THROMBOSIS Printed
RESEARCH in the
II, Suppl. Pergamon
States
United
SECTION
RHEOLOGICAL
OBSERVATION
ON
Akira Okaira
THE
vol. 8, Press,
1976 Inc.
VII
DEFORMATION
OF
THROMBUS
Kikuchi
Memorial Tokyo Hitachi Tokyo, Jaran
Hospital,
Al 3STRACT The intravascular portion of hemostatic thrombus grows, deforms and fractures repeatedly even after the completion The faster the blood flow, the more active of hemostasis. the thrombus growth as well as the deformation and fracture. The growth begins in height or width of thrombus and follows in length. The surface layer of thrombus itself flows downstream irregularly in figure and in motion. The surface layer flow and the partial deformation of thrombus such as dislocation and rotation contribute the thrombus growth in length. The blood flow is concluded to have an inconsistent effect on thrombus development: one is constructive supplying platelets to be adhered or cohered, the faster the more; the other is destructive offering shear stresses on the surface and presumably’ normal pressures to the whole body of thrombus, also the faster the higher. INTRODUCTION The mechanical injury to a microvessel causes sometime no bleeding because of the endothel adhesion (1, 2, 3). In a case without bleeding, the platelets are caused to adhere to the adhered endothels surrounding the wound and form a thrombus just similar as the hemostatic plug. In both cases with or without bleeding, the intravascular portion of thrombus grows, deforms and fractures repeatedly even after the completion of hemostasis (4, 5). The changes in volume and shape of thrombus can modify the blood flow which must, on the contrary, influence the development of thrombus. On the relation between the blood flow and the thrombus development, rheological observations were atempted and some moving pictures were made. 345
KIKUCHI
MATERIAL
Suppl.
II
AND METHODS
Mesenteric microvessels, under eighty micra in the inner diameter, of a rabbit which was anesthetized with Nembutal were micro-punctured with a microscopic knife mounted on a micromanipulator (4). A Nikon microscope and Bolex 16 mm camera was used. Micropuncturing was done by giving a tiny pore with a sharp knife so that there might occur least disarrangement of vessel geometry and minimum disturbance in lamenar flow.
RESULTS The bleeding, when it occurred, stopped within sixty seconds without rebleeding. Micropuncturing on the center line of a vessel, formed a thrombus into a tadpole-like shape, and by a marginal injury a conical thrombus was obtained. The tadpole-like shape corresponds to the plain view of thrombus and the conical one corresponds to the side view. Both shapes of thrombus grew, deformed and fractured repeatedly for some time during while they became to be streamlined step by step and finally kept The faster the flow speed in appearance prior to this shape unchanged. the longer the duration of deforming (from several minutes in a injury, small venule to over-thirty minutes in an arteriole with high flow rate). In arterioles the detached fragment of thrombus caused frequently embolization with a temporary pause of blood flow which was recovered in several seconds owing to the plustic deformation of embolus advancing peripherally. Except such pauses, the arteriolar thrombosis per se never caused an interruption of the blood flow at the site of injury, probably because an arteriole has sufficient branching to drive the emboli peripherally. The tadpole-like shaped thrombus began in a round shape surrounding the wound ( Fig. la ), grew at first in width, narrowing the blood flow on both sides and then became slender by a slight deformation ( Fig. lb ) simultaneously showing a tail which was trailing frequently and sometimes torn downstream. The growth in width and the deformation was repeatedly seen in a vessel with faster flow. Such repetitions made the thrombus streamlined step by step. On the boundary of thrombus there was observed a thin flow layer of thrombus itself, especially obviously from the shoulder to the tail. The surface flow layer of thrombus was active and rather irregular in thickness and in movement in a rappid flow and less active and irregular in a gentle laminar flow. The conical thrombus began in a cone shape based on the injured side of vessel, with a rather steeper incline upstream and a more gentle slope It grew at first in height until the tip of cone nearly touched downstream. to the vessel wall at the opposite side of injury ( Fig. 2a ), then the top or its vicinity displaced a little downstream becoming lower in height ( Fig. 2b 1, This made the ascending incline concave slightly. Continuous cohesion of platelets turned the ascending incline from concave to convex and moreover
Suppl.
