Exam 4: Coagulation Flashcards
What are the 5 inherited risk factors for DVT?
- Antithrombin III deficiency
- Protein C deficiency
- Protein S deficiency
- Sickle cell anemia
- Activated protein C resistance
What are the 6 acquired risk factors for DVTs?
- Bedridden
- Surgery/trauma
- Obesity
- Estrogen use
- Malignancies
- Chronic venous insufficiency
What is DIC?
Disseminated Coagulation
Overstimulation of the blood clotting mechanism
What usually causes DIC?
Bacterial sepsis (gram-negative bacteria)
What are the 4 causes of DIC?
- Massive tissue injury
- Malignancy (cancer)
- Bacterial sepsis
- Abruptio Placentae
What are the 2 ways we regulate coagulation?
- Fibrin inhibition
- Fibrinolysis (breaking down fibrin)
What are protease inhibitors?
Enzymes that rapidly inactivate coagulation proteins
What 3 things break down active clotting factors?
- A1-antiprotease
- A2-macroglobulin
- A2-antiplasmin
What are the 4 types of coagulation modifier drugs?
- Anticoagulants
- Antiplatelet drugs
- Thrombolytic drugs
- Antifibrinolytic drugs
What are the 9 contraindications for taking heparin? What question do we normally think of when thinking of contraindications?
Will this patient likely bleed out? If so, that is a contraindication
1. Active bleeding
2. Hemophilia
3. Thrombocytopenia (decreased plts)
4. Severe HTN
5. Intracranial hemorrhage
6. Infective endocarditis
7. Active TB
8. GI ulcers
9. Advanced hepatic disease
What 3 things do blood vessels normally do when there is damage?
- Vasoconstriction
- Form platelet plugs
- Regulate coagulation and fribinolysis
What are the 4 phases of thrombogenesis?
- Adhesion
- Aggregation
- Secretion
- Cross-linking of adjacent platelets
What is the difference between the extrinsic and intrinsic pathway?
Extrinsic - exposes tissue factor
Intrinsic - damage endothelium
What is Virchow’s triad?
- Stasis
- Hypercoagulability
- Endothelial injury
What are the characteristics of white thrombi?
Thrombi in high-pressure arteries w/ abnormal endothelium
Only plt and fibrin crosslinking
Cause ischemia downstream
Forms fibrin clot
What are the characteristics of red thrombi?
Thrombi in low pressure veins
RBC build up around the white thrombus
There is lots of fibrin and a long tail b/c of the build up
They usually become detached and lead to pulmonary emboli
What are the treatments for DIC?
- Plasma transfusions (w/ plts or clotting factors)
- Treat the underlying cause
What are the 3 indirect thrombin inhibitors?
- Heparin
- LMW Heparin
- Fondapurinux
What are the 2 direct thrombin inhibitors?
- Lepirudin (Hirudin)
- Argatroban (Pradaxa)
How do indirect thrombin inhibitors work?
They inactivate factor Xa and enhance antithrombin activity
What is heparin’s MOA?
Binds and activates antithrombin; enhancing its activity and blocking thrombin
What is the MW of unfractionated/unpurified heparin?
5-30,000
Where is Heparin extracted from?
Pig intestinal mucosa and cow lung (porcine and bovine)
Family of molecules w/ different molecular weights
What is the difference between LMW heparin and unfractionated?
LMW heparin is more specific for factor Xa
How can you recognize LMW heparin drugs?
-parin
What are the major toxicities of heparin?
BLEEDING
HIT and TTP
What is HIT?
Heparin induced thrombocytopenia; heparin is recognized by the immune system and makes antibodies against it causing the body to get rid of platelets
Who is more prone to hemorrhage while taking heparin?
Elderly women and patients with renal failure
What two lab tests do we do to monitor bleeding/coagulation time?
aPTT and PT
What is PT and aPTT?
Prothrombin time - assesses the extrinsic system
Activated partial thromboplastin time - monitors the intrinsic pathway
Explain PT
Looks at the extrinsic system
Tissue factor is added and we record the time it takes to clot
We compare these numbers to normal patients (INR) and see the difference
What is a normal INR?
0.8-1.2
Explain aPTT
Looks at the intrinsic system
We add phospholipids to induce the intrinsic pathway
What is a normal aPTT?
