The anticoagulant protein is Protein S which is dependent-vitamin K identified by Seattle for the first time in 1979. It assists in helping activated protein C target substrates such as FVa and FVIIIa by acting as a cofactor, if there is a deficiency in Protein S frequently it triggers venous thromboembolism. While there is a modest association between Protein S deficiency and arterial thrombosis evidence remains inconclusive. A protein S deficit is either inherited or acquired and it is frequently associated with vitamin K deficiency and nephrotic syndrome. People with homozygous and heterozygous genetic deficits of Protein S experience thrombotic events.
Epidemiology
Familial deficiency accounts for 0.03 to 0.13% cases of protein S deficiency in healthy blood donors which is rare and more common in particular populations. But it rises to 3-5% in people with a family history or past history of thrombosis. The frequency of the condition may change if criteria for identifying protein S deficiency are changed and thrombophilic disorder is highly influenced by race, with major variations observed across African, American, Japanese, and white populations. Although the clinical consequences of elevated levels of protein S antigen in men are unknown, they do tend to occur. In people with genetic protein S deficiency the age factor influences thrombosis, heterozygous people usually have episodes before the age of 40–45.
Anatomy
Pathophysiology
Protein S plays a crucial role among the body’s anticoagulant proteins by regulating the coagulation process. It serves to control clots in pathological and physiological contexts by activating procoagulant factors. Activated protein C (APC) operates within the protein C system, where protein S acts as a nonenzymatic cofactor. During clotting the complexes like tenase and prothrombinase are anchored by the activated forms of factor VIII (FVIIIa) and factor V (FVa), which forms on membrane surfaces. While Protein S and APC are capable of inactivating FVa independently, the involvement of factor V is essential for APC and protein S to effectively deactivate FVIIIa. Protein S acts as APC-independent anticoagulant which directly inhibits the enzyme complex factor Xa/factor Va prothrombinase.
Etiology
Protein S deficiency can be either from hereditary or acquired factors in which 2 genes linked to the human protein S are functional PROS-α and nonfunctional PROS-β, which results in evolutionary duplication. The PROS1 gene spans over 80 kb and comprises 15 exons and 14 introns. More than 200 mutations in PROS-α have been noted which is root cause of protein S deficiency and thrombophilia with majority of point mutations. In a case-control study involving 603 han chinese patients with venous thromboembolism, 24 different mutations were found in 34 patients with protein S deficiency.
Reduced protein S levels are linked to a variety of acquired diseases, which are due to the use of contraceptive pills, warfarin and associated conditions like nephrotic syndrome, vitamin K deficiencies, and myeloproliferative problems. The levels of protein S might decrease or abnormal during pregnancy and it is not a determinant factor to lead thrombosis. Sickle cell disease is a less recognized disease caused by protein S deficiency which is not independently induce a thrombophilic state.
Genetics
Prognostic Factors
Clinical History
History:
Protein S deficiency can result in lower limb edema, pain, redness, discoloration, and cellulitis. It is associated with deep vein thrombosis (DVT), thrombophlebitis, or pulmonary embolism.
A hereditary thrombophilia like protein S deficiency, may be indicated by a family history of thrombosis in early life or through recurring occurrences.
Physical Examination
The examination for symptoms of pulmonary embolism or venous thrombosis can easily be misdiagnosed in cases of DVT. Unusual thrombosis locations may indicate thrombophilia’s that are hereditary.
Deep vein thrombosis:
This condition primarily affects the lower limbs and is characterized by enlarged, rigid, and noncompressible veins.
Keep an eye out for symptoms like localized inflammation and venous blockage which might be DVT.
Calf discomfort, edema, and the Homan sign are classic DVT symptoms and less than one-third of patients exhibit these symptoms.
Muscle strains, Baker cysts, and postphlebitic syndrome are conditions which are marked by persistent discomfort and swelling are examples of differential diagnosis.
Pulmonary Embolism:
The right ventricular dysfunction is not a unique to PE but shows a raised pulmonic component of the second heart sound, left parasternal lift, and protruding neck veins.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Thrombophilia Testing:
Because hereditary protein S deficiency is uncommon, it is not advised for all VTE patients.
Unknown thrombosis site and recurrent thrombosis with age group 45–50 years old with a family history of thrombosis, pregnancy-related thrombosis, and patients receiving hormone replacement treatment.
