard ◽  
W Dietrich ◽  
C Kluft
Keyword(s):  
Cardiopulmonary Bypass ◽  
Plasminogen Activator ◽  
Postoperative Blood Loss ◽  
Control Group ◽  
High Dose ◽  
Contact Activation ◽  
Single Chain ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
High Dose Aprotinin

SummaryIntraoperative high-dose aprotinin administration has been shown to reduce the intra-and postoperative blood loss in cardiac surgery. The haemostatic effect has been attributed to platelet preserving properties and to inhibition of contact activation reducing thrombotic and fibrinolytic activity during and after cardiopulmonary bypass (CPB).Here we report on the effects of aprotinin on urokinase-type plasminogen activator, especially on the protection of the zymogen singlechain urokinase-type plasminogen activator (scu-PA). scu-PA occurs cell associated as well as free in the circulation (concentration 50 pM, half-life 5 min), and is potentially activated by kallikrein and plasmin, both potent targets for aprotinin. The generated active two-chain u-PA (tcu-PA) is a powerful activator of fibrinolysis.Sixteen male patients undergoing myocardial revascularization were randomly assigned to aprotinin treatment (A) or control group (C).Plasma concentration of total u-PA antigen and of the specific forms scu-PA(zymogen) and tcu-PA(active enzyme) were measured at different stages intraoperatively and two hours postoperatively. After an initial drop due to haemodilution at the onset of CPB, the concentrations of circulating u-PA forms restored intraoperatively in A, but remained subnormal in C until the end of the observation period. The concentration of total u-PA antigen of shed mediastinal blood was both in A and C two-fold higher than in the circulation, but the antigen was preserved as the zymogen scu-PA in A and largely converted to an inactive, non activatable form in C. Intra- and postoperative blood losses were less than half the amount in A as compared to C.It is concluded that without aprotinin administration activation of circulatory scu-PA occurs, accompanied by stimulation of fibrinolysis and bleeding, finally resulting in elimination of tcu-PA complexed with endogenous inhibitors. Furthermore, cellular release of scu-PA occurs at or near the bleeding sites, as evidenced by the two-fold higher u-PA antigen concentration in the shed mediastinal blood. The released scu-PA is also activated and subsequently converted to an inactive form unless aprotinin is administered. High-dose aprotinin application during CPB effectively protects circulating and released scu-PA from activation and attenuates bleeding consequences.

Agents that modify haemostasis after cardiopulmonary bypass

Perfusion ◽  
1993 ◽  
Vol 8 (1_suppl) ◽  
pp. 6-12
Author(s):  
Richard D Weisel
Keyword(s):  
Cardiopulmonary Bypass ◽  
Inflammatory Response ◽  
Platelet Activation ◽  
Platelet Function ◽  
Heart Surgery ◽  
Postoperative Bleeding ◽  
Whole Body ◽  
Antifibrinolytic Agents ◽  
Review Reports

Reducing the whole body inflammatory response to cardiopulmonary bypass may reduce postoperative bleeding. Dipyridamole decreases platelet activation, deposition, and depletion. Antifibrinolytic agents may further reduce bleeding by reducing fibrinolysis and maintaining platelet function. This review reports the author's experience with dipyridamole and antifibrinolytic agents, membrane and bubble oxygenators, as well as the effects of warm and cold heart surgery.

Nitroglycerin and Sodium Nitroprusside: Potential Contributors to Postoperative Bleeding?

2012 ◽  
Vol 15 (2) ◽  
pp. 92 ◽  
Author(s):  
Donald Clark ◽  
Stephanie Tesseneer ◽  
Curtis G. Tribble
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Sodium Nitroprusside ◽  
Platelet Activation ◽  
Postoperative Bleeding ◽  
Antihypertensive Agents ◽  
Platelet Inhibition ◽  
Clinical Consequence ◽  
Platelet Dysfunction ◽  
Knowing That

Postoperative bleeding is common in patients undergoing cardiac surgery with cardiopulmonary bypass. Most cases of severe postoperative bleeding not due to incomplete surgical hemostasis are related to acquired transient platelet dysfunction mediated by platelet activation during contact with the synthetic surfaces of the cardiopulmonary bypass equipment. Antihypertensive agents nitroglycerin and sodium nitroprusside have been shown to have platelet inhibitory properties, yet the clinical consequence in terms of postoperative bleeding has been little studied. Knowing that cardiopulmonary bypass causes platelet dysfunction, it is prudent for physicians to be aware of the additional platelet inhibition caused by these commonly used antihypertensive agents.

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