35-45 seconds
What is the reversal for heparin?
STOP THE DRUG
Give protamine sulfate
How does protamine sulfate work?
Since it is positively charged, it binds together w/ negatively charged heparin and gets rid of the heparin
What are the effects of protamine sulfate on LMW and fondaparinux?
Less effect on LMW and no effect on fondaparinux
Where does protamine sulfate come from?
Salmon sperm
Why do we need to taper protamine sulfate?
Excess can act as an anticoagulant
What is fondaparinux?
Pentasaccharide molecule of heparin that is synthetic
What is the benefit of fondaparinux?
Less bleeding risks
What can fondaparinux be used for?
HIT
What is the difference between Hirudin (Lepirudin) and Argatroban/Dabigatran (Pradaxa)
Hirudin binds both to the active and substrate recognition sites of thrombin
Pradaxa binds only to the thrombin active site
Where do we get hirudin from?
Leeches
Where do we get Argatroban and Pradaxa from?
Biological sources
What are 3 coumarin anticoagulants?
Warfarin (coumadin)
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Where was warfarin discovered?
University of wisconsin
What was warfarin originally used for?
Rat poison; cause for cattle hemorrhagic disease
How is warfarin administered? What is the bioavailability? What is the half life? What is the delay in onset?
Orally; 100%; 36 hours; 8-12 hours
What is the MOA of warfarin?
Warfarin blocks the gamma carboxylation of several glutamate residues
Warfarin will block vitamin K reductase
What 4 clotting factors production are blocked by warfarin?
2, 7, 9, 10
1972
What are the 3 main toxicities of warfarin?
- Hemorrhagic disorder in the fetus
- Birth defects
- Cutaneous necrosis
What is warfarin’s therapeutic range determined by? What’s the target ranges for warfarin?
INR; 2-3
What are the 3 important things to do when reversing warfarin?
- Stop the drug and give vitamin K
- Give FFP that contain clotting factors
- Give factor 9 concentrates
What are rivaroxaban (xarelto) and apixaban (eliquis) specific for? What is the benefit of them? What is their reversal?
Specific for acting on Xa
They cause less problems w/ bleeding out
There is no reversal
What do fibrinolytics do?
Rapidly lyse thrombi and catalyze the formation of serine protease plasmin
What are the 3 fibrinolytics?
- TPA
- Streptokinase
- Urokinase
Where is TPA produced?
Directly in the spot of damage and recombinantly in the lab
Where are streptokinase and urokinase synthesized from?
Streptococci and the kidney
What are 3 antiplatelets?
- Aspirin
- Clopidogrel (plavix)
- Abciximab
How does ASA work?
COX1 selective; prevents activation of arachidonic acid cascade and produces less TXA
This inc. bleeding time and reduces plt aggregation
How does clopidogrel (plavix) work?
Irreversibly inhibits the ADP receptor on plts and reduces platelet aggregation
What does plavix reduce?
Ischemic events
When is plavix generally used?
Angioplasty and stent placements
How does abciximab work?
Targets GP2b and 3a = which are the glycoproteins that cause plt aggregation to occur
Blocks receptors and blocks aggregation
What 3 drugs are used for bleeding disorders?
- Vitamin K
- FFP (plasma fractions)
- Desmopressin
Is vitamin k water or fat soluble? Where does it come from? What does vitamin K help with? Where does vit. K work on?
Fat-soluble
Leafy green veggies and gut bacteria
Helps w/ making residues needed for clotting factors
Works on prothrombin, and factors 7,9 and 10
What does desmopressin do? What 2 things does it help with?
Inc. factor 8 availability
Mild hemophilia A and Von Willebrand disease
What are 2 fibrinolytic inhibitors?
- Aminocaproid acid
- Tranexamic acid (TXA)
What are the 4 uses for aminocaproic acid?
- Adjunctive hemophilia therapy
- Bleeding from fibrinolytic therapy
- Intracranial aneurysms
- Post-surgical bleeding
What does TXA do?
Decreases the risk of death in major bleeding by inhibiting the conversion of plasminogen to plasmin
How does aminocaproic acid work?
Competitively inhibits plasminogen activation and stabilizes the clot and prevents it from breaking down