THROMEWS
II
367
DEFORMATION
I _.
The outlines
_.._ ._D-. structures .
Fig. A tadpole-like shaped from 16 mm film.
thrombus
1. in a venule.
a:
About seven seconds after injury. figure at the lower hand of venule of microscopic knife.
b:
About twenty is occurring.
seconds
afterwards.
Reprints
The vague is a shadow The deformation
of
o_- _____-
366
Suppl.
KIKUCHI
Fig.
II
2
A conical thrombus Reprints arteriole. 16 mm film.
in an from
The blood runs from the left hand to the right. The dark field at the left side of picture is extravasated blood.
a:
Growth
in height.
b:
Displacement of the top portion. The lower right region by the thrombus is free from blood flow.
c:
“A mountain with a Several erysaddle”. throcytes seen in the lower right region by the thrombus are in circular motion (eddies),
d:
Fracture is beginning. The arrow indicates a crack.
( Published by kind permission of the Editor and Publisher of the Journal of Japanese Society of Internal Medicine 1
Suppl.
II
THROMBUS
369
DEFORMATION
constructed here another top, resulted in a shape, as a whole, of “a mounway, when the stenosis, shorter tain with a saddle” ( Fig. 2c 1. In similar or longer in length, had been developed as a result of thrombus growth, there occurred a partial deformation in thrombus, *mainly in dislocation, sometime in rotation and rarely in landslide like collaps at the rear side of Thus the thrombus gained its length, and it was the same as the thrombus. narrowed path way of blood. The fracture of thrombus occurred most frequently at the time when there had developed a narrow channel commonly along the vascular wall at the opposite side of injury, or rarely a little apart from the wall halfway winding to penetrate through the thrombus. The fracture was whole and ductile in most cases, beginning gently as a rule in a crack on the ascending incline ( Fig. 2d ) but rarely occurring suddenly just like a brittle fracture, and left the thrombus stump at the site of injury. In case of brittle-like fracture, the thrombus stump showed apparent elasticity at the moment of fracture. After the fracture, the platelets still continuously cohered to the thrombus stump forming a conical shape again and the events from the growth in height to fracture occurred repeatedly, the faster the blood flow, the more repeatedly. The surface layer flow of thrombus, above described, was observed also along the conical surface. However, it was hardly recognizable in the stenotic segment of arteriole because of its too rappid movement. In arterioles it was first visible in the post-stenotic lumen where the surface layer flow was slowing down in speed and becoming to cease to move along the down slope of the cone. In arteriols, small deformations such as dislocation or rotation were more contributable to the thrombus growth than the surface layer flow.
Fig. A thrombus in a venule from 16 mm film. a:
About ten seconds injury.
3
with relative after
b:
rappid
flow.
About twenty afterwards.
Reprints
seconds
‘r70
KIKIJCHI
Suppl.
II
The surface layer flow of thrombus was most apparently observed on In such a case, the deformation a thrombus in a venule with high flow rate. rate is adequate to follow and the vessel lumen is flat and thin in depth so that the detailed figures are continuously observable without frequent reFig. 3-5, the reprints from 16 mm adjustments of the microscopic focus. film, show a venular thrombus resulted from a crossing injury by which the blood flow is concentrated into the upper side of vessel, A slender pore across the center line of vessel is surrounded by the adhered endothels seen oval in Fig. 3b. Fig. 3a is a picture about ten seconds after the ) of wound injury. Platelets have gathered at the right side ( downstream The lower in close contact with the upper half of the endothel adhesion.
Fig.
4
The surface layer flow of thrombus in another higher magnification at the same point as Fig.
series 3.
under
THROMEUS
Fig.
