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Questions and Answers
What is the normal partial thromboplastin time (PTT) in seconds?
What is the primary function of von Willebrand Factor in the body?
What is the most common inherited bleeding disorder?
What is the primary cause of bleeding in vitamin K deficiency?
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What is the primary treatment for vitamin K deficiency?
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What is the characteristic feature of hemophilia A?
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What is the characteristic feature of hemophilia B?
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What is the primary laboratory test used to diagnose von Willebrand Disease?
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What is the primary mechanism of action of desmopressin in von Willebrand Disease?
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What is the primary indication for aminocaproic acid in von Willebrand Disease?
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Which of the following vitamin K-dependent clotting factors has the shortest half-life?
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What is the primary reason why newborns are at risk for vitamin K deficiency?
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Which of the following is a characteristic of bleeding in vitamin K deficiency?
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What is the effect of antibiotics on the risk of vitamin K deficiency?
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Which of the following is NOT a characteristic of hemophilia A?
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What is the effect of vitamin K deficiency on the partial thromboplastin time (PTT)?
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Which of the following is a treatment for von Willebrand Disease?
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What is the primary mechanism of action of von Willebrand Factor?
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Which of the following is a characteristic of hemophilia B?
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What is the primary cause of bleeding in hemophilia A and hemophilia B?
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What is the primary mechanism of vasoconstriction in vascular hemostasis?
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What is the primary function of platelets in hemostasis?
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What is the lifespan of platelets in the blood?
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What percentage of platelets are stored in the spleen?
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What is the result of the primary hemostasis process?
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What is the secondary hemostasis process?
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What is the final result of the hemostasis process?
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What is the role of platelets in secondary hemostasis?
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What is the primary mechanism of platelet activation in hemostasis?
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What is the role of vasoconstriction in hemostasis?
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Study Notes
Hemostasis
- Hemostasis is the physiological process that stops bleeding, resulting in a thrombus (blood clot) composed of blood cells and fibrin strands.
Plasma Proteins
- Plasma proteins play a crucial role in hemostasis
- These proteins are synthesized in the liver and activated when triggered by endothelial damage
- They form an insoluble protein: fibrin, which prevents blood loss
Formation of the Hemostatic Plug
- Primary hemostasis involves:
- Vascular hemostasis: transient vasoconstriction and vWF activation following endothelial injury
- Platelet hemostasis: adhesion, activation, and aggregation of platelets, resulting in the formation of a platelet plug
- Secondary hemostasis involves the activation of the coagulation cascade, leading to the formation of a fibrin clot
Vascular Hemostasis
- Immediately after injury, there is a localized vasoconstriction due to:
- Local myogenic spasm (systemic release of adrenaline)
- Local release of Thromboxane A2 (TXA2) and serotonin by platelets
- Nervous factors (stimulation of nerve impulses + nerve reflex is vasoconstriction)
Platelet Hemostasis
- Platelets are small cytoplasmic fragments derived from megakaryocytes
- They have a life span of 8-10 days and approximately 1/3 of the platelet pool is stored in the spleen
- Platelets bind to von Willebrand factor (vWF) via the platelet GPIb receptor at the endothelial injury site
