Hemorrhagic Diathesis and DIC Overview

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which of these options is NOT a common cause of excessive bleeding?

Increased fragility of vessels

Bacterial infection (correct)

Vitamin K deficiency

Platelet deficiency or dysfunction

Which of these clotting factors is affected in both Hemophilia A and von Willebrand Disease?

Factor VIII (correct)

Factor IX

Factor XI

Factor X

Which of the following is NOT a clinical manifestation of Disseminated Intravascular Coagulation (DIC)?

Thrombocytopenia

Increased platelet count (correct)

Bleeding from mucous membranes

Microangiopathic hemolytic anemia

What is the primary function of von Willebrand factor (vWF)?

Promotion of platelet adhesion to the subendothelial matrix (B) Signup and view all the answers

Which inherited bleeding disorder is most commonly associated with a deficiency of factor IX?

Hemophilia B (C) Signup and view all the answers

What is the most common type of von Willebrand disease?

Type 1 (A) Signup and view all the answers

Which of the following is NOT a common symptom of von Willebrand disease?

Joint pain (A) Signup and view all the answers

What is the inheritance pattern of hemophilia A?

X-linked recessive (B) Signup and view all the answers

Which of these is the most common hereditary disease associated with life-threatening bleeding?

Hemophilia A (D) Signup and view all the answers

What is the primary treatment for hemophilia A?

Factor VIII infusion (D) Signup and view all the answers

Which factor deficiency is associated with Christmas disease?

Factor IX (B) Signup and view all the answers

What is the primary characteristic of disseminated intravascular coagulation (DIC)?

Excessive activation of coagulation (B) Signup and view all the answers

Which of the following is NOT a common consequence of DIC?

Increased platelet count (C) Signup and view all the answers

What is the primary mechanism that triggers DIC?

Both A and B (C) Signup and view all the answers

Which of the following is a major consequence of widespread fibrin deposition in the microcirculation during DIC?

Organ ischemia (A) Signup and view all the answers

Study Notes

Hemorrhagic Diathesis and Disseminated Intravascular Coagulation (DIC)

Learning Objectives: Summarize clotting factors and mechanisms, describe causes of excessive bleeding, and detail hemorrhagic diathesis related to clotting factor abnormalities. Also, cover the etiology, pathophysiology, clinical presentations, and investigations for hemophilia A, B, von Willebrand disease, and DIC.

Introduction - Coagulation System

Clotting Factors: The system includes numerous factors, each with a specific role.
Factor I: Fibrinogen
Factor II: Prothrombin
Factor III: Tissue factor, tissue thromboplastin
Factor IV: Calcium
Factor V: Labile factor, proaccelerin, an AC-globin
Factor VI: Accelerin, eliminated by the International Committee on Blood Clotting Factors
Factor VII: Proconvertin, stable factor
Factor VIII: Antihemophilic A factor (AHF)
Factor IX: Antihemophilic globulin (AHG), Plasma thromboplastin component (PTC), Christmas factor
Factor X: Antihemophilic B factor (AHB), Stuart-Prower factor, autoprothrombin III
Factor XI: Plasma thromboplastin antecedent (PTA)
Factor XII: Hageman factor, glass factor, contact factor
Factor XIII: Fibrin stabilizing factor (FSF), fibrinase
Prekallikrein: Fletcher factor
High Molecular Weight Kininogen: Fitzgerald factor, Williams factor, Flau Jeac factor, Contact activation cofactor

Coagulation Pathway

Intrinsic Pathway: Starts with contact of blood with negatively charged surfaces like collagen. Involves factors XII, XI, IX, VIII, X, V, II, I, and calcium.
Extrinsic Pathway: Initiated by tissue damage, involving tissue factor (TF), VII, X, V, II, I, and calcium.
Common Pathway: Both intrinsic and extrinsic pathways converge on this stage. Common components include factors X, V, II, and I. The process leads to the formation of thrombin and fibrin for clot formation.

Clotting Mechanism

Initiation: Coagulation begins with the extrinsic or intrinsic pathways.
Activation: Both pathways converge to activate a serine protease called thrombin.
Conversion: Thrombin converts fibrinogen to fibrin, creating a stable clot.

Bleeding Disorders / Hemorrhagic Diatheses

Causes of Excessive Bleeding: Can originate from increased vessel fragility (e.g., vitamin C deficiency), platelet deficiency/dysfunction, or coagulation defects.

Types: Inherited and acquired deficiencies of clotting factors.
Inherited Deficiencies: Often affect a single clotting factor. Include Hemophilia A (deficiency in factor VIII), von Willebrand disease, and Hemophilia B (deficiency in factor IX).
Acquired Deficiencies: Multiple factors are affected and may be due to decreased protein synthesis or shortened half-life. Can result from vitamin K deficiency, severe liver disease, or disseminated intravascular coagulation (DIC).

von Willebrand Disease

Factor von Willebrand (vWF): Crucial for stabilizing factor VIII and platelet adhesion to the subendothelial matrix.
Deficiency: Leads to the most common inherited bleeding disorder in humans.
Platelet Function: A defect in platelet function despite normal platelet counts.

Pathogenesis of von Willebrand Disease (vWD)

Factor VIII Levels: vWF deficiency leads to a secondary decrease in factor VIII levels.
Symptoms: Common symptoms include spontaneous bleeding from mucous membranes (e.g., epistaxis), excessive bleeding from wounds, heavy menstrual bleeding (menorrhagia).

Hemophilia A (Factor VIII Deficiency) and Hemophilia B (Factor IX Deficiency)

Hemophilia A: Most common hereditary disease associated with life-threatening bleeding. Caused by mutations in factor VIII, which is a critical cofactor for factor IX in the coagulation cascade. It's an X-linked recessive trait. 30% of patients experience new mutations without family history.
Hemophilia B: Severe factor IX deficiency. Clinically indistinguishable from hemophilia A. Factor VIII and IX function together for factor X activation.

Disseminated Intravascular Coagulation (DIC)

Definition: A thrombohemorrhagic disorder characterized by abnormally excessive activation of coagulation. Leading to microvascular thrombi formation throughout the body. Not a primary disease. Often a complication of another condition.
Etiology and Pathogenesis: DIC is triggered by release of tissue factor or thromboplastic substances into circulation, or widespread injury to endothelial cells.
Consequences: Widespread deposition of fibrin obstructs blood flow, leading to ischemia of organs. Consumption of coagulation factors and platelets results in hemorrhagic diathesis. Microangiopathic hemolytic anemia (fragmented red blood cells).
Clinical conditions related to DIC: Malignant neoplasms, such as acute myeloblastic leukemia; sepsis; major trauma; extensive surgery; severe burns; hypoxia; acidosis; and shock.
Patho-morphology: Thrombi (blood clots) are frequently found in the brain, heart, lungs, kidneys, adrenals, spleen, and liver. Any tissue can be affected.

Investigations and Treatment

Diagnosis: Involves factor assays (e.g., factor VIII or IX assays) depending on the specific condition.
Treatment: Treatments focus on stabilizing the patient, identifying underlying cause and addressing it quickly. Infusions of recombinant factor VIII or IX, blood products and/or anticoagulation may be considered. Somatic gene therapy is under development.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Explore the intricacies of hemorrhagic diathesis and disseminated intravascular coagulation (DIC) in this comprehensive quiz. Review the various clotting factors, their roles, and the underlying mechanisms causing excessive bleeding. Additionally, gain insights into the etiology and clinical presentations of disorders such as hemophilia A and B, and von Willebrand disease.