Type 1 deficiency is due to an insufficient quantity, type 2 to abnormal function, and type 3 to a shift from free protein s to bound protein s. Apixaban does not interfere with protein s or activated. Protein c deficiency is a disorder that increases the risk of developing abnormal blood clots. When someone bleeds, the blood begins a complicated series of rapid chemical reactions involving proteins called blood coagulation factors to stop the bleeding. We assayed for free protein s antigen, protein c antigen, and antithrombin iii and tested for lupuslike. The frequency of type i heterozygous protein s and protein c deficiency in 141 unrelated young patients with venous thrombosis.
Free protein s levels are elevated in familial c4bbinding. Protein s is a vitamin kdependent plasma glycoprotein that functions as a nonenzymatic cofactor of activated protein c in the inactivation of the procoagulant factors va and viiia, and plays an important role in regulating thrombin generation. The only way to know if you have protein s deficiency is by a blood test. Investigation of blood coagulation revealed a temporary protein c, protein s and factor ii deficiency. Jun 07, 2016 protein c deficiency is a disorder that increases a person s risk to develop abnormal blood clots due to a deficiency of the protein c, a protein in the body that prevents blood clotting.
Effects of protein deficiency on the pregnant woman and. Apixaban causes a false increase in activated protein c resistance apcr ratios and possibly protein s activity. The most important natural anticoagulants are protein c, protein s, and antithrombin which used to be called. During 20112016, 68 women with recurrent pregnancy loss rpl and protein s deficiency both the free antigen and function of protein s were reduced were initially enrolled. Protein deficiency affects the transport of many essential nutrients that are normally bound to protein carriers in the plasma, and thus correction of protein synthesis improves the apparent deficiency of specific nutrients. Free protein s deficiency in a family with venous thrombosis. Jordan a shavit, david ginsburg, in emery and rimoin s principles and practice of medical genetics, 20. The proteolytic activation of pc by thrombin occurs on the surface of endothelial cells and involves thrombomodulin and endothelial pc receptor. At the site of thrombin thrombomodulin complex formation, protein c gets converted into activated protein c, which in the presence of cofactor protein s, proteolyses and inactivates factor va and viiia.
Protein c deficiency is less common than factor v leiden or mutation in the prothrombin gene g20210a. If the protein s or c deficiency is due to an inherited genetic change, the quantity of protein c or protein s available and the degree of activity can be used to help determine whether you have one copy heterozygous or two copies of the mutation. Protein s deficiency is associated with an increased risk of thrombosis. Protein c has a short half life 8 hour compared with other vitamin kdependent factors and therefore is rapidly depleted with warfarin initiation, resulting in a transient hypercoagulable state. Protein s deficiency hematology and oncology merck. Deficiencies of natural anticoagulants, protein c, protein s. Inherited deficiency of protein c can lead to familial thrombophilia increased tendency toward thrombosis. Activated protein c resistance and dna analysis was performed for all patients taking rivaroxaban. Most vte events in heterozygous protein s deficiency occur in persons younger than 4045 years. Individuals with mild protein c deficiency are at risk of a type of blood clot known as a deep vein thrombosis dvt. Protein s deficiency brochure university of iowa health care other symptoms of blood clots include dizziness, headache, changes in vision, lack.
Protein s, a vitamin kdependent physiological anticoagulant, acts as a nonenzymatic cofactor to activate protein c in the degradation of factor va and factor viiia. Coagulation guidelines for unexplained bleeding disorders. Acquired protein c deficiency is a clinically similar disorder caused by development of an antibody against protein c. A protein s measurement is a test used to measure the amount of protein s in your body.
Iii normal total antigen, reduced free antigen and. Protein s is a vitamin kdependent anticoagulant protein. Diagnosing protein c deficiency protein c activity or functional protein c is the best test to know whether or not a person has protein c deficiency. A deficiency of protein s predisposes to recurrent venous thromboembolism and fetal loss. Protein c and protein s tests are used to help investigate the cause of. Protein c deficiency is uncommon asians and africans, and is most commonly seen in caucasians 4.
