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145 Cards in this Set
- Front
- Back
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3 major stages of hemostasis
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primary, secondary, fibrinolysis
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What are the three most common factors released by endothelial cells when vessel trauma occurs?
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von Willebrand factor, tissue factor, tissue plasminogen activator
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What are the two types of activation for secondary hemostasis?
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extrinsic (tissue factor) or intrinsic (collagen exposure)
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Fibrin degradation product that indicates complete clot formation
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D-dimer
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Glycoprotein IB and vWF are necessary for...
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platelet adhesion
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What proteins are necessary for platelet aggregation?
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GPIIb/IIa complex and fibrinogen
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What factors does thrombin activate?
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XIII and I (fibrinogen)
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What does XIIIa produce in the fibrin clot?
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stabilized cross-linking resulting in d-dimers
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Which anticoagulant is used for coagulation studies?
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3.2% Sodium Citrate
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What effects would a short draw have on the PT and APTT?
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The results would be falsely prolonged
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Which coagulation test is NOT affected by thrombocytopenia?
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PT and APTT
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What converts fibrinogen to fibrin?
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Thrombin
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At what temperature are coagulation tests performed?
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37 degrees Celsius
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What is the reference range for an APTT?
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26-34 seconds
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vWF is produced by...
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endothelial cells in blood vessels
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Where does secondary hemostasis normally occur?
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On the surface of aggregated platelets
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A normal PT and a prolonged APTT indicates...
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an intrinsic pathway deficiency
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A common name for Factor IIa is...
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thrombin
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A positive D-dimer indicates the presence of...
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Factor XIII
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What protein is the primary inhibitor of the fibrinolytic system?
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alpha 2 anti-plasmin
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A normal APTT and a prolonged PT indicates...
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Factor VII deficiency or coumadin therapy
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Photo-optical determination of a clot is based upon...
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Wavelength changes due to turbidity of the clot
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How does heparin prevent thrombin formation?
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Amplifies ATIII and inactivates thrombin
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Mechanisms for thrombocytopenia
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decreased platelet production, increased platelet destruction, pooling in spleen, increased platelet consumption
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Hemostasis is achieved by interaction of...
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blood vessels, platelets, coagulation factors, fibrinolytic factors
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Thombosis
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Stagnation of blood flow as a result of arterial disease or mechanical impedance, disturbance of the endothelial cell anticoagulation effects, leads to formation of a thrombus clot and hypercoagulable state
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primary hemostasis
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platelet adhesion to exposed , temporarily arrests bleeding but plus is fragile and easily dislodged
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Platelet adhesion is mediated by...
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glycoprotein IB and vWF
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Causes of thrombocytopenia
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defective production in the bone marrow, disorders of distribution and dilution, destruction of platelets
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Decreased numbers of megakaryocytes may be caused by...
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Congenital: Fanconi's anemia, maternal infection during pregnancy
Acquired: alcoholism, thiazide diurectivs, chemotherapy, use of radiation, etc. Marrow replacement with malignant cells (lymphoma, leukemia, myeloma, etc.) |
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Ineffective platelet production may be caused by...
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Hereditary thrombocytopenia, vitamin B12 or folate deficiency, erythroleukemia (Di Guglielmo's), proximal nocturnal hemoglobinuria
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Destruction of platelets may be caused by...
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tissue injury, obstetric complications, neoplasms (promyelocytic leukemia, carcinoma), bacterial and viral infections, intravascular hemolysis
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Thrombocytopenia can be defined as a platelet count less than...
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140,000/microliter
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Thrombocytosis can be defined as a platelet count greater than...
