Podcast
Questions and Answers
Which factor is known as the contact-sensitive protein in the intrinsic coagulation system? (2 correct)
Which factor is known as the contact-sensitive protein in the intrinsic coagulation system? (2 correct)
The majority of clotting factors are synthesized in the kidneys.
The majority of clotting factors are synthesized in the kidneys.
False
What is released into the blood to activate the extrinsic coagulation pathway following tissue injury?
What is released into the blood to activate the extrinsic coagulation pathway following tissue injury?
tissue thromboplastin
The _____ system of coagulation contains all substrates necessary for clotting within the circulating blood.
The _____ system of coagulation contains all substrates necessary for clotting within the circulating blood.
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Match the following terms related to coagulation with their descriptions:
Match the following terms related to coagulation with their descriptions:
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What primarily causes edema formation?
What primarily causes edema formation?
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Congestive heart failure can lead to systemic and local edema
Congestive heart failure can lead to systemic and local edema
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Name one condition that can lead to systemic edema known as anasarca.
Name one condition that can lead to systemic edema known as anasarca.
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Match the following conditions with their descriptions:
Match the following conditions with their descriptions:
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Which process primarily promotes platelet adhesion?
Which process primarily promotes platelet adhesion?
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Chronic Thrombotic Thrombocytopenic Purpura (TTP) primarily affects children.
Chronic Thrombotic Thrombocytopenic Purpura (TTP) primarily affects children.
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What is the term used for swelling due to fluid accumulation in body cavities?
What is the term used for swelling due to fluid accumulation in body cavities?
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Increased shear stress on the endothelium can lead to the release of ___________ factors promoting hemostasis.
Increased shear stress on the endothelium can lead to the release of ___________ factors promoting hemostasis.
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What is characterized by low protein content and a specific gravity of 1.020?
What is characterized by low protein content and a specific gravity of 1.020?
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Decreased colloid osmotic pressure can contribute to the formation of edema.
Decreased colloid osmotic pressure can contribute to the formation of edema.
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What role do prostacyclin and nitric oxide play in hemostasis?
What role do prostacyclin and nitric oxide play in hemostasis?
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The presence of __________ is often indicative of immune thrombocytopenic purpura (ITP).
The presence of __________ is often indicative of immune thrombocytopenic purpura (ITP).
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Which of the following is NOT a characteristic of Immune Thrombocytopenic Purpura?
Which of the following is NOT a characteristic of Immune Thrombocytopenic Purpura?
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What is the primary factor deficiency in Hemophilia A?
What is the primary factor deficiency in Hemophilia A?
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Vitamin K deficiency affects the synthesis of factors II, VII, IX, and X.
Vitamin K deficiency affects the synthesis of factors II, VII, IX, and X.
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What does the Prothrombin time (PT) test check for?
What does the Prothrombin time (PT) test check for?
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Hemophilia B is a deficiency of factor _____ .
Hemophilia B is a deficiency of factor _____ .
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Match the following coagulation factors with their known deficiency disorders:
Match the following coagulation factors with their known deficiency disorders:
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Which of the following is NOT a risk factor for thromboembolism?
Which of the following is NOT a risk factor for thromboembolism?
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DIC is a primary disorder of coagulation.
DIC is a primary disorder of coagulation.
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What is the main outcome of a pulmonary embolus?
What is the main outcome of a pulmonary embolus?
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In disseminated intravascular coagulation (DIC), platelet count is usually _____ .
In disseminated intravascular coagulation (DIC), platelet count is usually _____ .
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Which factor does von Willebrand factor primarily help stabilize?
Which factor does von Willebrand factor primarily help stabilize?
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Thrombosis can occur in both intravascular and extravascular spaces.
Thrombosis can occur in both intravascular and extravascular spaces.
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What laboratory result is expected in patients with hemophilia?
What laboratory result is expected in patients with hemophilia?
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The enzyme ____ is released to induce fibrinolysis.