5
311
DEFORMATION
half at the right hand of wound is empty, namely, a dead space where eddies are frequently seen in case of very high speed of flow. About twenty seconds afterwards ( Fig. 3b ), the thrombus gained its length and volume. By these two pictures alone, the platelets seemed to have accumulated to the rear side of thrombus. However, in fact, the growth in length was caused from the surface layer flows. Fig. 4 indicates that at least each surface of such a portion which is protruding into the flow lines, corresponds to the surface layer flow. Along the flow line, the surface layer flow runs downstream and rotates around the promontery at the rear side of thrombus hanging into the dead space as an icicle seen in Fig. 4a-b. Thus, the surface layer flows come to standstill in the dead space which is variable in shape and scale according to the blood flow which is also influenced by the thrombus development. Under high power field the surface layer flow of thrombus is visible first just downstream at the concentrated segment of blood flow as a mass of platelets irregular in shape. Fig. 5 is composed of selected reprints from 16 mm film
in a Series
of
KIKUCHI
372
Suppl. II
events within three seconds. The vague granular structure which is neary touching the vessel wdl on this microscopic focal plane, undergoes deformation through Fig. 5a-c during while the loosely connected platelets ( the part looking more granularly ) were floated away building a narrow blood channel ( arrow ) along the vessel wall. The surface layer flow is hardly visible near the stenosis. It can be seen only when it becomes to flow slowly a little past the stenosis, though not apparent in selected pictures from 16 mm film. The surface layer flow decelerates the moving speed as it runs downstream, and finally ceases to move.
DISCUSSION Several investigators reported that in experiments on the transsection of microvessel, the hemostatic plug in proximal arteriolar segment grows to a larger volume in a much shorter time than in other vessel segment ( 6, 7 ). Our experiments were performed by giving a tiny pore on a microvessel so that there might occur least deformation or disarrangement of vascular geometry and minimum disturbance in laminar flow. It has been reported that the intravascular portion of hemostatic thrombus grows at first in height or in width, in such a way that the faster the blood velocity in appearance prior to injury, the more the thrombus growth ( 5 ). The growth of thrombus is caused from the continual adhesion or cohesion of platelets. Then Suppose that a pinpoint injury is given on the intima of a vessel. the neighbouring platelets are caused to adhere to the injured point.. The adhering region will make an approximate hemispher ( Fig, 5a ). When the maximum distance between the point injury and the platelet to be adhered is r (mm), the hemisphere is approximately estimated as: 1 9ir3 2 This estimation represents a stagnant state of blood. When there is a flow with a mean velocity v (mm/set), every platelet contained in the blood column passing through the hemisphere must be exposed to the force to compel it to adhere ( Fig. 5b 1. Then the total number of platelets expected to calculated as: be adhered ( N ) in unit time is approximately N =$-7Er2vn Where n is the number of platelets contained in one cubic milli-meter of blood, Of course the magnitude of r in the flowing state of blood may differ from the stagnant state. Considering the practical intimal injury as a sum of pinpoint injuries, this formula can explain the fact that the faster the blood flow, the more rappid the thrombus growth. The surface layer flow of thrombus itself was found to decelerate its speed and ultimately to cease to move along the down slope of a conical thrombus, These findings are comparable to the decreasing speed of blood flow past the stenosis. The surface layer flow of thrombus must be resulted from the shear stresses caused from the flowing blood. While the shear
Suppl.
II
THROMBUS
DEFORMATION
Fig.
373
6
stresses exceed the cohesive forces between the platelets which constitute the thrombus, the surface layer of thrombus will be able to flow. However, the thrombus is not solid but rather viscous and moreover ununiform in viscoelasticity and its surface is uneven. The boundary of thrombus is thus not so sharply definit as a solid surface in rheological sense that the surface layer flow of thrombus may be equal to the boundary layer of viscous fluid in close contact with a solid surface. The thrombus growth in length is mainly resulted from the surface layer flow and partially from the deformation such as dislocations and rotations of small portions of the thrombus mass. Aschoff reported that in a flow model using sand-suspended water, there were seen eddies just before and past an obstacle or stenosis and that in the region of eddies the sands deposited. of platelet The growth of thrombus depends on the accumulation
374
KIKUCHI
Suppl.
