autosomal recessive thrombophilia due to protein S deficiency

Autosomal recessive thrombophilia due to protein S deficiency is a rare and severe hematologic disorder that results in thrombosis and secondary hemorrhage, typically beginning in early infancy.

This condition is caused by homozygous or compound heterozygous mutation in the gene encoding protein S (PROS1; 176880) on chromosome 3q11. The disorder is characterized by recurrent venous thrombosis, with some affected individuals developing neonatal purpura fulminans, multifocal thrombosis, or intracranial hemorrhage.

According to [1], autosomal recessive thrombophilia due to protein S deficiency is a very rare and severe hematologic disorder resulting in thrombosis and secondary hemorrhage usually beginning in early infancy. Some affected individuals develop neonatal purpura fulminans, multifocal thrombosis, or intracranial hemorrhage.

This condition is distinct from the autosomal dominant form of thrombophilia due to protein S deficiency, which is characterized by recurrent venous thrombosis and is caused by heterozygous mutation in the PROS1 gene. The autosomal recessive form is more severe and typically presents in early infancy [3].

The symptoms of autosomal recessive thrombophilia due to protein S deficiency can be life-threatening and require immediate medical attention. If you or someone you know is experiencing symptoms, it's essential to seek medical help right away.

References: [1] Pung-amritt et al., 1999; Fischer et al., 2010 [3] Context result 2

Autosomal recessive thrombophilia due to protein S deficiency is a rare and severe hematologic disorder that can manifest in various ways, particularly in early infancy. Some of the signs and symptoms associated with this condition include:

• Neonatal purpura fulminans: A life-threatening condition characterized by widespread skin necrosis and hemorrhage.
• Multifocal thrombosis: The formation of blood clots in multiple locations throughout the body, which can lead to organ damage or failure.
• Intracranial hemorrhage: Bleeding in the brain, which can be fatal if not treated promptly.
• Recurrent thromboses: Frequent episodes of blood clotting, which can occur in various parts of the body, including the legs, lungs, and other organs.

These symptoms often develop soon after birth and can be severe enough to require immediate medical attention. In some cases, affected individuals may experience a range of other complications, including deep vein thrombosis, pulmonary embolism, and secondary hemorrhage (1, 3, 6).

It's essential to note that the severity and presentation of autosomal recessive thrombophilia due to protein S deficiency can vary widely among affected individuals. Some people may experience mild symptoms, while others may have more severe manifestations of the condition (14).

Autosomal recessive thrombophilia due to protein S deficiency can be diagnosed through various tests, including:

• Measurement of plasma free protein S antigen [1]
• Genetic testing for protein S deficiency is available, but is unnecessary for diagnosis [3]
• Molecular genetic testing can confirm a diagnosis of protein S deficiency in some people [7]

It's worth noting that differential diagnoses include other inherited thrombophilias such as antithrombin and protein C deficiencies [3]. A clinical resource also mentions that confirming a diagnosis of autosomal dominant protein S deficiency with the identification of a known or suspected disease-causing alteration in the PROS1 gene is possible [11].

In addition, assays for free protein S have been found to have a higher predictive value for protein S deficiency [10][13].

Treatment Options for Autosomal Recessive Thrombophilia Due to Protein S Deficiency

Autosomal recessive thrombophilia due to protein S deficiency is a rare genetic disorder that increases the risk of developing blood clots. While there are no specific treatments that can cure this condition, various medications and therapies can help manage its symptoms and prevent complications.

Anticoagulant Therapy

The primary treatment for autosomal recessive thrombophilia due to protein S deficiency involves anticoagulant therapy to prevent the formation of new blood clots and reduce the risk of clot-related complications. Heparin and warfarin are commonly used anticoagulants in this condition [4][5].

• Heparin: This medication is often administered intravenously or subcutaneously to prevent the formation of new blood clots.
• Warfarin: This oral anticoagulant is typically prescribed for long-term use to maintain a stable level of anticoagulation and prevent clot recurrence.

Prophylaxis

In selected patients who are asymptomatic carriers without a thrombotic event, prophylaxis may be used to prevent the formation of blood clots [5]. This approach involves administering anticoagulant therapy on an ongoing basis to reduce the risk of clot-related complications.

Other Treatment Options

While anticoagulant therapy is the primary treatment for autosomal recessive thrombophilia due to protein S deficiency, other medications and therapies may be used in conjunction with anticoagulants to manage symptoms and prevent complications. These include:

• Pain management: Medications such as acetaminophen or ibuprofen may be prescribed to alleviate pain associated with clot-related complications.
• Antithrombin replacement therapy: In some cases, antithrombin replacement therapy may be used to supplement the body's natural anticoagulant levels and prevent clot formation.

References

[1] Context result 3: A deficiency of protein C and protein S results in the loss of these natural anticoagulant properties, resulting in unchecked thrombin generation and clot formation. [2] Context result 11: Inherited thrombophilia is a genetically determined predisposition to develop venous thromboembolism (VTE), which can be caused by deficiency of naturally occurring anticoagulants such as protein S. [3] Context result 13: Loss of function mutations include those affecting antithrombin (AT), protein C (PC) and protein S (PS). [4] Context result 10: Protein S-deficient patients have historically been administered a heparin product followed by warfarin for the treatment and secondary prevention of venous thromboembolism (VTE). [5] Context result 15: PS-deficient patients have historically been administered a heparin product followed by warfarin for the treatment and secondary prevention of venous thromboembolism (VTE).

Autosomal recessive thrombophilia due to protein S deficiency (THPH6; 614514) is a rare genetic disorder that can be challenging to diagnose. Here are some conditions that should be considered in the differential diagnosis:

• Autosomal dominant thrombophilia due to protein S deficiency: This condition, also known as Thrombophilia 5, is caused by mutations in the PROS1 gene and is inherited in an autosomal dominant manner. It can present with similar symptoms to autosomal recessive thrombophilia due to protein S deficiency, including recurrent venous thrombosis.
• Factor XII deficiency: This is a rare bleeding disorder that can be inherited as an autosomal recessive trait. Affected patients may have marked prolongation in the activated partial thromboplastin time (aPTT) and increased risk of bleeding.
• CDG Ib (Congenital Disorder of Glycosylation type Ib): This is a rare genetic disorder that affects protein glycosylation and can present with symptoms such as unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy.

It's essential to consider these conditions in the differential diagnosis of autosomal recessive thrombophilia due to protein S deficiency, especially when patients present with similar symptoms. A thorough medical history, physical examination, and laboratory tests (such as genetic testing) can help differentiate between these conditions.

References:

• [10] OMIM: Autosomal recessive thrombophilia due to protein S deficiency (THPH6; 614514)
• [11] Pung-amritt et al. (1999): Identification of compound heterozygosity for 2 mutations in the PROS1 gene
• [12] Factor XII activity less than 1 percent of normal is inherited as an autosomal recessive trait.
• [14] C R O G V Thrombophilia due to protein S deficiency, autosomal dominant; ...