Protein S deficiency or other congenital thrombophilia may be present in patients with VTE whom dont have acquired risk factors. 8.2% of pediatric VTE cases had protein S deficiency and with some of those cases also having concurrent risk factors. Various diagnoses include paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, antithrombin deficiency, disseminated intravascular coagulation, early pregnancy loss, Factor V Leiden mutation, immobilization, malignancy, and metastatic cancer with a primary Site.
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Protein S contributes to the body’s natural anticoagulant system by helping to cleave factors Va and VIIIa. Protein S is a cofactor for activated protein C that is dependent on vitamin K. Heterozygous deficits of protein S and protein C expose individuals to venous thrombosis due to parallel in genetic transmission, prevalence, testing, therapy, and precautions.
Neonatal purpura fulminans which is similar to cases of protein C deficit result from homogeneous protein S insufficiency. Hypercoagulability is exacerbated by acquired deficiency of protein C and protein S and in disseminated intravascular coagulation (DIC), vitamin K insufficiency, liver disease, warfarin medication, estrogen replacement therapy, pregnancy, and inflammation.
The diagnosis is based on total or free plasma protein S antigenic tests, the unbound form of protein S is marked as free protein S. Though there are protein S activity tests available, antigen assays are more reproducible due to their easier technical setup and high false-positive rate.
A pure protein S concentrate is not used in the same way as in protein C shortage when it comes to treating venous thrombosis-related protein S deficit. Protein S replacement in thrombotic crises is accomplished using normal plasma.
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
nonpharmacological-treatment
Dietary concerns:
Diet should be maintained in patients with protein S deficiency and who are on warfarin stabilize the intake of vitamin K. Heparin Preventive Measures for Heterozygous Protein S Deficiency:
Heparin is used during surgery, trauma, pregnancy, and prolonged bed rest. Deficits in protein S and protein C increases clotting and raise the risk of fetal loss. Pregnant women who have a history of fetal death, severe eclampsia, or recurrent eclampsia, and protein S deficiency should be on this drug.
Pregnant woman who have other thrombophilic disease associated with protein S deficiency may vary. If using oral anticoagulants throughout pregnancy, switch to a full dose and then start with oral anticoagulants after giving birth. Patients with recurrent thrombosis should take warfarin through out the life.
Use of Anticoagulants
Unfractionated IV heparin or SC heparins are the options for initial anticoagulation treatment. After 1-3 days of successful heparinization following warfarin medication may be started.
Heparin:
It is given by continuous IV infusion to treat acute thrombosis and prevention of thrombosis done by subcutaneous route.
Enoxaparin:
The factor Xa and thrombin inhibition is acheived by increasing antithrombin III activity.
Dalteparin:
It enhances the activity of antithrombin III by blocking the thrombin and factor Xa.
Tinzaparin:
This drug increases antithrombin III activity by inhibiting thrombin and factor Xa.
Warfarin:
This anticoagulant inhibits action of vitamin K and prevents thrombotic disorders.
The anticoagulant protein is Protein S which is dependent-vitamin K identified by Seattle for the first time in 1979. It assists in helping activated protein C target substrates such as FVa and FVIIIa by acting as a cofactor, if there is a deficiency in Protein S frequently it triggers venous thromboembolism. While there is a modest association between Protein S deficiency and arterial thrombosis evidence remains inconclusive. A protein S deficit is either inherited or acquired and it is frequently associated with vitamin K deficiency and nephrotic syndrome. People with homozygous and heterozygous genetic deficits of Protein S experience thrombotic events.
Familial deficiency accounts for 0.03 to 0.13% cases of protein S deficiency in healthy blood donors which is rare and more common in particular populations. But it rises to 3-5% in people with a family history or past history of thrombosis. The frequency of the condition may change if criteria for identifying protein S deficiency are changed and thrombophilic disorder is highly influenced by race, with major variations observed across African, American, Japanese, and white populations. Although the clinical consequences of elevated levels of protein S antigen in men are unknown, they do tend to occur. In people with genetic protein S deficiency the age factor influences thrombosis, heterozygous people usually have episodes before the age of 40–45.
Protein S plays a crucial role among the body’s anticoagulant proteins by regulating the coagulation process. It serves to control clots in pathological and physiological contexts by activating procoagulant factors. Activated protein C (APC) operates within the protein C system, where protein S acts as a nonenzymatic cofactor. During clotting the complexes like tenase and prothrombinase are anchored by the activated forms of factor VIII (FVIIIa) and factor V (FVa), which forms on membrane surfaces. While Protein S and APC are capable of inactivating FVa independently, the involvement of factor V is essential for APC and protein S to effectively deactivate FVIIIa. Protein S acts as APC-independent anticoagulant which directly inhibits the enzyme complex factor Xa/factor Va prothrombinase.
