Bleeding Disorders 2

Primary Haemostatic Disorders

• Manifestations include petechiae, epistaxis, and menorrhagia.
• Disorders like thrombocytopenia and von Willebrand disease (VWD) usually present with immediate bleeding symptoms.

Gender Distribution in Disorders

• Primary haemostatic disorders exhibit equal gender distribution; secondary coagulation disorders disproportionately affect males (>80%).

Bleeding Symptoms

• Immediate bleeding symptoms are typically seen in thrombocytopenia and VWD.
• Delayed bleeding symptoms are characteristic of coagulation disorders like haemophilia.
• Intramuscular hematomas can occur in primary haemostatic disorders (e.g., thrombocytopenia and VWD).

Thrombocytopenia

• Defined as a platelet count of less than 150 x 10^9/L; treatment is usually initiated below 50 x 10^9/L.
• Causes include failure of marrow production (e.g., leukemia), immune destruction (e.g., ITP), and non-immune destruction (e.g., TTP, DIC).
• Splenomegaly can lead to increased platelet pooling and thrombocytopenia.

Disorders of Platelet Function

• Can be inherited or acquired, including defects in adhesion, activation, secretion, and aggregation.
• Common medications that impair platelet function include aspirin, which irreversibly inhibits thromboxane A2 production.

von Willebrand Disease (VWD)

• Most common inherited bleeding disorder; prevalence is 1 in 100 (asymptomatic) and 1 in 10,000 (symptomatic).
• Caused by autosomal dominant or recessive mutations affecting von Willebrand factor (vWF).
• VWD characterized by prolonged aPTT, low levels of vWF and FVIII, normal platelet count and morphology.
• Treatment may include desmopressin (inducing vWF release) and administration of vWF concentrates.

Glanzmann's Thrombasthenia

• Extremely rare disorder resulting from αIIbβ3 deficiency, leading to impaired platelet aggregation.
• Patients experience prolonged bleeding despite normal platelet counts.

Thrombotic Thrombocytopenic Purpura (TTP)

• Associated with vWF multimer accumulation leading to platelet aggregation and thrombosis.
• Diagnosis includes thrombocytopenia, schistocytosis, and elevated LDH.
• Treatment primarily involves plasma exchange.

Disseminated Intravascular Coagulation (DIC)

• Characterized by widespread fibrin deposition, leading to simultaneous thrombosis and bleeding.
• Treatment varies depending on bleeding or thrombotic manifestations; fresh frozen plasma for bleeding, heparin for thrombosis.

Haemophilia

• Haemophilia A: deficiency in Factor VIII, X-linked recessive disorder, affecting males, prevalence 1 in 5000 to 1 in 10,000.
• Treatment includes FVIII concentrate administration, with DDAVP for mild cases.
• Haemophilia B: deficiency in Factor IX, similar prevalence and inheritance pattern as Haemophilia A.

FXI Deficiency

• Caused by recessive autosomal mutation, almost exclusively found in Ashkenazi Jewish population.
• Specific treatment information not provided, but typically involves replacement therapy for deficiencies.

General Considerations

• Education on management, avoiding aspirin and contact sports, and blood product awareness is crucial for patients with bleeding disorders.
• Genetic counseling is advised for inherited conditions.### Factor Deficiencies and Treatments
• FXI Deficiency: Treatment involves the administration of Factor XI concentrate.
• FVII Deficiency: Caused by an autosomal recessive mutation; treated with Factor VII concentrate.
• FV Deficiency: A rare autosomal recessive disorder treated using fresh frozen plasma (FFP).
• FXIII Deficiency: A rare autosomal recessive disorder characterized by severe bleeding shortly after birth; treated with Factor XIII concentrate.

Fibrinogen Deficiencies

• Apofibrinogenemia: Complete absence of fibrinogen, inherited in an autosomal recessive manner, leading to severe bleeding symptoms.
• Hypofibrinogenemia: Reduced fibrinogen levels creating milder symptoms compared to apofibrinogenemia.
• Dysfibrinogenemia: Abnormal fibrinogen molecules inherited in an autosomal dominant manner, resulting in either bleeding (50%) or thrombotic (10%) complications.

Coagulation Disorders

• DIC (Disseminated Intravascular Coagulation): Characterized by simultaneous thrombosis and bleeding due to widespread fibrin deposition, leading to thrombocytopenia and potential severe bleeding.
• Liver Disease: Impairs synthesis of various coagulation factors as well as thrombopoietin, affecting overall coagulation ability.
• Vitamin K Deficiency: Affects the post-translational modification of several clotting factors, decreasing their functionality.
• Warfarin Use: Inhibits vitamin K epoxide reductase, impairing clotting factor synthesis due to reduced vitamin K cycling.

Acquired Hemophilia

• Characteristics: Presence of an autoantibody against Factor VIII; can be idiopathic or associated with other conditions such as autoimmune diseases, malignancies, pregnancy, or drug use.
• Diagnosis: Confirmed through inhibitor assays.
• Treatment Options: Human FVIII is ineffective; alternatives include recombinant porcine FVIII and immunosuppressive therapy.

Platelet Count and Function

• Causes of Thrombocytopenia: Includes failure of marrow production, shortened lifespan, immune causes (e.g., ITP), non-immune causes (e.g., TTP, DIC), sequestration, and dilution.
• Inherited Platelet Function Defects: Consist of adhesion defects (e.g., VWD, BSS), activation defects, secretion defects (e.g., Gray platelet syndrome), and aggregation defects (e.g., Glanzmann's thrombasthenia).
• Acquired Platelet Function Defects: Encountered in conditions such as aspirin use, chronic renal failure, cardiopulmonary bypass, and hematological diseases.

Coagulation Defect Categorization

• Inherited Coagulation Defects: Include specific factor deficiencies (e.g., Hemophilia A, B) and fibrinogen abnormalities (apo/hypo/dysfibrinogenemia).
• Acquired Coagulation Defects: Include DIC, liver disease, vitamin K deficiency, and acquired hemophilia.