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63 Cards in this Set
- Front
- Back
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What is the function of GP1b for coagulation?
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Initial slowing and loose binding of the platelet to the collagen and to activated platelets (binds to VWF GP1b binding domain)
This binding activates the platelet |
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What is the function of GP2b/3a for coagulation?
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(Only activated after plt activation); 2ndary binding of the platelets to the collagen and to activated platelets (binds to VWF GP2b/3a binding domain and fibrinogen)
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What is the role of VWF for early coagulation?
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VWF is found on the surface of platelets and collagen. It has BP1b and GP2b/3a binding domains where the platelets can bind.
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Which type of VWD is defined by low levels (but still present) of VWF?
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Type 1 (80% of total cases of VWD)
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What is the mechanism of type 2a VWD?
RCo level? VWF ag level? |
Lack of large (more active) VWFs due to either destruction or accelerated lysis. Results in decreased activity (low RCo). VWF ag level is variable from low to increased (feedback?)
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What is the mechanism of type 2B VWD?
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Increased VWF binding to GP1b
----> increased clearance of VWF (esp. large ones) and plts from circulation ---> lowed VWF ag, lowered RCo |
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How can one distinguish type 2A from 2B VWD?
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Similar lowering of RCo and VWF ag. Therefore, test ristocetin at 0.5 as well as the usual 1.5 mg/ml. 0.5 will aggregate in 2B due to the gain of function.
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Low VWF ag levels. What type of VWD is it?
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Type 2B VWD - gain of function
- Large multimers are lost due to premature binding so Ag and RCo are low |
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What is the difference between Type 2B VWD and Platelet type VWD?
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Show the same on studies. 2B is due to a change in the VWF leading to increased binding. Platelet type is due to defective plt rec causing increased binding.
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What is the mechanism and testing manifestations of Type 2M VWD?
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Decreased ability of VWF to bind platelet (GP 1b).
Normal VWF ag, disproportionately lower RCo |
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What is the mechanism and testing manifestations of Type 2N VWD?
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Mutations in Factor 8 binding so that VWF binds okay to F-8 but the complex gets cleared quicker then normal. WFF ag = RCo
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What is Type 3 VWD?
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A complete absence of VWF
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What population has been found to have a 25-30% lower level of VWF levels than "normal".
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Blood Group O individuals
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How could a type A women with subclinical VWD have child with clinically significant VWD?
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Type O individuals have lower circulating levels of VWF. She could have a type O child.
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What molecular interaction is Ristocetin an indirect measurement of?
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The GP 1b and VWF interaction
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What coagulation disorders (2) show a complete absence of response to Ristocetin?
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Bernard Soulier syndrome
GP 1b (one b in BSS) absent ristocetin (AR bernARd) also VWD type 3 These can be differentiated by adding normal plasma. VWD will correct while BSS won't. |
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What coagulation disorder show response to ristocetin at 1.5 mg/ml but does not respond to AA, TRAP, collagen, ADP or risto at 0.5 mg/ml?
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Glanzmann Thromasthenia
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What coagulation disorders (2) show a complete absence of response to Ristocetin?
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Bernard Soulier syndrome
GP 1b (one b in BSS) absent ristocetin (AR bernARd) also VWD type 3 |
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What coagulation disorder shows response to ristocetin at 1.5 mg/ml but does not respond to AA, TRAP, collagen, ADP or risto at 0.5 mg/ml?
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Name the disorder
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Aspirin
-Plts fail to aggregate with arachadonic acid. ADP and Collagen responses can often be abnormal also |
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How does a platelet functional defect appear on platelet aggregation studies?
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Decreased or absent response to ADP. Other studies are pretty much normal
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What is the effect of a Factor XIII deficency on PTT and PT?
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No effect
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What must always be done after a prolonged isolated PT or PTT?
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repeat and 1:1 mixing study
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What is the significance of an increased PTT that corrects with a 1:1 mixing study?
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Factor deficiency
8, 9, 11, 12 or vWF |
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Which coagulation factor is not decreased with liver disease?
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8
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Which common coagulation disease show the highest RR for venous thromboembolism?
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Homozygous Factor V leiden (80x), heterozygous also shows significant risk
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What is the mechanism of Factor 5 Leiden?
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Point mutation of factor 5 at cleavage site for protein C.
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What is the normal function of activated protein C?
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Inactivates Factor V and VIII
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Which factor deficiency will result in normal PT and PTT but will have bleeding?
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Factor 13 (transglutaminase)
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What is the specific function of vitamin K for activating factors 10, 9 7 and 2?
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Adds a diglucuronide moiety allowing the factor to interact with lipid membranes
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Patient with prolonged aPPT without history of bleeding. What are the 3 disorders that can result in this? Is it safe to have surgery?
