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Iron deficiency anemia
Anemia of chronic disease
Hemolytic disease of the newborn
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Autoimmune hemolytic anemia
Pyruvate kinase deficiency
Paroxysmal nocturnal hemoglobinuria
Sickle cell disease (NORD)
Anemia of chronic disease
Folate (Vitamin B9) deficiency
Vitamin B12 deficiency
Acute intermittent porphyria
Porphyria cutanea tarda
Vitamin K deficiency
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Von Willebrand disease
Disseminated intravascular coagulation
Antithrombin III deficiency
Factor V Leiden
Protein C deficiency
Protein S deficiency
Polycythemia vera (NORD)
Essential thrombocythemia (NORD)
Langerhans cell histiocytosis
Monoclonal gammopathy of undetermined significance
Microcytic anemia: Pathology review
Non-hemolytic normocytic anemia: Pathology review
Intrinsic hemolytic normocytic anemia: Pathology review
Extrinsic hemolytic normocytic anemia: Pathology review
Macrocytic anemia: Pathology review
Heme synthesis disorders: Pathology review
Coagulation disorders: Pathology review
Platelet disorders: Pathology review
Mixed platelet and coagulation disorders: Pathology review
Thrombosis syndromes (hypercoagulability): Pathology review
Lymphomas: Pathology review
Leukemias: Pathology review
Plasma cell disorders: Pathology review
Myeloproliferative disorders: Pathology review
Protein S deficiency
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Robyn Hughes, MScBMC
Protein C and S are two anticoagulation proteins that inactivate coagulation factors Va and VIIIa in the coagulation cascade. This means, they act like brakes on coagulation, limiting clot formation and preventing clots from growing too big. So, when either of these proteins is deficient, it leads to a hypercoagulable state, meaning a person is at increased risk of developing a clot that could block blood flow. The most common places for such clots to develop are in the deep veins of the legs and in the vessels that carry de-oxygenated blood through the lungs.
Normally, protein C and protein S are 2 of many proteins or enzymes that regulate the complex process called hemostasis. This is where a solid clot forms in the flowing, liquid blood to plug the defect in a damaged blood vessel. It has two steps; Primary hemostasis involves the formation of a platelet plug at the site of injury, and secondary hemostasis involves coagulation, where several clotting factors come into play to form a fibrin mesh over the platelet plug to reinforce it, and form the blood clot. The main role of protein C and protein S is to prevent excess coagulation, or fibrin formation, during secondary hemostasis.
Protein C and S prevent excess coagulation by interacting with several other proteins involved in a complex system of checks and balances. So, it starts with a protein called thrombomodulin, which is on endothelial cells that line our blood vessels, and together with thrombin, they form a complex that also includes protein C and protein S.
When protein S joins this complex, it activates the proteolytic site of protein C, which cleaves and inactivates active factor V, a cofactor for factor X in the common pathway, and factor VIII, a cofactor for factor IX in the intrinsic pathway. The factor V degradation product also binds to this complex and further enhances its ability to cleave more active factor V and active factor VIII. By inhibiting both the intrinsic and common pathway, less fibrin is produced and coagulation slows down dramatically.
Protein S deficiency is a disorder associated with an increased risk of venous thrombosis. Protein S, a vitamin K-dependent natural anticoagulant, acts as a nonenzymatic cofactor to activate protein C in the proteolytic degradation of factor Va and factor VIIIa. Decreased levels or impaired function of protein S leads to decreased degradation of factor Va and factor VIIIa and an increased risk of blood clots, which can cause complications like deep vein thrombosis (DVT) and pulmonary embolism (PE). Treatment includes anticoagulant medications and avoiding drugs that predispose to hypercoagulability, such as oral contraceptives.
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