Blood Interaction with a Bioline Heparin Coated HIA-VAD: A Study on Calves

1997 ◽  
Vol 20 (1) ◽  
pp. 43-50 ◽  
Author(s):  
K.W.H.J. Van Der Kamp ◽  
C.P.E. Magielse ◽  
J.M. Elstrodt ◽  
J. Van Der Meer ◽  
W. Van Oeveren ◽  
...  
Keyword(s):  
Blood Cell ◽  
Degradation Products ◽  
Blood Compatibility ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Mechanical Trauma ◽  
Control Group ◽  
Implantation Procedure

The blood compatibility of ventricular assist devices developed by the Helmholtz Institute Aachen (HA-VAD's) was tested on calves. Seven calves received a non-coated HIA-VAD (control) and three a Bioline heparin coated device. The circulatory support of these HIA-VAD's lasted one week. Mechanical blood cell trauma estimated by hematocrit (Hct), hemoglobin (total Hb) and free plasma hemoglobin (free Hb) levels did not differ in either group. All HIA-VAD's in the control group remained thrombus free, except on one occasion when an inflow cannula was obstructed by a thrombus located in the tip. After circulatory support, the animals in this group seemed clinically healthy. However, thrombus formation was observed in the three heparin coated HIA-VAD's. One animal in this group died from complications after re-operation for pneumothorax on the fifth day of support, whereas the other two animals seemed clinically healthy. In these three animals, a stronge decrease in platelet numbers was measured even after 24 hours of support which recovered after 72 hours. This decrease in platelet numbers was associated with a lower degree of platelet aggregation ability stimulated by ADP (p<0.05). Fibrin(ogen) degradation products (FDP) increased significantly immediately after the implantation procedure (p<0.05). Fibrinogen levels initially decreased during the implantation procedure, but increased thereafter in both groups. The FDP levels remained high in this group, although the FDP levels in both groups were decreased after the implantation procedure. The ex vivo measured circulating heparin levels were lower in the heparin coated HIV-VAD group despite the equally administrated heparin doses in both animal groups. No differences were measured in either group with regard to white blood cell (WBC) numbers and complement hemolytic activity (CH50). Despite these hemostatic changes, no mechanical trauma could be demonstrated after seven days of circulatory support.

Design Optimization of a Mechanical Heart Valve for Reducing Valve Thrombogenicity: A Case Study With ATS Valve

2010 ◽  
Author(s):  
Gaurav Girdhar ◽  
Yared Alemu ◽  
Michalis Xenos ◽  
Jawaad Sheriff ◽  
Jolyon Jesty ◽  
...  
Keyword(s):  
Heart Valves ◽  
Thrombus Formation ◽  
Anticoagulation Therapy ◽  
Mechanical Heart Valve ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Ventricular Assist ◽  
Mechanical Circulatory Support Devices ◽  
Artificial Hearts

Flow past mechanical heart valves (MHV) in mechanical circulatory support devices including total artificial hearts and ventricular assist devices, is primarily implicated in thromboembolism due to non-physiological flow conditions where the elevated stresses and exposure times are sufficiently high to cause platelet activation and thrombus formation. Mitigation of this risk requires lifelong anticoagulation therapy and less thrombogenic MHV designs should therefore be developed by device manufacturers [1].

Mechanical Circulatory Support Sources of Emboli and Neurological Outcome

2000 ◽  
Vol 4 (2) ◽  
pp. 115-120
Author(s):  
D.W. Quinn ◽  
T.J.J. Jones ◽  
T.R. Graham
Keyword(s):  
Mechanical Circulatory Support ◽  
Thrombus Formation ◽  
Neurological Complications ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Left Ventricular Assist Devices ◽  
Major Step ◽  
Myocar Dial ◽  
Wide Range

Long-term mechanical circulatory support devices are currently used as bridges to transplantation or myocar dial recovery and represent a major step forward in the treatment of end-stage heart failure. Examples of left ventricular assist devices/systems are Thoratec Labora tories (Berkley, CA), Baxter Novacor (Oakland, CA), and Thermo Cardiosystems Inc Heartmate (Woburn, MA). The CardioWest (Tucson, AZ) is the current total artifi cial heart device under clinical evaluation. These de vices are associated with neurological complications usually resulting from thromboembolic events to the cerebrum, cerebellum, or brainstem. The device itself is the commonest source of these emboli. Thrombus formation within the device occurs as a result of the interaction between the blood contacting surfaces of the device, the flow of blood through the device, and thrombotic tendency of the blood. There is a wide range of clinical presentation, from asymptomatic emboli detected by transcranial Doppler to devastating strokes. Strategies aimed to reduce the tendency to form throm bus are based on aggressive prevention with anticoagu lation and antiplatelet therapy and/or by design modifi cation. In particular, the use of a textured inner surface that encourages the formation of a pseudoneointima seems successful in reducing anticoagulation require ments and neurological complications.

