Thrombosis refers to the pathological process in which, under certain conditions, the formed elements of blood aggregate to form a thrombus within blood vessels (most commonly in small vessels), causing partial or complete vascular occlusion and resulting in impaired blood supply or venous return in the affected area. Based on the composition of the thrombus, thrombosis can be classified into platelet thrombi, red blood cell thrombi, fibrin thrombi, and mixed thrombi. According to the type of vessel where the thrombus forms, thrombosis can also be categorized as arterial thrombosis, venous thrombosis, or microvascular thrombosis.
Thromboembolism refers to the pathological process in which a thrombus detaches from its site of formation and partially or completely occludes other blood vessels during its migration through the bloodstream, leading to tissue and/or organ ischemia, hypoxia, and necrosis (in arterial thromboembolism) or congestion and edema (in venous thromboembolism).
Diseases caused by these two pathological processes are collectively referred to as thrombotic disorders in clinical practice.
Etiology and Pathogenesis
The causes of thrombotic disorders can be divided into inherited factors and acquired factors, the latter of which include various physiological states, diseases, and medication-related factors (e.g., heparin, contraceptives, antifibrinolytic drugs, or asparaginase). The pathogenesis of thrombosis is highly complex and not yet fully elucidated. However, Virchow's "Triad of Thrombogenesis" — comprising vascular wall injury, changes in blood composition, and hemodynamic abnormalities — continues to provide a useful framework for understanding the basic conditions and mechanisms underlying thrombosis. Recent research has expanded upon the elements of this triad, as described below.
Vascular Wall Injury
Endothelial cells of the vascular wall produce and release bioactive substances that exert both antithrombotic and prothrombotic effects. When endothelial cells are damaged by mechanical factors (e.g., atherosclerosis), chemical factors (e.g., certain drugs), biological agents (e.g., bacteria, viruses, or endotoxins), immune system responses, or vascular diseases, the balance between antithrombotic and prothrombotic mechanisms is disrupted. For instance:
- Increased release of von Willebrand factor (vWF) and platelet-activating factor promotes platelet adhesion, aggregation, and activation.
- Reduced production of prostacyclin (PGI2) and increased endothelin-1 levels result in vascular constriction.
- Greater tissue factor (TF) expression enhances procoagulant activity.
- Reduced anticoagulant activity and abnormal fibrinolytic mechanisms exacerbate thrombosis formation.
Changes in Blood Composition
Increased Platelet Activity
Enhanced platelet activation can result from endothelial damage, changes in shear stress within blood flow, certain medications, and a variety of diseases (e.g., pulmonary heart disease). Increased platelet activity contributes to thrombosis formation.
Abnormal Coagulation Factors
Several conditions elevate the risk of thrombosis, including:
- Increased fibrinogen levels due to diseases.
- Elevated Factor VII activity caused by poor lifestyle habits.
- Increased levels of Factors VIII, IX, and X following surgery or trauma.
- Congenital overexpression of coagulation factors V and VIII.
Weakening of the Anticoagulation System
Abnormalities in anticoagulant proteins — whether genetic or acquired — contribute to a propensity for thrombosis:
- Reduced or deficient levels of antithrombin (AT).
- Deficiency of protein C (PC) or protein S (PS).
- Resistance to activated protein C (APC-R) caused by structural abnormalities in Factor V or other factors.
Decreased Fibrinolytic Activity
Conditions that impair the breakdown of fibrin promote thrombosis formation and growth, including:
- Structural or functional abnormalities in plasminogen (e.g., dysplasminogenemia).
- Impaired release of plasminogen activators (PA).
- Overproduction of plasminogen activator inhibitors.
Hemodynamic Abnormalities
Increased blood viscosity, reduced deformability of red blood cells, or other factors can lead to systemic or localized blood flow stasis, creating favorable conditions for thrombosis. Examples include hyperfibrinogenemia, hyperlipidemia, dehydration, and polycythemia.
Clinical Manifestations
Thrombophilia
Thrombophilia refers to genetic or acquired predispositions that increase the likelihood of thrombosis. Hereditary thrombophilia is characterized by a family history of thrombosis, recurrent and/or multiple thrombotic events without clear precipitating factors, onset at a young age (under 45 years), poor response to conventional antithrombotic treatment, and is most commonly associated with hereditary protein C (PC) deficiency. Acquired thrombophilia may occur in conditions such as malignancies, nephrotic syndrome, and antiphospholipid syndrome.
Clinical Features of Different Types of Thrombosis
Venous Thrombosis
This is the most common form of thrombosis and often involves deep veins, such as the popliteal vein or femoral vein. Clinical features include:
- Local swelling and pain at the site of thrombus formation.
- Impaired venous blood return from the distal region of the thrombus, manifesting as distal swelling, tension pain, and changes in skin color.
- Thrombus detachment leading to embolization of blood vessels, which may result in dysfunction or damage to related organs, such as pulmonary embolism.
Arterial Thrombosis
This occurs more frequently in the coronary arteries, cerebral arteries, mesenteric arteries, and limb arteries. Clinical features include:
- Sudden onset, often accompanied by severe localized pain, such as angina, abdominal pain, or intense limb pain.
- Hypoxia and ischemia of tissues in the affected arterial territory, leading to structural and functional abnormalities of organs or tissues, including myocardial infarction, heart failure, cardiogenic shock, arrhythmias, altered consciousness, or hemiplegia.