Protein S deficiency can be either from hereditary or acquired factors in which 2 genes linked to the human protein S are functional PROS-α and nonfunctional PROS-β, which results in evolutionary duplication. The PROS1 gene spans over 80 kb and comprises 15 exons and 14 introns. More than 200 mutations in PROS-α have been noted which is root cause of protein S deficiency and thrombophilia with majority of point mutations. In a case-control study involving 603 han chinese patients with venous thromboembolism, 24 different mutations were found in 34 patients with protein S deficiency.
Reduced protein S levels are linked to a variety of acquired diseases, which are due to the use of contraceptive pills, warfarin and associated conditions like nephrotic syndrome, vitamin K deficiencies, and myeloproliferative problems. The levels of protein S might decrease or abnormal during pregnancy and it is not a determinant factor to lead thrombosis. Sickle cell disease is a less recognized disease caused by protein S deficiency which is not independently induce a thrombophilic state.
History:
Protein S deficiency can result in lower limb edema, pain, redness, discoloration, and cellulitis. It is associated with deep vein thrombosis (DVT), thrombophlebitis, or pulmonary embolism.
A hereditary thrombophilia like protein S deficiency, may be indicated by a family history of thrombosis in early life or through recurring occurrences.
The examination for symptoms of pulmonary embolism or venous thrombosis can easily be misdiagnosed in cases of DVT. Unusual thrombosis locations may indicate thrombophilia’s that are hereditary.
Deep vein thrombosis:
This condition primarily affects the lower limbs and is characterized by enlarged, rigid, and noncompressible veins.
Keep an eye out for symptoms like localized inflammation and venous blockage which might be DVT.
Calf discomfort, edema, and the Homan sign are classic DVT symptoms and less than one-third of patients exhibit these symptoms.
Muscle strains, Baker cysts, and postphlebitic syndrome are conditions which are marked by persistent discomfort and swelling are examples of differential diagnosis.
Pulmonary Embolism:
The right ventricular dysfunction is not a unique to PE but shows a raised pulmonic component of the second heart sound, left parasternal lift, and protruding neck veins.
Thrombophilia Testing:
Because hereditary protein S deficiency is uncommon, it is not advised for all VTE patients.
Unknown thrombosis site and recurrent thrombosis with age group 45–50 years old with a family history of thrombosis, pregnancy-related thrombosis, and patients receiving hormone replacement treatment.
Protein S deficiency or other congenital thrombophilia may be present in patients with VTE whom dont have acquired risk factors. 8.2% of pediatric VTE cases had protein S deficiency and with some of those cases also having concurrent risk factors. Various diagnoses include paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, antithrombin deficiency, disseminated intravascular coagulation, early pregnancy loss, Factor V Leiden mutation, immobilization, malignancy, and metastatic cancer with a primary Site.
Protein S contributes to the body’s natural anticoagulant system by helping to cleave factors Va and VIIIa. Protein S is a cofactor for activated protein C that is dependent on vitamin K. Heterozygous deficits of protein S and protein C expose individuals to venous thrombosis due to parallel in genetic transmission, prevalence, testing, therapy, and precautions.
Neonatal purpura fulminans which is similar to cases of protein C deficit result from homogeneous protein S insufficiency. Hypercoagulability is exacerbated by acquired deficiency of protein C and protein S and in disseminated intravascular coagulation (DIC), vitamin K insufficiency, liver disease, warfarin medication, estrogen replacement therapy, pregnancy, and inflammation.
The diagnosis is based on total or free plasma protein S antigenic tests, the unbound form of protein S is marked as free protein S. Though there are protein S activity tests available, antigen assays are more reproducible due to their easier technical setup and high false-positive rate.
A pure protein S concentrate is not used in the same way as in protein C shortage when it comes to treating venous thrombosis-related protein S deficit. Protein S replacement in thrombotic crises is accomplished using normal plasma.
Nutrition
Dietary concerns:
Diet should be maintained in patients with protein S deficiency and who are on warfarin stabilize the intake of vitamin K. Heparin Preventive Measures for Heterozygous Protein S Deficiency:
Heparin is used during surgery, trauma, pregnancy, and prolonged bed rest. Deficits in protein S and protein C increases clotting and raise the risk of fetal loss. Pregnant women who have a history of fetal death, severe eclampsia, or recurrent eclampsia, and protein S deficiency should be on this drug.
