Coagulation Flashcards
tunica intima
- inner layer of vessel
- endothelium
tunica media
- middle layer
- smooth muscle
tunica externa
- outer layer
- connective tissue
4 steps of hemostasis
- vascular spasm
- formation of platelet plug
- coagulation and fibrin formation
- fibrinolysis when clot is no longer needed
Collagen
procoagulant
vWF
- procoagulant
- fx: plt adhesion
- synthesized by vascular endothelium
- anchors PLT to vessel wall at site of vascular injury
- carries inactivated factor 8
fibronectin
- procoagulant
- fx: cell adhesion
protein C
- anticoagulant
- fx: degrades factor 5a & 8a
protein S
- anticoagulant
- fx: cofactor for protein C
antithrombin
- anticoagulant
- fx: inactivates 2a, 9a, 10a , 11a, 12a
tissue pathway factor inhibitor
- anticoagulant
- fx: inhibits tissue factor
thrombomodulin
- anticoagulant
- fx: regulates naturally occurring anticoagulants
plasminogen
- fibrinolytic
- fx: precursor to plasmin
tPA
- fibrinolytic
- fx: activates plasmin
urokinase
- fibrinolytic
- fx: activates plasmin
alpha-antiplasmin
- antifibrinolytic
- fx: inactivates tPA, urokinase
plasminogen activator inhibitor
-antifibrinolytic
- fx: inhibits plasmin
thromboxane A2
vascular smooth muscle vasoconstrictor
ADP
vascular smooth muscle vasoconstrictor
serotonin
vascular smooth muscle vasoconstrictor
nitric oxide
vascular smooth muscle vasodilator
prostacyclin
vascular smooth muscle vasodilator
Where are platelets produced?
bone marrow by megakaryocytes
normal PLT count
150,000 - 300,000
Lifespan of a PLT
8-12 days
PLT cleared by?
- macrophages in reticuloendothelial system
- spleen
External Membrane of PLT
Glycoproteins
- adhere to injured endothelium, collagen,
fibrinogen
- GpIb attaches activated PLT to vWF
- GpIIb-IIIa complex links PLT together to form
plug
Phospholipids
- prostaglandin synthesis
- produce thromboxane A2–> activates PLT
Internal component of PLT
- Actin & myosin = PLT contraction
- Thrombosthenin = PLT contraction
- ADP = PLT activation & aggregation
- Ca+
- Fibrin stabilizing factor = crosslinks fibrin
- Serotonin = activates nearby PLTs
- Growth factor = repair damaged vessel wall
Natural PLT inhibition
In the absence of vascular injury, the endothelium inhibits PLT fx by secreting:
- Prostaglandin I2 = inhibits vWF, TxA2 activation
- Nitric oxide = inhibits TxA2 receptor
PLT receptors
- GPIb
- ADP
- TxA2
- Thrombin
- GPIIb-IIIa
Hemostasis: Vascular spasm
Immediately following vascular injury, the vessel contracts to reduce blood flow to area
2 functions:
1. reduces blood loss
2. help procoagulant remain in affected area
Primary hemostasis: Platelet Plug
- Adhesion
- Activation
- Aggregation
Adhesion
- Injury exposes collagen
- PLT adhere to collagen via GpIa/IIa & Gp VI
- vWF released from endothelium, binds to GpIb, anchors PLTs
Activation
- Collagen & thrombin activate PLT
- PLT release ADP & TXA2 –> nearby PLT active
- PLT contract & release fibrinogen, fibronectin, vWF, PLT factor 4, PLT growth factor
- PLT swell, misshapen, sticky –> stick to other PLT & injury site
Activated PLT express GpIIb & GpIIIa on surface
Aggregation
- GpIIb/IIIa complex links activated PLT together to form PLT plug
3 steps required to form PLT plug
- Adhesion
- Activation
- Aggregation
vWF binds to the PLT during which step?
Adhesion
How does the injured vessel initially activate the PLT plug?
Endothelial injury exposes collagen. Exposed collagen at the site of vascular injury activates PLT
Clotting factor mnemonic
Foolish
People
Try
Climbing
Long
Slopes
After
Christmas
Some
People
Have
Fallen
Factor 1
Fibrinogen (liver)
Factor 2
Prothrombin (liver)
Factor 3
Tissue factor (vascular wall)
Factor 4
Calcium ions (diet)
Factor 5
Labile factor (liver)
Factor 7
Stable factor (liver)
Factor 8
Antihemophilic factor (liver)
Factor 9
Christmas factor (liver)
Factor 10
Stuart-Prower factor (liver)
Factor 11
Plasma thromboplastin antecedent (liver)
Factor 12
Hageman factor (liver)
Factor 13
Fibrin stabilizing factor (liver)
Coagulation cascade
- Extrinsic = 3, 7 “can be purchased for 37c”
- Intrinsic = 8, 9, 11, 12 “ if you can’t buy IP for $12, can buy for $11.98
- Final common = 1, 2, 5, 10, 13 “can be purchased at 5 & dime (10) for 1 or 2 dollars on 13th of month”
Which coagulation factors are vitamin K dependent?
II, VII, IX, X
Which clotting factors are a part of the extrinsic pathway?
III, VII
Extrinsic pathway measured by what lab?
PT, INR
What drug inhibits intrinsic pathway?
warfarin
How fast can a clot form via the extrinsic pathway?
~15 sec
Intrinsic pathway measured by what lab?
