Background

• Antithrombin deficiency is a rare inherited disorder that affects the body’s natural anticoagulant system, leading to an increased risk of abnormal formation of blood clots or thrombosis. Antithrombin is a crucial protein that regulates blood coagulation by inhibiting clotting factors, particularly thrombin and factor Xa.
• Deficiency in antithrombin can be caused by mutations in the SERPINC1 gene and is usually inherited in an autosomal recessive or dominant manner. The severity of the deficiency can vary, with some individuals being asymptomatic carriers, while others may experience recurrent thrombotic events, such as deep vein thrombosis (DVT) or pulmonary embolism (PE).
• The diagnosis is made through laboratory tests measuring antithrombin levels and functional activity. Treatment and management aim to reduce the risk of thrombosis and may involve anticoagulant therapy, genetic counseling, and lifestyle modifications. Early diagnosis and appropriate care are essential to prevent thrombotic complications and improve patient outcomes. 

Epidemiology

Prevalence: 

• Antithrombin deficiency is estimated to occur in 1 in 5,000 individuals in the general population. This prevalence may vary depending on the specific population and region being studied. 

Inheritance: 

• Antithrombin deficiency follows an autosomal dominant or autosomal recessive pattern of inheritance. In autosomal dominant inheritance, an individual only needs to inherit one copy of defective gene from one parent to develop the disorder. In autosomal recessive inheritance, both copies of the gene must be affected for the disorder to manifest. 

Geographical Distribution: 

• The prevalence of antithrombin deficiency is not uniform across different regions or ethnic groups. It has been reported in various populations worldwide, but some regions may have a higher prevalence due to genetic factors or specific founder mutations. 

Type of Antithrombin Deficiency: 

• Antithrombin deficiency can be classified into two main types: Type I, which involves a quantitative deficiency with reduced production of antithrombin protein, and Type II, which involves a qualitative deficiency with normal or increased production of antithrombin protein but reduced functional activity. 

Clinical Manifestations: 

• The severity of antithrombin deficiency can vary among individuals, and some may be asymptomatic carriers without any clinical manifestations. However, in individuals with significant antithrombin deficiency, the condition may increase the risk of developing abnormal blood clots or thrombosis. 

Risk Factors and Complications: 

• Antithrombin deficiency has an increased risk of venous thromboembolism (VTE), like deep vein thrombosis (DVT) and pulmonary embolism (PE). It may also increase the risk of arterial thrombosis, such as stroke or heart attack. Additionally, antithrombin deficiency can contribute to pregnancy-related complications, including recurrent miscarriages and preeclampsia. 

Anatomy

Pathophysiology

Role of Antithrombin in the Coagulation Cascade: 

• coagulation cascade is the series of enzymatic reactions which culminate in the formation of a stable blood clot. It is essential to prevent excessive bleeding after injury or trauma. During the coagulation process, various clotting factors interact and activate each other, leading to the conversion of fibrinogen into fibrin, which forms the clot. 

Antithrombin’s Inhibitory Action: 

• Antithrombin is a natural anticoagulant protein synthesized in the liver and released into the bloodstream. It plays a critical role in regulating coagulation by activity of thrombin and factor Xa inhibition, two central components of the coagulation cascade. Thrombin is a key enzyme responsible for converting fibrinogen into fibrin, while factor Xa is involved in the activation of prothrombin to thrombin. By neutralizing these factors, antithrombin effectively limits the coagulation process and prevents excessive clot formation. 

Types of Antithrombin Deficiency: 

• Antithrombin deficiency can be classified into two main types: Type I and Type II. 
• Type I: Involves a quantitative deficiency, where there is a reduced production of antithrombin protein. 
• Type II: Involves a qualitative deficiency, where the antithrombin protein is produced in normal or increased amounts but does not function effectively in inhibiting clotting factors. 

Increased Risk of Thrombosis: 

• In individuals with antithrombin deficiency, the decreased inhibitory action on thrombin and factor Xa leads to an imbalance favoring coagulation. This imbalance can result in an increased risk of abnormal blood clot formation or thrombosis. Venous thromboembolism (VTE) like deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common clinical manifestation of antithrombin deficiency. Arterial thrombosis, such as stroke or heart attack, may also occur, though less frequently than venous thrombosis. 

