Coagulation Disorders Flashcards
Test 4
What does hemostasis mean?
The ability of the body to stop itself and bleeding out
Coagulation causes ______
hemostasis
What causes injury?
A break in the epithelial or endothelial layers
What activates the clotting cascade?
Exposed collagen & vWF from injury to the endothelial layer
vWF =
Von Williebrand Factor
What does a red thrombus consist of vs a white thrombus?
Red: lots of RBC trapped in a vein
White: fibrin & platelets in an artery
What is an embolism?
When a thrombi breaks off & moves through vessels
What does thrombogenesis mean?
Formation of a thrombi
Describe how thrombogensis works
A brick & mortar structure that will clog a bleeding area
Bricks = platelets
Mortar (glue) = fibrin
Damage to blood vessels cause ________
Vasoconstriction
What does serotonin do in ther peripheral vascular?
increases vascular tone
T/F: Thrombocytes are cells
F
What are Thrombocytes?
Components that are broken off of megakaryocytes
they allow for platelet aggregation by degranulation to activate other platelets in the are
this allows platelts to stick together by fibrin & form a clot
Define coagulation
Forming a clot
Define Fibrinolysis
dissolving an existing clot (lyse)
Describe the 4 platelet phases
- exposure of collagen & vWF -> causes platelets to ADHERE to surface
- adhesion to the surface causes platelet AGGREGATION
- platelets SECRETE substances: serotonin (primary) ADP, TXA2
- The secretion encourages CROSS-LINKING OF ADJACENT PLATELETS which allows a clot to form (coagulation)
AASC
A megakaryocyte is a _______ cell
bone marrow
What do endothelial cells produce? What does this do?
PGI2 - prostacyclin (part of AA cascade)
Inhibits platelet aggregation
What does prostacyclin (PGI2) do?
Inhibit platelet aggregation
Describe the platelet aggregation pathway
- Cell wall damage d/t injury to the epithelial and endothelial cells; This releases collagen & vWF
- Collagen binds to GP1a receptor & vWF binds to GP1b receptor which causes a signaling in the platelet & activates the release of Serotonin, ADP, & TXA2 (Thromboxane A2)
- Once released, these bind to their respective receptors on other platelets which causes degranulation.
- A positive feedback system is activated
T/F: both platelet aggregation and coagulation cascade are required in order to form a staple clot
T
What are the 2 clotting cascade pathways called?
Intrinsic (Inside): damage to endothelial
extrinsic (outside): exposes tissue factor
What is the common pathway in the clotting cascade? What does this mean?
Xa
Both pathways meet here
What does factor Xa do?
Converts Prothrombin to Thrombin
What is the active form of Prothrombin?
Thrombin
What general effects does Thrombin have?
-Converts Fibrinogen to Fibrin
-Activates platelets
-Increases production of more thrombin
What is the active form of fibrinogen?
Fibrin
When you get to ________ you are in the common pathway
factor Xa
Describe the extrinsic pathway in the clotting cascade
- Trauma activates factor VII
- factor VII -> factor X
- factor Xa –> converts prothombin to thrombin
- thrombin -> activates platelets & converts fibrinogen to fibrin
What factors are involved in the extrinsic pathway in order?
7
10
2
1
13
Describe the intrinsic pathway in the clotting cascade
- Trauma to the endothelial layer activates factor XII
- factor XII -> XI
- XI -> IX
- IX -> X
- factor Xa –> converts prothombin to thrombin
- thrombin -> activates platelets & converts fibrinogen to fibrin
What is thrombin’s MAIN effect?
convert fibrinongen to fibrin
What factors to thrombin effect? How?
-Activates factor XIII (13): allows for cross link
– V (5): assists factor Xa
– IIX (8): assists Xa but isnt needed
– XI (11): intrinsic cascade
– Protein C: C+S INHIBIT factor V & IIX
Active protein C inhibits which factors? What does this cause?
Factors V & IIX
Prevents conversion of prothrombin to thrombin
What does antithrombin do?
Blocks thrombin & has effects on factor X
What factors are your thrombin activators?
5, 8, 11, 13, & Protein C
What factors are your thrombin inhibitors?