II
adhesions or cohesions, but the eddies are circular movement of the same small volume of blood which can supply few platelets. The dead space of eddies was filled not by accumulation of platelets but by occupation of thrombus parts deformed. The fracture of thrombus was caused partially or totally. Welch reported in the experiment on intimal injury of femoral artery of dogs that the thrombus showed apparent viscosity and elasticity and that there was found “such parts, even when severely lacerated, entirely free from thrombi or with only a thin layer of plates”. Such a finding would be a sort of fracture in large scale. As to the relation between the blood flow and the fracture, shear stresses may play one of the most important roles but other factors such as normal stress, pulsatil flow in arteriols and the cohesive forces between platelets should be considered. Our experiments were not quantitative. However it will be concluded that the blood flow has an inconsistent effect on the development of thrombus, constructive and destructive as described in ABSTRACT.
REFERENCES 1.
Herzog, Pfluegers
F. Die Rolle der Capillaren Arch. ges. Physiol.: 207,
2.
Experimentelle Tannenberg. Mechanismus der spontanen 147, 721. 1927.
bei der Blutstillung. 476. 1925.
Untersuchungen ueber den Blutstillung. Arch. Klin. Chir.
of haemostasis T.I. and Tsai, C. The mechanism vessel. J. Physiol.: 107, 280. 1938.
3.
Chen, pheral
4.
Kikuchi,A. observation Proceedings Pan-Pacific
:
in peri-
, Oya, M., Yamanaka, M. and Aoki, N. Microscopic Mechanism of hemorrhage and hemostas of capillaries. of the VIIIth. International Congress of Hematology, Press, Tokyo, 1962, p. 1770.
5.
R,heology Kikuchi,A. 2, 271. 1970.
of thrombus
formation.
6.
Arfors, K. -E. and Bergqvist, contraction in microvascular 9_ 22. 1975.
7.
Arfors, K. -E. and Bergqvist, D. Influence of blood experimental haemostatic plug formation. Thrombos 4, 447. 1974.
8.
Aschoff, L. Thrombose 52, 205. 1912.
9.
Welch, Phila.:
D. Platelet haemostasis.
Jap.
aggregability Microvasc.
und Sandbankbildung.
W. H. The structure 13, 281. 1887.
of white
J.
thrombi.
is.
Med. : and vessel Rec. :
flow velocity is Res. :
on
Beitaege
path,
Anat. :
Trans.
Path.
Sot.
RESEARCH in the
II, Suppl. Pergamon
States
United
SECTION
RHEOLOGICAL
OBSERVATION
ON
Akira Okaira
THE
vol. 8, Press,
1976 Inc.
VII
DEFORMATION
OF
THROMBUS
Kikuchi
Memorial Tokyo Hitachi Tokyo, Jaran
Hospital,
Al 3STRACT The intravascular portion of hemostatic thrombus grows, deforms and fractures repeatedly even after the completion The faster the blood flow, the more active of hemostasis. the thrombus growth as well as the deformation and fracture. The growth begins in height or width of thrombus and follows in length. The surface layer of thrombus itself flows downstream irregularly in figure and in motion. The surface layer flow and the partial deformation of thrombus such as dislocation and rotation contribute the thrombus growth in length. The blood flow is concluded to have an inconsistent effect on thrombus development: one is constructive supplying platelets to be adhered or cohered, the faster the more; the other is destructive offering shear stresses on the surface and presumably’ normal pressures to the whole body of thrombus, also the faster the higher. INTRODUCTION The mechanical injury to a microvessel causes sometime no bleeding because of the endothel adhesion (1, 2, 3). In a case without bleeding, the platelets are caused to adhere to the adhered endothels surrounding the wound and form a thrombus just similar as the hemostatic plug. In both cases with or without bleeding, the intravascular portion of thrombus grows, deforms and fractures repeatedly even after the completion of hemostasis (4, 5). The changes in volume and shape of thrombus can modify the blood flow which must, on the contrary, influence the development of thrombus. On the relation between the blood flow and the thrombus development, rheological observations were atempted and some moving pictures were made. 345
KIKUCHI
MATERIAL
Suppl.
II
AND METHODS
Mesenteric microvessels, under eighty micra in the inner diameter, of a rabbit which was anesthetized with Nembutal were micro-punctured with a microscopic knife mounted on a micromanipulator (4). A Nikon microscope and Bolex 16 mm camera was used. Micropuncturing was done by giving a tiny pore with a sharp knife so that there might occur least disarrangement of vessel geometry and minimum disturbance in lamenar flow.
