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150 Cards in this Set
- Front
- Back
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What are the 5 factors involved in hemostasis?
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1) Platelets
2) Vessels 3) Coagulation factors 4) Fibrinolytic factors 5) Inhibitors |
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What is primary hemostasis?
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Formation of a platelet plug
-Injury to the lining of a blood vessel exposes collagen fibers; platelets adhere and get sticky |
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How do platelets adhere to the vessel subendothelium?
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von Willebrand's factor
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What is secondary hemostasis?
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Cascade of enzyme conversions (coagulation cascade) that lead to formation of fibrin
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What factors are involved in the intrinsic pathway?
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8,9,11,12
-If you can't sell it for $12, sell it for $11.98 |
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What are 2 lab tests that assess the intrinsic and common pathways?
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Partial thromboplastin time (PTT)
Activated coagulation time (ACT) |
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What lab test assess the extrinsic and common pathways?
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Prothrombin time (PT)
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Does the intrinsic or extrinsic pathway feed into the common pathway?
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Both of the pathways-hence the name the common pathway
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What is the precursor for fibrin and where is it located?
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Fibrinogen, it's present in circulation-increases in circulation w/ inflammation
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What process breaks down blood clots?
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Fibrinolysis
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What is the key to stimulating the break down of fibrin to fibrin degradation products?
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Conversion of plasminogen to plasmin
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True or false. Plasminogen has both activators and inhibitors that occur naturally in the body.
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True
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What is a pharmaceutical application of tissue plasminogen activator?
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Can give to patients that have a heart attack or stroke because helps break down thrombus (converts plasminogen--> plasmin)
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______are crucial components for the control of the coagulation system.
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Endogenous inhibitors-present for every step of hemostasis including inhibitors of platelet function, coagulation cascade and the fibrinolytic system.
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True or false. Blood vessels are normally thrombogenic.
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False, normally non-thrombogenic, but with right stimuli can become procoagulant
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What do endothelial cells produce when stimuli makes them procoagulant?
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1) Tissue factor
2) von Willebrand's factor 3) plasminogen activator inhibitor PAI-1 (inhibits fibrinolysis) |
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What does tissue factor (produced by procoagulant endothelial cells) do?
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Combines with factor VIIa and factor X to form the extrinsic factor Xa to initiate coagulation cascade
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What factors are involved in the extrinsic pathway?
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VIIa
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What factors are involved in the common pathway?
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X--> Xa
Prothrombin-----Va----> thrombin Fibrinogen----> fibrin |
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True or false. Blood vessels are normally thrombogenic.
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False, normally non-thrombogenic, but with right stimuli can become procoagulant
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What do endothelial cells produce when stimuli makes them procoagulant?
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1) Tissue factor (activates extrinsic pathway)
2) von Willebrand's factor 3) plasminogen activator inhibitor PAI-1 (inhibits fibrinolysis) |
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What does tissue factor (produced by procoagulant endothelial cells) do?
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Combines with factor VIIa and factor X to form the extrinsic factor Xa to initiate coagulation cascade
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What factors are involved in the extrinsic pathway?
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VIIa (+Tissue factor)
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What factors are involved in the common pathway?
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X--> Xa
Prothrombin-----Va----> thrombin Fibrinogen----> fibrin |
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What are platelets in mammals?
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Cytoplasmic fragments of megakaryocytes produced in bone marrow
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What do you call the process of platelet formation?
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Thrombopoiesis
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True or false. Megakaryocytes are multinucleated.
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True, they can have up to 64 nuclei
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How can you tell the difference b/w a megakaryocyte and osteoclast?
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Can see the individual nuclei in the osteoclast
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True or false. Platelets are pretty uniform in size.
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False, vary in size and shape with small purple granules
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How long are platelets in circulation?
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~5-9 days
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What animals have thrombocytes instead of platelets like in mammals?
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Reptiles, birds
-Know not lymphocytes if clumped together=thrombocytes |
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What does the activated factor VII produced by the extrinsic pathway do?
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Activates factor X in the common pathway
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What extravascular protein is involved in the extrinsic pathway?
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Tissue factor
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**Where do the intrinsic and extrinsic pathways converge?
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At the activation of factor X
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What pathway initiates coagulation in vivo and which acts to amplify (but not initiate) the coagulation cascade?
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Extrinsic-initiates
Intrinsic-amplifies |
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What is the main enzyme responsible for the fibrinolysis?
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Plasmin
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What do endothelial cells release at the same the coagulation cascade is activated?
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tissue plasminogen activator
-Plasminogen--> plasmin--> fibrinolysis |
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What is the main activator of plasminogen?
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Tissue plasminogen activator
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What does plasmin do?
