Term
| Describe the action of antithrombin |
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Definition
Antithrombin is a natural anticoagulant It blocks the action of thrombin which converts fibrinogen to fibrin |
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Term
| How is antithrombin deficiency acquired? |
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Definition
| It is a genetically acquired trait |
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Term
| What are the types of antithrombin deficiency? |
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Definition
Type 1 - low levels of antithrombin Type 2- normal levels of antithrombin but decreased activity |
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Term
| How does antithrombin deficiency manifest itself? |
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Definition
Never before teen years Plateau in the 40's Should be suspected in spontaneous thrombosis |
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Term
Antithrombin deficiency Venous and arterial Y or N |
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Definition
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Term
In what percent of patients with a spontaneous venous thromboembolic event will antithrombin deficiency be found? |
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Definition
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Term
| How common is antithrombin deficiency in the general population? |
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Definition
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Term
| At what activity levels does antithrombin deficiency carry the highest risk for thrombosis? |
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Definition
| Activity levels less than 60% |
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Term
| What is the APLA syndrome stand for in thrombphilias? |
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Definition
| Antiphosholipid antibody syndrome |
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Term
| What are the three classes of Antiphosholipid antibody syndrome? |
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Definition
1. Anticardiolipin antibodies 2. Lupus anticoagulant 3. Antibodies directed toward specific molecules know as beta-2-glycoproteins |
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Term
| What are the two main classifications of antiphospholipid syndrome and how are they distinquished? |
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Definition
1. Primary- no known autoimmune disorder 2. Secondary-know autoimmune disorder such as lupus |
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Term
| How does antiphospholipid syndrome play a role in thrombophilia> |
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Definition
| Antibodies are produced which interfere with phospholipids involved in the coagulation cascade |
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Term
What is the prevalence of the antiphospholipid syndrome in the general population? What percent of those have primary aps? |
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Definition
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Term
| In patients with lupus, what percent will develop antiphospholipid syndrome? |
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Definition
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Term
| What is more common anticardiolipin antibodies or lupus anticoagulant. To what degree? |
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Definition
| Anticardiolipin antibodies are 5x more common than lupus anticoagulant |
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Term
| In patients diagnosed with Primary antiphospholipid syndrome what % will go on to be diagnosed with a autoimmune disorder? |
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Definition
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Term
| Antiphospholipid syndrome is a risk factor for what type of thrombosis? |
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Definition
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Term
| What is a common presentation for antiphospholipid syndrome? |
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Definition
| Complications of pregnancy |
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Term
How are patients treated with antiphosholipid syndrome that have had a thrombotic event? Diagnosed without thrombosis? |
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Definition
Often lifelong anticoagulation Aspirin is the general recommendation |
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Term
| What is the gene position of the Prothrombin gene mutation? |
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Definition
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Term
| What role does prothrombin play in anticoagulation? |
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Definition
| Prothrombin is the precursor to thrombin which is required to convert fibrinogen to fibrin for clotting |
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Term
| What is the result of the Prothrombin gene mutation? |
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Definition
| It results in Increased circulating thrombin |
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Term
| What percent of the population is heterozygous for the Prothrombin gene mutation? |
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Definition
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Term
If you have the Prothrombin gene mutation what is the risk of venous thromboembolism? What if you are on OCP's |
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Definition
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Term
| What is the role of anticoagulation in Prothrombin gene mutation? |
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Definition
| Anticoagulation only after multiple thrombotic episodes |
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Term
What does activated Protein C do? What is it's abbreviation? |
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Definition
| Activated protein C or APC is a natural anticoagulant by combining with Protein S on the surface of a platelet it inactivates FactorVa and VIIIa |
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Term
| How is Protein C deficiency acquired? |
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Definition
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Term
| Protein C deficiency--venous, arterial clots or both? |
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Definition
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Term
| What are the two types of Protein C deficiency? |
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Definition
Type 1 decreased levels Type 2 amount normal but decreased activity |
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Term
| What happens when Protein C combines with thrombomodulin? |
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Definition
The activated form of protein C is formed or APC |
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Term
How prevalent is protein C in the population? What is the increased risk with Protein C deficiency for venous thrombosis |
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Definition