Pregnancy Complications: 

• Antithrombin deficiency can increase the risk of pregnancy-related complications, such as recurrent miscarriages, stillbirths, and preeclampsia. During pregnancy, the hemostatic system undergoes physiological changes, and antithrombin deficiency can exacerbate the prothrombotic state, leading to adverse pregnancy outcomes. 

Etiology

Genetic Inheritance: 

• Antithrombin deficiency follows an autosomal dominant or autosomal recessive pattern of inheritance, depending on the specific mutation and type of deficiency. 

Autosomal Dominant Inheritance: 

• In autosomal dominant inheritance, an individual only needs to inherit one copy of defective gene from one parent to develop the disorder. This means that a child has a 50% chance of inheriting faulty gene from a parent who has the disorder. Individuals with one abnormal gene (heterozygous) will have antithrombin deficiency, and the severity of the deficiency may vary among affected individuals. 

Autosomal Recessive Inheritance: 

• In autosomal recessive inheritance, an individual must inherit two copies of defective gene, one from each parent, to manifest the disorder. This means that both parents must carry abnormal gene without showing symptoms of antithrombin deficiency. Offspring of carriers (heterozygous) have a 25% chance of inheriting two abnormal genes and having antithrombin deficiency. 

De Novo Mutations: 

• In some cases, individuals may have antithrombin deficiency due to de novo mutations. These are new mutations that occur spontaneously in the affected individual and are not inherited from the parents. De novo mutations can lead to antithrombin deficiency in individuals with no family history of the disorder. 

Acquired Antithrombin Deficiency: 

• In rare cases, antithrombin deficiency can be acquired rather than inherited. Acquired antithrombin deficiency can be caused by various medical conditions and factors, such as liver disease, disseminated intravascular coagulation (DIC), nephrotic syndrome, or certain medications (e.g., heparin). Acquired antithrombin deficiency is not genetic and differs from the inherited form of the disorder. 

Genetic Mutations: 

• The genetic mutations responsible for antithrombin deficiency can be various point mutations, deletions, or insertions in the SERPINC1 gene. These mutations lead to impaired synthesis or function of the antithrombin protein, affecting its ability to inhibit clotting factors and regulate blood clotting. 

Variable Penetrance: 

• Antithrombin deficiency can exhibit variable penetrance, meaning that individuals with the same genetic mutation may have different degrees of deficiency and varying risk of developing thrombotic events. 

Genetics

Prognostic Factors

Type of Antithrombin Deficiency: 

• Antithrombin deficiency can be classified into two main types: Type I and Type II. Type I involves a quantitative deficiency with reduced production of antithrombin protein, while Type II involves a qualitative deficiency with normal or increased production of antithrombin protein but reduced functional activity. The type of deficiency can influence the severity of the disorder and the risk of thrombotic events. 

Extent of Antithrombin Deficiency: 

• The severity of antithrombin deficiency, as measured by the level of antithrombin activity in the bloodstream, can impact the risk of thrombosis. Individuals with more pronounced deficiencies are at a higher risk of developing abnormal blood clots or thrombotic events. 

Genetic Mutation and Inheritance Pattern: 

• The specific genetic mutation responsible for antithrombin deficiency and the inheritance pattern can also affect the risk of thrombotic events. Some mutations may lead to more severe deficiencies and a higher risk of thrombosis than others. 

Personal and Family History of Thrombosis: 

• A history of previous thrombotic events, such as deep vein thrombosis (DVT) or pulmonary embolism (PE) can be a significant prognostic factor. Individuals with a history of thrombosis are at an increased risk of recurrent events and may require more aggressive anticoagulation therapy. 

Additional Risk Factors: 

• Certain risk factors can further increase the likelihood of thrombosis in individuals with antithrombin deficiency. These risk factors include older age, obesity, smoking, hormonal therapy (e.g., oral contraceptives, hormone replacement therapy), prolonged immobility, and major surgeries. 

Pregnancy and Hormonal Status: 

• Pregnancy and the use of hormonal therapies can alter the hemostatic system, potentially exacerbating the prothrombotic state in individuals with antithrombin deficiency. Pregnant women with antithrombin deficiency may require specialized management to reduce the risk of pregnancy-related complications. 

Compliance with Anticoagulation Therapy: 

• The effectiveness of anticoagulation therapy, such as with heparin or warfarin, in preventing thrombotic events depends on the patient’s adherence to treatment. Compliance with prescribed anticoagulants is essential for reducing the risk of thrombosis. 

