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Last Update: August 8, 2023.

Continuing Education Activity

Thrombosis is a blood clot within blood vessels that limits the flow of blood. Acute venous and arterial thromboses are the most common cause of death in developed countries. The mortality rate varies with the location and acuity of thrombosis. Myocardial infarctions and cerebrovascular accidents (CVAs) account for the highest proportion of thrombosis-associated deaths in the United States. This activity reviews the basic pathophysiology, provoking risk factors, and evaluation of venous and arterial thromboses and highlights the role of interprofessional team members in collaborating to provide well-coordinated care and enhance outcomes for affected patients.


  • Review the etiologic factors associated with venous or arterial thromboses.
  • Explain when the diagnosis of venous or arterial thromboses should be considered.
  • Describe how to properly evaluate for venous or arterial thromboses.
  • Outline the importance of enhancing care coordination among the interprofessional team to ensure proper evaluation and management of venous and arterial thromboses.
Access free multiple choice questions on this topic.


Thrombosis is the formation of a blood clot (partial or complete blockage) within blood vessels, whether venous or arterial, limiting the natural flow of blood and resulting in clinical sequela. The ability of blood to flow freely in vessels relies on complex homeostasis that exists between blood cells (including platelets), plasma proteins, coagulation factors, inflammatory factors and cytokines, and the endothelial lining within the lumen of arteries and veins. When there is an imbalance with this physiologic process, there can be an increased risk of developing a thrombosis versus a coagulopathy (increased risk of bleeding). In certain clinical circumstances, patients can be at increased risk of thrombosis and bleeding simultaneously (e.g., disseminated intravascular coagulopathy-DIC, or in patients with underlying malignancy who develop a coagulopathy). As such, the diagnosis and management of thrombosis are complex. They can arise in any organ system, and their clinical presentation can vary depending on underlying comorbidities and presence (or absence) of provoking factors. Many factors can impact management decisions, including whether venous or arterial, acute or chronic, first or subsequent episode, family history, risk factor assessment, and hemodynamic stability. The use and duration of anticoagulation or antiplatelet therapy depend on a careful evaluation of these factors. Furthermore, a decision to pursue an exhaustive hypercoagulable workup to further evaluate for inherited or acquired conditions that predispose to thrombosis is controversial. It should only be completed in carefully selected patients or with subspecialty hematology evaluation prior.

Together, acute venous and arterial thrombosis accounts for the most common causes of death in developed countries.[1] This mortality depends on location and acuity of thrombosis, with myocardial infarction and cerebrovascular accident (CVA) or stroke accounting for the highest proportion of thrombosis-associated death in the United States.[1] An understanding of the basic pathophysiology of thrombosis and provoking risk factors can aid clinicians in the diagnosis, workup, and management of this condition. However, the topic is incredibly broad with many management-specific differences and decisions depending on etiology, risk factors, the location of thrombus (venous or arterial), and selection of anticoagulant or antiplatelet therapy. Many patients may require subspecialty evaluation with cardiologists, pulmonologists, neurologists, and/or hematologists. The state of the science on arterial and venous thrombosis is continually evolving, as is our understanding of provoking risk factors, hypercoagulability testing, and medical management.

There are also many unique presentations that add complexity to the diagnosis and treatment decisions, such as in acquired antiphospholipid syndrome or with heparin-induced thrombocytopenia & thrombosis (HITT). As such, many of these case- or disease-specific details and management aspects are beyond the scope of this review article. Readers are encouraged to consult additional references for further reading, including regularly-updated subspecialty society guidelines (e.g., American Society of Chest Physicians, American Heart Association, & American Society of Hematology). This review will focus primarily on the basic pathophysiology of venous and arterial thrombosis, including assessment of provoking risk factors and further workup that may be advisable following the initial presentation. This article will also briefly review the management of venous thrombosis and thromboembolism.


