This plaque can suddenly burst rupture , followed by a blood clot. Arterial thrombosis can occur in the arteries that supply blood to the heart muscle coronary arteries. This can lead to a heart attack. When arterial thrombosis occurs in a blood vessel in the brain, it can lead to a stroke.
The symptoms of thrombosis may look like other blood disorders or health problems. Always see your healthcare provider for a diagnosis.
Your healthcare provider will take your medical history and give you a physical exam. Other tests may include:. Thrombosis can block the blood flow in both veins and arteries.
Complications depend on where the thrombosis is located. The most serious problems include stroke, heart attack, and serious breathing problems. Health Home Conditions and Diseases. There are 2 main types of thrombosis: Venous thrombosis is when the blood clot blocks a vein.
Veins carry blood from the body back into the heart. Arterial thrombosis is when the blood clot blocks an artery. Arteries carry oxygen-rich blood away from the heart to the body. What causes thrombosis? Venous thrombosis may be caused by: Disease or injury to the leg veins Not being able to move around immobility for any reason A broken bone fracture Certain medicines Obesity Inherited disorders, or a greater likelihood of having a certain disorder based on your genes Autoimmune disorders that make it more likely your blood will clot Medicines that increase your risk of clotting such as certain birth control medicines Arterial thrombosis may be caused by a hardening of the arteries, called arteriosclerosis.
What are the risk factors for thrombosis? Thromboembolism remains a leading cause of death and disability. Thrombi may partially or totally obstruct arteries or veins, leading to local ischemic complications and they can embolize to the cerebral arteries and lungs, where they may cause stroke or other life-threatening conditions. There are approximately 1 million incident cases of deep venous thromboembolism each year and over 60, deaths per year from recognized pulmonary embolism in the United States alone 1 , 2.
Stroke kills about , people each year, or 1 in 20 deaths in the US 3. Insights into the pathophysiology of thrombotic disorders have come from studies using a variety of designs, ranging from detailed in vitro molecular and cellular approaches, ex vivo pathological studies, in silico multiscale thrombosis modeling to in vivo animal models and clinical trials. Yet, there are remarkably few detailed analyses of thrombus structure that further our understanding of their relationship to vascular origin and duration in vivo , as well as the composition or the internal structural features of thrombi most closely associated with the risk of embolization.
The composition, physical properties, and evolution of venous and arterial thrombi are likely to differ mainly due to various local conditions and time since formation. In patients with coronary artery disease, thrombi commonly arise from the rupture of atherosclerotic plaque and exposure of procoagulant components, such as collagen and lipid-rich activated macrophages bearing tissue factor 4 , leading to myocardial infarction if thrombi become obstructive.
Similar events may lead to in situ arterial thrombosis in the cerebral or other circulations. Whether these perceived differences in pathogenesis affect thrombus structure has received relatively little investigation but may be important for the risk of extension and embolization and approach to therapy. Thrombi also undergo structural changes as they age. For example, the composition of coronary artery thrombi obtained from patients with ST-elevation myocardial infarction evolve over time such that fibrin content doubles each hour during clinically manifesting ischemia, whereas the relative platelet content halves each hour 7 , 8.
These changes have been associated with formation of a dense, stiff fibrin network that impairs responsiveness to anti-platelet therapy and thrombolysis over time 9 , A similar increase in stiffness over time associated with changes in structure occurs with aging of venous thrombi Knowing more about changes in thrombus structure over time is desirable, because they could influence the treatment approach and prognosis. Until recently, RBCs have been viewed as passive bystanders in these processes.
It is generally thought that RBCs are trapped in venous clots and might thereby increase vascular occlusion, but that they otherwise contribute little to arterial occlusion. There is now increasing evidence that RBCs play a substantial role in clotting Sub-fractions of RBCs express phosphatidylserine on their surface and thus support thrombin generation 13 , RBCs also suppress plasmin generation and as a result inhibit clot lysis 15 , Platelet-driven clot contraction results in compression of RBCs into a tightly packed interior core with an accompanying shape change to polyhedral cells, named polyhedrocytes, whereas fibrin and platelets are mostly on the surface Polyhedrocytes have also been observed in intracoronary thrombi taken from patients post ST-elevation myocardial infarction 8 , 17 , 18 as well as in ex vivo thrombi, venous clots and postmortem pulmonary emboli 12 , 19 , In vitro studies of clot contraction have demonstrated that the kinetics of clot contraction are accelerated and extent of contraction is enhanced by higher platelet levels and inhibited by RBCs and higher fibrinogen concentrations Despite the clinical importance, a comprehensive analysis of these and the above-mentioned features to human arterial and venous thrombi and emboli has not been reported.
