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Biomedical subjects

S F Mohammad

Publications and source records attributed to S F Mohammad.

At least 19 recordsLinked to original sources

The effects of aprotonin on platelets in vitro using whole blood flow cytometry.

UNLABELLED: We sought to evaluate the effects of aprotinin on the number and function of the platelet glycoprotein (GP) IIb-IIIa receptor and on the expression of P-selectin in vitro in order to gain insight into the potential mechanisms involved in the platelet-protective action of aprotinin during cardiopulmonary bypass. Aprotinin at 50 to 200 kallikrein inhibiting units/mL decreased the expression of activated GP IIb-IIIa complex in response to adenosine diphosphate or thrombin receptor activator peptide 6 in a dose-dependent manner in both citrated and heparinized whole blood experiments. Aprotinin inhibited adenosine diphosphate-induced platelet aggregation, but it exhibited no effect on the expression of GP IIIa and P-selectin. These results indicate that aprotinin interferes with the platelet fibrinogen receptor function during pharmacological activation. Reduced aggregability and platelet adhesion to fibrinogen adsorbed to synthetic surfaces in the presence of aprotinin may prevent platelet consumption during clinical cardiopulmonary bypass. This in vitro study demonstrates that aprotinin decreases the agonist-induced expression of activated GP IIb-IIIa receptors that play a major role in platelet aggregation and adhesion to biomaterial surfaces. IMPLICATIONS: This in vitro study demonstrates that aprotinin decreases the agonist-induced expression of activated glycoprotein IIb-IIIa receptors that play a major role in platelet aggregation and adhesion to biomaterial surfaces.

Adenosine Diphosphate↗

The effects of heparin, protamine, and heparinase 1 on platelets in vitro using whole blood flow cytometry.

UNLABELLED: The effects of heparinization and the reversal of heparin activity on platelet function after cardiopulmonary bypass have not been well defined. Flow cytometry has become a convenient and powerful technique for characterizing platelets. We examined the expression of a secretion marker (P-selectin) and an aggregation marker (activated fibrinogen receptor GP IIb-IIIa) on normal platelets in response to heparin, heparinase 1, and protamine in vitro using whole blood flow cytometry. Unfractionated heparin increased adenosine diphosphate-induced expression of P-selectin and GP IIb-IIIa in a dose-dependent manner. Heparinase 1 alone decreased both markers of platelet activation. Protamine alone increased P-selectin expression but had no effect on GP IIb-IIIa expression. Heparinase 1 antagonized the stimulatory effect of heparin on both markers. In contrast, protamine antagonized the effect of heparin on GP IIb-IIIa expression but potentiated the effect of heparin on P-selectin expression. These in vitro observations suggest that 1) both heparin and its reversal agents affect platelet secretion and aggregation, and 2) heparinase 1 reverses heparin-induced platelet preactivation more effectively than protamine. IMPLICATIONS: This experimental in vitro study demonstrates that heparin and its reversal agents affect platelet secretion and aggregation.

Adult↗

An in-vitro model to study device-induced thrombosis and embolism: evaluation of the efficacy of tirofiban, aspirin, and dipyridamole.

A bovine in-vitro model was developed to investigate device-induced thromboembolism (TE) and its pharmacological intervention, using a stent as a prototype device. Emboli were assessed continuously using a light-scattering microemboli detector (LSMD). Thrombus on the stent was assessed gravimetrically at the end of the experiment. The contribution of the stent as the predominant source of detectable thromboemboli in this model was verified by placing LSMD probes upstream and downstream of the stent. The effectiveness of ethylenedinitrilo-tetraacetic-acid (EDTA) and three anti-thrombogenic agents (aspirin, dipyridamole, and tirofiban) for mitigating device-induced TE was also assessed. The results show that 1) the model has potential to study device-induced TE and the efficacy of possible interventional strategies, 2) the LSMD is capable of continuous, non-invasive, real-time assessment of embolism, 3) the assessment of embolization may constitute an important part of evaluating hemocompatibility, 4) tirofiban is effective in reducing both stent-induced thrombosis and embolism above certain concentrations.

Animals↗

Reduced NFAT1 protein expression in human umbilical cord blood T lymphocytes.

