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133 Cards in this Set
- Front
- Back
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What is the first phase of hemostasis?
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Vasoconstriction
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What is the mechanism of vasoconstriction in the first phase of hemostasis?
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Reflex neurogenic mechanisms
Release of vasoconstrictor substances (endothelin) |
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What are the delta granules released by platelets?
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Seratonin
Calcium ATP ADP |
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Which glycoprotein binds to fibrinogen?
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GP 2b/3a
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Which glycoprotein binds to collagen?
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GP 1a/2a
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Which glycoprotein binds to von Willebrand factor?
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GP 1b/9
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Which platelet activation receptor binds to thrombin?
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Protease activated receptor 1
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The main platelet inactivation receptor binds to what substance?
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Prostacyclin
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What are the three different pathways for platelet activation?
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Phospholipase C
Phospholipase A2 Adenylyl cyclase (inhibitory) |
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What agonists stimulate phospholipase C and phospholipase A2 pathways?
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Thrombin
Thromboxane A2 Collagen |
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What is the end result of the phospholipase C pathway?
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Exposure of GP 2b/3a receptor (binds fibrinogen)
Platelet shape change Release of platelet granules |
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What occurs in the phospholipase A2 pathway?
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Production of arachidonate, which is metabolized by COX pathway to thromboxane A2.
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What does thromboxane A2 do?
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Activates neighboring platelets and promotes vasoconstriction
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What is a reversible inhibitor of the COX pathway?
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NSAID (ibuprofen)
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What is an irreversible inhibitor of the COX pathway?
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Aspirin
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Does COX-1 or COX-2 inhibit platelets?
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COX-1
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What occurs in the adenylyl cyclase pathway?
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ATP converted to cAMP --> platelet response inhibited
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What inhibits the adenylyl cyclase pathway?
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Thrombin
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What stimulates adenylyl cyclase pathway?
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Prostacyclin
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Where is vWF synthesized and stored?
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Weibel-Palade bodies
Megakaryocytes |
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What secretes vWF?
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Activated platelets
Endothelial cells |
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What factors can stimulate the release of vWF?
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Thrombin
Histamine DDAVP |
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What factors stimulate tissue repair?
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PDGF
TGF-beta |
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What factor promotes neutrophil adhesion and inflammatory response?
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P-selectin
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What is endomitosis?
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Mitosis of chromosomal components but without cytoplasm division
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Where is thrombopoietin made?
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Liver and kidney
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In the case of thrombocytopenia, what organs can increase thrombopoietin?
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Spleen and bone marrow
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What gene encodes for thrombopoietin?
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c-mpl
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In the differentiation stage of megakaryocyte development, what factors are stimulatory?
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IL-6
Il-11 Thrombopoietin |
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In the proliferative stage of megakaryocyte development, what factors are stimulatory?
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Thrombopoietin
IL-3 IL-6 IL-11 Stem cell factor GM-CSF |
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What are the three stages of megakaryocyte development?
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Proliferative
Differentiation Maturation |
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What is the role of Factor XIII?
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Turns hydrogen bonds of polymerized fibrin monomers into covalent cross-links---forms stable clot
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How does thrombin act as a feedback enhancer.
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Loops back to activate:
Factor V Factor VIII Factor XI |
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What factor is prothrombin?
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Factor II
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Which factors are also made in other organs?
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Factor I
Factor VIII |
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Where is Factor VIII made?
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Liver
Endothelium |
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Where is fibrinogen (factor I) made?
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Liver
Megakaryocytes |
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What complex is important in the cross talk between the extrinsic and intrinsic pathway of the coagulation cascade?
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Tissue Factor-Factor VII complex
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What forms a functional prothrombinase?
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Factor X, calcium, membrane phospholipids
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What factors are dependent on vitamin K?
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Factor 2, 7, 9, 10
Protein C and Protein S |
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The post-translational modification of factor proteins by Vitamin K is known as what?
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Gamma-carboxylation
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What is the importance of calcium in the coagulation cascade?
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Links the active gamma carboxylated factors to phospholipids-->localizes reaction and increases efficiency of reactions
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What agonists are typically used in platelet aggregation tests?
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ADP
epinephrine collagen ristocetin |
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What agonists have a primary and secondary wave of aggregation?
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ADP and epinephrine
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Abnormal ristocetin test is indicative of what disease?
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vWF disease or Bernard Soulier Syndrome
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What histological feature distinguishes Bernard-Soulier syndrome from vWF disease?
