Effects of Angiotensin-Converting Enzyme Inhibition on Thromboelastogaphy for Infants and Children Presenting for Elective Cardiac Surgery.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1225-1225
Author(s):  
Michael L Schmitz ◽  
Edgar D St. Amour ◽  
Kimo Stine ◽  
Mark A Austen ◽  
Chanhee Jo ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Platelet Aggregation ◽  
Plasminogen Activator ◽  
Whole Blood ◽  
Infants And Children ◽  
Clot Formation ◽  
Coagulation Cascade ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Clot Strength ◽  
Elective Cardiac Surgery

Abstract Introduction: Thromboelastography (TEG) is a point-of-care whole blood coagulation test used commonly with cardiac and liver operations, surgeries for which intraoperative and postoperative bleeding and coagulopathies occur and transfusion is likely. Angiotensinconverting enzyme inhibitors (ACEI) have been found to decrease plasminogen activator inhibitor I (PAI-1), increase tissue plasminogen activator (tPA), decrease tissue factor (TF) production by monocytes, and decrease platelet aggregation. Methods: With IRB approval, kaolin-activated heparinase TEG data were collected on 634 infants and children under 18 yr presenting for elective cardiac surgery between January 2004 and December 2007 for retrospective review utilizing the Haemoscope Thromboelastograph® Coagulation Analyzer (Haemoscope Corp., Niles, IL). Six TEG parameters are analyzed: R (reaction time to reach clot initiation), K (time to reach 20 mm amplitude after R), alpha (clot kinetics), MA (maximum amplitude), LY30 (amount of lysis 30 min after MA), and CI (coagulation index). Infants and children are analyzed based on preoperative therapy with an ACEI. Results: In those receiving ACEI, the time to initial fibrin formation is faster (R, p=0.0007), although subsequent clot formation is slower (K, p=0.0201; alpha, p=0.0092) than without ACEI drugs. Moreover, there is markedly less fibrinolysis (LY30, p=0.0019) in those receiving an ACEI. Clot strength and overall clot dynamics (MA and CI, p=NS) were similar in both groups (Table 1). Subjects with baseline oxygen saturation of 88% differ in that they do not have a significant change in K or alpha but do have a higher CI. Table 1. Ranges for Kaolin-activated Heparinase Thromboelastography Parameters Group R (min) K (min) alpha (degrees) MA LY30% CI Control 7.27±2.20 1.83±0.68 65.0±8.4 64.2±6.4 2.28±2.87 −0.68±2.81 ACEI 6.54±1.88 1.99±0.81 62.7±10.2 63.3±5.8 1.12±2.05 −0.39±2.87 p value 0.0007 0.0201 0.0092 NS 0.0019 NS Discussion: A number of investigators have found antithrombotic effects of ACEI drugs in adults but children have not been studied. The TEG provides an ex vivo means of assessing whole blood clotting dynamics. This preliminary analysis of infants and children reveals a delay in the time required to initiate clot via the intrinsic coagulation cascade as activated by kaolin (R) and slowed clot formation (K and alpha). Final clot strength shows no difference and LY30 shows less fibrinolysis. A shift in plasma hemostasis towards fibrinolysis would potentially delay R, prolong K, decrease alpha, and increase LY30. Paradoxically, we see a decrease in R and LY30. Reduced platelet aggregation is consistent with slowed kinetics of clot formation (K and alpha) but would be expected to cause a reduction in MA that is not seen. Further analysis of this data will separate the subjects into age groups as TEG parameters vary with age in infants and children. Also, since there is evidence that enalapril may not have the antiplatelet effects of captopril and may increase tPA in women but not men, further analysis of gender and type of ACEI given will be completed.