The enzyme ____ is released to induce fibrinolysis.
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What does the Partial Thromboplastin Time (PTT) test evaluate?
What does the Partial Thromboplastin Time (PTT) test evaluate?
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Von Willebrand disease is characterized by spontaneous bleeding from mucous membranes.
Von Willebrand disease is characterized by spontaneous bleeding from mucous membranes.
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What element is essential for the conversion of pro-enzymes to their active forms during coagulation?
What element is essential for the conversion of pro-enzymes to their active forms during coagulation?
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Which pathway is activated by the release of tissue thromboplastin following tissue injury?
Which pathway is activated by the release of tissue thromboplastin following tissue injury?
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Which factor initiates the intrinsic coagulation pathway upon contact with a foreign surface?
Which factor initiates the intrinsic coagulation pathway upon contact with a foreign surface?
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What is the primary role of the coagulation cascade?
What is the primary role of the coagulation cascade?
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How does the endothelial lining contribute to hemostasis?
How does the endothelial lining contribute to hemostasis?
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What laboratory finding is characteristic of Thrombotic Thrombocytopenic Purpura (TTP)?
What laboratory finding is characteristic of Thrombotic Thrombocytopenic Purpura (TTP)?
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Which substance is critical for platelet aggregation?
Which substance is critical for platelet aggregation?
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What does a peripheral blood smear typically show in cases of immune thrombocytopenic purpura?
What does a peripheral blood smear typically show in cases of immune thrombocytopenic purpura?
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Which physiological response contributes to the constriction of blood vessels during hemostasis?
Which physiological response contributes to the constriction of blood vessels during hemostasis?
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What is the main pathological feature of Hemolytic Uremic Syndrome (HUS)?
What is the main pathological feature of Hemolytic Uremic Syndrome (HUS)?
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Chronic passive congestion, also referred to as 'nutmeg liver', is primarily associated with which condition?
Chronic passive congestion, also referred to as 'nutmeg liver', is primarily associated with which condition?
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Which factor deficiency is related to Glanzmann thrombasthenia?
Which factor deficiency is related to Glanzmann thrombasthenia?
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What is the role of renin in the renal system related to edema?
What is the role of renin in the renal system related to edema?
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What is a key clinical feature of Hemophilia A?
What is a key clinical feature of Hemophilia A?
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Which of the following correctly defines disseminated intravascular coagulation (DIC)?
Which of the following correctly defines disseminated intravascular coagulation (DIC)?
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What laboratory result is often seen in patients with von Willebrand disease?
What laboratory result is often seen in patients with von Willebrand disease?
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What is the primary treatment strategy for Hemophilia B?
What is the primary treatment strategy for Hemophilia B?
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What role does tissue factor play in secondary hemostasis?
What role does tissue factor play in secondary hemostasis?
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In the context of coagulation, which factor deficiency is associated with vitamin K deficiency?
In the context of coagulation, which factor deficiency is associated with vitamin K deficiency?
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Which of the following conditions is often associated with increased risk of thromboembolism?
Which of the following conditions is often associated with increased risk of thromboembolism?
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What defines an embolus in the context of thromboembolism?
What defines an embolus in the context of thromboembolism?
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What is a common result of the laboratory tests in patients with DIC?
What is a common result of the laboratory tests in patients with DIC?
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What is the primary mechanism by which thrombotic events occur?
What is the primary mechanism by which thrombotic events occur?
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Which of the following is NOT a feature of DIC?
Which of the following is NOT a feature of DIC?
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What is a common symptom in patients with von Willebrand disease?
What is a common symptom in patients with von Willebrand disease?
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Which of the following actions is taken to manage a patient with hemophilia?
Which of the following actions is taken to manage a patient with hemophilia?
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What is the leading cause of lower extremity edema?
What is the leading cause of lower extremity edema?
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Study Notes
Fluid & Hemodynamic Derangements
- Hydrostatic pressure and plasma colloid osmotic pressure can affect fluid balance, leading to edema.