In this study, we used high resolution scanning electron microscopy to examine how the vascular origin and aging affect the structure and composition of in vivo human arterial and venous thrombi extracted from living patients and postmortem pulmonary emboli. We determined the proportions composed of different forms of fibrin, the presence of biconcave, polyhedral and intermediate compressed forms of RBCs, and echinocytes, as well as volume fractions of the thrombi comprised by leukocytes, platelets, and cellular microvesicles.
These results revealed unique characteristics and differences between arterial and venous thrombi as well as between their younger and older thrombi. These differences in composition among various types of thrombi not only reflect the mechanisms of their formation but also have implications for why some thrombi embolize and differ in their responsiveness to antithrombotic treatments. We used high resolution scanning electron microscopy to examine the structure and composition of the exterior and interior of 45 freshly aspirated arterial thrombi, 25 venous thrombi from open thrombectomy, and 10 postmortem pulmonary emboli for technical details of obtaining thrombi and patient characteristics see the Supplemental Material and Methods.
We imaged 10—12 randomly selected areas and collected 10—12 images from each specimen, resulting in about total images. We then selected representative images from randomly chosen portions of 6 arterial thrombi, 5 venous thrombi, and 6 pulmonary emboli that contained all the typical structural elements seen in all the specimens, and the overall composition and structural elements contained in these portions were quantified.
The following structural elements were included in the analysis: fibrin individual fibers, bundles, sponge ; individual platelets, platelet aggregates and degranulated platelets; RBCs biconcave, polyhedral, intermediate forms, balloon-like forms, echinocytes ; white blood cells WBCs ; cellular microvesicles; and space between structures. However, the appearance of the fibrin was surprisingly inhomogeneous and differed considerably from clots formed in vitro , which are generally composed of a branching network of individual thin fibers These arterial thrombi were dense, meaning little unoccupied space was present.
They also showed evidence of clot contraction, in that polyhedrocytes were commonly interspersed among fiber bundles During clot contraction, platelets pull on fibrin fibers and compress RBCs, resulting in a transformation of shape from biconcave cells to polyhedral and various intermediate forms with formation of fiber bundles Other RBCs appear balloon-shaped, as if they had been squeezed through the network of fibrin fibers or were otherwise deformed, as reported previously 23 , Representative scanning electron microscope images of thrombi and emboli.
Structures identified in arterial and venous thrombi and pulmonary emboli. Panels A—C are images of arterial thrombi. Panels D—F are images of venous thrombi. Panels G—I are images of pulmonary emboli. A Arterial thrombus: fibrin structure is primarily composed of fiber bundles 1 and B fibrin sponge 2. B , C Dense contracted thrombi with platelet aggregates 3 with fibrin on the outside and red blood cell balloons 4 trapped in the fibrin mesh; some white blood cells were also present 5.
D Venous thrombus, mostly fibrin structure is primarily composed of fiber bundles 1 and individual fibrin fibers 6. E Tightly packed RBCs in the form of polyhedrocytes 7 with a few fibrin fibers. F Fibrin fibers 6 ; RBCs present as polyhedrocytes and echinocytes 8.
G Pulmonary embolus, bundles of fibrin 1 with intermediate forms of RBCs trapped inside 9. H Mostly polyhedrocytes 7 and extracellular microvesicles 10 as well as many white blood cells are present 5.
I Individual fibrin fibers 6 and intermediate forms of RBCs 9. Quantitation of structures identified in pulmonary emboli, arterial and venous thrombi.
Thrombi were obtained from patients and prepared for scanning electron microscopy and their composition was quantified as described in the Materials and Methods section.