Clinical History

Age: 

• Antithrombin deficiency is typically diagnosed in individuals who have experienced thrombotic events, such as deep vein thrombosis (DVT), pulmonary embolism (PE), or other venous or arterial thromboembolism. The age of diagnosis can vary, with some individuals presenting in childhood, adolescence, or adulthood, depending on the severity of the deficiency and the presence of risk factors. 

Physical Examination

Vital Signs: 

• Blood pressure, heart rate, respiratory rate, and temperature should be recorded to assess the patient’s general health status. 

General Appearance: 

• The overall appearance of the patient, including any signs of distress or discomfort, can be observed during the examination. 

Extremities: 

• Physical examination of the extremities may reveal signs of deep vein thrombosis (DVT), such as unilateral leg swelling, pain, warmth, or redness. It is essential to assess for signs of a pulmonary embolism (PE), such as shortness of breath, chest pain, and signs of decreased oxygenation. 

Skin and Mucous Membranes: 

• Petechiae, purpura, or other skin changes suggestive of thrombocytopenia (low platelet count) should be noted, although thrombocytopenia is not a direct feature of antithrombin deficiency. 

Abdominal Examination: 

• An abdominal examination may reveal signs of venous thrombosis, such as distended veins, tenderness, or swelling in the abdomen or pelvis. 

Neurological Examination: 

• In cases of arterial thrombosis affecting the brain (stroke) or other neurological events, a neurological examination may be pertinent to assess motor function, sensory perception, and cognitive status. 

Pregnancy-related Examination: 

• In pregnant women with antithrombin deficiency, the physical examination should focus on signs of preeclampsia, such as hypertension, proteinuria, and edema. 

Age group

Associated comorbidity

• The presence of underlying medical conditions or comorbidities can influence the risk and severity of thrombotic events in individuals with antithrombin deficiency. Common associated comorbidities may include: 
• Obesity 
• Hypertension 
• Hyperlipidemia 
• Diabetes mellitus 
• Autoimmune disorders 
• Inflammatory conditions 

Associated activity

Acuity of presentation

• The acuity of presentation refers to the time frame and severity of the symptoms or thrombotic events. Antithrombin deficiency can present in various ways, such as: 
• Acute onset of symptoms during an active thrombotic event, such as sudden leg swelling and pain in DVT or sudden shortness of breath in PE. 
• Subacute presentation with less severe symptoms, such as chronic leg swelling or discomfort in DVT or mild breathing difficulties in PE. 
• Asymptomatic carriers who may be diagnosed incidentally during family screening or when evaluated for other medical conditions. 

Differential Diagnoses

Protein C Deficiency: 

• Protein C deficiency is another inherited disorder that affects the body’s anticoagulant system. Like antithrombin deficiency, protein C deficiency can lead to an increased risk of thrombosis. Laboratory testing for protein C levels and functional activity can help differentiate between the two conditions. 

Protein S Deficiency: 

• Protein S is another natural anticoagulant protein that works in conjunction with protein C to regulate blood clotting. Deficiency in protein S can also result in an increased risk of thrombosis. Laboratory testing for protein S levels and functional activity can aid in distinguishing protein S deficiency from antithrombin deficiency. 

Factor V Leiden Mutation: 

• It is a genetic mutation that makes the factor V clotting protein more resistant to inactivation by protein C. This mutation is a common cause of inherited thrombophilia and can increase the risk of thrombosis.  

Prothrombin Gene Mutation (Factor II Mutation): 

• The prothrombin gene mutation (also known as the factor II mutation) is another genetic alteration that can predispose individuals to thrombosis. It involves a point mutation in the prothrombin gene, leading to increased production of prothrombin, a clotting factor.  

Acquired Thrombophilia: 

• Acquired thrombophilia refers to conditions in which the risk of thrombosis increases due to non-genetic factors. These can include certain medical conditions (e.g., autoimmune disorders, cancer), medications (e.g., estrogen-containing contraceptives, hormone replacement therapy), and lifestyle factors (e.g., smoking, immobility). 

Lupus Anticoagulant and Antiphospholipid Syndrome: 

• Lupus anticoagulant is an acquired antiphospholipid antibody that can cause a paradoxical increase in the risk of blood clotting. When it is associated with other antiphospholipid antibodies, it is referred to as antiphospholipid syndrome, which is a systemic autoimmune disorder with thrombotic tendencies. 