The cause of thrombosis is multifactorial. As noted, thrombosis occurs when there is an imbalance in endogenous anticoagulation and hemostasis through a complex pathophysiologic mechanism. Historically, three common factors predispose to thrombosis: 1) damage to the endothelial lining of the vessel wall; 2) a hypercoagulable state, and 3) arterial or venous blood stasis. These three factors are known by the eponym "Virchow's triad." Rudolf Virchow proposed Virchow's triad in 1856, and he described how the presence of these three factors increases thrombosis. Endothelial wall damage is caused by different factors, which can include direct disruption of the vessel via catheter placement, trauma, or surgery.   Hypercoagulability is a general hematologic concept that merely means an increased risk of thrombosis (i.e., thrombogenic) via enhanced levels of prothrombotic components in the bloodstream. This hypercoagulability is due to a variety of alterations in the coagulation and hemostatic system, which can result from inflammatory factors, variations in the viscosity of blood and blood components, increased cytokines, and prothrombotic proteins in circulation, or deficiencies of natural or endogenous anticoagulant factors.

Hypercoagulable states can be acquired or inherited. Inherited forms are rare, but include examples such as antithrombin III deficiency, protein C and S deficiencies, factor V Leiden (activated protein C resistance), or prothrombin gene mutations (among many others). Acquired hypercoagulability is far more common and can result from medications (e.g., oral contraceptives, estrogen or other hormonal replacement), recent inflammatory conditions such as pregnancy, surgery, trauma, or infection, and chronic inflammatory conditions (e.g., morbid obesity, rheumatologic disease, ulcerative colitis, heavy smoking). Two specific types of acquired hypercoagulable states that can lead to both venous and arterial thrombus include the acquired antiphospholipid syndrome and heparin-induced thrombocytopenia & thrombosis (HITT);. However, beyond the scope of this review, clinicians must be aware of these conditions as potential contributors to acute thrombosis. Malignancy (occult or diagnosed) is also a well-known risk factor for hypercoagulability, as tumor cells can express a variety of procoagulant proteins, including increased expression tissue factor.  Some malignancies, especially solid tumors, are known to significantly increase the risk of thrombosis (e.g., pancreatic cancer). The third aspect of Virchow's triad includes arterial or venous stasis of the blood, which could be due to immobility, pregnancy, or impaired blood flow resulting from previous thrombosis (e.g., residual blood clot, remodeling or fibrosis of blood vessels, or atherosclerosis). Long trips with limited mobility can also become a relative risk factor for thrombosis, especially if concurrent additional risk factors are present (as above).  

Thus when evaluating any thrombosis, one must appreciate Virchow's triad and carefully consider the various provoking risk factors that can predispose to thrombosis. Typically, venous thrombosis is initiated by endothelial damage, while arterial thrombosis starts with atherosclerosis. However, some studies have proven that there is a link between these two types of thrombosis. For instance, Prandoni et al. (2006) speculated that these two types of thrombosis are triggered by the same biological stimuli that activate coagulation and inflammatory pathways.[2] Both kinds of thrombosis have similar risk factors, including age, obesity, smoking, chronic inflammation, metabolic syndrome, as well as others previously described. Upon identification of a confirmed thrombosis, a clinician should carefully assess whether any provoking factors may have predisposed to the clot. In other words, it is paramount to determine whether the thrombosis was likely provoked or unprovoked, as each has management implications. Knowledge of the location (e.g., proximal vs. distal) and extent of the thrombosis can also guide further workup and may alter the treatment approach.

When considering venous thromboembolism (VTE), an appreciation of the anatomy of the deep veins of the extremities and the pulmonary system is helpful. For example, the deep veins of the lower extremity include the femoral, iliac, and popliteal veins. Thrombosis can also occur in the veins of the upper extremity like in the subclavian, axillary, brachial veins. Other thrombosis sites include superior vena cava thrombosis, jugular vein thrombosis, cerebral venous sinus thrombosis, cavernous sinus thrombosis, retinal vein occlusion. The latter sites are less common, and with the identification of an isolated thrombus in one of these sites, one must consider the potential for other explanatory diagnoses or predisposing conditions (e.g., Budd-Chiari syndrome with hepatic thrombus or cirrhosis and associated splenic vein thrombus). Many myeloproliferative disorders or clonal disorders with acquired bone marrow failure have correlations with rare sites of venous or arterial thrombosis (e.g., paroxysmal nocturnal hemoglobinuria (PNH) may have cerebral venous or abdominal thrombosis as presenting feature). Thrombosis of superficial veins is also possible, especially with provoking factors such as intravenous catheterization or localized cellulitis; treatment of superficial vein thrombosis does not typically require any anticoagulation.  