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450,000/microliter
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Mild thrombocytopenia
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100-150 x 10^9/Liter
usually no bleeding disorders associated with this condition |
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Severe thrombocytopenia
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Less than 50 X 10^9/Liter
spontaneous bleeding is a major concern |
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Prolongation of bleeding time is ____ proportional to the platelet count
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inversely
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Primary thrombocytosis (thrombocythemia)
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proliferative disorder of platelets
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Secondary thrombocytosis
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Increase in platelets secondary to another cause such as IDA, chronic inflammatory disease, splenectomy, and trauma (rebound thrombocytosis)
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Idiopathic (Immune) Thrombocytopenia
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Autoimmune disorder, causes thrombocytopenia, laboratory finding of: increased mean platelet volume, decreased platelet count, increased bone marrow platelet production, increased marrow megakaryocyte, normal bleeding time and platelet associated IgG present
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Acute ITP
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Usually occurs in children 2-6 years old, usually follows viral infection (Rubella, Chickenpox, CMV), may also be associated with toxoplasmosis, duration of 2-6 weeks, platelet count can be less than 20 x 10^9/L, caused by viral attachment and antigenic alteration of platelet membrane proteins leading to formation of IgG autoantibodies, self-limiting, can be treated with corticosteroids
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Chronic ITP
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Occurs in adults 20-40 years old, usually in women of childbearing age (3x more than men), slow asymptomatic onset, duration of months to years, platelet count between 30-80,000/microliter, splenectomy is the most common treatment, immunosuppressive chemotherapy may also be used
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Thrombotic Thrombocytopenia Purpura
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TTP, excessive deposition of platelet aggregates in renal and cerebral vessels, believed to be caused by vascular wall dysfunction, 3x more common in women than men, clinical symptoms neurologic, fever, renal disease, thrombocytopenia, microangiopathic hemolytic anemia
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Inherited megakaryocytic hypoplasia
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Fanconi's anemia, thrombocytopenia with absent radius, trisomy syndrome
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Acquired megakaryocytic hypoplasia
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Aplastic anemia, drug toxicity, prolonged hypoxia, viral infection, congenital states (May Hegglin anomaly, Bernard-Soulier syndrome, Wiskott-Aldrich syndrome)
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Nonimmunologic platelet loss or destruction may be caused by...
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severe hemorrhage, extensive transfusion, consumption
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HUS
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intraglomerular thrombi formation with renal dysfunction, proteinura and hematuria
Associated with verotoxin producing E. coli in children Purpura and bleeding from mucous membranes, renal failure, high mortality rate in young children |
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HUS in adults...
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secondary to pregnancy, HIV infection, malignant hypertension and organ transplantation
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Three components of hemostasis
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coagulation factors, blood vessels (endothelium), platelets
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Four regions of platelet structure
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Peripheral, Membrane, Organelles, Structural
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"Fuzzy" surface of platelet containing glycoproteins
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glycocalyx
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Function of GPIb
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adhesion (binds vWF)
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Function of GPIIb/GPIIIa
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aggregation (through fibrin)
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An agent that induces platelet activation
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agonist
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Five commonly used aggregating reagents (platelets)
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ADP, epinephrine, serotonin, ristocetin, collagen, thromboxane A2, thrombin
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Platelet Functions Tests
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Bleeding time, Platelet function analysis, Platelet aggregometry, Platelet secretion study, Flow cytometry
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Three types of qualitative platelet disorders
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adhesion defect, aggregation defect, granular defect
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Defects of adhesion
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Primary: Bernard-Soulier Syndrome
Secondary: Uremia, DIC, Paraproteinemia |
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Bernard-Soulier disease
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Autosomal recessive disorder characterized by lack of the vWF adhesion receptor GPIb
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Laboratory findings of Bernard-Soulier disease
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Mild to moderate thrombocytopenia
Platelet anisocytosis (including giant platelets) Prolonged bleeding time (>20 minutes common) Decreased platelet adhesion normal clot retraction Normal PF3 Normal platelet aggregation studies except for ristocetin |
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Diseases of Platelet Aggregation
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Glanzmann's thrombasthenia
Afibrinogenemia |
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Glanzmann's Thombasthenia
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Autosomal recessive disorder (homozygous only), Defect in GPIIb/IIIa complex
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Bernard-Soulier is usually recognized in what age group?
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Children
Hemorrhagic problems usually decrease with age |
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Clinical Presentation of Glanzmann's Thombasthenia
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Bruising, epistaxis, ecchymoses at birth/early in life, bleeding from mucous membranes, GI bleeding, menorrhagia
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Glanzmann's Thrombasthenia is usually recognized in what age group?