Protein C with 5 & 8
Antithrombin with 10
What factors are involved in the intrinsic pathway in order?
12
11
9
10
What factor is prothrombin/thrombin?
II
2
What is hemophilia?
Factor 8 deficiency
Where do DVTs form?
Large veins of lower limbs
DVT =
Deep vein thrombosis
Why are DVTs an emergency?
They are in the veins. They are break off go into the heart and into the pulm artery and cause a PE.
What type of thrombi is associated with DVTs?
Red Thrombi
What is Virchow’s Triad? How is that related to DVTs?
- Stasis: decreased skeletal muscle movement = decreased blood flow
- Hypercoagulability: dt genetics or leaky veins esp varicose veins
- Endothelial injury: exposes collagen
SHE
Increases the likelihood of developing DVTs
Describe a white thrombus
-platelets & fibrin crosslinked
occurs in high pressure arteries
-will get stuck in capillary beds downstream
Caused by damage to endothelium; plaque
Describe a red thrombus
-RBC around a white thrombus (platelets & fibrin)
occurs in veins
–has a long tail d/t being built up for awhile d/t low pressure area
High Risk for PE
What are DVT risk factors?
Genetics:
Antithrombin III deficiency, Protien C deficiency, Protein S deficiency, Sickle cell anemia, Activated protein C resistance
Lifestyle:
Bedridden, surgery, trauma, obesity, estrogen, use, malignancies, chronic venous, insufficiency
How does sickle cell anemia contribute to DVT risks?
RBC become trap and damage endothelium cells
How often should you stretch her legs when flying for a long time?
Every 2-3 hours
Why is it important to keep coagulation localized?
unregulated coagulation can cause DIC (microclots everywhere)
Describe DIC
Disseminated coagulation
Microclots everywhere
Uses up all platelets & clotting factors
Increases risks of bleeding out
medical emergency High mortality
Causes: Trauma; gram neg. bacterial infection/sepsis, cancer, abruptio placentae
What is the Tx for DIC?
Plasma/Platelet transfusion
Tx underlying cause
What are 2 ways to prevent over coagulation?
Fibrin inhibition
Fibrinolysis
What are the 3 proteins that break down active clotting factors?
A1-antiprotease
A2-macroglobulin
A2-antiplasmin
What 4 things rapidly inactivate coagulation proteins?
A1-antiprotease
A2-macroglobulin
A2-antiplasmin
antithrombin
What does plasminogen convert to? what does it do?
plasmin
-Regulation of coagulation by breaking down & limiting fibrin/fibrinogen into split products
- remodels & limits extension of thrombus
Describe endogenous tPA
Tissue plasminogen activator
Released from injured cells
Converts plasminogen to plasmin
What 3 things permit conversion of plasminogen to plasmin?
tPA
Urokinase
Streptokinase
What 2 things protect clots from lysis and stop conversion of prothombin to thrombin?
Aminocaproic acid
TXA
What are the 4 classes of coagulation modifiers?
- Anticoahulants: prevent clot formation
- Antiplatelets: inhibit platelet aggregation
- Thrombolytics/Fibrinolytic: breakdown existing clots
- Hemostatics/Antifibrinolytics: promote blood coagulation
Where are coagulation factors produced?
Liver
What is the antiplatelet prototype?
ASA
What is the anticoagulant oral prototype?
Warfarin
What is the anticoagulant IV prototype?
Heparin
What is the thrombolytic prototype?
Streptokinase
Drugs: Heparin
Please list and compare all 3
Class: Indirect Thrombin inhibitor
MOA: Binds & activates antithrombin (conformational change) enhance AT activity 1000x -> inactivates factor Xa -> inhibits thrombin
- Unfractioned Heparin
-MW 5,000-30,000
-unpurified
-made from pig intestine/cow lung - LMW Heparin
-More specific for factor Xa -> less effect on thrombin -> less effect on coagulation
--parin - Fondaparinux
-Pentasaccharide
-synthetic
-Selective for factor X –> least effective –> least bleedind risk
-no interaction with thrombin
What lab is used for heparin?
aPTT
PT
Which heparin is useful for HIT?
Fondaparinux
What is the suffix for LMW heparin?