As noted, arterial thrombosis can present as an acute stroke, myocardial infarction, or acute on the chronic peripheral arterial disease. Other less common sites can include renal arteries, mesenteric arteries, and retinal arteries.  In addition to acute management (not reviewed here), secondary prevention focuses on reducing cardiovascular risk factors such as obesity, high cholesterol, diabetes, high blood pressure, and encouraging lifestyle modification such as smoking cessation. The increased incidence of obesity, hypertension, and hypercholesterolemia all contribute to the risk of acquiring an arterial thrombosis.[3] Other risk factors include underlying connective tissue or rheumatologic conditions (e.g., SLE, vasculitis), as well as the aforementioned rare HITT, antiphospholipid syndrome, myeloproliferative disorders, and PNH (all of these can predispose to both venous and arterial thrombosis).  

Age and gender also contribute to the development of thrombosis, with advancing age associated with a relatively increased risk of thrombosis. For instance, studies have shown that elderly persons have increased production of prothrombotic coagulation factors such as von Willebrand factor and thrombin. The elderly also may experience a normal physiologic activation of platelets compared to younger persons.[4]


The epidemiology of thrombosis varies depending on whether it is venous vs. arterial, provoked vs. unprovoked, and the first episode vs. subsequent episode. In venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), the annual incidence is 1 per 100000 in children, 1 per 10000 in reproductive age, 1 per 1000 in later middle age, and 1 per 100 in elderly.[5] Reports also indicate that the incidence of pulmonary embolism 29 to 48 per 100000 person-years and deep vein thrombosis incidence is 45 to 117 per 100000 person-years.[6] Naess et al. also found that the incidence is higher in women compared to men and increased in patients with cancer compared to those without cancer.[5] Studies demonstrate that there is an increased incidence of venous thrombosis in people of European descent compared with non-Europeans.[7] Compared to the western world, which includes mostly people of European descent, people from Taiwan have an incidence rate of 15.9 per 100000.[8]


As noted, Virchow's triad (i.e., endothelial damage, hypercoagulability, & venous or arterial blood stasis) plays a significant role in the pathophysiology of thrombosis. Damage to the vessel wall leads to the production of pro-inflammatory (and prothrombotic) cytokines, an increase in available tissue factor, the proliferation of adhesion molecules, and enhanced platelet activation. Cytokines initiate inflammation-promoting interaction between leukocytes and endothelial cells.[9] Inflammation is a normal body reaction to unwanted stimuli such as foreign pathogens or infection and endothelial damage, whether acute (e.g., trauma or surgery) or chronic (underlying inflammatory disorders or peripheral vascular disease). The activation of the leucocytes and endothelial cells causes the formation of adhesion molecules, which will eventually initiate clot formation.[9] The body's endogenous anticoagulants, such as protein C & S and Antithrombin-III, prevent the formation of thrombosis through a complex regulatory mechanism that maintains homeostasis. When an imbalance exists in the formation and lysis of clot, it can generate thrombosis; this explains why patients with thrombophilias such as protein C, protein S, and antithrombin III deficiencies are prone to acquiring blood clots. As noted in the Etiology section, a myriad of additional acquired provoking risk factors and comorbidities (e.g., recent surgery, inflammation, infection, pregnancy, estrogen therapy, morbid obesity, or smoking, among others) also increase a chance of developing thrombosis.