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Lyses both fibrin and fibrinogen releasing fibrin degradation products
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What happens to fibrin degradation products after fibrinolysis?
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Removed from circulation by macrophages
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What forms D-dimers?
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When cross-linked fibrin is hydrolyzed by plasmin
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What are the 4 natural anti-coagulants?
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1) Antithrombin III
2) Thrombin 3) Protein C 4) Protein S |
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How does antithrombin III prevent coagulation?
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Binds with and inactivates thrombin (therefore stopping fibrinogen--> fibrin)
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What anticoagulant works by enhancing antithrombin III?
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Heparin
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How does thrombin prevent coagulation?
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Activates protein C
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How does protein C prevent coagulation?
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Inactivates factors V and VIII
-Therefore stops common pathway bc prothrombin----Va----> thrombin |
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How does protein S prevent coagulation?
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Facilitates protein C
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What would be a clinical use of a fibrinolysis-inhibitor?
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Stabilizing clots
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What is a fibrinolysis inhibitor used in race horses?
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Aminocaproic acid-don't want horses to get blood into their airways bc decreases performance
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True or false. Vessels disorders are common.
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False, RARE!
-But almost always vasculitis |
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What are 2 general types of vessel disorders?
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Acquired
Hereditary |
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What is an example of an acquired vessel disorder? What is it usually related to?
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Vasculitis-usually infection related
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What is an example of a hereditary vessel disorder?
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Ehlers Danlos syndrome-collagen disorders (collagen important for vessels!)
-Think of Kevin Tangeman! |
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How are disorders of hemostasis classified?
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Based on the component of hemostasis that is abnormal
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What are the 2 classifications of hemostasis disorders?
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1) Vessel disorders
2) Platelet disorders |
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True or false. Platelet disorders are more common than vessels disorders.
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True
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What are the clinical signs commonly seen in animals with platelet disorders?
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-Bleeding at body surfaces or mucous membranes (epistaxis)
-Petechiae & ecchymoses *Don't always see these signs |
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What is petechiae? What is ecchymoses?
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Petechiae: hemorrhage that is a couple of millimeters
Ecchymoses: hemorrhage up to about 1 cm |
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What does spontaneous bleeding occur in animal with platelet disorders?
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When platelets reach < 20,000/ul
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*What are the 4 basic mechanisms of thrombocytopenia?
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1) Decrease in platelet production
2) Increase in platelet destruction or consumption 3) Increase in platelet utilization 4) Increase in platelet sequestration |
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What are 7 causes of decreased platelet production?
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1) Drugs
2) Estrogen-exogenous or endogenous 3) Infectious agents 4) Toxins-aflatoxin B , bracken fern 5) Chemicals-exposure to benzene or trichloroethylene 6) Radiation 7) Myelophthisis |
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What are some drugs that cause decrease in platelet production?
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Chloramphenicol
Griseofulvin Sulfadiazine Chemotherapeutic agents |
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What are some infectious agents that cause decrease platelet production?
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FeLV
Equine infectious anemia BVD African swine fever virus Parvovirus Ehrlichial species Rickettsial species |
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True or false. A common form of decreased platelet production is when antibodies are directed against precursors in the bone marrow.
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False, it's a rare form of decreased platelet production where megakaryocytes are formed in the marrow, but an antibody directed against them causes destruction of cells before platelets are mature & released
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When an animal has overall bone marrow hypoplasia (pancytopenia or aplastic anemia) what is the first cell line to go missing? Last?
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Neutrophils because they have the shortest circulating life span
Platelets will be next to disappear from peripheral blood as they circulate for about 3-10 days -Erythrocytes are last to drop |
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What is the most common cause of an increase in platelet destruction?
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Immune-mediated thrombocytopenia-platelets are destroyed in peripheral blood faster than produced
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True or false. Immune-mediated thrombocytopenia is more common in females.
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True
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What are the clinical signs of immune-mediated thrombocytopenia?
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Epistaxis
Hematuria Petechiae |
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How do you diagnose immune-mediated thrombocytopenia?
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-Take a bone marrow sample and will see increased megakaryocytes and platelets
-IgG detection |
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How do you treat immune-mediated thrombocytopenia?
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Corticosteroids
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Immune-mediated thrombocytopenia may be associated with what 2 other disorders?
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Immune-hemolytic anemia
Systemic lupus |
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What are 3 causes of platelet destruction?
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1) Immune-mediated thrombocytopenia
2) Drug induced 3) Immune mediated in some infections |
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What are 2 drugs that can cause platelet destruction and in what animals?
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Heparin-related in horses
Trimethoprim-sulfa in dogs (folate deficiency) |
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What is the most common use for heparin in horses?
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Flushing catheters
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What are 3 infections that cause platelet destruction?