Influence of Nanopolymers with Different End-Functionalities on Platelet Function and the Coagulation Cascade - An Ex-Vivo Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4038-4038
Author(s):  
Meera Chitlur ◽  
Erin Ware ◽  
Sujata Kannan ◽  
Wendy Hollon ◽  
Steve Buck ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Surface Charge ◽  
Platelet Function ◽  
Whole Blood ◽  
Clot Formation ◽  
Coagulation Cascade ◽  
Cancer Drug ◽  
Dendritic Polymers ◽  
Drug Concentrations

Abstract Dendritic polymers are branched nanopolymers with a central core and multiple peripheral functional groups that offer great potential as high payload delivery vehicles carrying multiple copies of drug molecules, targeting ligands and imaging agents to their site of action. Their nanoscopic dimensions offer exciting possibilities for achieving high intracellular drug concentrations in many therapeutic areas including anti-cancer drug delivery. Biocompatibility and biodistribution of dendritic polymers may be influenced by surface charge and concentration. One of the major challenges in their use is the effect on coagulation. The objective of this study was to determine the effect of change in surface charge and concentration of dendritic polymer on cellular and enzymatic components of coagulation. Materials and Methods: The effect of increasing concentrations (1, 10, 100, and 1000mcg/ml) of polyamidoamine (PAMAM) dendrimers with -COOH (anionic), -OH (neutral), and -NH2 (cationic) end functionalities, on platelet function and coagulation was evaluated using thromboelastography, whole blood aggregation, and flow cytometry. The thromboelastographic profile and platelet aggregation studies were obtained on samples of whole blood incubated for thirty minutes with dendrimer. Platelets were incubated with FITC labelled dendrimer for 30,60 and 120 mins, to determine uptake and platelet activation using flow cytometry. All tests were performed in triplicate. RESULTS: Thromboelastography: No significant effect on clot formation (time to clot formation and size) was seen with PAMAM-COOH (COOH) or PAMAM-OH (OH). Prolonged time to initiation of clot and decreased size were noted with 100 and 1000mcg/ml of PAMAM-NH2(NH2) as shown in figure1, indicating impairment of both the enzymatic and cellular components of the coagulation system. Whole Blood Aggregation: Neither platelet aggregation nor secretion were significantly affected by COOH or OH. Platelet aggregation was significantly decreased with NH2 at 100 and 1000mcg/ml. Flow Cytometry: Spontaneous CD62 activation was seen in platelets incubated with NH2. No spontaneous CD62 activation was noted with COOH or OH even at 1000mcg/ml. Platelet uptake of FITC labeled dendrimer was assessed at 30, 60 and 120mins of incubation. Increased uptake of FITC labeled dendrimer was noted at 2 hours with NH2. TEG clotting Profiles with PAMAM-NH2. TEG clotting Profiles with PAMAM-NH2. CONCLUSIONS: Surface charge of the dendritic nanopolymers plays a significant role on its effect on coagulation and platelet function. The anionic -COOH terminated and neutral -OH terminated dendrimers had no effect on hemostasis even at the highest concentrations while the cationic-NH2 was associated with inhibition of platelet aggregation and delayed clot initiation at higher concentrations. This would indicate that the anionic and neutral dendrimers would serve as better vehicles than cationic dendrimers for targeted delivery of therapeutic agents.

The Haemocompatibility of Biomaterials In Vitro: Investigations on the Mechanism of the Whole-blood Clot Formation Test

1992 ◽  
Vol 20 (3) ◽  
pp. 390-395 ◽  
Author(s):  
Thomas Groth ◽  
Katrin Derdau ◽  
Frank Strietzel ◽  
Frank Foerster ◽  
Hartmut Wolf
Keyword(s):  
Whole Blood ◽  
Blood Clotting ◽  
Blood Clot ◽  
Formation Rate ◽  
Clot Formation ◽  
Coagulation Cascade ◽  
Contact Activation ◽  
Human Fibrinogen ◽  
Static Conditions

Twenty years ago Imai & Nose introduced a whole-blood clotting test for the estimation of haemocompatibility of biomaterials in vitro In our paper a modification of this assay is described and the mechanism of clot formation further elucidated. It was found that neither the inhibition of platelet function nor the removal of platelets from blood significantly changed the clot formation rate on glass and polyvinyl chloride in comparison to the rate tor whole blood. Scanning electron microscopy demonstrated that platelets were not involved in clot formation near the blood/biomaterial interface. Thus, it was concluded that the system of contact activation of the coagulation cascade dominates during clot formation under static conditions. The latter conclusion was supported by the fact that preadsorption of human serum albumin or human fibrinogen onto the glass plates used, decreased the clot formation rate in the same manner.

