Axial Dependence of Collagen–Induced Thrombus Formation in Flowing Non-Anticoagulated Human Blood

1995 ◽  
Vol 73 (01) ◽  
pp. 126-131 ◽  
Author(s):  
Helge E Roald ◽  
Kjell S Sakariassen
Keyword(s):  
Blood Flow ◽  
Platelet Adhesion ◽  
Potent Inhibitor ◽  
Thrombus Formation ◽  
Collagen Fibrils ◽  
Downstream Location ◽  
Perfusion Chamber ◽  
Platelet Concentration ◽  
Platelet Thrombus ◽  
Platelet Thrombi

SummaryPlatelet thrombus formation on collagen fibrils is most pronounced at the upstream end of the surface, and it gradually decreases along the axis in parallel with the direction of the blood flow. This phenomenon, known as axial dependent platelet thrombus formation, is explained by the balance of the platelet supply to the surface and the consumption of platelets by growing thrombi.In the present study we have affected this balance by (A) inhibiting the growth of platelet thrombi by aspirin (ASA) or clopidogrel, and thus increasing the platelet concentration at the surface, and by (B) utilising blood from cigarette smokers, who have enhanced thrombus formation immediately after smoking, and thus decreasing the platelet concentration at the surface. Thrombus formation in non-anticoagulated blood was triggered by collagen fibrils positioned in a parallel-plate perfusion chamber at a wall shear rate of 2600 s_1which is characteristic for moderately stenosed arteries. Morphometrical assessment of thrombus formation was performed at axial positions of 1 and 13 mm downstream to the blood flow inlet at the collagen surface.Platelet-collagen adhesion and thrombus volume in blood from nonsmokers were decreased at the downstream location by 39% (p ≤0.0001) and by 60% (p ≤0.0001), respectively. However, increasing the platelet concentration at the surface by partially inhibiting the thrombus growth by ASA or clopidogrel, reduced substantially the axial decrease in platelet adhesion and thrombus volume. The largest reduction was observed with clopidogrel which was also the strongest inhibitor of the thrombus growth at both axial positions investigated. The corresponding figures in blood from smokers with enhanced thrombus formation were 38% (p ≤0.0001) and 72% (p ≤0.001). Thus, enhanced upstream platelet consumption increased the axial reduction in thrombus volume, but not in platelet adhesion.These data substantiate the view that the “axial dependence phenomenon” may be explained by the balance between the platelet supply to the surface and the consumption of platelets by growing thrombi. It is also apparent that clopidogrel is a more potent inhibitor of platelet thrombus formation than ASA.

scholarly journals The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo

2021 ◽  
Vol 10 (22) ◽  
pp. 5349
Author(s):  
Lydie Crescence ◽  
Markus Kramberg ◽  
Martine Baumann ◽  
Markus Rey ◽  
Sebastien Roux ◽  
...  
Keyword(s):  
Blood Flow ◽  
Guinea Pigs ◽  
Thrombus Formation ◽  
P2y12 Receptor ◽  
Early Application ◽  
Acute Thrombosis ◽  
Thrombosis Model ◽  
Platelet Thrombus ◽  
Platelet Thrombi

Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl3-induced thrombosis in rats. Here, we report the anti-thrombotic effect of selatogrel after subcutaneous applications in guinea pigs and mice. Selatogrel inhibited platelet function only 10 min after subcutaneous application in mice. In addition, in a modified Folts thrombosis model in guinea pigs, selatogrel prevented a decrease in blood-flow, indicative of the inhibition of ongoing thrombosis, approximately 10 min after subcutaneous injection. Selatogrel fully normalised blood flow; therefore, we speculate that it may not only prevent, but also dissolve, platelet thrombi. Thrombus dissolution was investigated using real-time intravital microscopy in mice. The infusion of selatogrel during ongoing platelet thrombus formation stopped growth and induced the dissolution of the preformed platelet thrombus. In addition, platelet-rich thrombi were given 30 min to consolidate in vivo. The infusion of selatogrel dissolved the preformed and consolidated platelet thrombi. Dissolution was limited to the disintegration of the occluding part of the platelet thrombi, leaving small mural platelet aggregates to seal the blood vessel. Therefore, our experiments uncovered a novel advantage of selatogrel: the dissolution of pre-formed thrombi without the disintegration of haemostatic seals, suggesting a bipartite benefit of the early application of selatogrel in patients with acute thrombosis.