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Canine ehrlichiosis
Canine distemper Equine infectious anemia |
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What 2 things can cause increase in platelet utilization?
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DIC
Possibly infections, snakebite |
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True or false. Platelet sequestration is a common cause of thrombocytopenia.
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False, uncommon but may occur in splenomegaly-maybe due to a hemangiosarcoma
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What are the 2 types of thrombocytosis?
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Primary & secondary
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True or false. Secondary thrombocytosis is much more common than primary thrombocytosis.
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True, primary is very uncommon
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What is primary thrombocytosis?
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Essential thrombocythemia- form of hematopoietic neoplasia that is neoplasia of megakaryocytes so get increased platelet production
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What is secondary thrombocytosis usually related to? (4)
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1) Inflammation
2) Iron deficiency 3) Non-hematopoietic neoplasia 4) Following splenectomy or blood loss |
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True or false. Secondary thrombocytosis is usually non-specific and clinical.
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False, non-clinical and non-specific
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What is the treatment for secondary thrombocytosis?
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Treat the underlying issue that is causing it (inflammation, iron deficiency, non-hematopoietic neoplasia and following splenectomy or blood loss)
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What is the problem with thrombocytosis?
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Hypercoagulability
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What is a thrombopathy?
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Refers to disorders of platelet function
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What are most thrombopathies related to?
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Decreased aggregation or adhesion
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What are the 2 general categories of thrombopathies?
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Hereditary
Acquired |
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What are 3 hereditary conditions that result in decreased aggregation (thrombopathy)?
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1) Glanzmann thrombasthenia
2) Basset Hound thrombopathy 3) Chediak Higashi Syndrome |
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What is wrong with cells in animals that have Chediak Higashi Syndrome?
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Abnormal granules in platelets as well as possibly other cell types, platelets show decreased aggregation and impaired platelet plug formation
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What is the most common inherited bleeding disorder in dogs?
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von Willebrand's disease (vWD)
-Especially dobermans |
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True or false. Von Willebrand's disease results in decreased aggregation of platelets.
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False, decreased adhesion
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What produces von Willebrand's factor?
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Endothelial cells
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von Willebrand's factor circulates bound to ______.
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Factor VIII
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What is the most common type of von Willebrand's disease?
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Type I
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What type of von Willebrand's disease is the most severe?
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Type 3
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What is type 2 von Willebrand's disease?
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Uncommon decrease of large multimers
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What is type 3 von Willebrand's disease?
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Absence of all multimers (no detectable von Willebrand's)
-Most severe |
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What do you want to do with an animal that has von Willebrand's disease?
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Fix so don't pass on
Have to give constant blood transfusion bc very short lived |
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What tube do you want to put blood for a VWF assay?
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Citrated blood (blue top tube)
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What does it mean if an animal has a quantitative ELISA assay for VWF antigen of 70-180%?
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No von willebrand's disease
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What does it mean if an animal has a quantitative ELISA assay for VWF antigen of 0-49%?
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Diagnostic for von Willebrand's disease
-50-69% means suspicious or carrier |
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True or false. Animals with von Willelbrand's disease will have a prolonged partial thromboplastin time.
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False, doesn't cause enough reduction in Factor VIII to affect the PTT
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What is the most common acquired thrombopathy?
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Effect of drugs on decreasing platelet aggregability.
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What is the most common type of von Willebrand's disease?
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Type I
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What type of von Willebrand's disease is the most severe?
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Type 3
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What is type 2 von Willebrand's disease?
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Uncommon decrease of large multimers
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What is type 3 von Willebrand's disease?
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Absence of all multimers (no detectable von Willebrand's)
-Most severe |
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What do you want to do with an animal that has von Willebrand's disease?
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Fix so don't pass on
Have to give constant blood transfusion bc very short lived |
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What tube do you want to put blood for a VWF assay?
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Citrated blood (blue top tube)
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What does it mean if an animal has a quantitative ELISA assay for VWF antigen of 70-180%?
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No von willebrand's disease
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What does it mean if an animal has a quantitative ELISA assay for VWF antigen of 0-49%?
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Diagnostic for von Willebrand's disease
-50-69% means suspicious or carrier |
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True or false. Animals with von Willelbrand's disease will have a prolonged partial thromboplastin time.
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False, doesn't cause enough reduction in Factor VIII to affect the PTT & vWF is involved in primary hemostasis so would have abnormal buccal mucosal bleeding time
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What is the most common acquired thrombopathy?
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Effect of drugs on decreasing platelet aggregability.
-Aspirin, NSAIDS |
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What are 4 examples of acquired thrombopathies?
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1) Drugs-aspirin, NSAIDS
2) Uremia-may increase platelet adhesion 3) Liver disease-through accumulation of FDPs which inhibit fibrinogen binding to platelet receptors 4) Some infectious agents |
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What do the clinical signs of coagulopathies often include?