Inhibition of Platelet Glycoprotein β3 by Chimeric Monoclonal Antibody Prevents Arterial Thrombosis in Beagle Dogs,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3357-3357
Author(s):  
Shundong Ji ◽  
Miao Jiang ◽  
Ningzheng Dong ◽  
Xia Bai ◽  
Changgeng Ruan
Keyword(s):  
Bleeding Time ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Dose Range ◽  
Negative Control Group ◽  
Negative Control ◽  
Platelet Glycoprotein ◽  
Control Group ◽  
Beagle Dogs

Abstract Abstract 3357 In this present study in beagle dogs, we evaluated the antithrombotic efficacy of Pulaimab, the chimeric monoclonal antibodies SZ21-F(ab)2 fragments against platelet glycoprotein (GP) β3, in a modified Folts model. The Folts model is widely accepted to be effective and clinically relevant for testing potential anti-thrombotic agents, in this model the cyclic flow reductions (CFRs) are caused by platelet dependent thrombi that form under high-shear conditions at injured stenosed sites of an artery. Thirty beagle dogs of either sex, weighing 7.5 to 14 kg, were randomly divided into five groups of six (three females and three males), the details were following: negative control group (injected normal saline), positive control group (injected 0.2mg/Kg of Reopro), and three experimental groups [injected 0.2, 0.4, 0.8 mg/Kg of SZ21-F(ab)2, respectively]. A dose range from 0.2 to 0.8 mg/kg of Pulaimab significantly reduced the CFRs by 21–73%, without reduction of platelet numbers and prolongation of the bleeding time. Ex vivo ADP-induced platelet aggregation was equally reduced. The present study demonstrates that the inhibition of platelet GP αIIbβ3function by SZ21-F(ab)2 is a powerful intervention to prevent platelet thrombus formation in injured arteries without thrombocytopenia and prolongation of the bleeding time. We therefore conclude that F(ab)2 fragments of inhibitory anti-GPβ3 antibodies may be useful compounds to prevent thrombosis. Disclosures: No relevant conflicts of interest to declare.

Ex Vivo Expansion Reduces Neutropenia Post Autologous Transplantation of Peripheral Blood Hematopoïetic Stem Cells in Patients with Follicular Lymphoma. A Randomized, Double Blind Trial,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4009-4009
Author(s):  
Helene Trebeden-Negre ◽  
Sylvain Choquet ◽  
Michelle Rozenzwajg ◽  
Nabih Azar ◽  
Francois Lefrère ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Autologous Transplantation ◽  
Ex Vivo Expansion ◽  
Control Group ◽  
Double Blind ◽  
Cd34 Cells ◽  
The Mean

