Women who are heterozygous for protein c deficiency are considered at moderately increased risk of pregnancyassociated vte on a scale of mildmoderatesevere. Deficiencies of natural anticoagulants, protein c, protein. Most vte events in heterozygous protein s deficiency occur in persons younger than 4045 years. Along with this reduction in specific activity, we noted the abnormal electrophoretic mobility of the protein s in the presence of calcium ions.
The function of protein s is to stop the action of two activated clotting proteins named factor v and factor viii. Sep 20, 2018 protein s deficiency is a hereditary disorder, but the age of onset of thrombosis varies by heterozygous versus homozygous state. Deficiency of protein c in congenital thrombotic disease. Excessive binding of protein s to c4bbinding protein may result in a deficiency of active protein s in the plasma. Jul 19, 2016 protein c deficiency and previous vte are additional risk factors. Protein c and d dimer are related to portal vein thrombosis in patients with liver. We report the findings in two patients with portal hypertension and bleeding varices due to portal vein thrombosis in whom a deficiency of protein c was present. Women with protein c deficiency have a higher risk of developing clots both during and after pregnancy.
If protein c cannot control blood clotting, abnormal blood clots may form. Protein c deficiency nord national organization for rare. Pcd is either ad of variable penetration, or acquired, and due to dic, warfarin therapy, hepatic disease and postoperatively. Hereditary protein c deficiency is transmitted as an autosomal dominant disorder. Women with previous vte should be screened for inherited and acquired thrombophilia ideally before pregnancy. Deficiency of protein c in patients with portal vein thrombosis. The proteins are natural substances that help prevent blood clots. Vitamin function food sources symptom of deficiency symptom of excess vitamin b12 helps produce red. Abnormal protein c and protein s results determined within 24 hours of acute thromboembolic events need to be confirmed but a normal result effectively rules out deficiency with only one test. 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 c deficiency genetic and rare diseases information. The hereditary form of protein s deficiency is caused by a mutation in a gene called pros1 this condition is inherited in an autosomal dominant manner, which means that an individual who inherits only one mutated copy of pros1 has an increased chance of developing symptoms of this disease.
Jun 07, 2016 protein c deficiency can be inherited or acquired later in life. We assayed for free protein s antigen, protein c antigen, and antithrombin iii and tested for lupuslike. Protein c is a vitamin kdependent glycoprotein synthesized in the liver. In this study we aimed to investigate the therapeutic effect of low molecular weight heparin upon women with recurrent. Protein s deficiency definition of protein s deficiency by. Similarly, combined deficiency of proteins c and s can lead to hypercoagulable state and rarely presents as a cerebrovascular accident. This disorder is transmitted as autosomal dominant and is seen in 0. Protein s is a vitamin kdependent plasma protein that inhibits blood clotting by serving as a cofactor for activated protein c also a vitamin kdependent protein, and the clinical manifestations of its deficiency are virtually identical to those of protein c deficiency. This protein plays a role in controlling the blood clotting process. Jan 04, 2019 protein c deficiency is a congenital or acquired condition that leads to increased risk for thrombosis. Inactivating factors ii and x halts the clotting cascade. People with hereditary protein c or protein s deficiency have about a. Protein c deficiency is a rare genetic disorder characterized by a deficiency of protein c, which is a natural anticoagulant. Pdf protein c pc and protein s ps are vitamin kdependent glycoproteins, that act as natural anticoagulants.
Portal vein thrombosis with protein cs deficiency in a. Three types of protein s deficiency have been described. Protein c deficiency is a blood clotting disorder that is usually related to abnormalities in the specific genes. The protein c pathway has an important function in regulating and modulating blood coagulation and ensuring patency of the microcirculation.
Other cases have also reported c and s protein deficiencies in patients with idiopathic portal hypertension accompanied by pvt16,17. A deficiency of pc is one of several hereditary abnormalities of haemostatic proteins that have been described in patients with a propensity for thromboembolic complications. Protein s deficiency is a rare genetic disorder of blood coagulation that is. The free form of ps is an important cofactor of apc. The body needs to obtain appropriate vitamins from food to maintain. 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.
