Bleeding Disorders: Thrombocytopenia, Hemophilia, and Coagulation - PDF

Bleeding disorders Quantitative Disorders o Increase destruction: A. Thrombocytopenia  platelet count < 100,000/uL  most common cause of clinically important bleeding.  Clinical presentation: petechiae, purpura and ecchymoses...

Bleeding disorders Quantitative Disorders o Increase destruction: A. Thrombocytopenia  platelet count < 100,000/uL  most common cause of clinically important bleeding.  Clinical presentation: petechiae, purpura and ecchymoses  Causes of Thrombocytopenia: o Decrease production  Ineffective thrombopoiesis  Megakaryocyte hypoplasia  Aplastic anemia  Congenital/Acquired hypoplasia  Ineffective thrombopoiesis  Infiltration of BM by malignant cells  TAR syndrome  Hereditary macrothrombocytopenia o Increase sequestration (spleen) o Dilution of Platelet (Multiple BT) 1. Immune Thrombocytopenic Purpura 2. Immunologic Drug-Induced Thrombocytopenia  Drug-dependent antibodies typically occur after 1 to 2 weeks of exposure to a new drug.  Mechanism: o Drug dependent Ab o Drug-Induced auto-Ab o Hapten-Induced Ab o Immune complex-Induced thrombocytopenia 3. Post-Transfusion Purpura  rare disorder  typically develops about 1 week after transfusion of platelet- containing blood products, FFP, whole blood, and packed or washed red cells.  (+) anti-HPA-1a (platelet antibodies) from recipient 4. Isoimmune Neonatal Thrombocytopenia  develops when the mother lacks a platelet-specific antigen that the fetus has inherited from the father --> IgG Ab from mothers attaches the fetal platelet antigen. 5. Thrombic Thrombocytopenic Purpura  rare disorder  related to accumulation of ultra large vWF ultimers in plasma to due deficient ADAMTS-13 6. Other Causes of Increased Platelet Consumption 1. Disseminated Intravascular Coagulation (DIC) - is a rare but serious condition that causes abnormal blood clotting throughout the body’s blood vessels 2. Hemolytic uremic syndrome (HUS) - is a condition that damages blood vessels in your kidneys and can cause acute Qualitative Disorders kidney failure.  Clinical presentation: B. Thrombocytosis o Excessive bruising  increase in circulating platelets (>450,000/uL) o Superficial (mucocutaneous) bleeding  Reactive thrombocytosis o elevation in the platelet count secondary to inflammation, trauma, or other underlying and seemingly unrelated conditions. o Platelet count: 450,000 - 800,000/ul 1. Glanzmann Thrombasthenia A. Alpha Granules Deficiency (Platelet Aggregation Defects)  bleeding disorder  abnormal in vitro clot retraction test and normal platelet count.  (+) population with high consanguity  deficient/abnormal (GP) IIb/IIIa complex B. Dense Granules Deficiency 2. Bernard-Soulier Syndrome (Platelet Adhesion Defects) Wiskott Aldrich Syndrome X-linked disease  manifest during infancy/childhood mutations in the WAS gene  ecchymoses, epistaxis, and gingival bleeding Immunodeficiency, thrombocytopenia,  GP Ib/IX/V complex is missing from the platelet surface or microthrombocytes and decrease dense granules exhibits abnormal function.  (+) Giant platelets 3. Storage-Pool Defects Hermansky Pudlak autosomal recessive tyrosinase positive oculocutaneous albinism defective lysosomal function ceroid-like deposition in the cells of the RES and profound platelet dense granule deficiency   Chronic Liver Disease  Chediak Higashi Syndrome  Anemia CABG oculocutaneous albinism,  Autoimmune Disease (Collagen Vascular Disease) frequent pyogenic bacterial infections Vascular Disorders giant lysosomal granules dense granule deficiency Thrombocytopenia with Absent Radius congenital absence of radius Coagulation Disorders cardiac abnormalities  Hereditary – either quantitative or qualitative defect in single coagulation factor structural defects in dense granules  Acquired – deficiency of multiple coagulation factors  Common Presentations: 4. Acquired Platelet Problems  Large ecchymosis and hematomas – delayed bleeding  Bleeding from the nose, gums, GIT, GUT  Uremia  Joint bleeds, muscle bleeds  Paraproteinemia (Multiple Myeloma and Waldenstrom  Excessive bleeding (Post-dental, post-surgical, trauma) Macroglobulinemia)  AML  Laboratory Evaluation:  Myeloproliferative Disorder  Screening Tests:  PNH  Drug (Aspirin) PT  APTT Thrombin Time  Special tests: Coagulation factor assays A. Hereditary Coagulation Disorders 1. Hemophilia A  x-linked recessive disorder that is due to defective and/or deficient factor VIII molecules  Incidence: 1 in 10,000 live births  Also known as “The Royal Disease”  Severity linked to level of VIII:C activity 2. Hemophilia B (Christmas disease)  Bleeding usually last up to 8 hours and as late as 1-3 days  Clinically indistinguishable from Hemophilia A (need to after trauma. It can occur in: perform specific assays to distinguish) Joints  Deficiency of factor IX Urinary tract Intracranial – major cause of death  Incidence: 1 in 25,000-30,000 Deep muscle 3. Von Willebrand Disease  Quantitative or qualitative absence of VWF  Clinical features: bleeding, bruising, epistaxis, menorrhagia  Lab results: VWF (plasma), factor VIII activity, Bleeding time, Normal Platelet count Types: 1. Type 1- most common form  Occurs as secondary complication of some diseases or conditions  Partial quantitative deficiency of VWF  Conditions associated with DIC:  Autosomal dominant  Infections/Septicemia  Prolonged bleeding time, normal platelet count  Intravascular Hemolysis 2. Type 2  Acute Liver Disease  - Qualitative alterations in the VWF structure and function  Tissue Injury 3. Type 3 – least common and most severe  Obstetric - complete absence of VWF in plasma or storage organelle  Malignancy - Autosomal recessive  Cardiovascular  Hypo/Hyperthermia Acquired VWD  Lymphoproliferative disease  Tumor  Autoimmune disease  Cardiac/valvular disease  Medications (valproic acid)  hypothyroidism B. Acquired Coagulation Disorders 1. Disseminated Intravascular Coagulation (DIC)  Defibrination syndrome/consumptive coagulopathy Laboratory Evaluation: D-dimer Antithrombin III Platelet Count PT PTT Fibrinopeptide A Platelet factor 4