The fibrin component was present as individual fibrin fibers, fibrin sponge and fibrin bundles; erythrocytes as biconcave, intermediate shapes, polyhedrocytes, echinocytes and balloon-like forms. The proportions of total volume occupied by these structures were calculated and presented as pie charts. The overall composition of venous thrombi differed significantly from arterial thrombi. Such changes could be caused by long-term metabolic changes or alteration of their environment after thrombus formation.
The platelet content 0. There were slight differences of emboli with parental venous thrombi, namely they were both composed primarily of fibrin fibers and RBCs. The volumes occupied by platelets 0. Three morphologically different fibrin structures were identified within all thrombi: individual fibrin fibers, fibrin bundles, and fibrin sponge.
Fibrin fibers, which typically predominate in in vitro blood clots, are generally long and relatively straight with occasional branch points Fig. The fibrin sponge is a fibrin network composed of very fine fibers, often with bound platelets and microvesicles Fig. Fibrin bundles are fibers that have associated laterally with other fibers Fig. Some fibrin fibers formed twisted structures, especially thicker fibers or bundles Fig.
In some images, fiber bundles were present together with thin fibers and cells or cellular microvesicles Fig. Fibrin fibers had either smooth or rough surfaces. In some sections, e. Fibrin structures in thrombi. There was great diversity in the structure of fibrin in thrombi and emboli.
A Very thick bundles of fibers that are sometimes twisted with large pores. B Thick bundles of fibers made up of thinner fibers and large pores. C Thrombus with a non-uniform distribution of thin fibers with large pores and platelet aggregates and fragments. Thrombi were visualized by scanning electron microscopy and their composition was quantified as described in the Materials and Methods section.
The fibrin components, different shapes of erythrocytes as well as white blood cells, platelets and microvesicles were identified in thrombi and compared here as a percentage of the total thrombus volume.
In contrast to fibrin clots formed under static conditions in vitro , fibrin in thrombi showed the effects of flow.
In thrombi, the fibers displayed a definite directionality or preferential orientation of fibers in a single direction, but the degree of anisotropy was highly variable. In some cases, parts of a thrombus with a dense mat of fibers were oriented in the same direction, with very few holes or gaps Fig.
The degree of anisotropy was quantified by the use of polar plots, showing numbers of fibers at different angles Fig. Some areas contained fibers that showed relatively random orientation, while others showed a moderate or a large amount of alignment. In a few cases where the orientation could be determined from the gross structure of the thrombus, it could be seen that the fibers were oriented in the direction of flow.
Orientation of fibrin fibers in thrombi. Some areas of some thrombi contained fibrin fibers largely oriented in a single direction. A Dense network of roughly horizontally oriented fibers.
B Dense fibers oriented diagonally. C Polar plots of the frequency of fibers with different orientation. Each plot is from a single micrograph and the absolute value of the angle is arbitrary, but only relative to the other fibers in an individual image, which is why the values are not given on the coordinate for angles.
Thrombi also showed effects of platelet-driven contraction on fibrin redistribution from being uniform throughout the clot to the surface Fig. Polyhedrocytes originate from intravital platelet-driven mechanical compaction of thrombi. Intermediate-shaped RBCs are partially compressed cells that are no longer biconcave but not yet polyhedral-shaped. All platelets found in arterial and venous thrombi and in pulmonary emboli were activated to different degrees with accompanying shape changes, most of them present as aggregates bound to fibrin.
All thrombi also contained clearly identified microvesicles, which may have derived from platelets, leukocytes, endothelial cells, or RBCs 26 , Microvesicle content was somewhat greater in arterial thrombi 5. However, the content of WBCs was significantly greater in pulmonary emboli 6.
Location- and time-dependent changes in composition of arterial and venous thrombi can be gleaned from analyses of individual thrombi in the Case Reports section see Supplement for details. To answer the question whether composition and distribution of the various thrombus components depend on location and time of formation, we compared the head of venous thrombi, representing the oldest part attached to the vessel wall, with the tail, the most recently formed segment that extends in the direction of blood flow and with the middle body section lying between the two Supplemental Figs.