Umbilical cord blood (UCB) stem cells from related and unrelated allogeneic donors have emerged as novel treatment for patients with hematologic malignancies. The incidence and severity of acute graft-versus-host disease (GVHD) after UCB transplantation compares favorably with that observed in recipients of matched unrelated donor allogeneic grafts, but remains a major cause of morbidity and mortality. It has been shown that stimulated lymphocytes from UCB have reduced production of cytokines including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which play a role in GVHD pathophysiology. We investigated the molecular mechanisms underlying this reduced cytokine production by analyzing expression of nuclear factor of activated T cells-1 (NFAT1) in UCB T cells. We detected no constitutive expression of NFAT1 protein in unstimulated UCB T cells compared with adult T cells. Moreover, although NFAT1 expression in UCB T cells was upregulated after prolonged (40 hours) T-cell stimulation, it was only partially upregulated when compared with adult controls. Our observation of minimal NFAT1 expression after stimulation correlated with reduced cytoplasmic IFN-gamma and TNF-alpha production in UCB T cells studied simultaneously. Reduced NFAT1 expression may blunt amplification of donor UCB T-cell alloresponsiveness against recipient antigens, thereby potentially limiting GVHD incidence and severity after allogeneic UCB transplantation.

Adult↗

Fibrinogen fragments and platelet dysfunction in uremia.

BACKGROUND: The uremic state is characterized by subnormal platelet aggregation. Fibrinogen fragments, usually absent in normal human blood, but present in uremic plasma, may play a role in uremic platelet dysfunction. METHODS: To examine this hypothesis, we investigated the availability and function of fibrinogen receptors [glycoprotein (GP) IIb-IIIa] on uremic and normal platelets, as well as the effect of fragments obtained from chymotrypsin digestion of human fibrinogen on normal platelets. The availability of fibrinogen receptors was examined using anti-GP IIb-IIIa antibodies and flow cytometry, whereas receptor function was assessed by the receptor's ability to mediate fibrinogen binding and platelet aggregation. RESULTS: Platelet aggregation and the availability of GP IIb-IIIa were lower in uremic patients when compared with normal controls. Flow cytometric analysis showed that fibrinogen fragments decreased the binding of anti-CD61, an activation-independent anti-GP IIIa monoclonal antibody, to resting normal platelets. These fragments also reduced the binding of PAC-1, an activation-dependent anti-GP IIb-IIIa monoclonal antibody, to adenosine diphosphate (ADP)-activated normal platelets. In addition, the binding of radiolabeled fibrinogen to activated normal platelets and platelet aggregation in response to ADP were both decreased by fibrinogen fragments. CONCLUSIONS: These findings suggest that fibrinogen fragments impair platelet function by occupying fibrinogen receptors prior to cell activation, thus preventing the binding of intact fibrinogen to platelets after subsequent stimulation. These observations also suggest a plausible mechanism by which endogenous fibrinogen fragments present in uremic plasma may contribute to platelet dysfunction.

Adenosine Diphosphate↗

The light-scattering whole blood aggregometer: a novel device for assessment of platelet aggregation in undiluted blood.

OBJECTIVE: A novel whole blood platelet aggregometer has been developed. Based on differential light-scattering principles, the device detects platelet aggregates in undiluted blood. The primary objectives of this report are to introduce the design of this novel device and to evaluate its ability to assess platelet aggregation. DESIGN: In the light-scattering whole blood aggregometer, anticoagulated blood is dispensed into a self-contained sample loop and circulated with the help of a peristaltic pump. Laser light is directed into the circulating blood, and the scattered light signals are converted to electrical signals and analyzed. When platelet aggregates pass through the illuminated region, they produce peak signals, which are detected and quantified; the platelet aggregation profile is the time-dependent development of the total aggregate volume. ASSESSMENT: After the calibration of the light-scattering signals using polystyrene microspheres, platelet aggregation was measured by the light-scattering aggregometer, and the results were compared with those obtained with the conventional turbidometric (based on light transmission) and electrical impedance aggregometers. Scanning electron microscopy was used to confirm the presence of platelet aggregates in the whole blood samples taken from the light-scattering aggregometer. RESULTS: Scanning electron micrographs and light-scattering observations confirmed that the peak signals detected after the addition of platelet aggregating reagents to blood were caused by platelet aggregates. Results of platelet aggregation and its inhibition in blood were similar to those obtained with the impedance whole blood aggregometer. CONCLUSION: The novel light-scattering whole blood aggregometer has been shown to be a valid device to measure platelet aggregation and may be well suited for the assessment of platelet function in research and clinical blood samples.