Protein c deficiency is associated with an increased incidence of venous thromboembolism relative risk 810, whereas no association with arterial thrombotic disease has been found. If a dvt travels through the bloodstream and lodges in the lungs, it can cause a life. Superficial thrombophlebitis is a characteristic feature of both protein cand protein s deficiencies. Protein s also has a protein cindependent anticoagulant activity,186 but the. Diagnosis is based on antigenic assays of total or free plasma protein s free protein s is the form unbound to the protein s carrier molecule, c4binding protein. Upon activation, apc forms a complex with protein s on a phospholipid surface to rapidly inactivate factors va and viiia. Protein c and protein s deficiency paolo aquino 18 february 2003 hemostasis the hematologic system is in a balanced flux between procoagulant and anticoagulant factors imbalance in either direction produces dire consequences. Protein c pc and protein s ps are vitamin kdependent glycoproteins, that act as natural anticoagulants. If tests show you have a protein c or a protein s deficiency, there are medicines and lifestyle changes you can make to reduce your risk of clots. Warfarininduced skin necrosis has been reported with protein s deficiency. Protein c deficiency occurs in approximately 1 of every 200 to 500 people, whereas protein s deficiency occurs in approximately 1 of every 500 individuals.
Protein s deficiency an overview sciencedirect topics. Congenital protein c or s deficiency is a lack of proteins c or s in the fluid part of the blood. To our knowledge, this is the first reported case of a temporary protein c and s. Protein s deficiency is a risk factor for thromboembolism. A form of inherited thrombophilia caused by a low level of protein c in the blood. This protein plays a role in controlling the blood clotting process.
Deficiencies of proteins c, s and antithrombin and activated. Laboratory testing issues for protein c, protein s, and antithrombin. To investigate whether this increase can mask a diagnosis of factor v leiden fvl or protein s deficiency in an actual population of patients undergoing apixaban treatment and hypercoagulation testing. Measurement of the free protein s concentration is the preferred screening test for protein s deficiency. Aside from the issue of protein c and protein s deficiency, the patient you are describing may have had one or more thrombotic blood clotting episodes that are independent of the protein c and protein s diagnosis. A dvt can travel through the bloodstream and lodge in. Protein s deficiency is a disorder that causes abnormal blood clotting. Sep 11, 20 protein c is one of the natural anticoagulants of the hemostatic system. There is a form due to inheritance of a single abnormal protein c gene in which affected individuals are at risk for developing blood clots, particularly a type.
Individuals with mild protein s deficiency are at risk of a type of clot called a deep vein thrombosis dvt that occurs in the deep veins of the arms or legs. Protein c pc and protein s ps are vitamin kdependent glycoproteins that play an important role in the regulation of blood coagulation as natural anticoagulants. In this study we aimed to investigate the therapeutic effect of low molecular weight heparin upon women with recurrent pregnancy loss and documented protein s deficiency. A form of inherited thrombophilia caused by a low level of protein s. That s because pregnancy is a risk factor for developing blood clots. Mar 04, 20 protein s deficiency has been divided into 3 different types based on the measurement of protein s antigen presence of the protein in the bloodstream, functional protein s activity ability of protein s to appropriately perform its function, the free protein s or unbound protein s and total protein s includes free protein s and protein s that is bound to another protein in the blood. The proteins are natural substances that help prevent blood clots. Thrombophilia due to heterozygous deficiency appears to be similar in frequency to protein c deficiency, and severe thrombosis has been reported in a few patients with apparent. In that instance, the patient must remain on some form of antithrombotic therapy to avoid a new adverse incident.