Protein s deficiency hematology and oncology merck. If you have problems viewing pdf files, download the latest version of adobe reader. A homozygous mutation in protein c or protein s is rare. 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. Protein s deficiency genetic and rare diseases information center. Protein c deficiency is associated with a small percentage of cases of inherited thrombophilia, as well as the even more uncommon findings of warfarininduced skin necrosis and neonatal purpura fulminans, and a possible weak association with pregnancy loss. The consequence of protein z or zpi congenital deficiency, or of acquired autoantibodies to protein z, in the pathophysiology of thrombosis, fetal loss, and cancer ovarian or gastric is not completely clear. The rare homozygous patients have neonatal purpura fulminans, as described above. Nov 30, 2016 protein s deficiency is associated with an increased risk of thrombosis. Inherited protein c deficiency is caused by mutations in the gene that provides instructions for making protein c, called the proc gene. Ps serves as an essential cofactor of activated protein c apc. If one inherits an abnormal protein s gene from one parent, it is called heterozygous. Protein s deficiency nord national organization for rare. Protein c deficiency is a recently described disorder characterized by a predisposition to develop thromboembolic disease.
Congenital protein c or s deficiency is an inherited disorder. Protein and amino acid requirements in human nutrition report of a joint whofaounu expert consultation the world health organization and the food and agriculture organization have worked to quantify the energy and nutrient needs of populations since 1949. Most people with protein c deficiency have inherited the abnormal protein c gene from one parent. Protein s deficiency is a disorder of blood clotting. Protein z deficiency hematology and oncology merck. This means it helps to prevent the blood from clumping together clotting too much. Such individuals may be at an increased risk of developing blood clots before 4045 years of age. 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. Cutaneous necrosis associated with protein s deficiency. It should be noted that because apc requires interaction with protein s for full activity, deficiencies in protein s are.
We describe here a case of a 25yearold man who presented with right middle cerebral artery territory infarct due to protein c and s deficiency. Such a deficiency can be inherited or acquired vitamin k deficiency, medications, infections, etc. 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. Activated protein c apc performs these operations primarily by proteolytically inactivating. If one inherits abnormal protein c genes from both parents, it is called homozygous protein c deficiency.
Protein c deficiency nord national organization for. Pc is activated by thrombin and the resulting activated pc apc inactivates membranebound activated factor viii and factor v. Get a printable copy pdf file of the complete article 578k, or click on a. Protein s deficiency is a disorder associated with increased risk of venous thrombosis. It circulates in the blood as an inactive enzyme precursor. We assayed for free protein s antigen, protein c antigen, and antithrombin iii and tested for. Sep 11, 20 protein c deficiency is a rare genetic abnormality that predisposes the patient to thrombophilia and leads to thrombosis, often at unusual sites. Protein s ps is produced by the liver, megakaryocytes, and endothelial cells. A protein s measurement is a test used to measure the amount of protein s in your body. The exact prevalence the common form of protein s deficiency the number of people who have the disorder in a given population and incidence new cases identified each year of the disorder overall is unknown. The propositus, his father, and his paternal uncle, who are severely affected, had 3849% of normal levels of protein c antigen, whereas unaffected family members had normal levels. Protein c deficiency is a rare genetic trait that predisposes to thrombotic disease. Protein s deficiency symptoms, diagnosis, treatments and. Proteinc deficiency presenting as pulmonary embolism and.
