Biochemistry of Coagulation - Goueli Flashcards
What is Hemostasis?
Physiological blood clotting in response to injury or vascular leak (keeping blood where it belongs)
What is Thrombosis?
Pathologic blood clotting
What is Hemorrhage?
Pathologic bleeding
What is involved in Hemostasis?
The process of coagulation and subsequent dissolution of clot
What is the process of clot degradation?
Fibrinolysis
What is a Primary Hemostasis?
Platelets become activated and aggregate at the site of injury, forming a temporary, loose platelet plug
What is a normal platelet count?
150,000 - 450,000 platelets
What are patients at risk for with
Increased risk of spontaneous hemorrhage
What are patients more at risk for with risk of spontaneous hemorrhage?
Intracranial hemorrhage
What are patients at risk for with
Increased difficulty clotting if already bleeding
What is the pathogenic issue in vonWillebrand’s disease?
Complex multimeric glycoprotein produced by and stored in the alpha granules of platelets; synthesized by megakaryocytes and found in subendothelial connective tissue
What is Bernard Soulier Syndrome?
Glycoprotein 1B deficiency
What is TTP (Thrombotic Thrombocytopenic Purpura)?
Characterized by profound thrombocytopenia and microangiopathic hemolytic anemia (red blood cell fragmentation)
What is the major cause of TTP?
Deficiency in ADAMTS13
What is ADAMTS13?
A disintegrin and metalloproteinase with thrombospondin Type 1 motif 13
What happens with ADAMTS13 is absent?
Persistence of conglomerates which causes platelet aggregation when the protein is subjected to high shear stress (due to lack of cleavage of high molecular weight vonWillebrand’s protein)
What are the 5 clinical features of TTP?
Thrombocytopenia Red Cell Fragmentation Fever Transient Neurologic Deficits Kidney Failure
What is the treatment of TTP?
Plasmaphoresis
Why is TTP considered a medical emergency?
Myocardial Infarction from platelet thrombi in coronary arteries causing death
What is ADP?
A potent platelet activate from alpha granules
What is the deficiency associated with Glanzmann thrombasthenia?
Defect in GPIIb protein
What does the GPIIb-GPIIIa receptor for vWF and fibrinogen do?
Allows for fibrinogen-induced platelet aggregation
What are the two pathways that lead to the formation of a fibrin clot?
Intrinsic and Extrinsic pathways
Where are clotting factors produced?
Liver
Where is the extrinsic pathway initiated and what initiates it?
Site of injury by Tissue Factor
What cascade process is Tissue Factor used in?
A cofactor in the factor VIIa-catalyzed activation of factor X
What is Tissue Factor?
An integral membrane protein that is expressed on the surface of activated monocytes and endothelial cells exposed to various cytokines
What factors are required in the extrinsic pathway?
Tissue Factor
Factor VII
What factors are required in the intrinsic pathway?
VIII, IX, X, XI, and XII
When activated platelets present Phosphatidylserine and Phosphatidylinositol on their surfaces, what is then able to bind?
Tenase Complex of Calcium, Factor VIIIa, IXa, and X for the activation of Factor X to Xa
What is the role of Factor Xa in the Common Pathway?
Converts Prothrombin (Factor II) to Thrombin (Factor IIa)
What is the role of Thrombin in the Common Pathway?
Converts Fibrinogen to Fibrin
What does Thrombin (Factor IIa) activate?
Factor XII, VIII, V, VIII, VII
If antithrombin III is deficient, what does this lead to?
Emphysema and Liver Dysfunction
What is the most important thrombin inhibitor that inhibits IXa, Xa, XIa, and XIIa, plasmin, and kallikrein?
Antithrombin III
How is the activity of Antithrombin III potentiated?
Heparin has an altered conformation which binds thrombin more readily
How does Warfarin (Coumadin) work?
Acts by blocking the vitamin K reductase enzymes used to regenerate active vitamin K, which results in reduced gamma-carboxylation of II, VII, IX, and X.
What else do Warfarin (Coumadin) block?
The activity of S and C (the coagulation breaks) which is the primary reason one needs to bridge the gap with Heparin
Where does high molecular weight heparin bind?
Plasma Proteins and Cell Surfaces, as well as Antithrombin III
If you have an elevated actiated partial thromboplastin time (aPTT), then what pathway is the factor deficiency in?
Intrinsic Pathway with factors XIII and XI
If you have an elevated international normalized ratio (INR), then what pathway is the factor deficiency in?
Extrinsic Pathway with factor IIV
What is thrombocytopenia?
Platelet count
What test is prolonged in Vitamin K deficiency?
PT (Prothrombin Time)
What are the indicated tests for DIC?
Prolonged PT Prolonged PTT Low Fibrinogen Level INCREASED D-Dimer Prolonged Bleeding Time Decreased Platelet Count Fragmented RBCs
What test is prolonged in PTT?
Prolonged Bleeding Time
VERY Low Platelet Count
Fragmented RBCs