Hypercoagulable States: 

• Various medical conditions and situations can lead to a hypercoagulable state and increase the risk of thrombosis. Examples include surgery, trauma, immobilization, pregnancy, and certain cancers. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

• Anticoagulant Therapy: Individuals with a history of thrombotic events or those at high risk of thrombosis may require anticoagulant therapy. The choice of anticoagulant and dosing will depend on the patient’s specific situation, age, medical history, and other medications they may be taking. Commonly used anticoagulants include: 
• Heparin: Initially, intravenous, or subcutaneous heparin may be used to rapidly control existing thrombosis. In some cases, heparin may be continued for a short period as a bridge to oral anticoagulants. 
• Oral Anticoagulants: Warfarin is commonly used for long-term oral anticoagulation. However, newer direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, or edoxaban may also be considered. 
• Antithrombin Concentrate: In certain high-risk situations, such as major surgeries or acute thrombotic events, intravenous administration of purified antithrombin concentrates may be used to supplement antithrombin levels and prevent or treat thrombosis. 
• Prophylaxis in High-Risk Situations: Individuals with antithrombin deficiency may require additional prophylactic measures to prevent thrombosis in high-risk situations, such as during surgery, prolonged immobility, or pregnancy. This may involve temporary adjustments in anticoagulation therapy or the use of mechanical prophylaxis (e.g., compression stockings) as needed. 
• Management of Bleeding Complications: For individuals with antithrombin deficiency experiencing bleeding episodes, treatment may involve the fresh frozen plasma or clotting factor concentrates administration to correct clotting abnormalities and control bleeding. 
• Genetic Counselling: Genetic counselling is essential for affected individuals and their families to understand the inheritance pattern and assess the risk of passing on the genetic mutation and receive guidance for family planning. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

non-pharmacological-treatment-of-antithrombin-deficiency

Lifestyle modifications: 

• Regular Physical Activity: Engaging in regular physical activity, such as walking, swimming, or biking, helps in the maintenance a healthy weight, and decreases the risk of blood clots.  
• Balanced Diet: Adopting a balanced and nutritious diet can promote overall health and reduce the risk of certain risk factors associated with thrombosis, such as obesity and high blood pressure.  
• Avoid Smoking & Limit Alcohol Intake: Smoking and consumption of alcohol may increase the risk of clot formation and other cardiovascular problems.  
• Hydration: Staying well-hydrated is essential to maintain proper blood flow and prevent the development of thick or sticky blood. Drinking plenty of water throughout the day is recommended. 
• Medication Adherence: If individuals with antithrombin deficiency are prescribed anticoagulant medications or other medications to manage underlying conditions, it is essential to adhere to the prescribed treatment plan and follow healthcare provider instructions. 
• Avoidance of Triggering Factors: For some individuals with antithrombin deficiency, specific trigger factors may increase the risk of clot formation, such as hormonal changes, prolonged immobility (e.g., during long flights or bed rest), or certain medications. Identifying and avoiding such triggers may be beneficial. 

use of Anticoagulants in the treatment of antithrombin deficiency

Parenteral Anticoagulation (Injectable Anticoagulants): 

• Heparin: Heparin is a fast-acting injectable anticoagulant often used in the acute management of thrombotic events or in situations where rapid anticoagulation is required. It works by enhancing the activity of antithrombin, thereby inhibiting clotting factors and preventing the formation of blood clots. 

Oral Anticoagulation: 

• Warfarin: Warfarin is a well-established oral anticoagulant that has been used for many years. It acts by inhibiting the synthesis of vitamin K-dependent clotting factors, including factor II (prothrombin), factor VII, factor IX, and factor X.  
• Direct Oral Anticoagulants (DOACs): DOACs are a newer class of oral anticoagulants that directly target specific clotting factors, such as factor IIa (thrombin) or factor Xa. Examples of DOACs include rivaroxaban, apixaban, edoxaban, and dabigatran. DOACs have a more predictable anticoagulant effect compared to warfarin and do not require frequent INR monitoring. 

Antithrombin Concentrate: 

• In certain high-risk situations, such as major surgeries or acute thrombotic events, intravenous administration of purified antithrombin concentrates may be used to supplement antithrombin levels and prevent or treat thrombosis. 

subsection: use of Antithrombin (AT) replacement therapy

Unfractionated Heparin (UFH): 

• UFH is a parenteral anticoagulant that can be administered intravenously or subcutaneously. It works by enhancing the activity of antithrombin, leading to the inhibition of various clotting factors, and preventing the formation of blood clots. 
• UFH is often used in the acute management of thrombotic events or in high-risk situations, such as before surgeries or invasive procedures. 

