Heme Part 2
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What is the most common congenital bleeding disorder?
von willebrands disease
What 2 components make up factor 8?
VWF and factor 8c
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
Treatment for type 1 VWD
Is DDAVP effective for VWD types 2 and 3?
- Variable effect for type 2
- Ineffective for type 3
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
T or F, VWD may contraindicate neuraxial anesthesia?
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
What is the most common cause of non-immune-mediated factor deficiencies?
abnormal production due to coumadin treatment
What are major causes of thrombocytopenia?
- decreased BM production
- -xrt and chemo
- -chronic dz
- -infiltration by cancer cells
- increased non-immune mediated consumption
- -tissue trauma
- -vascular grafts
- immune-mediated consumption-drugs
- -autoimmune disorders
Disseminated intravascular coagulation
- widespread activation of the clotting mechanism
- fibrin deposited throughout the vascular tree
- simultaneous depression of normal inhibitory mechanisms to prevent coagulation
What can trigger DIC?
TF (released from traumatized or dying tissue)
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
How can sepsis contribute to DIC?
Either the bacteria itself or the toxics released from the bacteria activate the clotting mechanism
TTP, ITP, and HIT can lead to _____.
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
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
What drugs can cause thrombocytopenia?
Decreased BM production- thiazide diuretics, sulfonamides, phenytoin, ETOH
Immune mediated consumption- heparin, quinidine, cephalosporins, vanco
How do cyclooxygenase (COX) inhibitors affect coagulation?
- Block thromboxane A2 generation
- Inhibit Plt granule release and Plt aggregation
What's an example of a COX inhibitor?
ASA and NSAIDs
How do phosphodiesterase inhibitors affect coagulation?
Decrease Plt aggregation
What are examples of phosphodiesterase inhibitors?
persantine and dipyridamole
How do glycoprotein 2b/ 3a inhibitors affect coagulation?
Bind to the 2b / 3a Plt receptor and prevent binding of fibrinogen
What are examples of 2b/ 3a inhibitors?
How do ADP receptor pathway inhibitors affect coagulation?
Prevent receptor signaling and irreversibly inhibit the ADP Plt activation pathway
What are examples of ADP receptor pathway inhibitors?
Plavix and ticlid
Vitamin K antagonist
Vitamin K is needed for synthesis of what factors?
2, 7, 9, and 10
What lab value is used to monitor coumadin levels?
PT or INR
Inhibits secondary hemostasis
What lab value is used to monitor heparin levels?
What is the reversal agent for selective Xa inhibitors?
There isn't one, even giving FFP won't reverse the anti-coagulation
Direct thrombin inhibitors MOA
Binds directly to thrombin to inhibit secondary hemostasis
What is the reversal agent for direct thrombin inhibitors?
There isn't one
What are examples of classes of anti-Plt meds?
COX inhibitors, phosphodiesterase inhibitors, GP 2b/ 3a inhibitors, ADP receptor pathway inhibitors
What are examples of anti-coagulant mediations?
warfarin, heparin, selective factor Xa inhibitors, direct thrombin inhibitors
Which 2 anti-coagulant meds are least selective?
Heparin and warfarin
What drugs are examples of anti-coagulation and fibrinolysis inhibitors (i.e. cause clotting)?
- Lysine analogues
- 3 factors that predispose to clot formation:
- abnormal blood flow
- endothelial injury
What factors can contribute to abnormal blood flow?
Turbulence (atherosclerotic plaques) or stasis
In the heart and arterial circulation, what is the primary factor contributing to thrombus formation?
What can cause endothelial injury?
Stress from HTN, turbulent blood flow, HL, hyperglycemia, vascular injury or infection
Form of inherited hyper coagulable disorder
What are examples of acquired hyper coagulable disorders?
- myeloproliferative d/o (polycythemia)
- nephrotic syndrome
- lupus anti-coagulant
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