- Thrombus detachment causing embolization-related symptoms and signs, such as cerebral embolism, renal embolism, or splenic embolism.
- Clinical manifestations resulting from ischemic necrosis of the affected tissue, such as fever.
Microvascular Thrombosis
This is commonly seen in conditions such as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP). Clinical features are often nonspecific and primarily involve thrombotic necrosis of skin and mucosal tissues, microcirculatory failure, and organ dysfunction.
Diagnosis
Key points for the diagnosis of this condition include:
Presence of Risk Factors for Thrombosis
Risk factors may include atherosclerosis, diabetes, nephropathy, malignancies, pregnancy, obesity, thrombophilia, recent surgery or trauma, prolonged contraceptive use, and others.
Symptoms and Signs of Thrombosis or Embolism
Clinical evaluation focuses on recognizing the signs and symptoms of thrombosis and embolic events in various vascular territories.
Imaging Studies
Color Doppler ultrasound is the most frequently used method in clinical practice. It is safe, noninvasive, and repeatable, making it a valuable tool for thrombosis screening.
Angiography was conventionally regarded as the "gold standard" for the diagnosis of thrombosis.
CT angiography (CTA) and magnetic resonance angiography (MRA) can provide direct visualization of thrombi in most major blood vessels. These modalities can serve as alternatives to angiography, especially in severely ill, elderly patients or those with contraindications to arterial or venous catheterization.
Radionuclide imaging is another method for detecting thrombosis.
Hematological Tests
Blood tests can be guided by the three main elements of the pathogenesis of thrombosis, as well as the patient’s clinical presentation. For patients with recurrent or multiple thrombotic events, family history assessments should be performed, and thrombophilia screening and molecular diagnostic testing should be considered.
Treatment
Elimination of Thrombosis Triggers and Treatment of Underlying Diseases
Management focuses on addressing conditions that predispose to thrombosis, such as preventing and treating atherosclerosis, controlling diabetes and infections, and treating malignancies.
Antithrombotic Therapy
Different therapeutic strategies are implemented depending on the site and duration of thrombus formation.
Thrombolytic Therapy and Interventional Thrombolysis
Thrombolytic therapy is primarily used for recent thrombus formation or thromboembolism. Selective application is advisable for patients at risk of limb gangrene due to deep venous thrombosis (DVT), or for hemodynamically unstable pulmonary embolism patients. For arterial thrombosis, treatment is most effective within 3 hours after onset and should not exceed 6 hours. For venous thrombosis, therapy is indicated during the acute or subacute phase, with a maximum timeframe of 2 weeks.
Administration involves systemic intravenous thrombolytics or catheter-directed delivery of thrombolytic agents into the affected site to dissolve the thrombus and restore normal blood flow. Common thrombolytic drugs include urokinase (UK), streptokinase (SK), and tissue plasminogen activator (t-PA).
Monitoring parameters for thrombolytic therapy include:
- Fibrinogen (Fbg) levels, which should be maintained at 1.2–1.5 g/L.
- Fibrin degradation products (FDP), ideally within 400–600 mg/L.
- Activated partial thromboplastin time (APTT) and thrombin time (TT), maintained at 1.5–2.5 times the normal control values.
Principles of Venous Thrombosis Treatment
Anticoagulation therapy is the first-line approach, with unfractionated heparin (UH) or low-molecular-weight heparin (LMWH) as preferred options. For patients allergic to heparin or experiencing heparin-induced thrombocytopenia (HIT), alternative anticoagulants such as argatroban may be used. The total treatment course generally does not exceed 10 days. For long-term anticoagulation, warfarin is commonly used, though pentasaccharides or newer anticoagulants that directly inhibit thrombin or Factor Xa (such as dabigatran, rivaroxaban, edoxaban, or apixaban) may also be considered. Dosing for anticoagulant therapy should be carefully individualized, with heparin doses typically monitored using APTT and warfarin using the international normalized ratio (INR). The duration of anticoagulant therapy for venous thrombosis can follow the recommendations outlined in the classic American College of Chest Physicians (ACCP) guidelines.
Principles of Arterial Thrombosis Treatment
Antiplatelet therapy is essential and continuous. Commonly used antiplatelet agents include aspirin, clopidogrel, and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists. Indobufen is also an alternative option.
Principles of Chronic Thrombosis Treatment
For chronic thrombosis that has not responded well to medical treatment and in cases with poor collateral circulation, surgical treatment may be considered. This may involve surgical removal of the thrombus or excision of the embolized vascular segment followed by reanastomosis or vascular bypass surgery.
Principles of Thrombophilia Treatment
In the acute phase, the treatment is similar to that for general thrombosis. Based on the specific cause, long-term (6–12 months) or lifelong anticoagulation may be necessary after the acute phase to prevent recurrence, with attention paid to the potential side effects of prolonged medication use (e.g., bleeding). Prophylactic anticoagulation may also be warranted when thrombophilic patients are exposed to other risk factors for thrombosis.
Symptomatic and General Supportive Care
This includes measures to alleviate pain, correct organ failure, dilate blood vessels, and improve circulation. Adjunctive therapies may involve agents to reduce blood viscosity, calcium channel blockers, vasodilators, and herbal formulations.