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Bleeding into body cavities (see dyspnea) and formation of hematomas
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What are the 2 general types of coagulopathies?
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Hereditary & acquired
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What is the most common inherited coagulopathy?
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Hemophilia A
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What is hemophilia A?
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Deficiency of factor VIII (intrinsic pathway)
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What will the buccal mucosal bleeding time, prothrombin time, partial thromboplastin time and activated coagulation time like an animal with hemophilia A?
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Bleeding time: Normal
Prothrombin time: Normal Partial thromboplastin time: prolonged Activated coagulation time: prolonged |
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What is hemophilia B?
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Deficiency of factor IX (intrinsic pathway)
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What are the PTT, PT, ACT and bleeding time of an animal with hemophilia B?
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Bleeding time: normal
PT: Normal PTT: prolonged ACT: abnormal |
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What are 4 acquired coagulopathies?
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1) Vitamin K deficiency/antagonists
2) Hepatopathies 3) Glomerulopathies 4) DIC |
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Why does vitamin K deficiency cause coagulopathy?
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Vitamin K is needed for production of factors II, VII, IX, and X
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How do Vitamin K antagonists work?
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Inhibit the recycling of vitamin K to its active form, thus causing a functional deficiency in coagulation
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What are 4 vitamin K antagonists?
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warfarin, coumarin, brodifacoum and sweet clover
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What is a big difference b/w warfarin and brodifacoum?
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Warfarin lasts for about 1 week but brodifacoum lasts for about 1 month so have to give vitamin K for one week
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What kind of liver disease causes coagulopathy?
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Severe liver disease, you see decreased synthesis of coagulation factors, antiplasmin and ATIII-have prolonged PT & PTT
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How do glomerulopathies cause coagulopathies?
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Loss of ATIII (a small protein) through the glomeruli can cause hypercoagulability.
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*True or false. Disseminated intravascular coagulation occurs as a primary disease, not a secondary disease.
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False, occurs only as a secondary not a primary disease
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What can trigger DIC?
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Many factors, coagulation system is activated and platelets and clotting factors are consumed.
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What are the 3 components for performing a clinical evaluation of a bleeding disorder?
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1) History
2) Physical exam 3) Laboratory examination |
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What do you want to do when sending off blood for coagulation testing?
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blue top-sodium citrate, want 9 parts blood to 1 part sodium citrate (i.e. fill the tube)
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What can you do if you can't run coagulation testing in 3-4 hours of collecting the blood?
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Freeze the plasma then run the tests
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When do you use EDTA when examining the coagulation of blood?
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Choice for platelet counts
-but some horses have platelets clump in EDTA but normal with sodium citrate (pseudothrombocytopenia) |
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How can you estimate platelet numbers?
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Use a blood smear and if count 5 fields then should have an average of 8-10 /field
-If decreased, look for clumps on feathered edge |
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At what platelet count can spontaneous bleeding occur?
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When platelet count gets below 20,000/ul
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What does the buccal mucosal bleeding time measure?
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Measure time to formation of clot
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What does a prolonged buccal mucosal bleeding time mean?
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Implies a problem with either platelet number, function, vessels wall or von Willebrand's factor
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What does platelet antibody testing test for?
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Tests for platelet surface-associated immunoglobulin for diagnosis of canine immune mediated thrombocytopenia; flow cytometry
-Most common cause of increased platelet destruction |
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What are the 3 coagulation assays?
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1) Activated clotting time (ACT)
2) Partial thromboplastin time (PTT) 3) Prothrombin time (PT) |
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What 2 tests evaluate platelet function?
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1) Buccal mucosal bleeding time (tests primary hemostasis)
2) Platelet antibody testing |
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What is the activated clotting time?
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Time of contact of blood w/ activator to first formation of fibrin strands
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What does the activated clotting time measure?
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Rough estimate of PTT
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What does the partial thromboplastin time measure?
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Intrinsic and common pathways
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What does the prothrombin time measure?
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Extrinsic and common pathways
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True or false. PTT and PT cannot be measured in house.
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False, there are in-house coagulation instruments
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True or false. There are special assays available for specific factors at specialized veterinary hemostasis laboratories.
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True
e.g. von Willebrand's factor, factor VIII (hemophilia A), Factor IX (hemophilia B) |
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How can you evaluate fibrinolysis in the lab?
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Fibrin degradation products
D-dimers-more specific has replaced FDPs in many labs including ours |
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What is thromboelastography used for?
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Produces tracing to show:
Hypercoagulability Hypocoagulability Normocoagulability |
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What do you put your blood in for thromboelastography?
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Whole blood or citrated blood
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