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What is the most common congenital bleeding disorder?
von willebrands disease
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What 2 components make up factor 8?
VWF and factor 8c
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The majority of cases of VWD are due to a qualitative or quantitative issue? Is it AD or AR?
- 80% are due to a quantitative issue, this is type 1 VWD
- AD
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Treatment for type 1 VWD
DDAVP
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Is DDAVP effective for VWD types 2 and 3?
- Variable effect for type 2
- Ineffective for type 3
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What is DDAVP? How does it work?
- Synthetic analogue of ADH
- IV administration stimulates VWF from endothelial cells to immediately increase VWF and factor 8 activity
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T or F, VWD may contraindicate neuraxial anesthesia?
T
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What diseases can cause an acquired hemophilia?
Diseases that produce autoantibodies (SLE or RA) or lymphoproliferative d/o (leukemia or lymphoma)
Acquired hemophilia is the most common
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What is the most common cause of non-immune-mediated factor deficiencies?
abnormal production due to coumadin treatment
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What are major causes of thrombocytopenia?
- decreased BM production
- -xrt and chemo
- -drugs
- -infections
- -chronic dz
- -infiltration by cancer cells
- increased non-immune mediated consumption
- -tissue trauma
- -vascular grafts
- -toxemia
- -DIC
- immune-mediated consumption-drugs
- -autoimmune disorders
- dilution
- sequestration
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Disseminated intravascular coagulation
- widespread activation of the clotting mechanism
- fibrin deposited throughout the vascular tree
- simultaneous depression of normal inhibitory mechanisms to prevent coagulation
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What can trigger DIC?
TF (released from traumatized or dying tissue)
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What conditions are associated with DIC?
sepsis, viremias, OB issues, extensive tissue damage, liver failure, extensive head injury, extensive vascular endothelial damage, hemolytic transfusion rxn, metastatic cancer, leukemia, snake venom
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How can sepsis contribute to DIC?
Either the bacteria itself or the toxics released from the bacteria activate the clotting mechanism
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TTP, ITP, and HIT can lead to _____.
thrombocytopenia
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What's the difference between type 1 and type 2 HIT?
- type 1- non-immune mediated
- -transient and clinically insignificant Plt decrease that occurs during 1st full day of full dose UF heparin
- type 2- immune mediated
- occurs in pts receiving heparin for > 5 days
- heparin must be d/c
- significant risk of thromboembolic event if heparin is continued
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What is the patho of HIT type 2
- -antibodies induce Plt activation and aggregation and so thrombi form
- -since Plts are being used to form thrombi, there's decreased Plt activity
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What drugs can cause thrombocytopenia?
Decreased BM production- thiazide diuretics, sulfonamides, phenytoin, ETOH
Immune mediated consumption- heparin, quinidine, cephalosporins, vanco
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How do cyclooxygenase (COX) inhibitors affect coagulation?
- Block thromboxane A2 generation
- Inhibit Plt granule release and Plt aggregation
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What's an example of a COX inhibitor?
ASA and NSAIDs
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How do phosphodiesterase inhibitors affect coagulation?
Decrease Plt aggregation
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What are examples of phosphodiesterase inhibitors?
persantine and dipyridamole
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How do glycoprotein 2b/ 3a inhibitors affect coagulation?
Bind to the 2b / 3a Plt receptor and prevent binding of fibrinogen
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What are examples of 2b/ 3a inhibitors?
Integrillin
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How do ADP receptor pathway inhibitors affect coagulation?
Prevent receptor signaling and irreversibly inhibit the ADP Plt activation pathway
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What are examples of ADP receptor pathway inhibitors?
Plavix and ticlid
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Warfarin MOA
Vitamin K antagonist
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Vitamin K is needed for synthesis of what factors?
2, 7, 9, and 10
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What lab value is used to monitor coumadin levels?
PT or INR
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Heparin MOA
Inhibits secondary hemostasis
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What lab value is used to monitor heparin levels?
PTT
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What is the reversal agent for selective Xa inhibitors?
There isn't one, even giving FFP won't reverse the anti-coagulation
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Direct thrombin inhibitors MOA
Binds directly to thrombin to inhibit secondary hemostasis
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What is the reversal agent for direct thrombin inhibitors?
There isn't one
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What are examples of classes of anti-Plt meds?
COX inhibitors, phosphodiesterase inhibitors, GP 2b/ 3a inhibitors, ADP receptor pathway inhibitors
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What are examples of anti-coagulant mediations?
warfarin, heparin, selective factor Xa inhibitors, direct thrombin inhibitors
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Which 2 anti-coagulant meds are least selective?
Heparin and warfarin
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What drugs are examples of anti-coagulation and fibrinolysis inhibitors (i.e. cause clotting)?
- Protamine
- Aprotonin
- Lysine analogues
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Virchow's triad
- 3 factors that predispose to clot formation:
- abnormal blood flow
- endothelial injury
- hypercoagulability
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What factors can contribute to abnormal blood flow?
Turbulence (atherosclerotic plaques) or stasis
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In the heart and arterial circulation, what is the primary factor contributing to thrombus formation?
endothelial injury
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What can cause endothelial injury?
Stress from HTN, turbulent blood flow, HL, hyperglycemia, vascular injury or infection
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Thrombophilia
Form of inherited hyper coagulable disorder
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What are examples of acquired hyper coagulable disorders?
- myeloproliferative d/o (polycythemia)
- malignancies
- pregnancy
- nephrotic syndrome
- lupus anti-coagulant
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