- Increased interstitial fluid pressure occurs when hydrostatic pressure exceeds plasma colloid osmotic pressure.
- Edema can be caused by injuries to the endothelial cells or blood vessel wall, increased hydrostatic pressure, increased interstitial sodium, decreased colloid osmotic pressure, and lymphatic obstruction.
- Edema can be categorized as local (acute inflammation, urticaria, venous thrombosis, left-sided heart failure) or systemic (anasarca) which can be caused by various factors like heart failure, cirrhosis, nephrotic syndrome, and fluid resuscitation.
- Anasarca is a form of generalized edema caused by multiple factors like malnutrition, hepatic synthesis disorders, nephrotic syndrome, heart failure, and decreased plasma oncotic pressure.
- The renin-angiotensin-aldosterone system plays a key role in regulating blood pressure, electrolyte balance, and fluid volume.
Congestive Heart Failure
- Congestive heart failure can lead to pitting edema.
Circulation Pathology
- Effusions are fluids within body cavities.
- Transudate is edema fluid with low protein content (specific gravity 1.020).
- Exudates are classified as purulent (pus), fibrinous, eosinophilic, and hemorrhagic.
Congestion
- Congestion is a condition of dilated blood vessels.
- Passive congestion happens due to mechanical effects (congestive heart failure, venous thrombosis) while active congestion (hyperemia) is caused by acute inflammation and hypersensitivity reactions.
Nutmeg Liver
- Nutmeg liver is a condition that happens due to chronic passive congestion.
Hemostasis
- Hemostasis is the process of blood coagulation leading to the formation of a stable fibrin-platelet hemostatic plug.
- The process involves vascular wall, platelets, and coagulation cascade.
- Endothelial cells in the vascular wall contain both thrombogenic factors (tissue factor, thromboxane A2) and anti-thrombogenic substances (tissue plasminogen activator, prostacyclin, nitric oxide, thrombomodulin).
- Subendothelial connective tissue promotes platelet adherence and release reactions.
- Muscular layer in the vascular wall constricts blood vessels through pain reflexes and vasoactive amines.
- Thrombocytopenia is a condition with decreased platelets due to decreased production or increased destruction.
Platelets
- Platelets are derived from megakaryocytes in bone marrow.
- Platelets adhere to von Willebrand factor adhered to subendothelial collagen.
- Platelet activation triggers shape change, degranulation, thromboxane A2 synthesis, and membrane expression of the phospholipid complex.
- Platelet aggregation occurs when additional platelets are recruited by ADP and thromboxane A2.
Fibrin-platelet Thrombus
- A fibrin-platelet thrombus is a platelet aggregate held together by fibrinogen.
Schistocyte
- A schistocyte is a fragment of a red blood cell found in peripheral blood smear that indicates microangiopathic hemolytic anemia.
Laboratory Tests for Platelets
- Tests include platelet count, bleeding time test, and platelet aggregometry.
Platelet Receptors
- Glycosylated Protein Ib (GpIb) binds to von Willebrand factor (vWF).
- Glycosylated Protein IIb-IIIa (GpIIb-IIIa) binds to fibrinogen.
- Deficiencies in these proteins can lead to bleeding disorders like Bernard-Soulier syndrome, Glanzmann thrombasthenia, and von Willebrand disease.
Immune Thrombocytopenia Purpura (ITP)
- ITP is characterized by antiplatelet antibodies against platelet antigens.
- Antibodies are made in the spleen and destroy platelets peripherally.
- ITP can occur in acute form (children following viral infection) or chronic form (childbearing women, SLE, AIDS).
Immune Thrombocytopenia Purpura (ITP) - Lab and Treatment
- Lab findings include decreased platelet count, prolonged bleeding time, and thrombocytopenia with enlarged immature platelets (megathrombocytes) on peripheral blood smear.
- Bone marrow biopsy shows increased numbers of megakaryocytes.