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Babies
Bleeding problems usually decrease with age |
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Laboratory findings of Glanzmann's Thrombasthenia
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Normal platelet count, abnormal clot retraction, PF3 availability decreased, platelet aggregation only with ristocetin (none with ADP, epinephrine, collagen or thrombin)
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Platelets in Gray Platelet Syndrome appear ____ in Wright's Stain
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Ghost-like
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Wiskott-Aldrich syndrome
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X-linked immune deficiency marked by small platelets and triad of thrombocytopenia, recurrent infections and eczema
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Chediak-Higashi anomaly
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albinism, recurrent infections, hemorrhagic tendencies, dense granule deficiency, giant lysosomes in WBCs
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The vasculature is comprised mostly of _______
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capillaries
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Primary type of tissue in contact with the blood in the lumen of the vessel
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Endothelial tissue
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Vasocontriction, vasodilation and vessel permeability are controlled by the ______
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autonomic nervous system
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Vasoconstriction
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Short-lived reflex reaction that can be sustained by release of serotonin and thromboxane A2
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Role of the endothelium
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inhibits coagulation under normal conditions, provides a smooth contiguous surface providing no site of platelet activation, negatively charged surface that repels platelets and hemostatic proteins
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Thrombogenic substances produced by endothelial cells
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thromboplastin, vWF
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Petechiae
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ruptures in vasculature that produce small skin hemorrhages, pinpoint lesions less than 2mm in size
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Palpable purpura
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Due to breach in integrity of the vessel itself as a result of inflammation and triggering of the coagulation cascade due to release of tissue factor
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Non-palpable purpura
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Due to increase in pressure inside the vessel or external physical pressure or trauma to the vessel
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Purpura
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ruptures in vasculature resulting in blood leakage 2mm to 1 cm in size
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Ecchymoses
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ruptures in vasculature resulting in blood leakage greater than 1 cm in size
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Hemosiderin in skin and tissue results in ______ following purpura
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yellow-brown macules
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Senile purpura
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Solar damage to skin and decreased collagen affects the integrity of the blood vessel wall, usually on forearms and hands
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Ehlers-Danlos Syndrome
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Hyperextensibility of joints, may display large ecchymoses, hematomas, bleeding from the gums, excessive postpartum bleeding and GI bleeding. Affects connective tissue of skin, vessels and bones.
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Scurvy
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Vitamin C deficiency (vitamin C is necessary for formation of collagen), follicular keratosis, petechiae and ecchymoses
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Dysproteinemia
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Causes extravascular fibrin deposition, marked extravasation of plasma proteins and coagulation factors due to increased vasculat permeability. Secondary to an inflammatory process or malignancy.
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Henoch-Schonlein Purpura sympoms
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symmetrical lesions over legs and buttocks progressing to necrotic lesions, seen mostly in children, affects kidneys, GI tract and CNS, exhibit abdominal and joint pain
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Cryoglobulinemia
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Cold-precipitated proteins found in the plasma, hemorrhage with palpable purpura, systemic manifestations (Urticaria, leg ulceration, arthritis, renal involvement, neuropathies), endothelial cells are altered resulting in increased vascular permeability
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Hereditary Hemorrhagic Telangiectasia
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Characterized by bleeding that occurs from telangiectasias, vessels have poor wall support and ability to contract is diminished, very common, number of lesions increase with age, bleeding usually begins in second or third decade of life, epistaxis, alimentary bleeding
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Recurrent thrombosis is due to...
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hereditary or acquired hypercoagulable risk factors
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Pathophysiology of recurrent thrombosis
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excessive clotting in combination with vascular inflammation
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Most common presentation of recurrent thrombosis
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deep vein thrombosis of lower extremities
can occur with or without pulmonary embolism |
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Thrombosis in a patient who has had previous pregnancies or surgery without thrombotic complications suggests that the hypercoagulable state is...
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acquired
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What are the high risk factors for recurrent thrombosis?
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Antithrombin deficiency, Protein C deficiency, Protein S deficiency
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What are the moderate risk factors for recurrent thrombosis?
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Factor V Leiden, Prothrombin mutation 20210A, hyperhomocysteinemia, oral contraceptive use
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What are the factors that lead to acquired hypercoagulable states?
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antiphospholipid antibody syndrome, trauma, pregnancy, advancing age, oral contraceptives, surgery, trauma
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What mutations/deficiencies lead to inherited hypercoagulable states?
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Protein C deficiency, Factor V Leiden, Protein S deficiency, antithrombin III deficiency
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Secondary hypercoagulable states
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Trousseau syndrome, heparin-induced thrombocytopenia, nephrotic syndrome, hyperviscosity, myeloproliferative disorders, paroxysomal nocturnal hemoglobinemia
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Arterial thrombosis is associated with...
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lipoprotein A, chronic DIC, antibodies associated with...
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What are the 4 events that result in pathogenic thrombosis?
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Extension of clot beyond beneficial size
Clot occurs at inappropriate site Clot embolizes to other site Fibrinolytic system fails |
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Activated protein C and protein S together inactivate...
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factors Va and VIIIa
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Protein S can directly inhibit...