RESULTS The bleeding, when it occurred, stopped within sixty seconds without rebleeding. Micropuncturing on the center line of a vessel, formed a thrombus into a tadpole-like shape, and by a marginal injury a conical thrombus was obtained. The tadpole-like shape corresponds to the plain view of thrombus and the conical one corresponds to the side view. Both shapes of thrombus grew, deformed and fractured repeatedly for some time during while they became to be streamlined step by step and finally kept The faster the flow speed in appearance prior to this shape unchanged. the longer the duration of deforming (from several minutes in a injury, small venule to over-thirty minutes in an arteriole with high flow rate). In arterioles the detached fragment of thrombus caused frequently embolization with a temporary pause of blood flow which was recovered in several seconds owing to the plustic deformation of embolus advancing peripherally. Except such pauses, the arteriolar thrombosis per se never caused an interruption of the blood flow at the site of injury, probably because an arteriole has sufficient branching to drive the emboli peripherally. The tadpole-like shaped thrombus began in a round shape surrounding the wound ( Fig. la ), grew at first in width, narrowing the blood flow on both sides and then became slender by a slight deformation ( Fig. lb ) simultaneously showing a tail which was trailing frequently and sometimes torn downstream. The growth in width and the deformation was repeatedly seen in a vessel with faster flow. Such repetitions made the thrombus streamlined step by step. On the boundary of thrombus there was observed a thin flow layer of thrombus itself, especially obviously from the shoulder to the tail. The surface flow layer of thrombus was active and rather irregular in thickness and in movement in a rappid flow and less active and irregular in a gentle laminar flow. The conical thrombus began in a cone shape based on the injured side of vessel, with a rather steeper incline upstream and a more gentle slope It grew at first in height until the tip of cone nearly touched downstream. to the vessel wall at the opposite side of injury ( Fig. 2a ), then the top or its vicinity displaced a little downstream becoming lower in height ( Fig. 2b 1, This made the ascending incline concave slightly. Continuous cohesion of platelets turned the ascending incline from concave to convex and moreover
Suppl.
THROMEWS
II
367
DEFORMATION
I _.
The outlines
_.._ ._D-. structures .
Fig. A tadpole-like shaped from 16 mm film.
thrombus
1. in a venule.
a:
About seven seconds after injury. figure at the lower hand of venule of microscopic knife.
b:
About twenty is occurring.
seconds
afterwards.
Reprints
The vague is a shadow The deformation
of
o_- _____-
366
Suppl.
KIKUCHI
Fig.
II
2
A conical thrombus Reprints arteriole. 16 mm film.
in an from
The blood runs from the left hand to the right. The dark field at the left side of picture is extravasated blood.
a:
Growth
in height.
b:
Displacement of the top portion. The lower right region by the thrombus is free from blood flow.
c:
“A mountain with a Several erysaddle”. throcytes seen in the lower right region by the thrombus are in circular motion (eddies),
d:
Fracture is beginning. The arrow indicates a crack.
( Published by kind permission of the Editor and Publisher of the Journal of Japanese Society of Internal Medicine 1
Suppl.
II
THROMBUS
369
DEFORMATION
constructed here another top, resulted in a shape, as a whole, of “a mounway, when the stenosis, shorter tain with a saddle” ( Fig. 2c 1. In similar or longer in length, had been developed as a result of thrombus growth, there occurred a partial deformation in thrombus, *mainly in dislocation, sometime in rotation and rarely in landslide like collaps at the rear side of Thus the thrombus gained its length, and it was the same as the thrombus. narrowed path way of blood. The fracture of thrombus occurred most frequently at the time when there had developed a narrow channel commonly along the vascular wall at the opposite side of injury, or rarely a little apart from the wall halfway winding to penetrate through the thrombus. The fracture was whole and ductile in most cases, beginning gently as a rule in a crack on the ascending incline ( Fig. 2d ) but rarely occurring suddenly just like a brittle fracture, and left the thrombus stump at the site of injury. In case of brittle-like fracture, the thrombus stump showed apparent elasticity at the moment of fracture. After the fracture, the platelets still continuously cohered to the thrombus stump forming a conical shape again and the events from the growth in height to fracture occurred repeatedly, the faster the blood flow, the more repeatedly. The surface layer flow of thrombus, above described, was observed also along the conical surface. However, it was hardly recognizable in the stenotic segment of arteriole because of its too rappid movement. In arterioles it was first visible in the post-stenotic lumen where the surface layer flow was slowing down in speed and becoming to cease to move along the down slope of the cone. In arteriols, small deformations such as dislocation or rotation were more contributable to the thrombus growth than the surface layer flow.