- Treatment involves corticosteroids, immunoglobulin therapy, and splenectomy.
Thrombotic Thrombocytopenic Purpura (TTP)
- TTP is characterized by widespread formation of fibrin-platelet thrombi.
- Deficiency of plasma metalloprotease (ADAMTS13) causes TTP.
- Clinical presentation includes fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, and renal failure.
Thrombotic Thrombocytopenic Purpura (TTP) - Labs
- Labs show decreased platelet count, prolonged bleeding time, and schistocytes on peripheral blood smear.
Hemolytic Uremic Syndrome (HUS)
- HUS is a thrombotic microangiopathy that commonly affects children.
- It often follows gastroenteritis caused by verotoxin-producing E.coli 0157:H7.
Kidney: Thrombotic Microangiopathy
- Thrombotic microangiopathy can affect the kidney.
Coagulation
- Coagulation is the process of transforming fluid blood into a gel matrix entrapping cellular components.
- Coagulation factors are synthesized by the liver and exist as pro-enzymes.
- Some conversions require calcium and occur on a phospholipid surface.
Coagulation: Intrinsic and Extrinsic Systems
- The intrinsic system relies on substrates present in circulating blood and is activated by contact with foreign surfaces like collagen, Ag-Ab complexes, or glass.
- The extrinsic system activates after tissue injury through the release of tissue thromboplastin which activates inactive factor VII to active factor VII.
Coagulation Cascade
- The intrinsic pathway is activated by Hageman factor (factor XII).
- The extrinsic pathway is activated by tissue factor or endothelial cell injury.
Coagulation
- HMWK (High Molecular Weight Kininogen) is a cofactor in the coagulation cascade
- Prekallikrein is activated to Kallikrein by XIIa (activated Factor XII)
- Kallikrein activates Factor XI, which in turn activates Factor IX
- Factors VIIIa and IXa activate Factor X in the presence of calcium ions (Ca2+) and phospholipid surfaces
- Activated Factor X (Xa) along with Factors Va and Ca2+ is involved in the conversion of Prothrombin (Factor II) into Thrombin (Factor IIa)
- Thrombin activates Factor XIII and cleaves Fibrinogen into Fibrin monomers
- Factor XIII (activated by thrombin) cross-links Fibrin monomers to form a stable fibrin clot
- The extrinsic pathway is initiated by tissue factor (TF)
- The intrinsic pathway is initiated by contact activation
- Both pathways converge to a common pathway for activation of Factor X
Coagulation Tests
- Prothrombin time (PT) measures the extrinsic and common coagulation pathways: VII, X, V, Prothrombin, and Fibrinogen
- Partial thromboplastin time (PTT) measures the intrinsic and common coagulation pathways: XII, XI, IX, VIII, X, V, Prothrombin, and Fibrinogen
- Thrombin time (TT) measures the time it takes for fibrinogen to convert to fibrin by thrombin
- Fibrin degradation products (FDP) measure the breakdown of fibrin by plasmin. They are elevated in Disseminated Intravascular Coagulation (DIC)
Hemostasis
- Primary hemostasis involves platelet adhesion, activation, aggregation, and the formation of a platelet plug
- Secondary hemostasis involves the coagulation cascade and the formation of a fibrin clot
- Vasospasm is triggered by the release of endothelin and reflex mechanisms
Hemophilia
- Hemophilia A (Classic Hemophilia): deficiency of Factor VIII, X-linked recessive
- Hemophilia B (Christmas Disease): deficiency of Factor IX, X-linked recessive
- Both Hemophilia A and B present with spontaneous hemorrhages, particularly into the joints (hemarthrosis), easy bruising, prolonged bleeding after surgery and trauma. They have a normal platelet count and bleeding time, but a prolonged PTT. Treatment: concentrate of the deficient factor is administered
von Willebrand Disease
- Von Willebrand Disease is an inherited bleeding disorder characterized by a deficiency or abnormality of vWF (von Willebrand factor)