Thrombosis occurs throughout our arterial system, especially in those with predisposing cardiovascular risk factors. In the heart, microthrombi can develop as a result of blood stasis in the ventricles or atria due to underlying valvular heart disease, cardiomyopathies, or arrhythmias such as atrial fibrillation predisposing to ischemic emboli and CVA. Arterial thrombosis (and microthrombi formation) typically initiates by the accumulation of lipid plaques in the arterial wall, provoking chronic inflammatory cells and platelet activation, as can be seen with coronary artery disease.[10] Platelets play a significant role in the development of arterial thrombosis compared to venous thrombosis, and this explains why antiplatelet agents form a cornerstone of the prevention and treatment of arterial thrombosis. The initial lipid plaques evolve into fibrous plaques. Fibrous plaques could rupture, and the erosion of the surfaces of some of these plaques could lead to the release of additional pro-coagulating factors.[10] This process is called atherosclerosis. Atherosclerosis allows the activation of platelets, causing adhesion and aggregation, which leads to the formation of a clot. The occlusion of vessels due to atherosclerosis and thrombin formation in the coronary arteries of the heart may lead to ischemic heart disease and myocardial infarction.


Histopathology of arterial vessels that contain thrombosis shows an area of fibrin with numerous platelets and leukocytes. Older layers tend to have fewer leucocytes compared to a new area. Red blood cells could also be present, and these lines are called lines of Zahn. In the arterial histopathology, there is usually a fibrous cap atheroma, which could contain a lipid-rich necrotic core.[10] In the venous system following acute thrombosis formation, an extensive remodeling process occurs. Neutrophils and macrophages infiltrate the fibrin clot from within the lumen of the vessel over weeks leading to cytokine release and, eventually, fibroblast and collagen replacement of fibrin. This remodeling and fibrosis can result in diminished blood flow long after the acute thrombosis resolves.

History and Physical

The signs and symptoms of thrombosis vary depending on the presumed location and acuity. Patients with deep vein thrombosis (DVT) often present with isolated extremity swelling, pain, warmth, and erythema at the site of the blockage. The patient typically describes the pain associated with a DVT as “crampy” located in the calf or thigh of the affected lower extremity (though can occur in any extremity). They may exhibit a decreased range of motion of the extremity, inability to ambulate, or radiation of pain (e.g., into the groin for LE DVT extending to femoral vein). Patients with acute pulmonary embolism (PE) may present with pleuritic chest pain, shortness of breath, fatigue, back pain, syncope, or even death if severe (e.g., PE associated with hemodynamic instability or right heart strain).[11] Signs include tachycardia, tachypnea, fever, and may include oxygen desaturation.

Most commonly, arterial thrombosis results in cardiac or cerebrovascular compromise. Those with acute thrombosis in the coronary arteries of the heart will often report “crushing” left-sided chest pain or heaviness with radiation to the left arm or jaw (classic presentation; though atypical presentations occur frequently). If thrombosis occurs in one of the cerebral arteries (e.g., ischemic stroke), symptoms may include acute onset of unilateral or bilateral weakness, headache, confusion, vision changes, dysarthria, dysphagia, paresthesias, difficulty ambulating, or frank paralysis of one or more extremities.


The evaluation of patients with venous thrombosis differs from that of suspected arterial thrombosis. This section will focus briefly on the workup for suspected venous thromboembolism (VTE).

When patients present to the emergency department with signs and symptoms suggestive of possible venous thrombosis (see previous section H&P findings), a well-validated scale known as the modified Wells' criteria is applied to help guide further diagnostic studies. For patients with high Wells score, a serum D-dimer should be checked. The D-dimer is a fibrin degradation product that is present in the blood after fibrinolysis. Its elevation is very sensitive (though less specific) to detect venous thrombosis. It is important to note that a D-dimer could also be elevated in other patients such as pregnant and post-surgical patients, or those with underlying malignancy. However, it aids clinicians in deciding whether to pursue further diagnostic imaging. A negative D-dimer result helps to rule out a clot and avoid unnecessary imaging studies or anticoagulation initiation. The pulmonary embolism rule-out criteria (PERC) is also occasionally applied to help decide whether the patient has developed an acute pulmonary embolism (PE), though not applicable for DVT. The modified Wells score can also be used if physicians suspect an acute DVT. When there is a high pretest probability for PE or DVT, imaging studies should be completed immediately without regard to D-dimer levels. For pulmonary embolism, the recommended imaging studies are CT angiography and ventilation/perfusion imaging (V/Q scan).  The V/Q scan is sometimes preferred over CTPA to avoid radiation exposure or intravenous contrast in those with underlying renal impairment.[12] However, not all facilities have V/Q scanning capabilities or expertise at interpreting the results, so CTPA is often used. Often, pulmonary emboli result from fragmentation of preexisting thrombosis in an extremity (i.e., DVT). Hence, compression sonography (Duplex US) of lower and/or upper extremities is also often performed to evaluate for concurrent DVT. This is especially important if a provoking catheter-related thrombosis is suspected, as the catheter may require eventual removal.  