0.2% of the population 7X increase in venous thrombosis |
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Term
| Explain the risk for heterozygous and homozygous copies of the Protein C gene |
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Definition
Homozygous not compatible with life Heterozygous venous thrombosis |
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Term
| How is Protein C deficiency treated? |
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Definition
| Because of the risk of venous thrombosis long term anticoagulation is recommended |
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Term
What is Protein C? What is it's action dependent on |
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Definition
| Vitamin K dependent anticoagulant protein |
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Term
| At what levels do Protein C and S deficiencies become clinically evident? |
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Definition
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Term
Explain Activated protein C resistance or APC resistance How is it acquired? |
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Definition
It is the inability for Protein C to perform its anticoagulant effect of inactivating Factors V and VIII It is both genetic and acquired |
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Term
| What is the most common genetically acquired form of Activated Protein C resistance? |
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Definition
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Term
| What is the estimated incidence of Activated protein C resistance in patients who have venous thromboembolism? |
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Definition
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Term
| What is the Factor V Leiden mutation? |
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Definition
| It is a point mutation that substitutes glutamine for arginine at position 506 |
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Term
| What does the Factor V mutation cause? |
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Definition
| It causes Factor V to be resistant to activated protein C resulting in a procoagulant state |
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Term
| What is the most common cause of activated protein C resistance? |
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Definition
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Term
| In what population does the Factor V Leiden mutation occur? |
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Definition
| Exclusively in the Caucasian population |
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Term
| How does Factor V Leiden mutation present? |
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Definition
| Usually with deep venous thrombosis. Less commonly with thrombosis in the portal vein or superficial venous system |
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Term
| What increase risk for venous thrombosis does Factor V Leiden carry- heterozygous? homozygous? |
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Definition
heterozygous 5-7X homozygous 80X |
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Term
| How do abnormal homocysteine levels affect coagulation and how does that occur? |
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Definition
Elevated levels of homocysteine can occur due to inherited defects in two enyzmes Elevated levels cause dysfunction in endothelial cells leading to a prothrombotic state Hyperhomocysteinemia augments Factors V and VIII and decreases activation of APC |
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Term
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Definition
| It is a Vitamin K dependent anticoagulant protein |
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Term
What is the incidence of Protein S deficiency? What are the two types? |
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Definition
Prevalence is 1:500 Type 1 decreased levels Type 2 normal levels but decreased activitity |
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Term
| What is the thrombotic effect of Protein S deficiency? |
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Definition
| Is a cofactor to activated Protein C and patients with Protein S deficiency have resistance to activated Protein C which leads to thrombosis |
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Term
What is th most common cause of familial thrombophilia? How much higher is th risk of VTE in heterozygous individuals? |
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Definition
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Term
What is the second most common inherited thrombophilia? What is the VTE risk? |
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Definition
Prothrombin gene mutation 3X |
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Term
| VTE events are reported in what percentage of antiphospholipid positive patients? |
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Definition
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Term
In cases of VTE rank the incidence of occurence and the percentage that it occurs of the following inherited thrombophilias antithrombin 3 Protein S Protein C Factor V Leiden Prothrombin gene mutation |
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Definition
Factor V Leiden 21% Prothrombin GM 6.2% Protein C 3.2% Protein S 2.2% Antithrombin deficiency 1.1% |
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Term
List the incidence in the population and then the frequency of all patients with VTE of the following thrombophilias Antithrombin 3 deficiency Protein C deficiency Protein S deficiency Factor V Leiden Prothrombin Gene mutation |
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Definition
Antithrombin 3 deficiency 0.02%-0.17% 1.1% Protein C deficiency 0.14-0.5% 3.2% Protein S deficiency_____2.2% Factor V Leiden 3.6-6% 21% Prothrombin gene mutation 1.7-3.0% 6.2% |
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Term
| How long should a thrombophilia w/u be delayed after an episode of DVT? |
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Definition
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Term
What thrombophilia tests are affected by warfarin? Heparin? |
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Definition
Protein C and S Mixing studies of antiphospholipid syndrome such as DRVVT Heparin--antithrombin levels and clot base assays for lupus anticoagulant |
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Term
| What 4 disorders can result in both arterial and venous thrombosis |
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Definition
Hyperhomocystinemia Antiphospholipid syndrome Cancer Heparin induced thrombocytopenia |
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Term
What test is used to determine LMWH efficacy? When should it be used? |
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Definition
Anti Factor Xa assay In pregnancy or morbidly obese |
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Term
Name 2 direct thrombin inhibitors How are they administered? |
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Definition
Lepirudin argatroban both IV |
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