Pregnant woman who have other thrombophilic disease associated with protein S deficiency may vary. If using oral anticoagulants throughout pregnancy, switch to a full dose and then start with oral anticoagulants after giving birth. Patients with recurrent thrombosis should take warfarin through out the life.
Cardiology, General
Unfractionated IV heparin or SC heparins are the options for initial anticoagulation treatment. After 1-3 days of successful heparinization following warfarin medication may be started.
Heparin:
It is given by continuous IV infusion to treat acute thrombosis and prevention of thrombosis done by subcutaneous route.
Enoxaparin:
The factor Xa and thrombin inhibition is acheived by increasing antithrombin III activity.
Dalteparin:
It enhances the activity of antithrombin III by blocking the thrombin and factor Xa.
Tinzaparin:
This drug increases antithrombin III activity by inhibiting thrombin and factor Xa.
Warfarin:
This anticoagulant inhibits action of vitamin K and prevents thrombotic disorders.
The anticoagulant protein is Protein S which is dependent-vitamin K identified by Seattle for the first time in 1979. It assists in helping activated protein C target substrates such as FVa and FVIIIa by acting as a cofactor, if there is a deficiency in Protein S frequently it triggers venous thromboembolism. While there is a modest association between Protein S deficiency and arterial thrombosis evidence remains inconclusive. A protein S deficit is either inherited or acquired and it is frequently associated with vitamin K deficiency and nephrotic syndrome. People with homozygous and heterozygous genetic deficits of Protein S experience thrombotic events.
Familial deficiency accounts for 0.03 to 0.13% cases of protein S deficiency in healthy blood donors which is rare and more common in particular populations. But it rises to 3-5% in people with a family history or past history of thrombosis. The frequency of the condition may change if criteria for identifying protein S deficiency are changed and thrombophilic disorder is highly influenced by race, with major variations observed across African, American, Japanese, and white populations. Although the clinical consequences of elevated levels of protein S antigen in men are unknown, they do tend to occur. In people with genetic protein S deficiency the age factor influences thrombosis, heterozygous people usually have episodes before the age of 40–45.
Protein S plays a crucial role among the body’s anticoagulant proteins by regulating the coagulation process. It serves to control clots in pathological and physiological contexts by activating procoagulant factors. Activated protein C (APC) operates within the protein C system, where protein S acts as a nonenzymatic cofactor. During clotting the complexes like tenase and prothrombinase are anchored by the activated forms of factor VIII (FVIIIa) and factor V (FVa), which forms on membrane surfaces. While Protein S and APC are capable of inactivating FVa independently, the involvement of factor V is essential for APC and protein S to effectively deactivate FVIIIa. Protein S acts as APC-independent anticoagulant which directly inhibits the enzyme complex factor Xa/factor Va prothrombinase.
Protein S deficiency can be either from hereditary or acquired factors in which 2 genes linked to the human protein S are functional PROS-α and nonfunctional PROS-β, which results in evolutionary duplication. The PROS1 gene spans over 80 kb and comprises 15 exons and 14 introns. More than 200 mutations in PROS-α have been noted which is root cause of protein S deficiency and thrombophilia with majority of point mutations. In a case-control study involving 603 han chinese patients with venous thromboembolism, 24 different mutations were found in 34 patients with protein S deficiency.
Reduced protein S levels are linked to a variety of acquired diseases, which are due to the use of contraceptive pills, warfarin and associated conditions like nephrotic syndrome, vitamin K deficiencies, and myeloproliferative problems. The levels of protein S might decrease or abnormal during pregnancy and it is not a determinant factor to lead thrombosis. Sickle cell disease is a less recognized disease caused by protein S deficiency which is not independently induce a thrombophilic state.
History:
Protein S deficiency can result in lower limb edema, pain, redness, discoloration, and cellulitis. It is associated with deep vein thrombosis (DVT), thrombophlebitis, or pulmonary embolism.
A hereditary thrombophilia like protein S deficiency, may be indicated by a family history of thrombosis in early life or through recurring occurrences.
The examination for symptoms of pulmonary embolism or venous thrombosis can easily be misdiagnosed in cases of DVT. Unusual thrombosis locations may indicate thrombophilia’s that are hereditary.
Deep vein thrombosis:
This condition primarily affects the lower limbs and is characterized by enlarged, rigid, and noncompressible veins.
Keep an eye out for symptoms like localized inflammation and venous blockage which might be DVT.