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factors VIIIa, Xa and Va
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Protein C is a zymogen molecule that is converted to a _________
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serine protease (activated protein C)
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Protein S is a _______ dependent glycoprotein
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vitamin K
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Antithrombin III is the most important inhibitor of _____
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clotting factor proteases
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Type I ATIII deficiency
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Decreased concentration of ATIII, decreased functionality when combined with heparin
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Type II ATIII deficiency
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normal concentration of ATIII but protein is defective
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Factor V Leiden
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mutation of factor Va that is resistant to the anticoagulant activity of activated protein C
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Factor V Leiden is an alteration of the ______ for binding of APC
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steric site
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Factor V Leiden is seen in _____ % of the patients with DVT
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10-30
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Essential thrombocythemia is what type of disorder?
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myeloproliferative
involves clonal expansion of platelets |
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4 causes of thrombocytosis
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Essential thrombocythemia, myeloproliferative disorder, myelodysplastic syndrome, reactive thrombocytosis
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What is the treatment of choice for thrombocytosis?
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aspirin
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3 major categories of fibrinogen disorders
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afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia
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Symptoms of afibrinogenemia
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gum bleeding, epistaxis, menorrhagia, GI hemorrhage, muscle hemorrhage, spontaneous abortions
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What is the reference range for fibrinogen?
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150-350 mg/dL
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Laboratory findings for afibrinogenemia
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Prolonged PT, APTT, thrombin, reptilase time, bleeding time
Abnormal platelet aggregation |
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Dysfibrinogemia is caused by...
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the biosynthesis of a structurally abnormal fibrinogen molecule that has defective conversion to fibrin
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A specimen with a prolonged thrombin time and a normal reptilase time indicates...
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a high amount of heparin
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Corrections in mixing studies are always associated with....
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factor deficiencies
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Mixing studies are used to...
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assess the cause of prolonged coagulation screening tests (PT, APTT)
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Mixing studies are dependent on what laboratory factors?
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Time and temperature
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Pooled normal plasma contains all coagulation factors at 100% activity level (T/F)
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True
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A lack of correction in a mixing study indicates...
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a circulating inhibitor
(acts on both patient plasma and pooled normal plasma) |
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Factor VIII inhibitor is both ______ and ______ dependent
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time, temperature
Will show correction initially, but not after 2 hours at 37 degrees celsius |
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Adsorbed plasma contains which factors?
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I, V, VIII, XI, XII and XIII
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Aged serum contains which factors?
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VII, IX, X, XI and XII
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Case study:
Severe bleeding hx PT of 11 sec APTT 130 sec APTT with adsorbed plasma 50 sec APTT with PNP 42 sec APTT with aged serum 135 sec Bleeding time 4 minutes |
Factor VIII deficiency
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DIC may cause
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tissue ischemia from occlusive microthrombi
bleeding due to consumption of platelets/coagulation factors and anticoagulant effect of FDPs |
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DIC affects these two organs most severely
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lungs, kidneys
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Most common cause of DIC
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sepsis
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How is DIC initiated?
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Thrombin is activated throughout the body, inducing the deposition of fibrin
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Intravascular thrombus formation in DIC triggers the secretion of _____ which results in increased fibrinolysis
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tissue plasminogen activator
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Underlying disorders that may cause DIC
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Infectious diseases, malignant disorders, acute promyelocytic leukemia, obstetric complications
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Clinical features of DIC
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bleeding manifestations, shock, dysfunction of the livers and kidneys
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What type of bleeding manifestations may indicate DIC?
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petechiae, ecchymoses, oozing from venipuncture/catheters, bleeding in mucosal surfaces, acute life threatening hemorrhage (GI, lungs, CNS)
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Mortality rate due to DIC
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31-86%
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Organisms most frequently associated with DIC
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Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris
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Laboratory features of DIC
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Increased PT, APTT, FDP and D-dimers
Decreased fibrinogen, platelet count (<100,000/microliter) |
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What laboratory test is definitive for acute DIC?
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Thrombin-ATIII complex (very specialized test)
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What is the primary treatment for DIC?
What are additional available treatments? |
treat the underlying condition
ATIII concentrate, low molecular weight heparin |
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Blood component therapy may be administered to patients with DIC (T/F)
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False, this provides "fuel to the fire" by providing more platelets and fibrinogen
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Why does DIC sometimes occur secondary to pregnancy?
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Pregnancy produces a hypercoagulable state and is associated with reduced fibrinolytic activity.
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Blood smear and cytology findings in DIC
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marked poikilocytosis and schistocytosis
increased red cell distribution width |
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Chemistry laboratory findings in DIC
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increased indirect bilirubin, increased lactate dehydrogenase, decreased haptoglobin
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A biphasic waveform detected during a PT or APTT test indicates...
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a hypercoagulable state (increase in presence of D-dimers)
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