S2 and S3. The head and tail contained more fibrin than the body, while the body of the thrombus contained more RBCs than either the head or tail. There was a higher content of fibrin bundles in the head than in the tail. Polyhedrocytes predominated in the body of the thrombus compared with the head and the tail, where there were more intermediate-shaped RBCs.
Regional differences within arterial thrombi were studied in thrombi removed surgically from abdominal aneurysms. Those thrombi were large and were composed of many layers, much like an onion, that were separated by dissection Supplemental Fig. The more superficial newer layers were composed of a network of fiber bundles having fairly uniform diameters, i.
Similar results were seen upon examination of two arterial graft thrombi from the same patient, one only a few hours old and the other 2 days old. In the present study, the composition of arterial and venous thrombi and pulmonary emboli was characterized quantitatively using high-resolution scanning electron microscopy.
Consequently, not all images could be quantified, but the conclusions were entirely consistent with qualitative results from examination of images from all thrombi and emboli. We extended that knowledge to the quantitative level and show that arterial thrombi contain a surprisingly large amount of fibrin, even more than the volume occupied by platelets.
Our results confirm prior studies showing that the proportion of RBCs in venous thrombi and pulmonary emboli is considerably higher than in arterial thrombi. Compressed polyhedral RBCs, termed polyhedrocytes, and intermediate-shaped forms both indicative of the intravital compaction of a thrombus mass , were also more common in venous thrombi and pulmonary emboli than in arterial thrombi.
More fibrin bundles were observed in arterial than in venous thrombi and pulmonary emboli, but more individual fibrin fibers were observed in pulmonary emboli than in arterial and venous thrombi.
WBCs were found more commonly in pulmonary emboli compared with arterial and venous thrombi, while microvesicles were more common in arterial thrombi and pulmonary emboli. These differences in composition may arise from the conditions under which the thrombi formed, as follows. Thrombus structure is affected by constriction of the vessel wall, activation or damage of the endothelium, blood flow and shear, fibrin polymerization, platelet-platelet and platelet-fibrin interactions, and the effect of platelet contractile forces on fibrin fibers and cells.
Increasing shear rate has a large impact on the fibrin network structure, promoting orientation and association of fibrin fibers into bundles 30 , 31 , 32 , 33 , We quantified this orientation in some thrombi, which is in agreement with our finding that arterial thrombi assembled at high shear rate contain more thick bundles some twisted than venous thrombi assembled at low shear rates. Arterial thrombi had higher platelet content, in agreement with earlier histological results 35 , which may contribute to fibrin bundle formation, since platelets pull on fibrin fibers 36 , decreasing the space between them, thereby promoting lateral association of fibers into bundles These structural signatures of clot contraction in ex vivo thrombi and thrombotic emboli derived from different vessels in human patients demonstrate that intravital contraction is common in vivo Our results also confirm and extend previous studies by demonstrating that RBCs are found within arterial thrombi.
The relative paucity of RBCs in arterial compared with venous thrombi can be attributed primarily to the high shear rate, but it is notable that a large fraction of those that were present were polyhedrocytes. In addition, many balloon-shaped RBCs were evident Fig. Polyhedrocytes that form during clot contraction were discovered initially in clots made in vitro , but the present studies extend this observation by showing their presence in all clinical thrombi examined. Differences Arterial thrombosis occur at places of arterial plaque rupture where the shear rate is higher, in contrast vein thrombosis occur at places where the vein wall is normal and blood flow and shear rate is low.
Location of the thrombus formation Arterial plaque rupture Normal vein wall Duration from initial insult to thrombus formation Takes a long time, often decades to happen Occur rapidly Shear rate High Low Microscopic appearance of clot Excess platelet and less fibrin, thus called white clot Less platelet and more fibrin, thus termed red clot Complication More chances of distal thrombosis Can cause pulmonary embolism Approach to treatment Risk factor modification eg, smoking cessation, diabetes control, obesity management plus anti-platelet drugs Prophylaxis against venous stasis and blood thinners.
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Namespaces Home Page Discussion. Views Read View source View history Help. Thrombosis Microchapters. Contributing Modern factor of Virchow's triad. Stasis, Endothelial wall defect, Hypercoagulability.
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