- vWF is produced by endothelial cells and megakaryocytes
- Symptoms can include: spontaneous bleeding from mucous membranes, prolonged bleeding from wounds, menorrhagia, and rarely, bleeding into joints
- Diagnosis: abnormal platelet response to ristocetin (adhesion defect)
- Treatment: for mild cases, desmopressin (ADH analogue) can stimulate vWF release from endothelial cells
Disseminated Intravascular Coagulation (DIC)
- DIC is a disorder characterized by widespread activation of the coagulation cascade
- Causes: obstetric complications (placental tissue factor), gram-negative sepsis (TNF), microorganisms (meningococcus, rickettsia), acute promyelocytic leukemia, adenocarcinomas
- Pathogenesis: activation of coagulation results in consumption of clotting factors, platelets. This causes an imbalance favoring fibrinolysis. It leads to microthrombi and microangiopathic hemolytic anemia
- Laboratory findings: decreased platelet count, prolonged PT/PTT, decreased fibrinogen, elevated fibrin split products (D-dimers)
- Treatment: treating the underlying cause
Thromboembolism
- Predisposing Factors: injury to vascular endothelium (atherosclerosis), changes in blood flow (stasis, turbulence), hypercoagulability (high platelets, clotting factors, low fibrinolytic activity)
- ** Thrombus** is a blood clot that forms inside a blood vessel
- ** Lines of Zahn** are alternating layers of platelets and fibrin found in thrombi
- Embolus is a detached intravascular mass that travels to a distant site
- Types of Emboli: thrombus, bone marrow, atheromatous debris, fat, bacteria, tumor cells, amniotic fluid, air
Pulmonary Embolism
- Origin: deep leg veins, prostatic and uterine venous plexus
- Outcome: resolution, infarction, chronic pulmonary hypertension, sudden death
Paradoxical Embolus
- Any venous embolus that crosses from the right to the left side of the heart through a septal defect
Infarct
- Localized area of necrosis resulting from circulatory insufficiency/ischemia
- Etiology: thrombus, embolus, low-output state
- Factors affecting development: degree of obstruction, rate of occlusion, vulnerability of tissue, presence of collateral circulation, pre-existing disease, oxygen-carrying capacity of blood
- Gross Pathology: wedge-shaped with apex pointing to occlusion
- Anemic infarcts (pale): solid organs with single blood supply
- Hemorrhagic infarcts (red): dual blood supply or collateral circulation, venous occlusion
Hemorrhage
- Terminology: petechiae, ecchymosis, purpura, epistaxis, hematemesis, hemoptysis, melena, hematochezia, hematuria, hemothorax, hemopericardium, hemoperitoneum, hematoma
Shock
- Systemic vascular collapse and tissue hypoperfusion
- Causes: cardiogenic (pump failure), hypovolemic (reduced blood volume), obstructive, septic (bacterial infection), neurogenic (generalized vasodilatation), anaphylactic (type I hypersensitivity)
- Stages: compensation (reflex mechanisms maintaining perfusion), decompensation (decreased tissue perfusion, reversible injury), irreversible (irreversible tissue injury and organ failure)
- Pathology: kidneys (acute tubular necrosis), lungs (diffuse alveolar damage), intestines (mucosal necrosis, hemorrhages), liver (centrilobular necrosis), adrenals (Waterhouse-Friderichsen syndrome)
Hemostasis
- Sequence of events leading to cessation of bleeding by formation of a stable fibrin-platelet hemostatic plug
- Involves the vascular wall, platelets, and coagulation cascade
Vascular Wall
- Endothelial cells contain both pro-thrombogenic and anti-thrombogenic substances.
- Pro-thrombogenic: Tissue factor (tissue thromboplastin), von Willebrand factor, thromboxane A2
- Anti-thrombogenic: Tissue plasminogen activator, anti-platelet aggregating prostaglandins (prostacyclin), nitric oxide, thrombomodulin
- Subendothelial connective tissue promotes platelet adherence and release reactions.