Protein c is a vitamin kdependent coagulation inhibitor that is synthesized by the liver and responsible for inactivating factor va and factor viiia after it is activated by thrombin. A deficiency of pc is one of several hereditary abnormalities of haemostatic proteins that have been described in patients with. Recently, we had the opportunity to observe a case of a cerebral arterial thrombosis in a young patient with active ulcerative colitis. Most patients are asymptomatic until after puberty.
In plasma, 40% of the protein s is free and functions as a cofactor for the anticoagulant effects of activated protein c. S deficiency is inherited and results in an unusually low level of protein s. Protein c deficiency is a rare genetic disorder characterized by a deficiency of protein c, which is a natural anticoagulant. Protein c deficiency leads to macro and microvascular thrombosis. There are no pa2 rticular symptoms of protein c deficiency unless. Thromboembolic complications may occur in inflammatory bowel disease. Protein c activity, protein s free antigen assay, antithrombin activity assay 4 persistent elevation of factor viii with normal crp test. Protein s functional activity was measured using the staclot protein s assay stago on a star evolution analyzer, and free protein s antigen was measured using the asserachrom free protein s assay stago. Congenital severe protein c deficiency is a lifethreatening state with neonatal purpura fulminans and pronounced coagulopathy.
It circulates in the blood as an inactive enzyme precursor. Because protein s binds and assists activated protein c in the degradation of coagulation factors va and viiia, deficiency of protein s predisposes to venous thrombosis. Women with protein c deficiency have a higher risk of developing clots both during and after pregnancy. Conditions that can lead to a protein c deficiency include. Protein c deficiency nord national organization for. Congenital protein c or s deficiency nicklaus childrens.
Deficient or dysfunctional protein c or protein s may be due to an underlying condition acquired, such as liver disease, kidney disease, severe infections or cancer, or can be inherited, passed from parent to child. There are no particular symptoms of protein s deficiency unless you. Protein c and protein s deficiency the fritsma factor. Protein s deficiency genetic and rare diseases information. Protein s deficiency is a disorder of blood clotting. Protein s deficiency is a disorder associated with increased risk of venous thrombosis. Protein s deficiency has been divided into 3 different types based on the measurement of protein s antigen presence of the protein in the bloodstream, functional protein s activity ability of protein s to appropriately perform its function, the free protein s or unbound protein s and total protein s includes free protein s and protein s that is bound to another protein in the blood.
Protein s, a vitamin kdependent protein, is a cofactor for activated protein cmediated cleavage of factors va and viiia. Protein c deficiency nord national organization for rare. A homozygous mutation in protein c or protein s is rare. Levels of antithrombin iii and protein c as well as plasminogen were normal. Laboratory testing issues for protein c, protein s, and. The test will determine the level of protein s in your blood. Nov 30, 2016 protein s is a cofactor for the action of activated protein c apc on activated factor v and activated factor viii.
Congenital protein c or s deficiency is an inherited disorder. There is a mild form in which affected individuals are at risk for developing blood clots, particularly a type of blood clot called. Synthesized in liver, protein c is a vitamin k dependent protein. Acquired protein c and s deficiency, inflammatory bowel. Deficiencies of coagulationinhibiting and fibrinolytic proteins in outpatients with deepvein thrombosis. The free form of ps is an important cofactor of apc. The only way to know if you have protein c deficiency is by a blood test. Nov 15, 2010 of the 468 subjects, 35% had protein s deficiency, 39% protein c deficiency and 26% had antithrombin deficiency. You may need these tests if you have certain risk factors. The remaining 60% of protein s is complexed to c4bbinding protein and is functionally inactive. This disorder is transmitted as autosomal dominant and is seen in 0. Pdf protein c pc and protein s ps are vitamin kdependent glycoproteins, that act as.