Electric Impedance↗

Involvement of fibrinogen in protamine-induced pulmonary hypertension.

Protamine reversal of heparin anticoagulation occasionally results in pulmonary hypertension as well as systemic hypotension. To examine the contribution of blood components to this induction of pulmonary hypertension, we developed an isolated rat lung perfusion model and perfused heparinized plasma, heparinized serum, and Hepes (4% bovine serum albumin, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 5 mM glucose, in warm physiological saline) buffer solution with or without fibrinogen. Perfusion with heparinized plasma and Hepes buffer solution with fibrinogen caused pulmonary hypertension; perfusion with heparinized serum or Hepes buffer solution without fibrinogen did not, suggesting that fibrinogen is involved in the induction of pulmonary hypertension. We also labeled protamine with 125I and compared the amounts of protamine accumulating in the lung with different concentrations of fibrinogen. The amount of protamine trapped in the lung increased according to the concentration of fibrinogen. Fibrinogen may accelerate the reaction between pulmonary endothelial cells and protamine or protamine-heparin complexes. In the mechanism of protamine-induced pulmonary hypertension, fibrinogen, as well as heparin and protamine, may be an essential component.

Animals↗

In vitro investigation of the St. Jude Medical Isoflow centrifugal pump: flow visualization and hemolysis studies.

Centrifugal blood pumps have become valuable therapeutic tools for cardiopulmonary bypass surgery. In addition, surgeons have used them as temporary ventricular assist devices, and this type of pump is also being developed for use as a permanent assist device and total artificial heart. However, centrifugal pumps create flow patterns that are significantly different from those the blood experiences physiologically. The St. Jude Medical Isoflow centrifugal pump has been used clinically during cardiopulmonary bypass surgery, yet no experimental results have been reported that describe the flow patterns within this pump or that quantify the hemolysis generated over a range of operating conditions. The purpose of this study was to investigate the flow patterns and hemolysis during 4 operating conditions. The experimental operating conditions included the design condition (6 L/min, 2,500 rpm, 350 mm Hg), a high flow condition (10 L/min, 2,500 rpm, 330 mm Hg), a low flow condition (2 L/min, 2,500 rpm, 370 mm Hg), and a near surge condition (2 L/min, 3,000 rpm, 550 mm Hg). The flow visualization results demonstrated that the flow within the impeller was well aligned with the impeller blades except near the inlet at the high flow condition. In contrast, the flow through the outlet was well aligned at the high flow condition while there was evidence of particle impact at the design condition, and the flow was disturbed at the low flow and near surge conditions. The indices of hemolysis (IH) for the 3 operating conditions at 2,500 rpm were 0.0082 +/- 0.0026 (mean +/- SD) for the design condition, 0.0035 +/- 0.0014 for the high flow condition, and 0.0326 +/- 0.0050 for the low flow condition. The indices for high and low flow were significantly different from that for the design condition (p < 0.05). The IH for the near surge condition (0.0748 +/- 0.0039) was significantly higher than that for all other conditions (p < 0.05). In addition to describing the flow patterns within the Isoflow, this study independently validated St. Jude Medical's reported IH at the design condition and showed how that IH significantly changed based on operating conditions.

Blood Flow Velocity↗

Pulsatile augmentation device for extracorporeal circulation.

A device has been designed, constructed, and tested to provide pulsatile pressure/flow to a standard extracorporeal bypass circuit. The pulsatile augmentation device is pneumatically driven similar to an artificial heart ventricle except that there are no valves. It is constructed of polyurethane by vacuum forming and high frequency welding. Drivers used are a modified Arrow-Kontron intraaortic balloon pump or the Utah artificial heart driver. In vitro testing with fresh bovine blood demonstrated acceptable blood compatibility and hemodynamic function. In vivo testing for 4 h in a right and left heart extracorporeal bypass circuit showed good pulse augmentation in pulmonary and systemic bypass circuits. The device shows promise for adding pulse to standard cardiopulmonary bypass and to extracorporeal right heart circulatory assist circuits.