Determining whether a blood clot classifies as provoked (most common) vs. unprovoked, and whether it is the first episode vs. subsequent are critical aspects of the initial evaluation that can guide further workup and treatment. Clinicians should take a careful personal and family history to document any thrombosis history or pregnancy morbidity. In carefully selected patients suspected of having an underlying hereditary thrombophilia, a targeted hypercoagulable workup may be indicated.  Such testing may include checking the amount of protein C and S, antithrombin III, or mutational testing for factor V Leiden or Prothrombin gene mutation. Acquired thrombophilia testing may also be indicated, such as antiphospholipid antibody testing. In general, a full hypercoagulable workup is rarely necessary and strongly discouraged on initial presentation in the absence of subspecialty evaluation with a hematologist; this is especially true in the acute setting, as many factors can affect the accuracy of test results (e.g., acute inflammation or consumption of coagulation factors due to acute thrombosis can lead to falsely low levels of some coagulation factors). Anticoagulation therapy can also interfere with the interpretation of test results in the acute setting (e.g., heparin can affect the interpretation of Antithrombin III). For antiphospholipid antibody testing, many medications (including several anticoagulants), as well as underlying connective tissue diseases such as SLE, can affect the testing result and interpretation of the lupus anticoagulant. When antiphospholipid antibody testing is indicated, the recommendation is that the tests be repeated 12 weeks apart. As such, clinicians should reserve such hypercoagulable testing to carefully selected patients (e.g., young patients with unprovoked thrombosis or in those with confirmed or strong family history thrombophilia). This testing is often performed in the outpatient setting after the acute phase of the thrombosis has resolved and under the guidance of a hematologist consultant.  

Malignancy can be an underlying provoking factor for thrombosis (both venous and arterial). In general, it is not recommended for patients to have an extensive malignancy workup in the absence of any clinical factors to suggest underlying malignancy as the provoking cause. Age-appropriate cancer screening is recommended for all patients. In carefully selected patients, especially in those over the age of 50 with seemingly unprovoked thrombosis, in whom malignancy is a possibility, further evaluation to search for occult malignancy as the culprit may be indicated.

Treatment / Management

The treatment of both arterial and venous thrombosis differs. Venous thromboembolism management encompasses the use of various anticoagulant agents that target procoagulant factors, while arterial thrombosis management is predominantly with antiplatelet agents as monotherapy or dual-antiplatelet therapy. There are many variations and combinations of these treatment options. As noted, many of the specific scenarios on anticoagulation and antiplatelet therapy indications are beyond the scope of this review article. Subspecialty consultation with pulmonology, cardiology, neurology, and/or hematology may be necessary in special cases. Please refer to societal guidelines (i.e., American Society of Chest Physicians, American Heart Association, & American Society of Hematology) for case- and disease-specific recommendations.