- Muscular layer constricts blood vessels, induced by pain reflexes and vasoactive amines (histamine and serotonin), dependent upon the amount of muscular tissue composing the vascular wall.
Platelets
- Circulating platelets: 150k to 400k per mm3
- Derived from megakaryocytes in the bone marrow
- Thrombocytopenia: Decreased platelet count
- Decreased production
- Increased destruction
Platelet Activation
- Three steps are critical:
- Platelet adhesion: vWF adheres to subendothelial collagen, then platelets adhere to vWF by glycoprotein Ib
- Platelet activation: Platelets change shape and degranulate, synthesizing thromboxane A2 and expressing phospholipid complex, a platform for coagulation cascade
- Platelet aggregation: Additional platelets are recruited by ADP and thromboxane A2, they bind to each other via fibrinogen using Gp IIb-IIIa
Deficiencies
- Bernard-Soulier syndrome: Deficiency in GpIb
- Glanzmann Thrombasthenia: Deficiency in GpIIb-IIIa complex
- von Willebrand disease: Deficiency in von Willebrand factor
Immune Thrombocytopenia Purpura (ITP)
- Etiology:
- Antiplatelet antibodies against platelet antigens (Gp IIb-IIIa and Gp Ib-IX)
- Antibodies are made in the spleen
- Platelets are destroyed by macrophages in the spleen due to Fc receptors binding IgG-coated platelets
- Forms:
- Acute ITP: Seen in children after viral infections, self-limited
- Chronic ITP: Usually seen in women, may be first sign of SLE or AIDS, causes petechiae, ecchymoses, menorrhagia, and nosebleeds
- Lab findings:
- Decreased platelet count and prolonged bleeding time
- Normal PT and PTT
- Peripheral blood smear shows thrombocytopenia with large immature platelets (megathrombocytes)
- Bone marrow biopsy shows increased megakaryocytes with immature forms
- Treatment:
- Corticosteroids - decrease antibody production
- Immunoglobulin therapy - bind Fc receptors on splenic macrophages
- Splenectomy - remove site of platelet destruction and antibody production
Thrombotic Thrombocytopenic Purpura (TTP)
- Pathology: Widespread formation of fibrin-platelet thrombi (hyaline thrombi) due to deficiency in plasma metalloprotease (ADAMTS13)
- Clinical presentation:
- Affects adult women
- Pentad of characteristic signs: Fever, Thrombocytopenia, Microangiopathic hemolytic anemia, Neurologic symptoms, Renal failure
- Labs:
- Decreased platelet count and prolonged bleeding time
- Normal PT and PTT
- Peripheral blood smear shows thrombocytopenia, schistocytes, and reticulocytosis
Hemolytic Uremic Syndrome (HUS)
- Another example of thrombotic microangiopathy
- Mainly affects children
- Follows gastroenteritis with bloody diarrhea
- Organism: Verotoxin-producing E.coli 0157:H7
- Similar clinical pentad as TTP
Coagulation
- Intravascular transformation of fluid blood into a gel matrix, entrapping cells
- Coagulation factors are synthesized by the liver, mostly pro-enzymes that must be activated
- Some conversions occur on a phospholipid surface, others require calcium
Intrinsic Coagulation Pathway
- All substrates for clotting are present in circulating blood
- Activated by contact with a foreign surface (collagen, antigen-antibody complexes, glass)
- Hageman factor (factor XII) is the contact-sensitive protein
Extrinsic Coagulation Pathway
- After tissue injury, phospholipid protein complex (tissue thromboplastin) is released into the blood
- Activates the extrinsic pathway, converting inactive factor VII to active factor VII
Edema
- Injury to endothelial cells/blood vessel wall
- Increased hydrostatic pressure
- Increased interstitial sodium
- Decreased plasma colloid osmotic pressure (albumin)
- Lymphatic obstruction
Edema Formation
- Increased interstitial fluid pressure due to hydrostatic pressure and sodium retention
- Decreased plasma colloid osmotic pressure due to low albumin levels