Abstract Abstract 4009 The ex vivo culture of Hematopoietic Stem Cells (HSC) with various combinations of cytokines can increase the number of mature hematopoietic cells that are theoretically capable of rapidly release neutrophils and platelet and reduce recovery duration post transplantation. In patients, the infusion of such cells has been reported, but the short-term effect was not clear. In a randomized, double blind study, we used expanded cells from 4×106/kg peripheral blood hematopoietic selected CD34+cells in comparison to a non manipulated graft containing the same number of CD34+ cells; we designed an ex vivo expansion protocol based on a cocktail of early or late acting cytokines with different culture duration in order to obtain progenitors at various stages of differentiation 1) primitive progenitors obtained from selected CD34+cells cultured for 8 days in presence of fetal liver tyrosine kinase 3 ligand (FLT3-ligand), stem cell factor (SCF), interleukin-3 (IL-3) and thrombopoietin (TPO), 50 ng/ml, each 2) committed megakaryocyte progenitors (Mks) obtained after culture for 10 days in presence of TPO et SCF (50 ng/ml, each) or 3) committed granulocytes and megakaryocyte (GMks) progenitors obtained after culture for 10 days in presence of TPO, SCF and G-CSF (100 ng/ml). Eighteen Non Hodgkin Lymphoma patients submitted to autologous transplantation after a myeloablative regimen consisting of AraC: Day (D)-6 to D-3: 200mg/m2/12h - VP16: 100mg/m2/12h: D-6 to D-3 - BCNU: 300mg/M2: D-6- Melphalan: 140mg/M2: D-2 could be evaluated. Patients in the Expansion Group received graft with 1×106/kg non manipulated cells combined with primitive progenitors issues from 2×106/kg CD34+ cells and Mks progenitors (Mks Expansion Group) or GMks progenitors (GMks Expansion Group) coming from 1×106/kg CD34+cells; unmanipulated cells were used as a source of immunocompetent cells. In the mean, patients of control group (n=10) received 1.3±0.9×108Total Nucleated Cells (TNC)/Kg, 2.7±1.2×106 CD34+/kg, 49±17×104/kg CFU-GM and 17.7±.7104CFU-Mks/kg; in the Mks (n=4) and GMks (n=4) Expansion group, they received respectively in the mean: 61.5±18.5 and 90.1±21.3×108TNC /Kg, 26.5±10.7 et 31± 11.2 x106CD34+/kg, 451± 188 et 557±216×104/kg CFU-GM, 358±212 et 39±18.1 x104/kg CFU-Mk. No cytokines were administered after transplantation. No toxicity was observed after cell infusion. The mean times to reach white blood cell (WBC) recovery (WBC >1x 109/l) was significantly shorter after administration of expanded cells, 14 (10–16), 12 (11–14) and 9 (9–10) days respectively in control, Mks and GMks Expansion Group (p=0.01). Median profound neutropenia (neutrophils<0,5×109/l) duration was 4 (4–5) days in the GMk Expansion Group versus 9 (7–11) in the Mks Expansion Group and 9 (6–14) in the control group (p<0.05); no patient demonstrated abrogation of neutropenia. In contrast, ex vivo expansion did not reduce the time to platelet recovery (>25 or50×109/L) despite numerous mature megakaryocytes and CFU-Mks in the Mks Expansion Group; that could be related to the colonies size, very small from expanded cells. No secondary hypoplasia was observed during the 12 months follow-up. This study shows that in comparison with unmanipulated cells, peripheral blood haematopoietic cells expanded from similar doses of CD34+ cells accelerate neutrophil recovery without impairing long-term haematopoiesis and open interesting perspectives in the field of allogeneic cord blood cell transplantation. Disclosures: Leblond: Roche, Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Characterization of platelet functionality in pediatric patients with kaposiform hemangioendothelioma / Kasabach-Merritt phenomenon

2021 ◽  
Author(s):  
Alexey Martyanov ◽  
Ivan Tesakov ◽  
Olga An ◽  
Julia-Jessica Korobkin ◽  
Anastasia Ignatova ◽  
...  
Keyword(s):  
Parallel Plate ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Lower Boundary ◽  
Calcium Mobilization ◽  
Control Group ◽  
Functional Responses ◽  
Kaposiform Hemangioendothelioma ◽  
Normal Ranges ◽  
Platelet Receptor

Background. Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy commonly associated with Kasabach-Merritt phenomenon (KMP) that includes thrombocytopenia and coagulation dysfunction. Platelet receptor CLEC-2 -tumor cell podoplanin interaction is considered the key mechanism of thrombocytopenia in KMP, however, the effect of long-term exposure to podoplanin on platelet function is unknown. Procedure. Here we examined blood samples from six patients with KHE and one KMP. Platelet calcium signaling and functional responses to conventional activation and CLEC-2 stimulation were analyzed by continuous and endpoint live cell flow cytometry. Platelet aggregation in response to ADP or rhodocytin was analyzed by low-angle light scattering approach (LaSca). Additionally, ex vivo thrombus formation on collagen was observed in parallel-plate flow chambers. Results. We demonstrate that in KHE/KMP platelet functional responses to strong stimulation were on the lower boundary of age-matched normal ranges, while calcium mobilization and fibrinogen binding upon stimulation with ADP alone were significantly lower than control values. Platelet di-aggregate formation in response to ADP was also diminished in most of the patients. Formation of platelet aggregates in collagen-coated parallel plate flow chambers was also noticeably lower than in the age-matched control group. Calcium mobilization in response to CLEC-2 stimulation was unaltered in the patients and could be blocked by low-molecular-weight inhibitors, 2CP and HB125. Conclusions. While platelet responsiveness in KHE/KMP is moderately altered, their CLEC-2 receptors remain functional and respond to inhibition. Therefore, our findings suggest that CLEC-2-targeting molecules are new potential agents in therapeutic management of this life-threatening condition.