Animals↗

Acute phase vascular endothelial injury: a comparison of temporary arterial occlusion using an endovascular occlusive balloon catheter versus a temporary aneurysm clip in a pig model.

We compared the degree of acute endothelial injury after temporary vessel occlusion using two different occlusion modalities--external clipping and endovascular balloon occlusion. The common carotid and subclavian arteries in eight weanling pigs were temporarily occluded with either a 5 Fr occlusion balloon catheter or a temporary microvascular clip for 0 (control), 5, 10, and 30 minutes. Two animals (eight vessels; four clip and four balloon occluded) were used at each time interval. Segments of each experimental vessel were harvested and analyzed by scanning electron microscopy. Each vessel specimen was graded on the following scale: Grade 1 showed no evidence of injury; Grade 2 showed minimal evidence of endothelial cell injury; Grade 3 showed moderate evidence of endothelial cell injury; Grade 4 showed marked evidence of endothelial cell injury; Grade 5 showed severe endothelial and subendothelial injury. Control vessels showed no evidence of injury. Grade 2 injuries were seen in both clip- and balloon-occluded vessels at 5 minutes. At 10 minutes, focal Grade 2 and 3 injuries were appreciated in the clip group, with diffuse Grade 2 and 3 injuries in the balloon group. After the 30-minute occlusion, the balloon group showed Grade 2, 3, and 4 injuries, whereas the clip group showed entirely Grade 2 injuries. The degree of injury with either occlusion modality was equivalent and worsened with time. However, clip-occluded vessels displayed injury that was confined to an area closely adjacent to the clip site, whereas balloon-occluded vessels demonstrated a more widespread injury centered around the balloon site.

Animals↗

111Indium labeling of microorganisms to facilitate the investigation of bacterial adhesion.

The ability of bacteria to adhere to polymeric interfaces has attracted considerable attention in recent years. Metabolic labeling of microorganisms with 35S-methionine or other beta-emitters is commonly utilized for quantification of bacterial adhesion to biopolymers. Since the use of these isotopes is cumbersome, the possibility of labeling the microorganisms with 111Indium, a strong gamma-emitter, was explored. This report demonstrates that bacteria can be easily labeled with 111Indium. Staphylococcus aureus, Staphylococcus epidermiids, and Pseudomonas aeruginosa were labeled with either 111Indium-oxine or 35S-methionine; and labeling efficiency, retention of incorporated labels, and growth kinetics of labeled bacteria were compared under identical experimental conditions. Bacteria labeled with 111In-oxine incorporated approximately 90% of radioactivity within 10 min, whereas 35S-methionine incorporation required many hours of incubation. Both the incorporated isotopes were gradually released by rapidly growing bacteria into the suspension medium. Of the total incorporated labels, approximately 20% 111In and 15% 35S were released in the surrounding medium every 24 h. No release of incorporated labels occurred when cells were fixed with 2.5% buffered glutaraldehyde. Growth kinetics and scanning or transmission electron microscopic analysis showed no detectable differences among control (nonlabeled), 111In-, or 35S-labeled bacteria. Labeling of bacteria with 111In-oxine does not interfere with bacterial adherence. These observations suggest that 111In incorporation provides a simple and rapid method of labeling of microorganisms. Compared to currently available techniques, the use of 111In-labeled bacteria will facilitate the quantitation of adherent bacteria to interfaces.

Bacteria↗

Interaction of heparin with polyallylamine-immobilized surfaces.

A new method to bind ionically and remove heparin from solution and dilute serum is described. Utilizing cellulose diacetate (CA) as the polymer substrate, a cationic polymer chain--poly(allylamine)-PALA--was immobilized directly onto the CA surface and onto the surface using poly(ethylene glycol) (PEG) spacer groups. The ionic interaction between the anionic heparin molecule and the cationic PALA polymer is specific and effective to remove heparin from the bulk solution. The binding properties of heparin onto the PALA and PEG-PALA surfaces were examined. The effects of PEG spacers on heparin binding onto the PALA-immobilized surface were investigated by varying the Mw of PEG spacers. PALA (Mw 8500)-immobilized surfaces exhibited enhanced heparin binding. The maximum heparin binding was observed in the region of PEG Mw 2000-4000. For the high-molecular-weight PALA (Mw 50,000)-immobilized surfaces, heparin binding was independent of the molecular weight of PEG. PEG spacers were also evaluated for their ability to prevent or decrease protein (albumin) adsorption. It was observed that at high albumin concentrations, the adsorption of proteins decreased with increasing chain length of PEG, up to Mw 3400. These observations suggest that low-molecular-weight PALA (Mw 8500)-immobilized CA surfaces with PEG spacers (Mw 3400) may provide increased heparin binding capacity and decreased protein adsorption.

