1. Laboratory Tests
   1. Prothrombin Time (PT)
      1. Adequacy of extrinsic and common coagulation pathways
      2. Time needed for plasma to clot in presence of exogenous tissue thromboplastin and Ca2+
   2. Partial Thromboplastin Time (PTT)
      1. Intrinsic and common clotting pathways
      2. Time needed for plasma to clot in presnence of kaolin (activates factor 12)
2. Disseminated Intravascular Coagulation (DIC)
   1. Secondary complication in a variety of diseases
   2. Extrinsic Initiation
      1. Release of tissue factor or thromboplastic substances into circulation
   3. Intrinsic Initiation
      1. Activation of Factor 12 or surface contact, collagen, or neg. charged sub.
   4. Waterhouse-Friderischsen syndrome- adrenal gland affected
   5. Sheehan postpartum pituitary necrosis
   6. Thrombocytopenia and prolonged PT & PTT
   7. Treatment directed at cause, not hemostatic consequences
3. Thrombocytopenia
   1. Immune Thrombocytopenic Purpura
      1. Idiopathic (ITP)
      2. Chronic Primary ITP: Anitplatelet Ig (Gp IIb/ IIIa or Ib/IX complexes)
      3. Chromic Primary ITP: Bone marry has increased # of megakaryocytes
      4. Diagnosis: exclusion of secondary ITP
      5. Clinical findings: petechiae (bruising), epistaxis (gum bleeding), and hemorrhages
   2. Heparin Induced Thrombocytopenia
      1. Clinic: 3-5% treated w/ unfractioned heparin
      2. IgG antibodies that bind factor 4, heparin dependant
      3. Cessation of heparin therapy breaks the cycle
   3. Spontaneous bleeding, prolonged bleeding time
   4. Normal PT and PTT
   5. Most common hematological manifestation of AIDS
4. Thrombotic Microangiopathies
   1. Thrombotic Thrombocytopenic Purpura
      1. Pentad- renal failiure
      2. ADAMTS13 degrades vWF
      3. Patient deficient in metalloprotease (ADMTS13)
   2. Hemolytic Uremic Syndrome
      1. Dominance of renal failure and no neurological symptoms (childhood)
      2. ADAMTS13 levels normal
   3. PT and PTT usually normal in both TTP and HUS
5. Coagulation Disorders
   1. Congenital
      1. X-linked Recessive: Hemophillia A (Factor VIII)- Classic
         1. reduction in factor 8 activity
         2. Factor 8 levels normal only functions reduced
         3. Spoontaneous hemorrhages in regions subject to trauma (joints/ hemarthroses)
         4. Prolonged PTT
         5. Recombinant factor 8 available
      2. X-linked: Hemophillia B (Factor IX)- Christmas
         1. Much less common
         2. Prolonged PTT, bleeding time normal
         3. Treatment: infusion of recombinant factor 9
      3. Autosomal: Von Willebrand Disease
         1. Prolonged bleeding time, normal platelet count
   2. Acquired
      1. deficiency in clotting factors- more common
      2. Vit. K essential for factors 7, 9, 10
6. Disorders of Peripheral Lymphoid Organs
   1. Spleen: Splenomegaly
   2. Thymus: Thymic hyperplasia
   3. Thymus: Thymoma
      1. Epithelial cell neoplasia
      2. T cells (thymocytes) neoplastic
      3. Malignant- Type I: cytologically benign, biologically aggressive
      4. Malignant-Type II: thymic carcinoma