Low Molecular Weight Heparin (LMWH): 

• LMWH is a subcutaneously administered anticoagulant that also enhances the activity of antithrombin, leading to the inhibition of specific clotting factors, particularly factor Xa. 
• LMWH is commonly used in the prevention and treatment of pulmonary embolism (PE), deep vein thrombosis (DVT), and other thrombotic events in individuals with antithrombin deficiency. 

Argatroban: 

• Argatroban is a direct thrombin inhibitor that works by directly blocking the activity of thrombin, a central clotting factor. It is administered intravenously. 
• Argatroban is an alternative anticoagulant used when heparins are contraindicated or when anticoagulation with heparins is ineffective. 

Plasma-derived AT Concentrate: 

• Plasma-derived AT concentrate is derived from human plasma and contains a concentrated form of antithrombin. It is purified and treated to ensure its safety and efficacy. 

• Plasma-derived AT concentrate is administered intravenously to individuals with antithrombin deficiency to supplement the deficient or dysfunctional antithrombin protein. By restoring the anticoagulant function of AT, it helps prevent the formation of abnormal blood clots and reduces the risk of thrombotic events. 
• Plasma-derived AT concentrate is a well-established treatment option and has been used for many years in the management of various congenital and acquired antithrombin deficiencies. 

Recombinant AT (rAT): 

• Recombinant AT is a newer form of AT replacement therapy that is produced using genetic engineering techniques. It is synthesized in the laboratory and is not derived from human plasma. 
• Recombinant AT has a structure and function identical to naturally occurring AT. Like plasma-derived AT concentrate, it is administered intravenously to individuals with antithrombin deficiency to supplement their antithrombin levels and restore anticoagulant function. 
• The advantage of recombinant AT is that it reduces the risk of transmitting infections associated with plasma-derived products and allows for a more consistent and standardized production process. 

Patients receiving asparaginase in the treatment of antithrombin deficiency

Asparaginase: 

• Asparaginase is an enzyme used as part of chemotherapy treatment for certain types of leukemia, such as acute lymphoblastic leukemia (ALL). It acts by breaking down the amino acid asparagine, which is essential for the growth and survival of leukemia cells. By depleting asparagine levels, asparaginase helps inhibit leukemia cell growth and induce cancer cell death. 
• However, asparaginase therapy can affect the coagulation system and may cause a decrease in antithrombin levels, potentially leading to an acquired antithrombin deficiency. This acquired deficiency is typically reversible once the asparaginase treatment is completed. During asparaginase therapy, patients may have an increased risk of thrombotic events due to the temporary decrease in antithrombin activity. 
• To manage the risk of thrombosis during asparaginase treatment, healthcare providers closely monitor coagulation parameters, including antithrombin levels, and may consider prophylactic anticoagulation in some cases. This management approach aims to balance the benefits of cancer treatment with the potential risk of thrombotic complications. 
• Patients with antithrombin deficiency or a history of thrombosis should be closely monitored during asparaginase therapy, and any signs of thrombosis or bleeding should be promptly addressed. The treatment plan should be individualized based on the patient’s medical history, cancer type, and overall health condition. Healthcare professionals, including hematologists and oncologists, play a vital role in managing the potential coagulation issues associated with asparaginase treatment in patients with antithrombin deficiency to optimize treatment outcomes and minimize complications. 

Use of Venous thromboembolism (VTE) treatment in antithrombin deficiency

Anticoagulation Therapy: 

• Anticoagulation is the primary treatment for VTE, and it helps prevent the growth of existing clots and the formation of new ones. The choice of anticoagulant and duration of treatment depends on several factors, including the type of VTE, the patient’s risk profile, and the presence of any other medical conditions. 
• Commonly used anticoagulants include unfractionated heparin (UFH), low molecular weight heparin (LMWH), warfarin, and direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, edoxaban, or dabigatran. 

AT Replacement Therapy: 

• In severe AT deficiency or in cases of recurrent VTE despite anticoagulation, AT replacement therapy may be considered to supplement the deficient or dysfunctional antithrombin protein. AT replacement therapy aims to restore the anticoagulant function of AT and reduce the risk of thrombotic events. 
• Plasma-derived AT concentrate or recombinant AT may be used for AT replacement therapy. 