Regarding venous thromboembolism (VTE), the American Society of Hematology (ASH) established a 2018 update to their guidelines for managing venous thrombosis, including prophylaxis use in hospitalized patients. In general, venous thrombosis divides into provoked or unprovoked etiologies; this is incredibly important as it helps to guide management and consideration of any further hypercoagulable workup that may be necessary for select patients. Furthermore, one must determine if the thrombosis is a first episode or recurrent episode, as this may change the duration of anticoagulation or antiplatelet therapy. A thorough personal and family history of VTE with careful assessment of provoking risk factors and comorbidities is essential. As noted, a provoked venous thrombosis results from reversible, modifiable, or acquired risk factors (e.g., recent surgery, trauma, infection, pregnancy, morbid obesity, OCP usage, long voyage, or immobility, heavy smoking, underlying malignancy, among others). Unprovoked thrombosis, on the other hand, occurs in the absence of any apparent or strong provoking factor. The treatment of venous thrombosis entails three stages, the initial, chronic, and extended stages,s according to Becattini C. et al. (2016).[13]  Treatment may vary depending on whether it is a first episode or recurrent episode, the extent of the thrombosis burden, whether provoking risk factors are transient or persistent, and whether symptoms resolve or remain chronic such as in post-thrombotic syndrome.  

Management of acute deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients typically includes anticoagulation with IV unfractionated heparin (UFH) or low molecular weight heparin with an eventual transition to oral anticoagulation as below. Anticoagulation promptly with heparin or LMWH provides a quick therapeutic range to avoid the progression of thrombosis and reduce associated mortality.[14] After initiating these intravenous anticoagulants, vitamin K antagonists (e.g., warfarin) can then be added for chronic and extended management once patients achieve a therapeutic INR. For an initial, provoked thrombosis (especially simple distal DVT), the recommended duration is typically 3 months.  For the first episode of provoked thrombosis with extensive clot burden, massive pulmonary embolism associated with hemodynamic compromise, or in patients with multiple persistent provoking risk factors, one should consider at least 3-6 months duration (or longer in select cases). Discontinuing therapy, before established guidelines on duration, can increase the risk of recurrent thrombosis. Medication compliance/adherence is very important to decrease the risk of recurrence. In patients with recurrent DVT or PE, the duration of therapy becomes more complex, and the determination of strong provoking or transient risk factors is important for guiding treatment. Patients with active malignancy as a provoking risk factor for thrombosis should typically continue anticoagulation therapy for 6 months or longer. Historically, LMWH has been preferred in those with thrombosis and malignancy. However, exceptions exist, and newer guidelines are now incorporating the use of certain direct oral anticoagulants (e.g., edoxaban) for management in patients with malignancy. Anticoagulation with thrombosis in pregnancy, perioperatively in those with thrombosis (especially orthopedic surgery), thrombosis in those with hereditary or acquired thrombophilia, and management of patients with recurrent or "breakthrough" thrombosis (despite therapeutic anticoagulation) becomes significantly more complicated. These cases are best managed under the guidance of a hematologist consultant.  

In those with true unprovoked thrombosis, the duration of therapy is typically longterm and can be lifelong. With the advent of newer direct oral anticoagulants (DOACs), many of which are non-inferior to older agents such as warfarin (with certain clinical exceptions, notably antiphospholipid syndrome or valvular A. Fib), the options for anticoagulation in acute thrombosis continues to expand. As of this writing, DOAC agents include dabigatran, edoxaban, rivaroxaban, and apixaban. Dabigatran is a direct thrombin inhibitor, while the other three are direct factor Xa inhibitors. The American Society of Hematology (ASH) has recommended in 2018 that the direct oral anticoagulants (DOACs) can be used in certain circumstances for the management of acute VTE while taking into consideration the risk of bleeding, renal impairment, and comorbidities that may reduce their efficacy (e.g., morbid obesity).[15]  When using unfractionated heparin, the partial thromboplastin time requires close monitoring, and the dose should be adjusted each time based on the value.  LMWH does not require monitoring, though occasionally for patients who are morbidly obese can be monitored by checking anti-Factor Xa levels. For vitamin K antagonists (i.e., warfarin), the PT/INR should be monitored and maintained in therapeutic range (INR typically between 2 and 3). With the DOACs, no routine blood monitoring is necessary; however, medication compliance/adherence remains paramount to assuring the efficacy of these medications. As of this writing, for patients with confirmed acute heparin-induced thrombocytopenia & thrombosis (HITT), a non-heparin anticoagulant such as argatroban should be utilized, and expert consultation with hematology is the recommendation.  In patients with confirmed antiphospholipid syndrome and acute thrombosis, vitamin k antagonism with warfarin is preferred, and consultation with hematology may be helpful. The use of DOACs in these settings is still under investigation.  