- This leads to transudation of fluid out of the capillaries and into the interstitial spaces
Edema Types
- Local: Acute inflammation, urticaria, venous thrombosis, left-sided heart failure
- Systemic (anasarca): Heart failure, Liver cirrhosis, Kidney nephrotic syndrome, Iatrogenic fluid resuscitation
Anasarca
- Generalized edema affecting a large area of the body
- Caused by multiple factors:
- Malnutrition: Deficient protein synthesis, low albumin levels
- Hepatic synthesis: Liver failure, decreased albumin production
- Nephrotic syndrome: Excessive protein loss in urine, low albumin levels
- Heart failure: Decreased cardiac output, increased capillary pressure
Congestive Heart Failure
- Pitting edema is a common manifestation
- Fluid accumulates in the interstitial spaces, causing swelling
Congestion
- Dilated blood vessel
- Passive congestion: Mechanical effect caused by conditions like congestive heart failure or venous thrombosis
- Active congestion (hyperemia): Acute inflammation, hypersensitivity reaction (Type I)
Hyperemia vs. Congestion:
-
Hyperemia: Increased inflow of blood, causes erythema (redness)
- Examples: Exercise, inflammation
-
Congestion: Decreased outflow of blood, causes cyanosis (blue discoloration) and hypoxia
- Examples: Obstruction, congestive heart failure
Nutmeg Liver
- Liver appearance in chronic passive congestion
- Pattern of red central veins surrounded by pale zones
- Indicates poor blood flow and oxygenation
Chronic Passive Congestion
- Long-standing congestion causing cell death
- "Nutmeg liver" is a classic example
Fibrin-platelet Thrombus
- Stable plug formed during hemostasis
- Composed of platelets and fibrin
Microangiopathic Hemolytic Anemia (MAHA)
- Characterized by schistocytes (fragmented red blood cells) in peripheral blood smears
Lab Tests for Platelets
- Platelet count: Normal 150 to 400K/mm3
- Bleeding time test: Normal 2 to 7 minutes
- Platelet aggregometry: Measures platelet function
Coagulation Cascade
- The coagulation cascade is a series of enzymatic reactions that lead to the formation of a fibrin clot.
- The intrinsic pathway is activated by contact with negatively charged surfaces, such as exposed collagen.
- The extrinsic pathway is activated by tissue factor, which is released from damaged cells.
- Both pathways converge at the common pathway, which leads to the activation of thrombin.
- Thrombin converts fibrinogen to fibrin, forming the fibrin clot.
- Several cofactors are involved in the coagulation cascade, including factor VIIIa, factor Va, and calcium ions.
Fibrinolysis
- Fibrinolysis is the process by which fibrin clots are broken down.
- Plasminogen is activated to plasmin by tissue plasminogen activator (tPA) and urokinase
- Plasmin breaks down fibrin into fibrin degradation products.
- Alpha2-antiplasmin is an inhibitor of fibrinolysis that prevents excessive clot breakdown.
Hemophilia A
- Hemophilia A is a bleeding disorder caused by a deficiency in factor VIII.
- It is an X-linked recessive disorder, predominantly affecting males.
- It is characterized by spontaneous hemorrhages, easy bruising, prolonged bleeding, and hematoma formation.
- Treatment involves factor VIII concentrate.
Hemophilia B
- Hemophilia B is a bleeding disorder caused by a deficiency in factor IX.
- It is an X-linked recessive disorder, clinically identical to hemophilia A.
Acquired Coagulopathies
- Vitamin K deficiency can lead to decreased synthesis of clotting factors, including II, VII, IX, X, and protein C and S.
- Liver disease can reduce the synthesis of nearly all clotting factors.
von Willebrand Disease
- von Willebrand Disease is a bleeding disorder characterized by a deficiency or qualitative defect in von Willebrand factor, a protein produced by endothelial cells and megakaryocytes.
