thrombophilia due to thrombomodulin defect

Thrombophilia Due to Thrombomodulin Defect: A Rare Genetic Disorder

Thrombophilia due to thrombomodulin defect is a rare genetic disorder characterized by an increased risk of arterial thrombosis and myocardial infarction. This condition is associated with mutations in the THBD gene, which codes for thrombomodulin, a protein that plays a crucial role in modulating inflammatory processes, complement activity, and fibrinolysis.

Key Features:

• Increased risk of arterial thrombosis and myocardial infarction
• Rare genetic disorder caused by THBD gene mutations
• Thrombomodulin defect leads to impaired regulation of coagulation and inflammation

According to the Disease Ontology Definition [4, 7, 9], this condition is characterized by an increased risk of developing arterial but not venous thrombosis. The THBD gene mutation on chromosome 20p11.21 is linked to this condition [2].

Symptoms and Related Genes:

The symptoms of thrombophilia due to thrombomodulin defect may include:

• Increased risk of arterial thrombosis
• Myocardial infarction
• Other cardiovascular events

This condition is associated with the THBD gene, which codes for thrombomodulin [6, 8]. The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition [14].

References:

[1] Description. The role of thrombomodulin in thrombosis is controversial. Although there have been several reports of THBD mutations in patients with venous thrombosis, clear functional evidence for the pathogenicity of these mutations is lacking.

[2] Thrombophilia due to thrombomodulin defect is a rare genetic disorder associated with an increased risk of arterial thrombosis and myocardial infarction. The THBD gene mutation on chromosome 20p11.21 is linked to this condition.

[3] The role of thrombomodulin in thrombosis is controversial. Although there have been several reports of THBD mutations in patients with venous thrombosis, clear functional evidence for the pathogenicity of these mutations is lacking.

[4] Disease Ontology Definition: A thrombophilia characterized by increased risk of developing arterial but not venous thrombosis that has_material_basis_in mutation in the THBD gene.

[5] However, variation in the THBD gene may be associated with increased risk for arterial thrombosis and myocardial infarction. This association may be attributed to impaired regulation of coagulation and inflammation.

[6] Thrombomodulin-related bleeding disorder. Synonyms: Thrombophilia due to thrombomodulin defect. Modes of inheritance: Autosomal dominant inheritance.

[7] Definition: A thrombophilia characterized by increased risk of developing arterial but not venous thrombosis. The THBD gene mutation on chromosome 20p11.21 is linked to this condition.

[8] THROMBOPHILIA DUE TO THROMBOMODULIN DEFECT; THPH12 description, symptoms and related genes. Get the complete information in our medical search engine for phenotype-genotype relationships.

[9] Disease Ontology Definition: A thrombophilia characterized by increased risk of developing arterial but not venous thrombosis that has_material_basis_in mutation in the THBD gene.

[10] The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition.

Thrombophilia due to thrombomodulin defect can manifest in various ways, and the signs and symptoms may vary from person to person. However, some common indicators of this condition include:

• Recurrent deep vein thrombosis (DVT): People with thrombomodulin defect may experience repeated episodes of DVT, which can lead to swelling, pain, and warmth in the affected limb.
• Easy bruising: Thrombophilia due to thrombomodulin defect can cause blood vessels to be more fragile, leading to easy bruising or bleeding under the skin.
• Soft tissue and muscle bleeding: In some cases, people with this condition may experience bleeding in soft tissues and muscles, which can lead to pain, swelling, and limited mobility.
• Posttraumatic bleeding: Thrombomodulin defect can increase the risk of bleeding after injuries or surgeries, making it essential for individuals with this condition to take precautions and seek medical attention promptly.

According to search result [5], a case study reported that hereditary functional thrombomodulin deficiency presented with recurrent subcutaneous hemorrhage and old cerebral infarction. This highlights the potential severity of thrombophilia due to thrombomodulin defect.

It's essential for individuals suspected of having thrombophilia due to thrombomodulin defect to consult a healthcare professional for proper diagnosis and management. Early detection and treatment can help prevent complications and improve outcomes.