Platelet Activity State in Human, Bovine, and Ovine Species Under Constant Shear Stress: A Comparative Study

2013 ◽  
Author(s):  
Phat L. Tran ◽  
Valerie M. Merkle ◽  
Tracy DeCook ◽  
Marcus Hutchinson ◽  
Jawaad Sheriff ◽  
...  
Keyword(s):  
Shear Stress ◽  
Blood Compatibility ◽  
Platelet Reactivity ◽  
Total Artificial Heart ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Large Animal ◽  
Platelet Activity ◽  
Bridge To Transplant ◽  
Large Animal Models

Mechanical circulatory support (MCS) devices, such as the total artificial heart and ventricular assist devices, are employed as bridge-to-transplant or destination therapies for advanced heart failure.[1] Recipients of these life-saving MCS devices have to endure life-long antiplatelet regimens to counteract thromboembolic events resulting from exposure of platelets to high shear stress. Often, large animal models, i.e. bovine and ovine, have been utilized to evaluate the performance and blood compatibility of these cardiovascular devices. Therefore, understanding and correlating the interspecies differences of platelet reactivity is crucial in optimizing the design of MCS devices.

scholarly journals Novel Stenotic Microchannels to Study Thrombus Formation in Shear Gradients: Influence of Shear Forces and Human Platelet-Related Factors

2019 ◽  
Vol 20 (12) ◽  
pp. 2967 ◽  
Author(s):  
Mathew Lui ◽  
Elizabeth E. Gardiner ◽  
Jane F. Arthur ◽  
Isaac Pinar ◽  
Woei Ming Lee ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Antiplatelet Agents ◽  
Circulatory Support ◽  
Type I ◽  
Base Shear ◽  
Related Factors ◽  
Variable Shear ◽  
Platelet Thrombi

Thrombus formation in hemostasis or thrombotic disease is initiated by the rapid adhesion, activation, and aggregation of circulating platelets in flowing blood. At arterial or pathological shear rates, for example due to vascular stenosis or circulatory support devices, platelets may be exposed to highly pulsatile blood flow, while even under constant flow platelets are exposed to pulsation due to thrombus growth or changes in vessel geometry. The aim of this study is to investigate platelet thrombus formation dynamics within flow conditions consisting of either constant or variable shear. Human platelets in anticoagulated whole blood were exposed ex vivo to collagen type I-coated microchannels subjected to constant shear in straight channels or variable shear gradients using different stenosis geometries (50%, 70%, and 90% by area). Base wall shears between 1800 and 6600 s−1, and peak wall shears of 3700 to 29,000 s−1 within stenoses were investigated, representing arterial-pathological shear conditions. Computational flow-field simulations and stenosis platelet thrombi total volume, average volume, and surface coverage were analysed. Interestingly, shear gradients dramatically changed platelet thrombi formation compared to constant base shear alone. Such shear gradients extended the range of shear at which thrombi were formed, that is, platelets became hyperthrombotic within shear gradients. Furthermore, individual healthy donors displayed quantifiable differences in extent/formation of thrombi within shear gradients, with implications for future development and testing of antiplatelet agents. In conclusion, here, we demonstrate a specific contribution of blood flow shear gradients to thrombus formation, and provide a novel platform for platelet functional testing under shear conditions.

scholarly journals Ultrastructural Study on in Vivo Blood Compatibility of Biolized Materials

1977 ◽  
Author(s):  
H. Harasaki ◽  
G. Picha ◽  
M. Helmus ◽  
A. Fields ◽  
R. Kiraly ◽  
...  
Keyword(s):  
Blood Compatibility ◽  
Thrombus Formation ◽  
Intercellular Junctions ◽  
Ultrastructural Level ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Cardiovascular Devices

The long-term implantation of cardiac prostheses has been hampered by the lack of thromboresistant blood interfacing materials. Glutaraldehyde treated pericardium and glutaraldehyde treated, gelatin-coated rubber have been utilized for the blood contacting materials of our devices. These “biolized” cardiac prostheses were implanted in calves: 8 total artificial hearts for up to 5 months, 7 left ventricular assist devices for up to 7 months, and a passive pump implanted in the aorta for 5 1/2 years. The blood-solid interaction and endothelialization of these materials were chronologically followed at an ultrastructural level using scanning and transmission electron microscopy.The devices implanted up to 40 days were covered by a thin layer of fibrinous material. The adhesion of blood corpuscles were minimal except for the region of diaphragm-housing junction. The majority of the adhered platelets were “contact” and “spread” platelets. Once this fibrin-rich layer was formed, no significant thrombus formation was observed. The endothelialization was observed in the portion of the pericardium surface adjacent to the inflow valve in the heart implanted for 145 days. The coverage of the endothelial cells was more complete in the passive pump. Although Weibel-Palade bodies were observed in the cytoplasm of these cells, they were characterized by the sparse microvillous projections, small number of pinocytotic vesicles, and widely opened intercellular junctions. In the subendothelial layer, no basement membrane was observed.The study showed the aldehyde treated collagen and gelatin are suitable materials as blood contact surfaces of the cardiovascular devices.