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Bernard-Soulier syndrome has giant platelets
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What is abnormal in Bernard-Soulier syndrome?
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Absent or defective GP Ib/IX receptor
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What abnormal platelet aggregation tests are seen in GT (Glanzmann Thrombasthenia)?
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ADP
Epinephrine Collagen |
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What drugs inhibit GP 2b/3a?
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Clopidogrel
Ticlopidine |
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What is ITP?
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Immune thrombocytopenic purpura
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Which type of patients will tend to develop chronic ITP?
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Patients in which preceding illness like vaccination or viral infection was NOT present
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What autoantibodies are found in chronic ITP?
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IgG
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What does IgG attack in chronic ITP?
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GP 2b/3a or GP 1b/IX
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What is the pathophysiology of type II HIT?
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Antibodies to heparin-platelet factor 4 develop and remove platelets from circulation --> thrombocytopenia
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Venous and arterial thrombi are serious causes of which type of HIT?
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Type II
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What is the classic pentad of clinical symptoms of TTP (thrombotic thrombocytopenic purpura)?
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Thrombocytopenia
Microangiopathic hemolytic anemia Fever Neurological symptoms Renal failure |
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What is the pathophysiology of TTP?
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Deficiency in ADAMTS13 resulting in abnormal cleavage of vWF-->abnormal platelet adhesion-->microthrombi
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What is the pathophysiology of HUS (hemolytic uremic syndrome)?
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E. coli O157:H7 that damages endothelial cells and causes abnormal platelet adhesion
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Which form of vWF disease is not treated with DDAVP?
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Type 2B--causes thrombocytopenia
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What is the mode of inheritance of hemophilia A and B?
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X linked recessive
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Hemarthrosis typically occurs in what joints in Hemophilia patients?
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Knee and elbow
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What are the most serious complications of hemophilia?
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Oropharyngeal and CNS bleeding
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What is the difference between Type I and Type II hemophilia A?
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Type I is due to decreased number of Factor VIII while type II is due to decreased functional activity with normal concentration
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What is the inheritance pattern of hemophilia C?
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Autosomal recessive
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What deficiency is seen in Hemophilia C?
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Factor XI
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What substances regulate fibrinolysis?
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Plasminogen Activator Inhibitor-1
Alpha 2 antiplasmin |
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What four tests are used as global hemostasis tests?
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Platelet count
Bleeding time aPTT PT |
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What disease in the newborn occurs due to vitamin K deficiency?
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Hemorrhagic Disease of newborn
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Which vWF disease shows increased RIPA test?
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vWF 2B
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Which vWF diseases have normal vWF multimers?
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Type 1 and Type 2N
(2N has decreased factor VIII binding) |
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Which vWF diseases are autosomal dominantly inherited?
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Type 1, Type 2A, Type 2B
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What do you use to treat vWF Type 3?
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vWF concentrate
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How does the amount of vWF vary in the blood type of the patient?
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O<A<B<AB
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What vWF screening tests can be temporarily NORMALIZED by trauma, stress, pregnancy, OC?
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Bleeding time
aPTT Decreased vWF antigen Decreased Factor VIII activity RIPA |
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What two primary hemostatic disorders show giant platelets in histology?
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Bernard Soulier
Glanzmann Thrombasthenia |
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What is abnormal in storage pool disorders?
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Platelet secretions/granules
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What disease has decreased release of delta platelet granules?
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Hermansky Pudlak
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What storage pool disorder shows decrease in release of alpha platelet granules?
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Gray platelet syndrome
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What 3 general ways can thrombocytopenia occur?
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Decreased production (ie. decreased thrombopoietin)
Increased sequestration Increased breakdown |
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What is abnormal in Glanzmann thromboasthenia?
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Loss of fibrinogen receptor GP2b/3a
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A prolonged aPTT will show in hemophilic patients if Factor VIII activity levels fall below what percent?
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Below 30%
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What clinical features is different between mild and moderate case of hemophilia?
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Mild case will have rare spontaneous hemarthroses; moderate will have occasional
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What tests are used to CONFIRM diagnosis of hemophilia A?
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Measurements of Factor VIII activity and concentration
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How do you diagnose Factor XIII deficiency?
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Factor XIII antigens or
Add 5M urea to clot --> dissolves H-bonds |
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In what population is Hemophilia C most often seen?
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Ashkenazi Jews
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What does antithrombin III bind?
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Heparin sulfate
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What factors does the antithrombin III system inhibit?
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Factors 2, 9, 10, 11
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Is the antithrombin III system reversible or irreversible?