Adsorption↗

Alprostadil: an effective antiplatelet agent for calves.

Aspirin and other nonsteroidal, antiinflammatory drugs inhibit human platelets, but their effect as an antiplatelet agent on bovine platelets is not certain. Since calves are used for cardiovascular implant research, need exists for an effective antiplatelet agent for this animal model. After screening a number of potential antiplatelet drugs for calves, Alprostadil (prostaglandin E1) appeared to be the most promising. Alprostadil was administered (intravenous continuous drip) to 8 calves. The concentration of the drug administered was gradually increased until 50% inhibition of platelet aggregation was obtained. Platelet function, blood pressure, body temperature, and hematologic parameters were closely monitored. For in vitro evaluation, Alprostadil was added to human or bovine blood, and the platelet aggregation and cyclic adenosine monophosphate levels were measured. Alprostadil inhibited both bovine and human platelets, although bovine platelets were relatively more responsive to this drug. At an infusion rate of approximately 0.20 micrograms/kg/min in vivo, Alprostadil showed 50% inhibition of platelet aggregation with slightly decreased blood pressure (7 +/- 6 mm Hg) but no adverse effects. Complete reversal of in vivo platelet inhibition was noted within 24 h after cessation of drug administration. This short half-life and the lack of significant adverse effects make Alprostadil an attractive antiplatelet agent for calves with cardiovascular implants.

Alprostadil↗

In vitro investigation of thrombogenesis in rotary blood pumps.

Thrombus formation at sealing and stagnation areas remains a major problem in the development of rotary blood pumps. Until now, the complex phenomena could only be studied in vivo. In this study, an in vitro mock circulation previously used for hemolysis studies was adapted for thrombosis evaluation. Blood was collected in the slaughterhouse with strict avoidance of air contact and was heparinized (1.5 U heparin/ml blood; activated coagulation time [ACT]: initially, 140-180 s; after collection, 400-600 s). During the test, the ACT decreased gradually. The tests were stopped after 90 to 180 min at an ACT of 1.5 times the initial value. Thrombus formation was observed at the same locations as observed in left-heart assist devices (sealing area, connecting bolts, and stagnant water areas at connectors). The thrombi were similar in shape, color, and histology to those found after 2 to 4 days in vivo. This test provides a valuable tool for evaluating thrombus formation in prototypes and screening tests of different rotary pump designs.

Animals↗

The influence of harvesting technique on endothelial preservation in saphenous veins.

To study optimal conditions of preparation of saphenous veins as coronary artery bypass grafts, segments of saphenous veins were obtained from 29 consecutive patients undergoing coronary artery bypass grafting. The saphenous vein segments were divided into three groups. In Group I, 10 saphenous vein segments were harvested using a "no-touch" technique without any other preparation aids. In Group II, 10 saphenous vein segments were removed while distended at 70-120 mm Hg with a balanced pH electrolyte solution at 37 degrees C. In Group III, consisting of 10 saphenous vein segments, nitroglycerin (1 microgram/ml) was added to the distending solution used in Group II. Samples of saphenous vein were assessed in a blind study using light and scanning electron microscopy to estimate endothelial cell preservation by the three harvest techniques. Saphenous veins receiving only a no-touch dissection technique without distention solution (Group I) revealed significantly better endothelial preservation (P less than 0.005). The administration of distention solution alone, or with nitroglycerin, to saphenous veins in situ using our operative technique during harvest does not appear to protect endothelial-integrity and may be harmful.

Dilatation↗

The role of plasma proteins in formation of obstructive protamine complexes.