The test will determine the level of protein c in your blood. Using free ps antigen as a surrogate assessment of the ps activity, the. Protein s is a cofactor for the anticoagulant activity of apc figure 733. Clinical relevance of decreased free protein s levels. This means it helps to prevent the blood from clumping together clotting too much. As with protein c, acute thrombosis, pregnancy, oral contraceptive use, comorbid disease, or use of warfarin can alter assay results. The prevalence of congenital ps deficiency in the general population experiencing their first venous thrombosis is approximately 1%. The treatment of protein s deficiency associated with venous thrombosis is identical to the treatment of protein c deficiency, with one exception. Protein c deficiency is a disorder that increases a person s risk to develop abnormal blood clots due to a deficiency of the protein c, a protein in the body that prevents blood clotting.
The mechanism of protein s has been one of the least understood amongst the vitamin kdependent coagulation proteins but it has a central role in the regulation of coagulation. Some factors, such as warfarin treatment, can also cause a temporary drop in protein c, so repeat testing may be necessary. Protein c deficiency is found in 610% of hypercoagulation cases. Pdf protein c and protein s deficiency practical diagnostic issues. Decreased antigen levels or impaired function of protein s leads to decreased degradation of factor va and factor viiia and an increased. Protein c is a vitamin kdependent glycoprotein synthesized in the liver. Sep 20, 2018 protein s deficiency is a hereditary disorder, but the age of onset of thrombosis varies by heterozygous versus homozygous state. Women and men have e same risk ofhaving protein c deficiency. These clots occur in the deep veins of the arms or legs, away from the surface of the skin. An imbalance between dietary protein and energy intake is associated with relatively. Sep 24, 2018 a blood test is the only way to identify protein c deficiency.
Some factors, such as warfarin treatment, can also cause a temporary drop in protein c. Protein s, a vitamin k dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activate protein c in the degradation of factor va and factor viiia. The rare homozygous patients have neonatal purpura fulminans, as described above. Thats because pregnancy is a risk factor for developing blood clots. The protein c pathway has an important function in regulating and modulating blood coagulation and ensuring patency of the microcirculation. Protein c and protein s deficiency school of medicine. Decreased antigen levels or impaired function of protein s leads to decreased degradation. Decreased protein c and protein s quantity may be related to insufficient production or to increased use.
This means it helps to prevent the blood from clotting too much. Protein c deficiency genetic and rare diseases information. These subjects were clinically followed up for a 12 year period and 11% of the ps deficient patients, 11% of the pc deficient patients and 8% of the antithrombin deficient patients had arterial thrombosis. Protein s deficiency nord national organization for. People with this condition have an increased risk of developing abnormal blood clots.
Pdf combined protein c and protein s deficiency presenting as. Deficiencies of natural anticoagulants, protein c, protein s, and. Rivaroxaban causes missed diagnosis of protein s deficiency. Levels of antithrom bin iii and protein c as well as plasminogen were normal. The levels of total protein s, which includes the value for the free and complexed. Protein c and protein s tests are used to diagnose clotting disorders.
Pc is activated by thrombin and the resulting activated pc apc inactivates membranebound activated factor viii and factor v. Protein c and protein s deficiency practical diagnostic issues article pdf available in advances in clinical and experimental medicine 224. Patients with protein c deficiency are at an increased risk of developing skin necrosis while on warfarin. Protein c pc is the central component of a major antithrombotic regulatory system with both anticoagulant and profibrinolytic properties. The disease belongs to a group of genetic disorders known as thrombophilias. Protein c deficiency is a genetic disorder characterized by a deficiency of protein c, which is a natural anticoagulant. In comparison to the normal individuals, the people suffering from inherited form of protein s deficiency have about a 2 to 11 times increased risk for developing a deep venous thrombosis or a pulmonary embolism. Protein s is a vitamin kdependent anticoagulant protein that was first discovered in seattle, washington in 1979 and arbitrarily named after the city of its discover. A blood test is the only way to identify protein c deficiency. Protein s deficiency nord national organization for rare. Protein c deficiency is a rare genetic trait that predisposes to thrombotic disease. Both protein c deficiency and protein s deficiency are inherited in an autosomal dominant pattern.
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