For patients who are admitted to the hospital, the American Society of Hematology (ASH), consistent with other subspecialty society guidelines have recommended that prophylactic-dose unfractionated heparin (UFH) or low molecular heparin (LMWH) should be used (with adjustment for renal impairment as indicated). If there is any contraindication to anticoagulation or high bleeding risk, mechanical prophylaxis of lower extremities should be employed.[16] Mechanical methods of prophylaxis include intermittent compression devices and graduated elastic compression stockings. With certain exceptions, it is not generally recommended to extend pharmacologic prophylaxis following hospitalization.[16] Prophylaxis should be strongly considered in acutely and critically ill patients who are hospitalized.[16]

Apart from pharmacological management, endovascular treatment is also used in some facilities to manage thrombosis. It is reported to be more successful if the thrombus is truly acute (i.e., formation two weeks before the presentation). Different endovascular methods include catheter-directed thrombolysis, percutaneous aspiration thrombectomy, venous balloon dilatation, pharmacomechanical catheter-directed thrombolysis.[17] The use of inferior vena cava (IVC) filters remains controversial in the acute setting and should only be considered in select cases. IVC filters carry their own risk of potential complications, and they can serve as a nidus for thrombus formation. In general, for acute venous thrombosis, the use of IVC filters should be avoided unless there is an absolute contraindication to anticoagulation or severe active bleeding. When used, a retrievable type of IVC filter is preferred, and anticoagulation should be offered as soon as safely feasible. A risk-benefit analysis of various options and informed patient decision-making is the key to the selection of these specialized intervention modalities, and subspecialty consultation is strongly advised.

Differential Diagnosis

An embolism is a differential diagnosis of thrombosis. In the later, the clot is formed in a location, causing the narrowing of vessels. In embolism, the clot travels from a primary site to a different location. For instance, in patients with deep venous thrombosis, the clot can get dislocated to the lungs ending up forming pulmonary embolism. Septic emboli should be considered in patients with risk of systemic infection, IV drug abuse history, or those with suspected or confirmed bacterial endocarditis. Chronic peripheral vascular disease can lead to similar symptoms in the extremities, and patients should have vascular surgery evaluation if suspected.


Prognosis of thrombosis varies depending on which type of thrombosis (venous or arterial), the location of the thrombosis, severity/extent of thrombosis, the persistence of provoking risk factors and comorbidities, and whether the first or subsequent/recurrent episode of thrombosis.  Patients with venous thromboembolism are at a higher risk than the general population for recurrent VTE, especially if they have underlying provoking risk factors. Up to 25% of patients who have experienced VTE may encounter a recurrent venous thrombosis within 10 years.[18]  The risk of recurrence is higher among patients with multiple cumulative provoking risk factors or underlying confirmed hereditary or acquired thrombophilia. An estimated 300000 deaths occur per year due to venous thromboembolism in the European Union.[19] Cardiovascular disease remains the leading cause of mortality in the U.S., and in patients with cerebrovascular disease, mortality is as high as 20% within the first 30 days of sustaining an ischemic CVA; as many as 30% survivors will be permanently disabled following a stroke.[17] Prevention of venous and arterial thrombosis is critical, and an understanding of lifestyle characteristics and modifiable risk factors should be conveyed to patients.