Formation of complexes between heparin and protamine (in saline), or heparin, plasma proteins, and protamine (in plasma) was assessed by measurements of light transmission through different test solutions. To examine the formation of these complexes, 125I-labeled protamine was used. Addition of 125I-protamine to plasma or blood resulted in the sedimentation of 125I-protamine in the form of insoluble complexes. This complex formation was not affected by the presence of heparin, suggesting that protamine-plasma protein interaction may be primarily responsible for precipitation of 125I-protamine. To assess the capability of these complexes to obstruct the pulmonary circulation, an in vitro experimental model was developed. Citrated serum, plasma, blood, or saline were allowed to flow through a glass bead column with the help of a peristaltic pump. A pressure transducer positioned before the column allowed pressure measurements at a constant flow rate during the experiment. Mixing of protamine with plasma or blood prior to their passage through the glass bead column resulted in a significant increase in pressure suggesting that the column was being clogged with insoluble complexes. The increase in pressure occurred both in the presence and absence of heparin in plasma or blood. Under identical experimental conditions, the increase in pressure was insignificant when protamine was added to saline or serum regardless of whether heparin was present or absent. This was further confirmed by the use of 125I-protamine. These observations suggest that protamine forms insoluble complexes with certain plasma proteins. Based on these observations, it is hypothesized that following intravenous administration, protamine immediately forms complexes in circulating blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Blood compatibility of PEO grafted polyurethane and HEMA/styrene block copolymer surfaces.

HEMA/styrene (HEMA/STY) block copolymers and poly(ethylene oxide) 4,000 M.W. (PEO4K) grafted Biomer (B-PEO4K) surfaces have been synthesized, characterized, and evaluated as blood-contacting materials. These surfaces have demonstrated improved blood compatibility, compared to Biomer, in in vitro and ex vivo experiments. Biomer vascular grafts (6 mm I.D. 7 cm in length) were fabricated by a dip coating process. The luminal surface was modified either with PEO grafting, HEMA/STY coating, or Biomer coating (control). These surface-modified grafts were implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. Surface protein layer thickness was measured by transmission electron microscopy (TEM). B-PEO4K and Biomer showed thick multilayers of adsorbed proteins (1000-2000 A) after 3 weeks to 1 month implantation. In contrast, HEMA/STY only showed a monolayer protein thickness (less than 200 A), even after 3 months. Visualization of adsorbed plasma proteins (albumin, IgG, and fibrinogen) was performed with scanning electron microscopy (SEM)/TEM using an immunogold double antibody technique. The pattern of protein distribution showed high concentrations of fibrinogen and IgG, and less albumin adsorbed onto Biomer and B-PEO4K. In contrast, HEMA/STY showed a patchy protein distribution pattern with high concentrations of albumin and IgG, and relatively less fibrinogen. Adsorbed monolayer patterns showed improved compatibility over multilayered proteins. The Biomer and B-PEO4K grafts occluded within 1 month, while HEMA/STY grafts were patent for over 3 months. The thin and stable adsorbed protein layer on HEMA/STY surfaces may be associated with the microdomain structures of the surface, and will play an important role in long-term in vivo blood compatibility. This manuscript will evaluate the long-term in vivo performance of these polymers, analyze the extent of protein adsorption onto the surfaces, and correlate protein layer thickness to the thrombogenicity of the polymer surfaces.

Adsorption↗

Loss of anticoagulant effect of heparin during circulation of human blood in vitro.

Device-induced thrombogenesis was studied in an in vitro model using human blood circulated through an artificial ventricle. A new constant pressure filtration technique was used to detect circulating microemboli, the activated partial thromboplastin time (APTT) test was used to monitor the blood for the presence of anticoagulant activity of heparin, and hemolysis was quantified by measuring the plasma free hemoglobin level. Circulation of blood through a 20-ml stroke volume pneumatically driven ventricle for 6-9 h resulted in a significant reduction of APTT, indicating the loss of the anticoagulant effect of heparin. Microemboli concentration was minimal until the APTT decreased below 125 s, at which time the microemboli concentration increased rapidly. This was presumed to be due to the formation of thrombi following a decrease in heparin activity. A significant increase in hemolysis was also noted when blood was pumped. None of these changes was noted in the nonpumped control blood. Spontaneous loss of heparin activity in blood circulated by a pneumatically driven pump may have clinical implications and may help understanding of the problems associated with device-induced thrombogenesis.

Adult↗