Enzymatic Removal of ADP from Plasma: Unaltered Platelet Adhesion but Reduced Aggregation on Subendothelium and Collagen Fibrils

1976 ◽  
Vol 35 (02) ◽  
pp. 334-341 ◽  
Author(s):  
Th B. Tschopp ◽  
H.R Baumgartner
Keyword(s):  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Rabbit Aorta ◽  
Creatine Phosphate ◽  
Collagen Fibrils ◽  
Arterial Blood Flow ◽  
Subsequent Formation ◽  
Arterial Blood ◽  
Enzyme Combination ◽  
Platelet Thrombus

SummarySubendothelium of rabbit aorta and fibrillar collagen were exposed to citrated human or rabbit blood which was circulated through a perfusion chamber under flow conditions similar to those found in arteries. The resulting platelet adhesion and subsequent formation of platelet micro thrombi on the exposed surfaces were measured in 0.8 μm thick sections by a morphometry technique using light microscopy.Removal of plasma ADP by the substrate-enzyme combination CP-CPK (creatine phosphate-creatine phosphokinase; 3 mM and 90 U/ml blood) did not affect the initial attachment and spreading of platelets on subendothelium, whereas platelet thrombus formation was strongly inhibited. On free collagen fibrils CP-CPK was much less inhibitory on platelet thrombus formation but platelet adhesion again was not affected. It is concluded that platelet aggregation induced by thrombogenic surfaces in the presence of arterial blood flow is at least partially governed by ADP released from adhering platelets. Platelet adhesion to the examined surfaces, however, does not seem to be mediated by plasma ADP.

The Effect of Platelet PlA Polymorphism on Experimental Thrombus Formation in Man Depends on Blood Flow and Thrombogenic Substrate

2001 ◽  
Vol 85 (06) ◽  
pp. 1097-1103 ◽  
Author(s):  
Kjell Sakariassen ◽  
Hélène Grandjean ◽  
Claire Thalamas ◽  
Bernard Boneu ◽  
Pierre Sié ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Flow Properties ◽  
Shear Rates ◽  
Perfusion Chamber ◽  
Platelet Receptor ◽  
Platelet Deposition ◽  
Coronary Syndromes ◽  
Platelet Thrombus

SummaryA number of studies have reported conflicting data on the association of the PlA1/PlA2 polymorphism of the GPIIIa gene and coronary syndromes. We have investigated the effect of this polymorphism on experimental platelet thrombus formation in man. Forty healthy male volunteers were genotyped for the PlA1/PlA2 polymorphism. Thrombus formation was induced ex vivo by exposing a tissue factor (TF) or a collagencoated coverslip in a parallel plate perfusion chamber to native blood for 2 and 4 min. The shear rates at these surfaces were 650 and 2,600 s–1. Platelet and fibrin deposition was quantified by immunoenzymatic methods. The frequencies of PlA1/PlA1 and PlA1/PlA2 genotypes were 52.5% and 47.5%, respectively. Ex vivo deposition of fibrin on TF was not affected by the PlA1/PlA2 polymorphism. However, the ex vivo platelet deposition at 650 s–1 was higher in blood from PlA1/PlA1 individuals than in PlA1/PlA2 individuals (P = 0.008 at 4 min). On collagen, neither fibrin nor platelet deposition was significantly affected by the PlA1/PlA2 polymorphism. Platelet thrombus formation is significantly influenced by genetic variations in the GPIIIa platelet receptor. This effect depends on the blood flow properties and the nature of the thrombogenic stimulus.

