Unit 3 Coagulation Flashcards
Factors that require vitamin K:
Vitamin K activates clotting and fibrinolysis factors factor II factor VII factor IX factor X protein C protein S
PT/INR
-measures extrinsic pathway
aPTT
- take out tissue factor
- just have phospholipid
- measures intrinsic pathway
Hemophilia A
- deficiency in factor 8
- inc aPTT
- muscle bleeding, bruising
Hemophilia B
- deficiency in factor 9
- inc. aPTT
- muscle bleeding, bruising
Factor 5 Leiden
- mutation in factor 5 that inhibits it from getting inactivated by protein C
- inc. clotting
Von Willebrand Disease
-most common bleeding disorder
-VW factor stored in weibel pilate bodies
-treated with desmopressin (DDAVP) before procedures (only works type 1)
-Type 1- low amounts
-Type 2- nonfunctional
Type 3- not present at all
Bernard-Soulier
-deficiency of GP1B
Immune Thrombocytopenic Purpura (ITP)
- antibodies attack platelets
- acute and chronic
- tx: steroids, IVIG (overwhelms immune system), rituximab (lowers B cells), splenectomy
Bleeding Time Test
-does not diagnose factor deficiencies
Primary Hemostasis
- platelet plug formation
- measure with bleeding time or PFA100
- defects lead to mucocutaneous bleeding
prothrombin G20210A
x
Plasmin
The key enzyme responsible for clot digestion (fibrinolysis).
-plasminogen is incorporated into clots and is activated by tPA and uPA, and it becomes plasmin
D-Dimer Test
x
Glycoprotein 2b3a
x
Heparin
- cofactor for antithrombin which greatly increases its ability to inactivate thrombin
- works in intrinsic pathway
- effects are immediate
- safe in pregnancy
- protamine reverses unfractionated heparin
- unfractionated heparin inactivates thormbin and factor 10 (IV)
- low molecular weight heparin also possible- inactivates factor 10 (injection)
- can be reversed with protamine sulfate (opposite charge of heparin) (hep is -)
- heparin induced thrombcytopenia- antibodies attack platelet factor 4-heparin complexes- tx in future with argatroban or leparudin
Warfarin
- works on extrinsic pathway
- takes a while for effects to begin (4 or 5 days)
- teratodenic- do not use in pregnant people
- oral
Desmopressin
- DDAVP
- stimulates VWF
- temporarily stop sx of VW disease
Argatroban
-drug that would be given if heparin is not working
mucocutaneous bleeding
-associated with platelets, VWF, and adherance
Idiopathic Thrombocytopenic Purpura
-antibody mediated destruction of platelets
TTP
ADAM
lupus anticoagulant
- antibodies mess up aPTT making it appear long
- pt is actually at risk for clots
- do mixing tests to confirm
citrate in blood tests
- chelates calcium
- add calcium when ready to run test
intrinsic tenase complex
- factors 8, 9, 10
- activates factor 10
extrinsic tenase complex
- TF and factor 7
- activates factor 10
prothrombinase
-factor 5, factor 10, prothrombin (factor 2)
factor 13
- covalently binds fibrins together in clot
- measuring of D-dimer is measurement of two fibrins between crosslink
central enzyme in blood coagulation
-thrombin
protein C
- protein S is cofactor
- activated by thrombin thrombomodulin to APC
- secondarily activated by vitamin K
tissue factor pathway inhibitor
- binds to 10a and then can bind to factor 7 and TF
- inhibits extrinsic pathway
plasminogen activation inhibitor 1 (PAI-1),
- inhibits fibrinolysis
- inhibits plasminogen activation by inibiting tPA and uPA
alpha2-antiplasmin
- inhibits fibrinolysis
- inhibits plasmin directly
thrombin-activatable fibrinolysis inhibitor (TAFI)
-activated by thrombo-thrombomodulin (which also activates protein C
endothelial lining prevention of clots
- makes heparin
- expressed thrombomodulin
- makes tPA and uPA
- vasodilates
secondary hemostasis
-coagulation cascade arm of hemostasis
3 Functions of Platelets
- adhere to endothelium and release granules
- aggregate and form plug
- provide phospholipid surface to support coag cascade
lupus anticoagulant
- have high aPTT but pt presents with clot
- antiphospholipid antibody
- causes clotting
- associated with lupus
- inc. risk of arterial and venous clotting
thrombin time (TT) test
- add thrombin to plasma
- if inc. it indicates problem with fibrinogen
DIC
-associated with ebola and APML
Mixing Studies
- mix pt plasma and normal plasma
- determines inhibitor vs. deficiency in clotting factors
Test for Hypercoagulability
-factor assay
Tissue Plasminogen Activator
- activates plasminogen to plasmin
- fibrinolytic agent
- use only in emergencies
- give at high dose compared to amount in body
Fibrinolytic Drugs
- break down fibrin
- break clots that are already there
- tissue plasminogen activator
Anti Platelet Drugs
- aspirin- prevents formation of thromboxane
- prevent clots from forming
- GP2B3A inhibitors
- ADP receptor blockers (plavix)
- works in arterial clots best