- After binding to vWF, platelets change their shape and release mediators that lead to the activation of more platelets
Coagulation Cascade
- The coagulation cascade involves the sequential activation of clotting factor zymogens
- There is a constant low level of activation in the blood, which amplifies with endothelial damage
- This leads to fibrin generation
- The extrinsic pathway of coagulation is triggered by endothelial injury
- The intrinsic pathway of coagulation is triggered by the activation of XII-Hagman factor
Regulation of Blood Coagulation
- Vitamin K acts as a cofactor for a group of proteins known as the vitamin K-dependent clotting factors (II, VII, IX, and X)
- Protein C and its cofactor protein S suppress the activity of the coagulation cascade
- Antithrombin (AT) inactivates several enzymes of the coagulation system
Fibrinolysis
- Fibrinolysis is the process of breaking down a blood clot
- It is necessary to prevent further propagation of the clot
- tPA, uPA, and PAI-1 are involved in fibrinolysis
Coagulation Testing
- Prothrombin time (PT) measures the time it takes for a clot to form in the extrinsic pathway
- Bleeding time measures how fast small blood vessels in the skin stop bleeding
- Partial thromboplastin time (PTT) measures the time it takes for a clot to form in the intrinsic pathway
Hemophilias
- Hemophilias are X-linked recessive diseases that mostly affect males
- Female carriers are usually asymptomatic
- Hemophilia A is a deficiency of factor VIII, and hemophilia B is a deficiency of factor IX
Vitamin K Deficiency
- Vitamin K deficiency can cause bleeding due to a deficiency of vitamin K-dependent clotting factors
- Causes include dietary deficiency, malabsorption, and use of antibiotics
- Treatment involves administration of vitamin K
Von Willebrand Disease
- Von Willebrand disease is the most common inherited bleeding disorder
- It is characterized by a deficient function of von Willebrand factor
- Clinical signs include easy bruising, skin bleeding, prolonged bleeding from mucosal surfaces, and heavy menstrual bleeding
- Diagnosis involves normal CBC and PT, increased PTT, and VWD screening tests
- Treatment involves administration of vWF concentrate, desmopressin, and aminocaproic acid.
Blood Clotting
- Blood clotting is the transformation of blood from a liquid into a solid gel form, involving the conversion of soluble fibrinogen to insoluble fibrin strands.
- Proteins synthesized in the liver are activated when triggered by endothelial damage, forming an insoluble protein called fibrin, which prevents blood loss through a fibrin mesh.
Basic Reactions Involved in Coagulation
- Sequential activation of clotting factor zymogens occurs, with a constant low level of activation in the blood.
- Amplification occurs when endothelial damage is triggered, leading to fibrin generation.
Extrinsic Pathway of Coagulation
- Triggered by endothelial injury, tissue factor (factor III) activates factor VII.
- Factor VIIa and tissue factor form a complex (TF-FVIIa), which requires calcium (factor IV) found on the surface of fibrocytes and activated platelets.
- TF-FVIIa activates factor X.
Intrinsic Pathway of Coagulation
- Triggered by the activation of XII-Hagman factor, which occurs when blood comes into contact with a foreign surface.
- vWF binds factor VIII, protecting it from proteolysis in the circulation.
Vitamin K Role in Coagulation
- Vitamin K acts as a cofactor for vitamin K-dependent clotting factors (II, VII, IX, and X), involved in the activation of blood-clotting proteins.
Anticoagulation
- Protein C and its cofactor protein S serve to suppress the activity of the coagulation cascade.
- Activated protein C forms a complex with protein S, which destroys the active blood coagulation cofactors factor VIIIa and Va.
- Antithrombin (AT) is a small protein molecule that inactivates several enzymes of the coagulation system.
Fibrinolysis
- After successful formation of a hemostatic plug, further propagation of the clot must be prevented by switching off blood coagulation and turning on fibrinolysis.
- Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are involved in fibrinolysis.
Coagulation Testing
- Prothrombin time (PT) measures the time to form a clot in the extrinsic pathway, with a normal time of around 10 seconds.
- Bleeding time measures how fast small blood vessels in the skin stop bleeding, with a normal range of 2-9 minutes.
- Partial thromboplastin time (PTT) measures the time to form a clot in the intrinsic pathway, with a normal time of around 30 seconds.
Hemophilias
- Hemophilias are X-linked recessive diseases that mostly affect males, with female carriers usually being asymptomatic.
- Hemophilia A is a deficiency of factor VIII, while Hemophilia B is a deficiency of factor IX.
Vitamin K Deficiency
- Deficiency of vitamin K-dependent factors can cause bleeding, with prolonged PT and PTT.