Management of Bleeding Complications: 

• In patients with antithrombin deficiency and VTE who experience bleeding complications, prompt management of bleeding and temporary discontinuation of anticoagulation may be necessary.  

Duration of Treatment: 

• The duration of therapy in patients with antithrombin deficiency and VTE is typically determined based on the individual’s risk factors for recurrent VTE. In many cases, long-term or lifelong anticoagulation may be necessary to reduce the risk of recurrence. 

surgical-procedures-involved-in-the-treatment-of-antithrombin-deficiency

Extracorporeal Membrane Oxygenation (ECMO): 

• ECMO is a life-supporting technique used in severe respiratory or cardiac failure, providing temporary oxygenation and removal of carbon dioxide outside the body. 
• In individuals with AT deficiency, ECMO may be necessary if there is severe respiratory or cardiac compromise that cannot be managed with conventional therapies. 
• While ECMO may be required in critical situations, it is crucial to closely monitor coagulation parameters and anticoagulant therapy during ECMO, as the procedure itself can activate the clotting system and increase the risk of thrombosis. 
• Anticoagulation is typically used during ECMO to prevent clotting within the circuit, and the choice and intensity of anticoagulation may need to be adjusted based on the patient’s coagulation profile. 

Cardiopulmonary Bypass (CPB): 

• CPB is a technique used during open-heart surgery to temporarily replace the function of heart & lungs, allowing the surgeon to operate on the heart while blood is rerouted and oxygenated outside the body. 
• Individuals with AT deficiency undergoing CPB may have an increased risk of thrombosis during and after the procedure due to the activation of the clotting system by the extracorporeal circuit. 
• Careful management of anticoagulation during CPB is essential to balance the risk of bleeding & thrombosis, and the specific anticoagulation protocol may vary based on the patient’s anticoagulant needs. 

Haemodialysis: 

• It is a renal replacement therapy used to filter waste products & excess fluids from the blood in individuals with kidney failure or severe kidney dysfunction. 
• In individuals with AT deficiency requiring haemodialysis, anticoagulation is often necessary during the procedure to prevent clotting within the dialysis circuit. The choice and intensity of anticoagulation will depend on the patient’s coagulation profile and risk of bleeding. 

Thrombectomy: 

• Thrombectomy is a procedure in which a specialized catheter is used to physically remove blood clots from blood vessels. It is commonly used in acute ischemic stroke caused by a large blood clot blocking a major brain artery or in specific cases of deep vein thrombosis (DVT) or pulmonary embolism. 
• Thrombectomy is also associated with a risk of bleeding, and in individuals with antithrombin deficiency, the decision to perform this procedure should be weighed against the bleeding risk and the potential benefits of clot removal. 

management-of-antithrombin-deficiency

Diagnosis and Evaluation: 

• The initial phase involves diagnosing antithrombin deficiency through laboratory tests to measure antithrombin levels and identify any genetic mutations associated with the condition. 
• Further evaluation may be done to assess the extent of the deficiency, identify any underlying conditions or risk factors, and rule out other potential causes of abnormal blood clotting. 

Acute Treatment and Thromboprophylaxis: 

• In the acute setting, such as when a patient presents with a thrombotic event, the focus is on providing prompt and appropriate treatment to manage the acute thrombosis and prevent its progression. 
• Anticoagulation therapy, which may include heparin, low molecular weight heparin, warfarin, or direct oral anticoagulants (DOACs), is often initiated to prevent further clot formation and reduce the risk of recurrent thrombosis. 

Long-Term Management: 

• Once the acute phase is controlled, the long-term management phase begins. This phase involves maintaining anticoagulation therapy to prevent recurrent thrombotic events and reduce the risk of complications. 
• The intensity and duration of anticoagulation may vary depending on the patient’s individual risk factors, bleeding risk, and response to therapy. 

AT Replacement Therapy (if indicated): 

• In severe cases of antithrombin deficiency or in individuals with recurrent thrombosis despite anticoagulation, AT replacement therapy may be considered to supplement the deficient or dysfunctional antithrombin protein. 
• AT replacement therapy aims to restore the anticoagulant function of AT and reduce the risk of thrombotic events. 

Medication

Future Trends

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References

• www.antithrombin deficiency: epidemiology, pathogenesis and treatment.ncbi.nlm.nih.gov 
• www.Inherited antithrombin deficiency.ncbi.nlm.nih.gov 
• www.antithrombin-iii-deficiency.sciencedirect.com