Platelet Interaction with Collagen Fibrils in Flowing Blood

1977 ◽  
Vol 37 (01) ◽  
pp. 017-028 ◽  
Author(s):  
Hans R. Baumgartner ◽  
Thomas B. Tschopp ◽  
Harvey J. Weiss
Keyword(s):  
Thrombus Formation ◽  
Collagen Fibrils ◽  
Fibrillar Collagen ◽  
Platelet Surface ◽  
Normal Adhesion ◽  
Platelet Thrombus ◽  
Flowing Blood ◽  
Platelet Thrombi ◽  
Storage Pool Disease ◽  
And Control

SummaryAnticoagulated whole blood from patients and control subjects was circulated through an annular perfusion chamber in which the fibrillar collagen of α chymotrypsin-digested subendothelium and intact subendothelium were exposed. The blood flow conditions corresponded to those in arteries (830 sec–1 wall shear rate). Platelet surface interaction was measured mor-phometrically.Decreased adhesion to fibrillar collagen associated with normal spreading and normal adhesion-induced formation of platelet thrombi was found with blood of patients with von Willebrand’s disease and the Bernard Soulier Syndrome, indicating a defect in the initial attachment reaction of platelets with collagen. Platelets of patients with thrombasthenia did normally adhere to the collagen fibrils and also lost their subcellular organelles during this reaction, but they totally failed to adhere to each other. In storage pool disease platelet thrombus formation was consistently inhibited whereas adhesion and spreading was inhibited in some patients and normal in others. In contrast adhesion was always normal after ingestion of aspirin which consistently caused a marked inhibition of platelet thrombi. These findings correspond – in essence – to those previously described on intact subendothelium. However, the observed defects are more pronounced on the fibrillar collagen than on intact subendothelium.

Collagen Coated Gelatine Tubes for the Investigation of Platelet Adhesion and Subsequent Platelet Aggregation Under Controlled flow Conditions

1975 ◽  
Author(s):  
R. Muggli ◽  
H. R. Baumgartner
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Surface Coverage ◽  
Neutral Salt ◽  
Flow Conditions ◽  
Platelet Surface ◽  
Perfusion Chamber ◽  
Artificial Surface ◽  
Platelet Thrombi ◽  
Controlled Flow

Aggregometer studies do not discriminate between platelet adhesion and platelet aggregation. Therefore, we prepared a homogenous collagen surface which could be exposed to whole blood in a perfusion chamber under controlled flow conditions.Artificial “vessel” segments were prepared by dipping glass rods into 20% gelatine and, after air-drying, cross-linking the gelatine in 2.5% glutaraldehyde. Segments of 1 cm length were then drawn on the rod of the perfusion chamber and coated with 300 μl of neutral salt soluble collagen (2.2 mg/ml). Surface coverage with collagen was virtually complete (96%–100%).Uncoated or collagen-coated gelatine segments were exposed to citrated rabbit blood for periods up to 40 min. Platelet-surface interaction was evaluated morphometrically. On uncoated segments surface coverage with platelets amounted to 31% and 50% after 10 min and 40 min (the corresponding ratios of contact/spread platelets were 2.6 and 1.5). Only 0.1% thrombi were found. On collagen-coated segments surface coverage with platelets amounted to 57% and 83% after 10 min and 40 min (the corresponding ratios of contact/ spread platelets were 0.1 and 0.0); platelet thrombi were found on 33% and 42% of the surface after 10 min and 40 min.Platelet adhesion and subsequent aggregation on the collagen-coated artificial surface is similar to that observed on α-chymotrypsin digested subendothelium. The results suggest that fibrillar collagen triggers rapid spreading on a surface, a reaction which is closely associated with the formation of platelet thrombi. The latter phenomenon is thought to be caused by the release of aggregating agents from the spreading platelets.