Calf discomfort, edema, and the Homan sign are classic DVT symptoms and less than one-third of patients exhibit these symptoms.
Muscle strains, Baker cysts, and postphlebitic syndrome are conditions which are marked by persistent discomfort and swelling are examples of differential diagnosis.
Pulmonary Embolism:
The right ventricular dysfunction is not a unique to PE but shows a raised pulmonic component of the second heart sound, left parasternal lift, and protruding neck veins.
Thrombophilia Testing:
Because hereditary protein S deficiency is uncommon, it is not advised for all VTE patients.
Unknown thrombosis site and recurrent thrombosis with age group 45–50 years old with a family history of thrombosis, pregnancy-related thrombosis, and patients receiving hormone replacement treatment.
Protein S deficiency or other congenital thrombophilia may be present in patients with VTE whom dont have acquired risk factors. 8.2% of pediatric VTE cases had protein S deficiency and with some of those cases also having concurrent risk factors. Various diagnoses include paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, antithrombin deficiency, disseminated intravascular coagulation, early pregnancy loss, Factor V Leiden mutation, immobilization, malignancy, and metastatic cancer with a primary Site.
Protein S contributes to the body’s natural anticoagulant system by helping to cleave factors Va and VIIIa. Protein S is a cofactor for activated protein C that is dependent on vitamin K. Heterozygous deficits of protein S and protein C expose individuals to venous thrombosis due to parallel in genetic transmission, prevalence, testing, therapy, and precautions.
Neonatal purpura fulminans which is similar to cases of protein C deficit result from homogeneous protein S insufficiency. Hypercoagulability is exacerbated by acquired deficiency of protein C and protein S and in disseminated intravascular coagulation (DIC), vitamin K insufficiency, liver disease, warfarin medication, estrogen replacement therapy, pregnancy, and inflammation.
The diagnosis is based on total or free plasma protein S antigenic tests, the unbound form of protein S is marked as free protein S. Though there are protein S activity tests available, antigen assays are more reproducible due to their easier technical setup and high false-positive rate.
A pure protein S concentrate is not used in the same way as in protein C shortage when it comes to treating venous thrombosis-related protein S deficit. Protein S replacement in thrombotic crises is accomplished using normal plasma.
Nutrition
Dietary concerns:
Diet should be maintained in patients with protein S deficiency and who are on warfarin stabilize the intake of vitamin K. Heparin Preventive Measures for Heterozygous Protein S Deficiency:
Heparin is used during surgery, trauma, pregnancy, and prolonged bed rest. Deficits in protein S and protein C increases clotting and raise the risk of fetal loss. Pregnant women who have a history of fetal death, severe eclampsia, or recurrent eclampsia, and protein S deficiency should be on this drug.
Pregnant woman who have other thrombophilic disease associated with protein S deficiency may vary. If using oral anticoagulants throughout pregnancy, switch to a full dose and then start with oral anticoagulants after giving birth. Patients with recurrent thrombosis should take warfarin through out the life.
Cardiology, General
Unfractionated IV heparin or SC heparins are the options for initial anticoagulation treatment. After 1-3 days of successful heparinization following warfarin medication may be started.
Heparin:
It is given by continuous IV infusion to treat acute thrombosis and prevention of thrombosis done by subcutaneous route.
Enoxaparin:
The factor Xa and thrombin inhibition is acheived by increasing antithrombin III activity.
Dalteparin:
It enhances the activity of antithrombin III by blocking the thrombin and factor Xa.
Tinzaparin:
This drug increases antithrombin III activity by inhibiting thrombin and factor Xa.
Warfarin:
This anticoagulant inhibits action of vitamin K and prevents thrombotic disorders.
Both our subscription plans include Free CME/CPD AMA PRA Category 1 credits.
Digital Certificate PDF
On course completion, you will receive a full-sized presentation quality digital certificate.
medtigo Simulation
A dynamic medical simulation platform designed to train healthcare professionals and students to effectively run code situations through an immersive hands-on experience in a live, interactive 3D environment.
medtigo Points
medtigo points is our unique point redemption system created to award users for interacting on our site. These points can be redeemed for special discounts on the medtigo marketplace as well as towards the membership cost itself.
Community Forum post/reply = 5 points
*Redemption of points can occur only through the medtigo marketplace, courses, or simulation system. Money will not be credited to your bank account. 10 points = $1.
All Your Certificates in One Place
When you have your licenses, certificates and CMEs in one place, it's easier to track your career growth. You can easily share these with hospitals as well, using your medtigo app.