It is rare, occurring in about 1 in 500 people in the united states. These people acquire the disease at some point in their lives due to a specific cause. Heritable thrombophilias are assumed important etiologies for recurrent pregnancy loss. The disease belongs to a group of genetic disorders known as thrombophilias. Protein s deficiency is a rare inherited disorder characterized by the formation of recurrent blood clots and emboli. Gene diagnosis of seven patients with hereditary protein s. Protein s is an endogenous vitamin kdependent anticoagulant that acts as a nonenzymatic cofactor for activated protein c apc. Patients with protein c or protein s deficiency associated with a hypercoaguable state protein c and protein s inhibit factors v and viii and inhibit coagulation vitamin k dependent patients with deficiency may develop skin necrosis due to thrombosis when anticoagulated with warfarin.
Congenital severe protein c deficiency is a lifethreatening state with neonatal purpura fulminans and pronounced coagulopathy. Protein s deficiency is an inherited thrombophilia associated with an increased risk of thromboembolism. Other proteins in the blood, such as protein s, usually regulate these chemical reactions to prevent excessive clotting. Protein c deficiency hematology and oncology merck. Thats because pregnancy is a risk factor for developing blood clots. Protein s deficiency and blood clots what is normal. Hps2 eluate, and n protein s functional activity after initiation of warfarin.
Protein c deficiency leads to macro and microvascular thrombosis. Protein s, a vitamin kdependent protein, is a cofactor for activated protein c. However, a french study has found a high number of patients with noncirrhotic pvt showed protein s deficiency and in a study from united kingdom, protein s deficiency was found in 38% of patients with pvt. Protein c and protein s deficiency in acute ischemic stroke. Protein c deficiency is less common than factor v leiden or mutation in the prothrombin gene g20210a. Hereditary protein s ps and protein c pc deficiencies are caused by gene mutations.
These mutations disrupt the protein s ability to control blood clotting. 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. These clots occur in the deep veins of the arms or legs, away from the surface of the skin. Inherited deficiency of protein c can lead to familial thrombophilia increased tendency toward thrombosis. Heterozygous individuals are quite frequent in the general population with estimates of 0. People suffering from this condition are predisposed to the development of abnormal blood clots. Both quantitative and qualitative abnormalities of protein s have been identified.
Congenital protein c or s deficiency is a lack of proteins c or s in the fluid part of the blood. Protein s is a protein that prevents clotting an anticoagulant, and requires vitamin k for its production and works with protein c. If there is a deficiency of protein s, these clotting proteins remain activated so there is more of a tendency for blood to clot. Protein c pc is the central component of a major antithrombotic regulatory system with both anticoagulant and profibrinolytic properties. One in 300 people has one normal gene and one faulty gene for protein c deficiency. A more complete list of reactions that may occur with chronic warfarin therapy can be viewed on medscape s web site. Prote c deficiency is not the most common ofthe thrombophilias but poses a significant thre. Thrombophilia testing in anticoagulated patients katrien devreese, md, phd ghent university hospital, belgium coagulation laboratory nthc 7the annual meeting 3032017. Protein c is a vitamin kdependent protein, as are coagulation factors vii, ix, and x. Protein s deficiency and blood clots what is normal clotting. Protein s deficiency msu center for bleeding and clotting. Protein c has the shortest half life of all the vitamink dependent factors in patients with protein c and s deficiency, there is an increased risk of skin necrosis because of the above. It is caused by mutations in the proc gene, and in most cases is. Deficiency of plasma protein s, protein c, or antithrombin iii and arterial thrombosis.
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 and s deficiency causes, symptoms, diagnosis. Protein s deficiency is an inherited thrombophilia associated with an. Because activated protein c degrades coagulation factors va and viiia, deficiency of protein c predisposes to venous thrombosis. If there is not enough protein c in the body, a person runs the risk of a.
Protein c deficiency can be inherited from one or both parents. Protein s is a vitamin kdependent plasma protein that inhibits blood clotting by serving as a cofactor for activated protein c. If there is not enough deficiency of the protein s. Various conditions have been shown to cause acquired protein c deficiency.