The Influence of Shear Rate and Red Cell Concentration on Platelet Adhesion and Thrombus Formation in Human Blood

1979 ◽  
Author(s):  
V.T. Turitto ◽  
H.J. Weiss ◽  
H. R. Baumgartner
Keyword(s):  
Platelet Adhesion ◽  
Cell Concentration ◽  
Thrombus Formation ◽  
Size Variation ◽  
Arrival Rate ◽  
Red Cells ◽  
Steady Increase ◽  
Shear Rates ◽  
Perfusion Chamber ◽  
Diffusion Controlled

The interaction of platelets with subendothelium requires the transport of platelets to the vicinity of the surface, as well as the basic cell-surface reaction. Exposure of subendothelium to human citrated blood flowing in an annular perfusion chamber at wall shear rates (α) of 50-10,000 sec-1 indicates that a diffusion controlled (DC) transport regime exists below 650 sec- l in which platelet adhesion (C+S) was strongly dependent on α, and thrombus formation (T) was absent . Above 800 sec-1, an apparently reaction controlled (RC) regime predominates in which C+S was independent of α, and T increased in both extent and size. Variation of hematocrit (H) from 0-701. in the RC regime (2600 sec-1) lead to a steady increase of C+S with H, and an exponential increase in T as H increased from 30 to 70%. In the DC regime (200 sec-1) virtually no thrombi were formed for all H, and C+S increased as H increased to 40%; above 40%, C+S became independent of H. Thus, at low α (venous), the platelet-subendothelial reaction is controlled primarily by the arrival rate of platelets at the surface and the red cells increase this transport for H up to 40%. At high α (microcirculatory) , the platelet-vessel wall reactivity becomes more dominant and red cells increase the ability of platelets to attach to the subendothelium.

Continuous mathematical model of platelet thrombus formation in blood flow

2012 ◽  
Vol 27 (2) ◽  
Author(s):  
A. Tokarev ◽  
I. Sirakov ◽  
G. Panasenko ◽  
V. Volpert ◽  
E. Shnol ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Blood Flow ◽  
Thrombus Formation ◽  
Platelet Thrombus

scholarly journals Susceptibility to Thrombosis in Normal Young, Aging, Cortisone-treated, Heparinized and X-irradiated Hamsters as Tested by Topical Application of Thrombin

Blood ◽  
1955 ◽  
Vol 10 (8) ◽  
pp. 831-840 ◽  
Author(s):  
HERBERT J. BERMAN ◽  
GEORGE P. FULTON ◽  
BRENTON H. LUTZ ◽  
DAVID L. PIERCE
Keyword(s):  
Thrombus Formation ◽  
Blood Platelets ◽  
Cheek Pouch ◽  
Whole Body ◽  
Minimum Concentration ◽  
In Vivo Test ◽  
Platelet Concentration ◽  
X Irradiation ◽  
Platelet Thrombus

Abstract 1. Thrombin applied topically to the everted cheek pouch of the hamster produced platelet and not red thrombi in exposed, uninjured blood vessels with circulating blood. Red thrombi were produced in stagnant blood. Thrombus formation occurred in the venules for the most part and seldom in arterioles or capillaries. 2. An in vivo test for platelet thrombus susceptibility, based on the thrombin reaction and the resistance of the hamster to thrombosis, has been described. 3. Thrombus susceptibility, measured by the thrombin test, increased with age and during cortisone treatment, and decreased after heparin injection and following large doses of whole body x-irradiation. 4. The thrombin susceptibility test could be correlated with the platelet count in x-irradiated hamsters, showing a relatively critical minimum concentration of blood platelets (100,000/cu.mm.) required for platelet thrombosis. 5. The relationship of platelet concentration to platelet thrombus formation and predisposition to hemorrhage has been discussed.

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