Hereditary coagulation disorders
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• Inherited Bleeding Disorders:
• Hemophilia A (Factor VIII deficiency).
• Hemophilia B (Factor IX deficiency).
• Von Willebrand disease.
• Congenital fibrinogen deficiency.
• Acquired Bleeding Disorders:
• Liver disease.
• Vitamin K deficiency.
• Disseminated intravascular coagulation (DIC).
• Anticoagulant therapy
The Diagnostic Triad :
• The diagnosis of a bleeding disorder is not always straightforward
- Personal History of Bleeding
- Family History of Bleeding
- Laboratory Tests
Hemophilia. :
• Deficiency of factor VIII or factor IX
• Unable to activate FX
• Lack adequate thrombin generation
The clinical severity of the disease correlates : inversely with the factor VIII or IX level.
Hemophilia Diagnosis:
• Family history
• Abnormal bleeding
• Prolonged aPTT
• Low FVIII or FIX activity
• Rule out other causes of factor deficiency.
Differential Diagnosis of Factor VIII Deficiency:
• Hemophilia A.
• Von Willebrand Disease.
• Acquired Hemophilia.
Differential Diagnosis of Factor IX Deficiency:
• Vitamin K deficiency
• Liver disease
Clinical Presentation of hemophilia:
• Joint bleeding
• Chronic pain
• Functional limitations
• Muscle bleeding
• Chronic neuropathic pain
• Intracranial bleeding
• Death
• Functional limitations
• Cognitive defect
• Hematuria
• Post-surgical bleeding.
Investigations of hemophilia:
• Complete blood count: normal platelet count.
• Tests of Coagulation
• PT normal
• APTT prolonged depending on degree of deficiency
• Mixing studies
• 50/50 mixture study of patient/normal plasma:
• Corrects = deficiency
• No correction = inhibitor
• Assay FVIII first, then FIX activity.
• Exclude VWD.
• Rule out other factors deficiency
The Treatment of Haemophilia:
• Fresh frozen plasma rich in all coagulation factors.
• Cryoprecipitate ( VIII, vWF, fibrinogen , XIII).
• Desmopressin (DDVP) increase plasma factor VIII level in mild hemophilia A (release of FVIII from endothelial cells).
• Factor replacement therapy.
• Gene therapy.
vWF disease : Two (main) functions:
• Facilitate platelet binding to subendothelial collagen (GPIb, GPIIb/IIIa), plateletplatelet interactions
• Protect clotting factor VIII. Von Willebrand disease:
• It is caused by defective or decreased von willebrand factor
• It is the most common inherited coagulation disorder.
• It is Autosomal dominant in most cases.
Classification of von Willebrand disease. :
vWF disease Presentation:
• Typically, there is
• Mucous membrane bleeding (e.g. epistaxis, menorrhagia),
• Excessive blood loss from superficial cuts and abrasions, and
• Operative and post-traumatic hemorrhage.
• The severity is variable in the different types.
• Hemarthroses and muscle hematomas are rare, except in type 3 disease.
Investigation of vWF disease:
• Complete blood count, platelet count
• PT
• aPTT
• Factor VIII
• von Willebrand Antigen
• von Willebrand Activity
• The platelet count is normal except for type 2B disease (where it is low).
• The PT is normal.
• The APTT may be prolonged.
• Types 1 and 2 are differentiated by using the ratio of vWF Activity ; vWF Antigen
• If the ratio of vWF Activity to vWF Antigen is >0.6 = Type 1
• If the ratio of vWF Activity to vWF Antigen is <0.6 = type 2 Treatment
• Treatment of Types 1 and 2 vWF:
• Local measures
• DDAVP
• Releases vW protein from storage
• May be ineffective in type 2 and do not use in 2b (overactive)
• Iron therapy
• If needed use vWF concentrates.
• Treatment of Type 3 vWF:
• Local measures
• vW concentrates
• Consider prophylaxis
• Genetic advice
Acquired von Willebrand’s disease:
• Malignant diseases
• Multiple Myeloma
• Immunologic disorders
• Systemic lupus erythematosus
• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Myeloproliferative neoplasm
• Other autoimmune diseases
• Other disorders
• Hypothyroidism
• Uremia