Fig. A thrombus in a venule from 16 mm film. a:
About ten seconds injury.
3
with relative after
b:
rappid
flow.
About twenty afterwards.
Reprints
seconds
‘r70
KIKIJCHI
Suppl.
II
The surface layer flow of thrombus was most apparently observed on In such a case, the deformation a thrombus in a venule with high flow rate. rate is adequate to follow and the vessel lumen is flat and thin in depth so that the detailed figures are continuously observable without frequent reFig. 3-5, the reprints from 16 mm adjustments of the microscopic focus. film, show a venular thrombus resulted from a crossing injury by which the blood flow is concentrated into the upper side of vessel, A slender pore across the center line of vessel is surrounded by the adhered endothels seen oval in Fig. 3b. Fig. 3a is a picture about ten seconds after the ) of wound injury. Platelets have gathered at the right side ( downstream The lower in close contact with the upper half of the endothel adhesion.
Fig.
4
The surface layer flow of thrombus in another higher magnification at the same point as Fig.
series 3.
under
THROMEUS
Fig.
5
311
DEFORMATION
half at the right hand of wound is empty, namely, a dead space where eddies are frequently seen in case of very high speed of flow. About twenty seconds afterwards ( Fig. 3b ), the thrombus gained its length and volume. By these two pictures alone, the platelets seemed to have accumulated to the rear side of thrombus. However, in fact, the growth in length was caused from the surface layer flows. Fig. 4 indicates that at least each surface of such a portion which is protruding into the flow lines, corresponds to the surface layer flow. Along the flow line, the surface layer flow runs downstream and rotates around the promontery at the rear side of thrombus hanging into the dead space as an icicle seen in Fig. 4a-b. Thus, the surface layer flows come to standstill in the dead space which is variable in shape and scale according to the blood flow which is also influenced by the thrombus development. Under high power field the surface layer flow of thrombus is visible first just downstream at the concentrated segment of blood flow as a mass of platelets irregular in shape. Fig. 5 is composed of selected reprints from 16 mm film
in a Series
of
KIKUCHI
372
Suppl. II
events within three seconds. The vague granular structure which is neary touching the vessel wdl on this microscopic focal plane, undergoes deformation through Fig. 5a-c during while the loosely connected platelets ( the part looking more granularly ) were floated away building a narrow blood channel ( arrow ) along the vessel wall. The surface layer flow is hardly visible near the stenosis. It can be seen only when it becomes to flow slowly a little past the stenosis, though not apparent in selected pictures from 16 mm film. The surface layer flow decelerates the moving speed as it runs downstream, and finally ceases to move.
DISCUSSION Several investigators reported that in experiments on the transsection of microvessel, the hemostatic plug in proximal arteriolar segment grows to a larger volume in a much shorter time than in other vessel segment ( 6, 7 ). Our experiments were performed by giving a tiny pore on a microvessel so that there might occur least deformation or disarrangement of vascular geometry and minimum disturbance in laminar flow. It has been reported that the intravascular portion of hemostatic thrombus grows at first in height or in width, in such a way that the faster the blood velocity in appearance prior to injury, the more the thrombus growth ( 5 ). The growth of thrombus is caused from the continual adhesion or cohesion of platelets. Then Suppose that a pinpoint injury is given on the intima of a vessel. the neighbouring platelets are caused to adhere to the injured point.. The adhering region will make an approximate hemispher ( Fig, 5a ). When the maximum distance between the point injury and the platelet to be adhered is r (mm), the hemisphere is approximately estimated as: 1 9ir3 2 This estimation represents a stagnant state of blood. When there is a flow with a mean velocity v (mm/set), every platelet contained in the blood column passing through the hemisphere must be exposed to the force to compel it to adhere ( Fig. 5b 1. Then the total number of platelets expected to calculated as: be adhered ( N ) in unit time is approximately N =$-7Er2vn Where n is the number of platelets contained in one cubic milli-meter of blood, Of course the magnitude of r in the flowing state of blood may differ from the stagnant state. Considering the practical intimal injury as a sum of pinpoint injuries, this formula can explain the fact that the faster the blood flow, the more rappid the thrombus growth. The surface layer flow of thrombus itself was found to decelerate its speed and ultimately to cease to move along the down slope of a conical thrombus, These findings are comparable to the decreasing speed of blood flow past the stenosis. The surface layer flow of thrombus must be resulted from the shear stresses caused from the flowing blood. While the shear
Suppl.