Homozygous individuals usually develop purpura fulminans as newborns. To determine the relationship between vitamin k dependent coagulation factors and natural anticoagulants, namely protein c and protein s, in various degrees of vitamin k deficiency, plasma values for clotting activity, protein induced by vitamin k absence pivkaii, protein c antigen, gammacarboxy protein c antigen, and protein s antigen including total and free fractions and. Protein s deficiency is a rare disorder that affects both men and women. Protein s deficiency genetic and rare diseases information. Acquired protein c deficiency refers to people who have protein c deficiency that is not because of a genetic cause i. That s because pregnancy is a risk factor for developing blood clots. Antithrombin iii deficiency protein c s deficiency factor v leiden prothrombin gene 20210a mutation blood group nono dysfibrinogenemia dysplasminogenemia hyperhomocystinemia reduced heparin cofactor ii activity elevated levels of clotting factors xi, ix, vii, viii, x, ii.
Protein c deficiency occurs in 1 of every 200 to 500 people, whereas protein s deficiency can be expected in 1 of every 500 individuals. Nov 03, 2016 women with protein c deficiency have a higher risk of developing clots both during and after pregnancy. Establishing a diagnosis of hereditary protein s deficiency may be difficult, particularly in the setting of an acute thrombosis or anticoagulant administration. We conclude that acquired protein s deficiency occurs in the nephrotic syndrome and may be a risk factor for the development of. Protein c and protein s deficiency practical diagnostic issues. Relationship between vitamin k dependent coagulation. Protein c deficiency definition of protein c deficiency by. Protein c and s are two anticoagulation proteins that inactivate coagulation factors va and viiia in the coagulation cascade.
Decreased antigen levels or impaired function of protein s leads to decreased degradation of factor va and factor viiia and an increased. 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. This means that if one parent has it, then each child has a 50. Congenital protein c deficiency is one of several inherited thrombophilias, which are a heterogeneous group of genetic disorders associated with an elevated risk of venous thromboembolism. People with this condition have an increased risk of developing abnormal blood clots. 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 is a potential risk factor for forming venous clots.
Many remain asymptomatic but up to 5% of familial thrombophilias are the result of protein c or protein s deficiency. Mar 04, 20 protein s deficiency is usually hereditary, but may be acquired. Plasma protein c exerts anticoagulatory effects by inactivating factors v and viii. Protein s, which circulates in plasma in a free and bound form, is an anticoagulant protein that stimulates both activated protein c apc and tissue factor pathway inhibitor tfpi. 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. If a dvt travels through the bloodstream and lodges in the lungs, it can cause a life. Antithrombin deficiency is the least common of the 3 deficiencies, occurring in 1 of every 2000 to 5000 people. Unlike in the caucasian populations, protein s and protein c deficiencies, instead of factor v lieden and prothrombin mutations, are relatively common in the han chinese population. Deficiency of these factors, acquired or hereditary, are associated with. Protein c deficiency is a shortage of one particular protein that is vital to regulating blood clots throughout the body. Protein s deficiency occurs in the nephrotic syndrome. I have been taking warfarin after initial coumadin treatment. Vitamin k dependent factors protein c and protein s act as anticoagulants by degrading the activated factors v and viii. Blood should be collected in a bluetop tube containing 3.
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. Protein s deficiency nord national organization for. Congenital protein c or s deficiency nicklaus childrens. Protein c deficiency is found in 610% of hypercoagulation cases. Because protein c and s are both vitamin k dependent anticlotting factors. This is the latest in a series of reports that aim to provide. Protein c levels in plasma were determined immunologically using the laurell rocket technique. Hematology an ad condition clinically and therapeutically similar to heterozygous protein c deficiency, characterized by pulmonary thrombosis, dvt, thrombophlebitis.
Protein s deficiency is a disorder that causes abnormal blood clotting. We are presenting a case of deep vein thrombosis dvt of lower limb which was subsequently found due to protein c deficiency. There was no familial deficiency of antithrombin iii and plasminogen. Vitamin function food sources symptom of deficiency excess. When someone bleeds, the blood begins a complicated series of rapid chemical reactions involving proteins called blood coagulation factors to stop the bleeding.
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