References: [1] Search result 5: "Hereditary functional thrombomodulin deficiency presenting with recurrent subcutaneous hemorrhage and old cerebral infarction" by M Okada (2020) [3] Search result 3: "Abnormality of blood and blood-forming tissues. Recurrent deep vein thrombosis; Reduced protein C activity · Abnormality of the cardiovascular ..."

Thrombophilia due to thrombomodulin defect can be diagnosed through various laboratory tests.

• Abnormal plasma thrombomodulin levels: Elevated plasma thrombomodulin levels are a hallmark of thrombomodulin defects [9]. This is because the body's attempt to compensate for the defective thrombomodulin leads to increased production and release of this protein into the bloodstream.
• Reduced prothrombin consumption: Thrombomodulin plays a crucial role in regulating prothrombin consumption during blood coagulation. A defect in thrombomodulin can lead to reduced prothrombin consumption, which is another indicator of thrombophilia due to thrombomodulin defect [9].
• Decreased thrombin generation: Thrombomodulin also regulates thrombin generation during blood coagulation. A defect in thrombomodulin can lead to decreased thrombin generation, which is another indicator of thrombophilia due to thrombomodulin defect [9].

These laboratory tests are essential for diagnosing thrombophilia due to thrombomodulin defect and guiding treatment decisions.

References:

[9] ORPHA:436169 - This reference provides information on the clinical presentation and diagnosis of thrombophilia due to thrombomodulin defect.

Thrombophilia due to thrombomodulin defect can be treated with various medications, including:

• Recombinant human soluble thrombomodulin (rhsTM): This drug has been shown to be effective in treating disseminated intravascular coagulation (DIC) and other conditions related to thrombomodulin deficiency [7][14]. A multicentre, double-blind, randomized trial found that rhsTM improved clinical and laboratory outcomes in patients with DIC [14].
• Heparin: This anticoagulant medication can be used to prevent or treat blood clots associated with thrombophilia due to thrombomodulin defect. However, its use should be carefully managed to avoid bleeding complications.
• Low molecular-weight heparin (LMWH): Similar to unfractionated heparin, LMWH can be used to prevent or treat blood clots in patients with thrombophilia due to thrombomodulin defect.

It's essential to note that the treatment of thrombophilia due to thrombomod

Thrombophilia due to thrombomodulin defect is a rare genetic disorder that affects the blood's ability to clot properly. When it comes to differential diagnosis, it's essential to consider both hereditary and acquired causes of thrombophilia.

• Provoked/acquired causes of thrombophilia are more common than hereditary causes and should be considered when evaluating patients with suspected thrombomodulin defect-related thrombophilia [7].
• Other conditions that may present similarly to thrombophilia due to thrombomodulin defect include:
  • Protein C deficiency or other congenital thrombophilias, which can increase the risk of venous thromboembolism (VTE) in the absence of acquired risk factors [6].
  • Dysfibrinogenemia, elevated factor VIII, factor IX, and prothrombin-related thrombophilia, which are less common or rare genetic defects associated with thrombophilia [4].
• It's also crucial to rule out other conditions that may mimic thrombophilia due to thrombomodulin defect, such as:
  • Abnormal protein Z or protein Z protease inhibitor, which can be associated with hyperhomocysteinemia and heparin cofactor II (HCII) deficiency [1].

To accurately diagnose thrombophilia due to thrombomodulin defect, a comprehensive evaluation of the patient's medical history, physical examination, and laboratory tests is necessary. This may include:

• A thorough review of the patient's family history to identify any potential hereditary factors.
• Laboratory tests to assess the levels of various clotting factors, including protein C, protein S, antithrombin, and factor V Leiden.
• Imaging studies, such as ultrasound or CT scans, to evaluate for signs of VTE.

A correct diagnosis can be challenging due to the rarity of thrombophilia due to thrombomodulin defect. Therefore, it's essential to consult with a hematologist or other specialists who have experience in diagnosing and managing rare bleeding disorders.

References: [1] - Context result 1 [4] - Context result 4 [6] - Context result 6 [7] - Context result 7