II
THROMBUS
DEFORMATION
Fig.
373
6
stresses exceed the cohesive forces between the platelets which constitute the thrombus, the surface layer of thrombus will be able to flow. However, the thrombus is not solid but rather viscous and moreover ununiform in viscoelasticity and its surface is uneven. The boundary of thrombus is thus not so sharply definit as a solid surface in rheological sense that the surface layer flow of thrombus may be equal to the boundary layer of viscous fluid in close contact with a solid surface. The thrombus growth in length is mainly resulted from the surface layer flow and partially from the deformation such as dislocations and rotations of small portions of the thrombus mass. Aschoff reported that in a flow model using sand-suspended water, there were seen eddies just before and past an obstacle or stenosis and that in the region of eddies the sands deposited. of platelet The growth of thrombus depends on the accumulation
374
KIKUCHI
Suppl.
II
adhesions or cohesions, but the eddies are circular movement of the same small volume of blood which can supply few platelets. The dead space of eddies was filled not by accumulation of platelets but by occupation of thrombus parts deformed. The fracture of thrombus was caused partially or totally. Welch reported in the experiment on intimal injury of femoral artery of dogs that the thrombus showed apparent viscosity and elasticity and that there was found “such parts, even when severely lacerated, entirely free from thrombi or with only a thin layer of plates”. Such a finding would be a sort of fracture in large scale. As to the relation between the blood flow and the fracture, shear stresses may play one of the most important roles but other factors such as normal stress, pulsatil flow in arteriols and the cohesive forces between platelets should be considered. Our experiments were not quantitative. However it will be concluded that the blood flow has an inconsistent effect on the development of thrombus, constructive and destructive as described in ABSTRACT.
REFERENCES 1.
Herzog, Pfluegers
F. Die Rolle der Capillaren Arch. ges. Physiol.: 207,
2.
Experimentelle Tannenberg. Mechanismus der spontanen 147, 721. 1927.
bei der Blutstillung. 476. 1925.
Untersuchungen ueber den Blutstillung. Arch. Klin. Chir.
of haemostasis T.I. and Tsai, C. The mechanism vessel. J. Physiol.: 107, 280. 1938.
3.
Chen, pheral
4.
Kikuchi,A. observation Proceedings Pan-Pacific
:
in peri-
, Oya, M., Yamanaka, M. and Aoki, N. Microscopic Mechanism of hemorrhage and hemostas of capillaries. of the VIIIth. International Congress of Hematology, Press, Tokyo, 1962, p. 1770.
5.
R,heology Kikuchi,A. 2, 271. 1970.
of thrombus
formation.
6.
Arfors, K. -E. and Bergqvist, contraction in microvascular 9_ 22. 1975.
7.
Arfors, K. -E. and Bergqvist, D. Influence of blood experimental haemostatic plug formation. Thrombos 4, 447. 1974.
8.
Aschoff, L. Thrombose 52, 205. 1912.
9.
Welch, Phila.:
D. Platelet haemostasis.
Jap.
aggregability Microvasc.
und Sandbankbildung.
W. H. The structure 13, 281. 1887.
of white
J.
thrombi.
is.
Med. : and vessel Rec. :
flow velocity is Res. :
on
Beitaege
path,
Anat. :
Trans.
Path.
Sot.