Thrombosis can give rise to complications if improperly managed an initial presentation. One significant, well-studied complication is a post-thrombotic syndrome, which is a complication of deep venous thrombosis. Reports are that about 20 to 50% of deep vein thrombosis patients will develop this condition within 1 to 2 years after presentation.[20] The risk factors for developing post-thrombotic syndrome are recurrent DVT at the same site, obesity, and poor compliance with anticoagulation. Patients usually present with chronic pain, heaviness, cramps, and swelling exacerbated during exercise and relieved with rest.[14] Studies have shown that the use of elastic compression stockings may help prevent this condition. Brandjes et al. observed a reported 50% reduction of post-thrombotic syndrome.[21] 

Pulmonary hypertension is also another complication seen as a result of chronic thromboembolism in the pulmonary vasculature. Estimates are that 0.1 to 9% of patients with a history of pulmonary embolism develop the pulmonary vascular disease.[14] Unlike the other types of pulmonary hypertension, chronic thromboembolic induced is curable by the removal of the clot in the vasculature.[14] This is called pulmonary endarterectomy.

Arterial thrombosis can result in many complications, particularly concerning cardiac and cerebrovascular disease resulting in significant morbidity and disability and the risk of recurrent events in the absence of lifestyle modifications and medical management.  

Another major complication associated with thrombosis is spontaneous hemorrhage (both intracranial and extracranial) that can result due to therapy with full-dose anticoagulation or antiplatelet agents.  Intracranial hemorrhage, when it occurs, is more devastating than extracranial. There are reports that the mortality of intracranial hemorrhage could be as high as 50% in patients using vitamin K antagonists (i.e., warfarin).[22] Patients treated with anticoagulation due to venous thromboembolism have a risk of major bleeding of 7.2 events per 100 person-years, the risk of fatal bleeding of 1.31 per 100 person-years, and a case fatality rate of 13.4% due to major bleed.[22] Assessing the risk of bleeding from anticoagulant or antiplatelet agents is an essential clinical objective, and patients should receive counsel on this risk and avoidance of situations that could predispose to bleeding (e.g., contact sports). Patients at particularly high risk of bleeding complications include the elderly, those with uncontrolled hypertension, those taking antiplatelet agents alongside anticoagulation, or those on warfarin, and multiple other medications that may interfere with warfarin metabolism.

Deterrence and Patient Education

As noted, the causes of venous and arterial thrombosis are multifactorial and context matters. Many acquired or modifiable risk factors can increase the likelihood of developing thrombosis. Patients should receive counseling regarding these risk factors and what they can do to ameliorate their risk. Patients who are known to have an underlying hypercoagulable state (e.g., those taking estrogen, pregnant women, or morbidly obese patients) should be informed of their risk of thrombosis. Patients should be counseled to avoid long periods of immobility (long trips) and to stretch often. The use of elastic compression stockings may be helpful. Smoking cessation should be reinforced.

For patients on anticoagulant or antiplatelet therapy, it is prudent to conduct a review of the risks of major bleeding.  Patients should be counseled on fall precautions while on these agents.

Enhancing Healthcare Team Outcomes

Primary physicians and other health professionals should help patients reduce their risk of thrombosis by providing accurate information on prevention and treatment. Both venous and arterial thrombosis share similar risk factors, and efforts should be made to educate and encourage patients to make healthy lifestyle choices. For example, chronic smokers should be encouraged to quit smoking. Those who are morbidly obese should be encouraged to change their diet and lifestyle accordingly.  Patients with metabolic syndrome or uncontrolled blood pressure should receive education on the importance of lifestyle modification and, when indicated, secondary prevention with medical management. 

Patients admitted to the hospital are also at higher risk of thrombosis. The American Society of Hematology (ASH) in 2018 recommended prophylaxis in patients admitted to hospital settings. Patients who do not get prophylaxis like unfractionated heparin (UFH), low molecular weight heparin (LMWH), or mechanical prophylaxis are at high risk of developing thrombosis. Therefore, care is necessary when managing patients admitted to the hospital, and daily reassessment of the risk of thrombosis is recommended in these settings.

Review Questions


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Disclosure: Damilola Ashorobi declares no relevant financial relationships with ineligible companies.

Disclosure: Muhammad Atif Ameer declares no relevant financial relationships with ineligible companies.

Disclosure: Roberto Fernandez declares no relevant financial relationships with ineligible companies.

Copyright © 2023, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Bookshelf ID: NBK538430PMID: 30860701


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