Enhanced platelet aggregation and activation under conditions of hypothermia

2007 ◽  
Vol 98 (12) ◽  
pp. 1266-1275 ◽  
Author(s):  
Ruben Xavier ◽  
Ann White ◽  
Susan Fox ◽  
Robert Wilcox ◽  
Stan Heptinstall
Keyword(s):  
Cardiac Surgery ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Baseline Levels ◽  
Spontaneous Aggregation ◽  
High Concentrations ◽  
Induced Aggregation ◽  
P2y12 Antagonist

SummaryThe effects on platelet function of temperatures attained during hypothermia used in cardiac surgery are controversial. Here we have performed studies on platelet aggregation in whole blood and platelet-rich plasma after stimulation with a range of concentrations of ADP, TRAP, U46619 and PAF at both 28°C and 37°C. Spontaneous aggregation was also measured after addition of saline alone. In citrated blood, spontaneous aggregation was markedly enhanced at 28°C compared with 37°C. Aggregation induced by ADP was also enhanced. Similar results were obtained in hirudinised blood. There was no spontaneous aggregation in PRP but ADP-induced aggregation was enhanced at 28°C. The P2Y12 antagonist AR-C69931 inhibited all spontaneous aggregation at 28°C and reduced all ADP-induced aggregation responses to small, reversible responses. Aspirin had no effect. Aggregation was also enhanced at 28°C compared with 37°C with low but not high concentrations of TRAP and U46619. PAF-induced aggregation was maximal at all concentrations when measured at 28°C, but reversal of aggregation was seen at 37°C. Baseline levels of platelet CD62P and CD63 were significantly enhanced at 28°C compared with 37°C. Expression was significantly increased at 28°C after stimulation with ADP, PAF and TRAP but not after stimulation with U46619. Overall, our results demonstrate an enhancement of platelet function at 28°C compared with 37°C, particularly in the presence of ADP.

Effects of fibrinogen and platelet supplementation on clot formation and platelet aggregation in blood samples from cardiac surgery patients

2014 ◽  
Vol 134 (4) ◽  
pp. 895-900 ◽  
Author(s):  
Caroline Shams Hakimi ◽  
Inger Fagerberg Blixter ◽  
Emma C. Hansson ◽  
Camilla Hesse ◽  
Håkan Wallén ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Platelet Aggregation ◽  
Clot Formation ◽  
Blood Samples

Abstract WP287: Deterioration in Recombinant Tissue Plasminogen Activator After Repeated Freezing and Thawing Cycles for Thromboelastography

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Sean Calo ◽  
Anja-Kathrin Jaehne ◽  
Kelly A Keenan ◽  
Jun Xu ◽  
Baruch Tawil ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Human Blood ◽  
Whole Blood ◽  
Recombinant Tissue Plasminogen Activator ◽  
Healthy Human ◽  
Clot Strength ◽  
Blood Samples ◽  
Freeze Dried ◽  
Tissue Plasminogen