scholarly journals Anticoagulation with VADs and ECMO: walking the tightrope

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 674-680 ◽  
Author(s):  
Leslie Raffini
Keyword(s):  
Thrombus Formation ◽  
Ventricular Assist Devices ◽  
Quality Data ◽  
Critically Ill Children ◽  
Circulatory Support ◽  
Ventricular Assist ◽  
Blood Flows ◽  
Patients With Heart Failure ◽  
Normal Hemostasis ◽  
Design And Manufacture

Abstract The evolution of devices for mechanical circulatory support (MCS), including ventricular assist devices (VADs) for patients with heart failure and extracorporeal membrane oxygenation (ECMO) for patients with acute cardiac or respiratory failure, has improved survival for subsets of critically ill children and adults. The devices are intricate and complex, allowing blood to bypass the heart or lungs (or both). As blood flows through these artificial devices, normal hemostasis is disrupted, coagulation is promoted, and in the absence of anticoagulation, a thrombus may form in the device, resulting in device failure or embolic stroke. Therefore, anticoagulation is necessary to prevent thrombus formation and maintain device function. However, patients on MCS also have very high bleeding rates. Titrating anticoagulation to prevent hemorrhagic complications and thrombotic events can be a challenge, and hematologists may be consulted in complex cases. Substantial variability remains in the approach to anticoagulant and antiplatelet therapy for patients on MCS, largely because of the lack of high-quality data. Improvements in the design and manufacture of these devices, as well as in the individualized titration of antithrombotic intensity, are expected to enhance outcomes. Several factors pertaining to both the device and the patient (adult and children) should be considered when attempting to optimize this delicate balance.

scholarly journals Heart Transplantation of Patients with Ventricular Assist Devices: Impact of Normothermic Ex-Vivo Preservation Using Organ Care System Compared with Cold Storage

2020 ◽  
Author(s):  
Zhuldyz Nurmykhametova ◽  
Rymbay Kaliyev ◽  
Timur Lesbekov ◽  
Serik Bekbossynov ◽  
Makhabbat Bekbossynova ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Cold Storage ◽  
Mechanical Circulatory Support ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Ischemic Time ◽  
Significant Difference ◽  
Care System

Abstract Background: Organ Care System (OCS) minimizes the cold ischemic time and allows for optimization of logistics and meticulous recipient preparation. Impact of normothermic ex-vivo preservation using OCS compared with cold storage (CS) for prolonged heart preservation especially beneficial for high-risk recipients bridged to transplantation with Mechanical Circulatory Support (MCS). Methods: Between 2012 and 2018, we performed a retrospective single-center review of prospectively collected data. All patients who underwent heart transplantation with MCS using the OCS Heart (n=25) versus standard cold storage were included in this study. Results: During this period, 300 patients were implanted with left ventricular assisted device (LVAD) and 35 (11.6 %) were bridged to heart transplantation. There was no significant difference in donor and recipient characteristics and risk factors. The Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score was a trend towards higher estimated risk of death at 1y in the OCS group (14.2 vs. 10.8% p= 0.083). Mean total ischemic time during preservation was statistically significantly longer in CS vs OCS group (210 (23) Vs 74.6 (13) min p=0.001). Median ex vivo normothermic heart perfusion time in OCS was 348.4(132; 955) min. There was significant difference in total out of body time between OCS group 423(67) Vs CS group 210(23) min p=0.002). The allografts were reperfused for 73 (33) vs 121 (45) minutes (p=0.01) before disconnection from cardiopulmonary bypass in OCS vs CS group. All patients were alive on the 30th days post implant in CS groups and 96% in OCS group (p=0.5). Conclusion: Normothermic ex-vivo preservation of the allograft during transportation with the organ care system might be beneficial for long-time out of body organ preservation in comparison of cold storage especially for recipients on mechanical circulatory support.

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