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Irreversible
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How is antithrombin III complex removed from the body?
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Reticuloendothelial cells in liver and spleen
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How is Protein C activated?
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Thrombin-thrombomodulin complex
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What is Protein S?
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Cofactor to protein C
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What factors does Protein C and S target?
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V and VIII
Also binds to Plasminogen activator inhibitor (PAI) |
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What are the two ways in which Protein C-S antagonizes the coagulation system?
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Removes thrombin
Cleaves factor V and VIII |
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What does Tissue Factor Pathway Inhibitor complex to?
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Factor Xa
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What does the Tissue Factor Pathway Inhibitor-Complex attack?
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Tissue Factor-Factor VII
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What are the three main coagulation inhibitor pathways?
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Antithrombin III
Protein C/Protein S System Tissue Factor Pathway Inhibitor |
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What proteins lyse fibrin into fibrin degradation products?
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Plasmin
Urokinase |
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What three proteins are involved at the beginning of the intrinsic pathway?
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Factor XII
Prekallikrein (PK) HMWK |
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What do platelets produce to inhibit platelet aggregation, especially when it is not needed?
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Prostacyclin
NO |
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How does thrombin play a role in the repair process?
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Activates endothelium to release leukocyte adhesion molecules and PDGF
Activates monocytes |
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DELAYED, prolonged bleeding that is recurrent is indicative of what group of bleeding disorder?
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Coagulative
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IMMEDIATE, prolonged bleeding that is NOT recurrent is indicative of what group of bleeding disorders?
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Platelet or vascular
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Most people will clot in what time frame?
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3-8 minutes
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What do platelet function tests analyze?
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The interaction between vWF and platelets
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What is the normal platelet range?
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150,000-400,000/ul
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What clinical features are seen with a platelet count of 40,000-150,000?
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No spontaneous bleeding
Abnormal bleeding with trauma |
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What clinical features are seen with a platelet count of 10,000-40,000?
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Spontaneous bleeding
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What clinical features are seen with a platelet count of <10,000?
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Severe spontaneous bleeding
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What results are seen with the aPTT, PT and TT in patients with DIC?
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Prolonged aPTT, PT, TT
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What is Waterhouse Fridereichsen syndrome?
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Hemorrhage of adrenal glands-sometimes seen in DIC and meningococcemia
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What is the clinical picture of acute versus chronic DIC?
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Acute--bleeding
Chronic--thrombotic complications |
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What is a very useful indicator of DIC?
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Increased D-dimers
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What factor level remains normal in coagulopathy of liver disease?
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Factor VIII
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What factor is first affected in coagulopathy of liver disease?
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Factor VII
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What factors are later affected in coagulopathy of liver disease?
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Factor 2, 5, 9, 10
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What affect does warfarin have on vitamin K?
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Inhibits reductase step in redox cycling
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A newborn presents with intense bleeding in the umbilical cord stump, CNS bleeds and visceral bleeds. What deficiency is present?
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Vitamin K
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What deficiencies result in an abnormal PT time?
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Factor 7, 10, 5, 2
Severe Factor 1 deficiency |
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What is added to the aPTT test to serve as platelet substitute?
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Phospholipids
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What deficiencies result in an abnormal aPTT time?
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Factors 9, 8, 10, 5, 2, 1
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What does the thrombin time test measure?
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The conversion of fibrinogen to fibrin
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What can happen with elevated homocysteine levels?
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Increased arterial or venous thrombosis
Atherosclerosis |
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Homocysteine metabolism is dependent on what vitamins?
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Vitamin B12
Folate - Vitamin B9 |
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What is abnormal in Factor V Leiden mutation?
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Factor V resistant to cleavage by Protein C
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What is the clinical presentation of homozygous protein C and S deficiency in newborns?
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Purpura fulminans
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Warfarin-induced skin necrosis is seen in what disorders?
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Heterozygous Protein C deficiency OR
Warfarin therapy without heparin |
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What is an example of an acquired thrombotic disorder?
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Antiphospholipid antibody syndrome (APAS)
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How is Factor XIII activated?
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Cleavage by thrombin
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Platelet aggregation studies should be avoided in which patients?
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Patients with thrombocytopenia or anti-platelet medications
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What is the preferred treatment for thrombotic thrombocytopenic anemia?
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Plasma exchange
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Where are arterial thrombi typically found?
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Coronary arteries>cerebral>femoral
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What is the effect of serotonin during hemostasis?
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Causes vasoconstriction
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What is the effect of ADP during hemostasis?
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Activates platelets
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