Background and Purpose: Thromboelastography (TEG) is often used to measure coagulation dynamics in the setting of acute ischemic stroke and thrombolytic therapy. The stability of thrombolytics has not been investigated in TEG. We conducted an experimental series to test the effects of recombinant tissue plasminogen activator (rtPA) on fibrinolysis in normal blood samples using TEG. Methods: Freeze dried rtPA powder was reconstituted in normal saline containing 0.2% bovine serum albumin (100 mg/24 mL), divided into 1 mL aliquots, and diluted to enable using a relatively large volume for complete mixing with blood samples. Aliquots and dilutions were frozen at -20°C. The same rtPA dilution was thawed to ambient temperature before each use and refrozen until the next use over 4 testing days. Blood was drawn into 3.2% sodium citrated collection tubes. rtPA (100 μL) was added to 1 mL whole blood to achieve a 636 ng/mL rtPA TEG sample concentration. Control-whole blood and rtPA-whole blood TEG was performed for 3 h on 4 healthy human blood samples. Maximum clot amplitude (mm) and absolute clot strength (dynes/cm 2 ) were measured. Data (mean±SD) were analyzed by t-tests and significance inferred at p <0.05. Results: Clot amplitude increased with thawing and refreezing (28±3, p=0.004; 35±2 p=0.01; 50±3, p=0.02; and 55±3, p=0.30; for testing cycles 1, 2, 3 and 4, respectively) compared to untreated samples (63±4). Clot strength also increased over the 4 cycles (2±0.3, p=0.007; 3±0.2, p=0.02; 5±05, p=0.01 and 6±0.7, p=0.30) compared to untreated (9±1.4). Lysis initiation time was gradually longer over the 4 tests (red arrows, Figure 1) suggesting delayed fibrinolysis. Conclusions: One repeatedly thawed and refrozen rtPA stock showed a delay in fibrinolysis in healthy human blood, suggesting a loss of potency. Thus, rtPA should be aliquoted for 1-time use for experiments using TEG. Further investigation into rtPA potency deterioration with storage after reconstitution is warranted.

Design and Development of a Unit-Use Cartridge for Coagulation Testing in Whole Blood

1999 ◽  
Author(s):  
Rhonda Cheadle ◽  
Andy Maczuszenko ◽  
Cindra Widrig Opalsky
Keyword(s):  
Blood Sample ◽  
Whole Blood ◽  
Clot Formation ◽  
Coagulation Cascade ◽  
Design And Development ◽  
Blood Samples ◽  
Coagulation Assays ◽  
Coagulation Testing ◽  
Functional Features ◽  
Whole Blood Samples

Abstract The following describes the development of a disposable cartridge for use at the patient bedside to perform traditional coagulation assays on fresh whole blood samples. The cartridge provides a means by which a blood sample can be metered and quantitatively mixed with reagents that activate the coagulation cascade. Clot formation is subsequently detected using a microfabricated sensor housed within the cartridge. The functional features of the cartridge and sensor are described.

Preservation of collagen-induced whole blood platelet aggregation by tranexamic acid therapy in primary cardiac valve surgery

Perfusion ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 507-513 ◽  
Author(s):  
Tetsuya Miyashita ◽  
Takahiko Kamibayashi ◽  
Yoshihiko Ohnishi ◽  
Junjiro Kobayashi ◽  
Masakazu Kuro
Keyword(s):  
Cardiac Surgery ◽  
Platelet Aggregation ◽  
Tranexamic Acid ◽  
Platelet Function ◽  
Whole Blood ◽  
Blood Platelet ◽  
Acid Group ◽  
Valve Surgery ◽  
Control Group ◽  
Blood Platelet Aggregation

Haemostatic disorder is one of the most common complications following cardiac surgery with cardiopulmonary bypass (CPB). Tranexamic acid reduces blood loss and allogeneic blood transfusion requirement in cardiac surgery. It had been thought that tranexamic acid inhibited fibrinolysis alone following CPB. In the present study, the haemostatic effects of tranexamic acid (20 mg/kg body weight bolus after induction of anaesthesia followed by continuous infusion at 2 mg/kg/h), including fibrinolysis and platelet function, were investigated in 22 patients (tranexamic acid group n = 12; control group n = 10) undergoing primary cardiac valve surgery. Fibrinolysis following CPB was reduced significantly in the tranexamic acid group. Following protamine administration, the reduction of collagen-induced whole blood platelet aggregation was mitigated significantly in the tranexamic acid group compared with the control group (36% reduction in the tranexamic acid group vs 58% in the control group; p = 0.011), although platelet counts did not differ between the two groups. In conclusion, tranexamic acid not only inhibits fibrinolysis directly, but also may preserve platelet function following CPB.

Sign in / Sign up

Export Citation Format

Share Document