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Autoimmune hemolytic anemia
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Hemolytic disease of the newborn
Paroxysmal nocturnal hemoglobinuria
Pyruvate kinase deficiency
Sickle cell disease (NORD)
Folate (Vitamin B9) deficiency
Vitamin B12 deficiency
Anemia of chronic disease
Iron deficiency anemia
Vitamin K deficiency
Langerhans cell histiocytosis
Essential thrombocythemia (NORD)
Polycythemia vera (NORD)
Acute intermittent porphyria
Porphyria cutanea tarda
Disseminated intravascular coagulation
Von Willebrand disease
Monoclonal gammopathy of undetermined significance
Thrombotic thrombocytopenic purpura
Antithrombin III deficiency
Factor V Leiden
Protein C deficiency
Protein S deficiency
Coagulation disorders: Pathology review
Extrinsic hemolytic normocytic anemia: Pathology review
Heme synthesis disorders: Pathology review
Intrinsic hemolytic normocytic anemia: Pathology review
Leukemias: Pathology review
Lymphomas: Pathology review
Macrocytic anemia: Pathology review
Microcytic anemia: Pathology review
Mixed platelet and coagulation disorders: Pathology review
Myeloproliferative disorders: Pathology review
Non-hemolytic normocytic anemia: Pathology review
Plasma cell disorders: Pathology review
Platelet disorders: Pathology review
Thrombosis syndromes (hypercoagulability): Pathology review
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Factor V Leiden Thrombophilia
Protein C or S Deficiency
At the emergency department, a 30 year old Caucasian female named Celia came in with pain and swelling in her right calf. She has a history of pregnancy loss and her mother has a history of recurrent episodes of venous thromboembolism. Her medical history is otherwise unremarkable. Coagulation studies show normal PTT. Next to Celia, there’s a 60 year old male called Nicholas who developed a painful lesion on his arm after starting anticoagulation therapy with warfarin. Now, there’s also a 26 year old African American female named Mary who has recurrent pregnancy losses. She was diagnosed with systemic lupus erythematosus about a year ago. She has no family history of thrombophilic disorder.
All of them suffer from thrombophilic disorders, or thrombosis syndromes, which are inherited or acquired diseases that predispose an individual to clot formation. Inherited disorders include factor V Leiden, prothrombin gene mutation, protein C and S deficiency, and antithrombin III deficiency, while the most important acquired disorder is antiphospholipid antibody syndrome. But before going into the individual thrombophilic disorders, let’s go through the normal coagulation system. The coagulation pathway is divided into an extrinsic and an intrinsic pathway, which join into a common pathway that ultimately result in the formation of fibrin clots. The extrinsic pathway starts when trauma damages a blood vessel, and exposes the cells under the endothelial layer, which have tissue factor in their membrane. Activated factor VII binds to tissue factor, forming a complex that then binds to and activates factor X. The intrinsic pathway starts when a circulating factor XII, activates factor XI, which then activates factor IX. Finally, factor IX forms a complex with factor VIII, and this complex binds to and activates factor X. In the common pathway. Activated factor X activates factor V, which converts prothrombin, or factor II, into thrombin. Thrombin then converts fibrinogen, or factor I, into fibrin, which cross-links to form a fibrin mesh that stabilizes the platelet plug. Now, prothrombin time, or PT assesses the extrinsic and common coagulation pathways, and partial thromboplastin time, or PTT assess the intrinsic and common coagulation pathways. Alright, but in order to prevent over-coagulation, the liver makes proteins C and S, which are vitamin K-dependent anticoagulant factors. In the presence of protein S as a cofactor, protein C acts by enzymatically inactivating factors V and VIII. Finally, a protein called antithrombin III inhibits factor X and factor II.
Thrombosis syndromes, also known as hypercoagulability, are a group of disorders characterized by an increased tendency to develop blood clots. These disorders can be inherited or acquired, and they can affect different parts of the body, including the veins and arteries. Thrombosis syndromes can be inherited, like factor V Leiden, prothrombin gene mutation, protein C and S deficiency, antithrombin III deficiency, or acquired like antiphospholipid syndrome.
Diagnosis can be made based on clinical presentation, coagulation studies, more specific lab tests like ELISA for antiphospholipid antibodies, as well as genetic testing to detect the specific mutations. Treatment involves a combination of anticoagulant therapy, lifestyle modifications, and management of the underlying conditions. Anticoagulant medications, such as warfarin and heparin, can help prevent blood clots from forming or growing.
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