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25 Cards in this Set
- Front
- Back
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What are 4 categories of platelet defects?
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1. Secretion Defects
2. Recruitment Defects (ADP receptor deficit, TxA2 synthetase def) 3. Cohesion Defect (αIIbβ3 deficiency) 4. Adhesion Defect (VWD) |
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What is Glanzmann's Thrombasthenia?
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Disease with decreased surface expression of αIIbβ3 on platelets.
Results in failure of platelet aggregation See easy brusing, epistaxis, menorrhagia |
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What is the most common defect in hemostasis?
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Von Willebrand Disease (~1/100)
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What are the 2 main functions of Von Willebrand Factor (VWF)?
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1. Facilitates platelet adhesion to injured endothelium
2. Binds and carries coagulation factor VIII in plasma |
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Where is VWF sythesized?
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Mainly in endothelial cells
Also in Megakaryocytes |
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What prevents VWF from binding to platelets when it is in plasma?
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Secreted VWF is proteolysed and maintains a curled conformation which "hides" the platelet binding site
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What organelles within endothelium secrete VWF?
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Weibel-Palade Bodies
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What is the structure of VWF?
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Multimeric protein
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VWF is proteolyzed by what
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ADAMTS13
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Why is VWF necessary in arterial circulation?
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Because it supports platelet arrest and adhesion at sites of vascular injury when arterial flow would otherwise tear the platelets away from collagen
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What is the inheritance pattern for vWD?
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Autosomal Dominant with variable penetrance
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What are the symptoms of VWD?
What are 2 symptoms that are NOT seen? |
Symptoms: Bruising, Bleeding following surgery, dental procedures, or trauma
NOT muscle or joint bleeding |
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What are the 3 types of VWD?
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Type 1: Decreased amounts of normal VWF
Type 2: Decreased amounts of abnormal VWF Type 3: Severely decreased VWF concentration and activity |
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What 4 tests can be run to confirm VWD?
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1. VWF Antigen - measure of protein concentration
2. Ristocetin (AB that activates VWF in plasma) co-factor activity (a measure of function) 3. VWF multimer analysis by gel electrophoresis (Normal in Type 1, Abnormal in Type II) 4. Increased aPTT (if VIII low) BUT normal PT |
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What is characteristic of the VWF seen in type 2?
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Has missense mutation which makes VWF more susceptible to proteolysis.
Therefore observed multimers are much smaller |
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What are 3 treatment options for VWD?
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1. DDAVP - causes release of VWF from endothelial storage sites
- may demonstrate tachyphylaxis (less effect the more its used) 2. Plasma Derived VIII concentrates that retain VWF activity 3. Anti-Fibrinolytic agents |
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What tests allows differentiation between Type 1 and 2 VWD?
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Multimer analysis
- Normal in Type 1, abnormal in Type 2 |
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What is deficient in Hemophilia A?
Hemophilia B? |
Hemophilia A: VIII
Hemophilia B: IX A/B are clinically INDISTINGUISHABLE Both impair activation of factor X (which prevents activation of thrombin) |
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When is bleeding normally seen (time-wise) in hemophilia A/B?
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It is delayed because factors VIII and IX are part of the intrinsic pathway.
Also because clotting problem and not a platelet problem |
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What are symptoms of hemophilia?
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1. Hemarthrosis (joint bleeding)
2. Urinary Tract bleeding 3. Muscle Bleeds 4. Excessive, delayed post operative bleeding |
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How is Hemophilia Tested?
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- History, Physical Exam
- Prolonged aPTT, Normal PT - Need specific factor assays for defining which type of hemophilia Note: Factor IX levels are always low at birth so diagnosis of Hemophilia B in neonatal period is difficult |
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What are the 2 main categories of Hemophilia treatment?
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1. Phrophylaxis
2. On Demand Tx |
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What does the "On-Demand" Tx of Hemophilia consist of?
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Episodic infusion of clotting factor in response to a bleeding episode
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What does Hemophilia Prophylaxis consist of?
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Routine infusion of clotting factors to prevent bleeding
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What are 3 specific treatment options for hemophila (ie drugs to give)?
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1. Plasma Derived Factor Concentrates (safety concerns with infection)
2. Recombinant VIII/IX (made in mammalian cell culture) 3. Recombinant VIIA - Can be used to circumvent factor VIII inhibitors - Widely used for tx of acute bleeding due to hereditary defects, acquired inhibitors, and trauma |