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Deficiency in factor 12, HMWK or PreK
Should not effect surgery |
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Elevated PT and PTT, normal platelets. Normal D-dimer. Normal PT and PTT before hospitalization.
Cause? |
Vit K deficiency due to antibiotic killing of normal gut flora.
(or patient started on Warfarin) |
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How does factor 13 deficiency present?
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Normal coag studies. Recurrent soft tissue hematomas.
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(Classically) how do you test for a factor 13 inhibitor?
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Clot lysis testing with 5M urea. Dissolves in < 3 hours (N=>24)---> mix with normal plasma. If still dissolves, then suspect inhibitor. Otherwise, deficiency of 13
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If an abnormal PT or PTT does not correct after a mixing study of normal plasma, what should be suspected and what should be done next?
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Suspect inhibitor is present
Dilute Russell's viper venom test (dRVVT) to test for lupus anticoagulant |
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How is a dilute Russell's viper venom test (dRVVT) interpretted?
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Venom=clotting, but limited phospholipid (PL) is given. If a Lupus anticoagulant(LA) is present, then it interferes with PL (no clot). If corrected with more PL, suspect LA
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Why are many PT and PTT assays sensitive to lupus anticoagulant?
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They have phospholipid-dependent clotting. Lupus anticoagulant interfers with phospholipids.
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What protein does protein S bind to in serum? What normal physiologic state can cause a lowered protein S level?
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C4b
Pregnancy due to increased C4b levels |
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What is the function of Protein C in coagulation?
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Activated protein C(APC)/protein S complex inactivates factor 5 and 8. Protein C is activated by the thrombin-thrombomodulin-endothelial protein C receptors complex.
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Which liver depended Factors (non-8) are least effected by liver disease.
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11 and 12 due to long half-lives
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Which factor deficiency can be seen post-CABG?
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Factor 5 - bovine thrombin used during surgery can contain factor 5, which in turn induces antibodies
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What do you give a patient with mild VWD for epistaxis?
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DDAVP (desmopressin acetate) nasal spray --> stimulates release of factor VIII from endothelial cells
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VWF multimer analysis shows reduced high molecular weight multimers and normal intermediate weight multimers. What is it?
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Type 2B VWD or platelet type vWD
2A will show decreased intermediate multimers |
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Suspect vWD but normal PTT
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Check if the fibrinogen (an acute phase reactant) is elevated since VWF and factor 8 can also be acutely elevated in that state.
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vWD with reduced activity vs. antigen but normal multimer analysis.
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Type 2M vWD
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T/F: The prolonged PTT in hemophilia A and B correct with 1:1 mixing studies with normal plasma
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True - Normal plasma would contain enough factor to correct the deficite.
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What is the effect of vWD on PFA-100 closer time? PTT?
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PFA-100 closure time is increased
PTT remains normal |
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What is the mutation seen in Factor V leiden?
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Arg 506 --> Gln
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What 3 thrombotic disease can cause arterial thrombosis?
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Homocysteine
antiphospholipid antibody Elevated factor 8 |
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What is the defect seen in gray platelet syndrome?
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Lack of alpha granule proteins
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What disease is caused by a deficiency of a disintegrin and metalloprotease with a thrombospondin type motif?
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TTP
A disintegrin and metalloprotease with thrombospondin 13 type motifs (ADAM TS 13) |
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What is the mechanics of thrombocytopenia in TTP?
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ADAM TS 13 is a vWF cleaving protease. Deficiency causes buildup of large vWF multimers -> microscopic thrombosis
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What is the genetics of Hemophilia A?
Hemophilia B? |
X-linked recessive
X-linked recessive |
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T/F Hemophilia A causes severe bleeding for levels 10% or less?
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False
Mild 5 to~50% Mod 1-5% Severe <1% |
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What test is used to screen for factor 13 deficiency?
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5M urea test
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What are the genetics of antithrombin 3 deficiency?
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Autosomal dominant
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Patient with skin necrosis after receiving warfarin. What is a likely genetic cause?
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Protein C deficiency
Wait till after acute episode to measure levels |
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What is the most common reason for activated protein C resistance?
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Factor 5 Leiden- resistant to APC cleavage but still functional
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T/F antiphospholipid syndrome is caused by an anticardiolipin antibody and is associated with SLE, AIDS, drugs or LP disorders.
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T
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Which coagulation factor is the first to show decrease with severe liver disease?
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Factor 7. It has the shortest half-life of all the liver dependant coag factors (all but 8).
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What are the last two coagulation factors to be effected by liver disease? Which factor is not effected?
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11 and 12- longest half-lives
8 - not produced in liver |
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Which factor deficiency can be seen post-CABG?
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Factor 5 - Due to use of bovine thrombin which induces factor 5 antibodies.
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What is the antibody in HIT syndrome?
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PF4 (platelet factor 4) - causes activation of platelets
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