- Dietary deficiency is rare, but can occur due to antibiotics, malabsorption, or a sterile GI tract in newborns.
- Treatment involves vitamin K supplementation.
Von Willebrand Disease
- Von Willebrand disease is a deficiency of von Willebrand factor, which binds platelets to endothelium and other platelets.
- Clinical signs include mild, non-life-threatening bleeding, easy bruising, skin bleeding, and prolonged bleeding from mucosal surfaces.
- Diagnosis involves normal CBC and PT, increased PTT, and increased bleeding time.
- Treatment involves vWF concentrate, desmopressin, and aminocaproic acid.
Protein S and Antithrombin
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Protein S anchors the activated protein C complex (APC) to the clot through Ca2+/γ-carboxyglutamate binding to platelet phospholipids.
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APC destroys the active blood coagulation cofactors factor VIIIa and Va by proteolytic cleavage, decreasing the production of thrombin.
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APC also stimulates endothelial cells to increase secretion of prostaglandin I2 (PGI2), which reduces platelet aggregation.
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Antithrombin (AT) is a small protein molecule that inactivates several enzymes of the coagulation system.
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Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids.
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Antithrombin degrades thrombin and factors IXa and Xa, and activates tissue plasminogen activator (tPA).
Fibrinolysis and Coagulation Testing
- Fibrinolysis is the process of preventing further propagation of the clot after successful formation of a hemostatic plug.
- Fibrinolysis is achieved by switching off blood coagulation and turning on fibrinolysis.
- Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are involved in fibrinolysis.
- D-dimer is a protein fragment produced by the body when a blood clot dissolves, and can be measured through a blood test.
Coagulation Pathways
- Prothrombin time (PT) measures the extrinsic pathway of coagulation, which involves adding plasma to tissue factor and measuring the time to form a clot.
- Bleeding time is a medical test that measures how fast small blood vessels in the skin stop bleeding.
- The basic reactions involved in coagulation include sequential activation of clotting factor zymogens, constant low-level activation in blood, amplification upon endothelial damage, and fibrin generation.
Extrinsic Pathway
- The extrinsic pathway is triggered by endothelial injury and involves the activation of factor VII by tissue factor.
- Tissue factor is expressed on the surface of subendothelial muscle cells and fibroblasts.
- The complex formed by factor VIIa and tissue factor (TF-FVIIa) activates factor X.
Intrinsic Pathway
- The intrinsic pathway is triggered by the activation of factor XII (Hageman factor) upon contact with a foreign surface.
- The intrinsic pathway involves the activation of factor VIII, which is protected from proteolysis by von Willebrand factor (vWF).
Vitamin K Role
- Vitamin K acts as a cofactor for vitamin K-dependent clotting factors (II, VII, IX, and X), which are involved in the activation of blood-clotting proteins.
Hemostasis
- Hemostasis is the physiological process by which bleeding stops, resulting in a thrombus (blood clot) consisting of blood cells and fibrin strands.
- Primary hemostasis involves vascular hemostasis (transient vasoconstriction and vWF activation) and platelet hemostasis (adhesion, activation, and aggregation of platelets).
- Secondary hemostasis involves the activation of the coagulation cascade, resulting in the formation of a fibrin clot.
Vascular Hemostasis
- Vascular hemostasis involves localized vasoconstriction immediately after injury, which is mediated by local myogenic spasm, local release of thromboxane A2 and serotonin, and nervous factors.
Platelet Hemostasis
- Platelets are small cytoplasmic fragments derived from megakaryocytes, with a life span of 8-10 days.
- Approximately 1/3 of the platelet pool is stored in the spleen.
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Description
This quiz covers the topics of hemostasis, plasma proteins, blood coagulation, and regulation of blood coagulation, as studied in Marks' Basic Medical Biochemistry, 6th edition, Chapter 43.