-parin
Describe HIT
Heparin Induced Thrombocytopenia
- heparin recognized by immune system, and making antibodies against it
- antibodies target are thrombocytes which deplete our platelets
- occurs 7-10 days after given heparin
Differentiate between PT, PTT and INR
PT/PTT
– Heparin
– Time to clot
INR
– Warfarin
–Time to clot compared to control
What labs use for warfarin?
INR
What are normal INR ranges?
Normal: 0.8 - 1.2
While taking warfarin: 2 - 3
What is the normal values for aPTT? what have to be added to this lab?
35-45
phospholipids
Drugs: Protamine Sulfate
Heparin Antidote
MOA: (+) charged drug; Heparin is (-) -> they bind and inactivate each other
Only want to give enough to counter heparin
EXCESS CAUSES ANTICOAGULANT
Most effect on unfractioned
No effect on fondaparinux
What are heparins contraindications related to?
Bleeding
Advanced hepatic disease related to clotting factors
Drugs: Lepirudin (Hirudin)
Class: Direct Thrombin inhibitors
Comes from leech saliva
Some surgeons still use leeches
MOA: Bind to both active & substrate recognition sites of thrombin
Drugs: Argatroban; Dabigatran (Pradaxa)
Class: Direct Thrombin Inhibitors
MOA: Bind only to thrombin active sites
Drugs: Warfarin
Class: Coumarin Anticoagulant
PO
MOA: Blocks gamma-carboxylation of glutamate residues on cloting factors 2, 7, 9, & 10.
- Prevents recyclin of vitamin K by inhibiting Vitamin K reductase
Discovered by University of Wisconsin
Originally was a rat poision
100% PO bioavailability
99% protein binding
36 hours half life
When is warfarin taking?
When weaning off heparin
What clotting factors does heparin effect?
2
7
9
10
T/F: You can take warfarin while pregnant
F
Warfarin reduces prothrombin activity to ____ of normal
25%
T/F: warfarin is metabolize differently in different people, so everyone will need a different does
T
Drug: Vitamin K
Warfarin ANTIDOTE
Confers activity on: Factors VII, IX, X, and prothrombin
Good sources come from green leafy vegetables & gut bateria
How do you reverse warfarin?
Stop drug
Vit K
FFP
Factor IX concentrates
Drugs: Rivaroxaban; Apixaban
Class: Indirect Thrombin inhibitors
MOA: Factor Xa inhibitors -> less specific for thrombin -> clotting cascade more closely controlled
No reversal
Drugs: tPA, Streptokinase, Urokinase
Class: Fibrinolytics
MOA: Lyse thrombi; catalyze formation of plasmin
Drugs: Aspirin
Class: Antiplatelets
MOA: Blocks COX1 which also inhibits Thromboxane A2 synthesis -> increases bleeding time
When should you stop taking aspirin before Sx?
A week beforehand
How many half life’s before a drug is out of your system?
4
Drugs: Clopidogrel (Plavix)
Class: Antiplatelet
MOA: Irreversibly inhibit ADP receptor on platelets
-8.7% reduction in ischemic events in comparison to aspirin
Drugs: Abiciximab
Class: Monoclonal antibody/antiplatelet
MOA: Block IIb & IIIa receptors on platelets preventing degranulation and aggregation
What are plasma fractions?
Isolations in plasma blood where we can get specific factors that we need
Ex) we can isolate and give a patient plasma with factor 8 in hemophilia
Drugs: FFP
Plasma is what our clotting factors are in girl!!!!!!!!!!!
Drugs: Desmopressin
Class: ??
MOA: Increases Factor VIII activity
Tx: Mild hemophilia A; Von WIlliebrand disease
Drugs: Aminocaproic acid; Tranexamic acid
Class: Fibrinolytic inhibitor
MOA: competitively inhibits plasminogen conversion to plasmin
-stabilizes clot & prevents breakdown
Aminocaproic acid Uses: Post surgical, bleeding, intracranial, aneurysm, bleeding from tPA, hemophilia therapy
Tranexamic acid uses: decrease risk of death in major bleeding in: trauma, postpartum, epistaxis, heavy menstrual bleeding