- It can cause prolonged bleeding from wounds, spontaneous bleeding from mucous membranes, and menorrhagia in females.
- Treatment with desmopressin, an anti-diuretic hormone (ADH) analogue, releases vWF from endothelial cells.
Disseminated Intravascular Coagulation (DIC)
- DIC is a serious condition that involves widespread activation of the coagulation cascade, leading to the formation of microthrombi throughout the body.
- It is secondary to other disorders, such as sepsis, obstetric complications, malignancy, trauma, and certain infections.
- DIC results in a bleeding diathesis due to depletion of platelets and clotting factors
- Labs show decreased platelet count, prolonged PT/PTT, decreased fibrinogen, and elevated fibrin split products (D-dimers).
- Treatment involves addressing the underlying condition.
Thromboembolism
- Thromboembolism is a condition in which a blood clot, or thrombus, forms in a blood vessel and breaks loose, traveling to another location.
- Three primary factors contribute to the formation of thrombi: injury to vascular endothelium, changes in blood flow, and hypercoagulability.
- Thrombi can evolve into emboli, organizing into vessel walls or being removed by fibrinolytic action.
- Lines of Zahn are a characteristic feature of thrombi, representing alternating layers of fibrin and platelets.
Emboli
- Emboli are detached intravascular masses that can travels to a site distant from the point of origin.
- Emboli can be composed of thrombi, bone marrow, atheromatous debris, fat, bacteria, tumor cells, amniotic fluid, and air, among others.
Pulmonary Embolus
- Pulmonary embolus is a condition where an embolus lodges in the pulmonary arteries.
- Most commonly originates from deep leg veins, prostatic, and uterine venous plexuses.
- Outcome: resolution, infarction, chronic pulmonary hypertension, or sudden death.
Paradoxical Embolus
- Paradoxical embolus is a venous embolus that reaches the systemic circulation through a septal defect in the heart.
Infarct
- An infarct is a localized area of necrosis caused by circulatory insufficiency or ischemia.
- Infarcts in the heart, brain, and lungs are significant causes of death worldwide..
- Vulnerability of tissue to ischemia, presence of collateral circulation, and pre-existing diseases influence infarct development.
- Infarcts are usually wedge-shaped with the apex pointing to the occlusion.
- Anemic infarcts occur in solid organs with a single blood supply.
- Hemorrhagic infarcts occur in organs with a dual blood supply or collateral circulation.
- Microscopic pathology: Ischemic coagulative necrosis (except brain, which undergoes liquefaction necrosis).
- Granulation tissue forms around the infarcted area, followed by fibrosis.
Hemorrhage
- Hemorrhage is excessive bleeding.
- Hematoma: localized hemorrhage within tissues.
- Types: Petechie, Ecchymosis, Purpura, Epistaxis, Hematemesis, Hemoptysis, Melena, Hematochezia, Hematuria, Hemothorax, hemopericardium, hemoperitoneum.
Shock
- Shock is a condition characterized by widespread hypoperfusion of cells and tissues due to reduced blood volume, cardiac output, or vascular tone.
- Causes: cardiogenic, hypovolemic, obstructive, septic, neurogenic, anaphylactic.
- Stages: compensation, decompensation, irreversible.
- Pathology:
- Kidneys: Acute tubular necrosis
- Lungs: diffuse alveolar damage
- Intestines: Superficial mucosal ischemic necrosis
- Liver: Centrilobular necrosis
- Adrenals: Waterhouse-Friderichsen syndrome (bilateral hemorrhagic infarction with acute adrenal insufficiency, often seen in meningococcal septic shock).
- Treatment: involves addressing the underlying cause and providing supportive care.
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Test your knowledge on the coagulation system with this quiz focusing on intrinsic and extrinsic pathways. Explore key factors, their synthesis, and the mechanisms involved in blood clotting following injury. Match terms and definitions to enhance your understanding of this critical biological process.