PTT, ACT
Intrinsic pathway inhibited by what drug?
heparin
What is the first factor to be depleted in the patient w/ vitamin K deficiency?
factor VII (also applies to liver failure & pt on coumadin)
4 mechanisms that counterbalance blot formation
- Vasodilation & washout of ADP & TXA2
- Antithrombin inactivating thrombin
- Tissue factor pathway inhibitor neutralizes tissue factor
- Release of protein C & S
2 enzymes that convert plasminogen to plasmin
- tPa
- urokinase
What 2 enzyme inhibitors turn off the fibrinolytic process?
- tPa inhibitor
- A2 antiplasmin
How are plasmin activators used therapeutically?
they help dissolve thrombi to restore blood flow
Fibrinolysis
aPTT
- Activated Partial Thromboplastin Time
- Assesses intrinsic & common pathways
- Monitors heparin
- ## Normal = 25-32 sec
PT
- Prothrombin time
- Monitors warfarin
- Normal = 12-14 sec
INR
- International Normalization Ratio
- Normal = ~1
- Target for coumadin = 2-3 x control
Activated clotting time
- Guides heparin dosing
- Normal = 90-120 sec
- > 400 for CPB
PLT count
- Monitors #, not function
- Normal = 150,000 - 300,000
Bleeding time
- Monitors PLT function
- Evaluates PLT plug
- Normal = 2-10 min
D- Dimer
- Monitors fibrinolysis
- Normal = < 500 mg/ml
Best predictor of bleeding during surgery
H&P
TEG components
R time
- time to begin forming clot
- normal = 6-8 min
- problem = coags
- Tx = FFP
K time
- Time until clot has achieved fixed strength
- Normal = 3-7 min
- Problem = fibrinogen
- Tx = cryo
Alpha angle
- Speed of fibrin accumulation
- Normal = 50-60 degrees
- Problem = fibrinogenn
- Tx = Cryo
Maximum amplitude
- Highest vertical amplitude on TEG
- Measure clot strength
- Normal = 50-60 mm
- Problem = PLT
- Tx = PLT +/- DDAVP
A60
- Height of vertical amplitude 60 minutes after maximum amplitude
- Normal = 5
- Problem = excess fibrinolysis
- Tx = TXA, aminocaproic acid
Normal
factor deficiency anticoagulation
impaired PLT number or function
primary fibrinolysis
hypercoagulation
DIC stage 1 (hypercoagulable)
DIC stage 2 (hypocoagulable)
Heparin inhibits which pathway?
intrinsic & final common pathway
Heparin MOA
- Inhibits intrinsic & final common pathways
- binds to AT3 & accelerates its anticoagulant ability
- neutralizes thrombin & activates factors 9, 10 ,11, 12
CPB dose for heparin
300-400 U/kg
therapeutic heparizination occurs when aPTT is:
1.5 - 2.5 x normal ( normal = 25-35 sec)
Can a pregnant patient receive IV heparin?
yes, it doesn’t cross placenta
Protamine
- derived from salmon sperm
- positively charged protamine & negatively charged heparin create neutralization
- dose = 1 mg for every 100 U heparin
Protamine SE
- Hypotension (histamine); push slow
- Pulmonary HTN ( TxA2 & 5HT release)
- Allergic reaction (previous sensitization to NPH, fish allergy, vasectomy)
Coumadin inhibits factors:
2, 7, 9, 10, protein C & S
Warfarin
- Inhibits vitamin K dependent factors (2, 7, 9, 10, protein C & S)
- Highly protein bound
- Monitored w/ PT/INR
- Antidote = Vit K, FFP, recombinant VIIa, prothromin complex concentrate
Risk factors for vit K deficiency
- Poor dietary intake
- ABX therapy kills off GI flora & reduces Vit K synthesis
- Malabsorption d/t obstructive biliary tract dz
- Hepatocellular dz
- Neonates do not have intestinal flora that synthesizes vit K
Clopidogrel
- ADP receptor inhibitor
- Stop 5-7 days preop
Ticlopidine
- ADP receptor inhibitor
- Stop 14 days preop
Prasurgel
- ADP receptor inhibitor
- Stop 7-10 days preop
Ticagreclor
- ADP receptor inhibitor
- Stop 5-7 days preop
COX inhibitor MOA
- prevent PLT aggregation by blocking cyclooxygenase 1
- stop conversion of arachidonic acid to prostaglandins & ultimately thromboxane A2
Aspirin
- COX inhibitor
- Stop 7 days preop
NSAIDs
- COX inhibitor
- Stop 1-2 days preop
Heparin
- Unfractioned - stop 6 hrs preop
- LWWH - stop 1-2 days preop
Warfarin
- Vit K antagonist
- Stop 2 -4 days preop
Antifibrinolytics
- Stop conversion of plasminogen to plasmin
- promote clot formation
- TXA, aminocaproic acid
Fibrinolytics
- conversion of plasminogen to plasmin
- break down clots
- tPA, urokinase, streptokinase, reteplase, alteplase
tPA
- Plasminogen activator
- Stop 1 hr preop
vWF Dz
- Most common inherited d/o of PLT fx
- Normal PLT count, Plt dysfunction
- Increased PTT & bleeding time
- Tx:
1. DDAVP - stimulates release of vWF & increases factor 8 activity
2. Cryo (8,13, fibrinogen, vWF)
3. FFP (all clotting factors)
4. Purified 8-vWF
Hemophilia A
- X linked
- Factor 8 deficiency
- Prolonged PTT
- Tx: factor 8 conc, FFP, cryo
Hemophilia B
factor 9 deficiency
DIC
- Disorganized clotting & fibrinolysis
- Thrombin formation creates microvascular clots that impair tissue perfusion causing hypoxia & acidosis
- Activates anticoagulant system leading to consumption of coag factors, fibrinogen, & PLT
- S/S
1. Ecchymosis
2. Petechiae
3. Mucosal bleeding
4. Bleeding at IV site - High risk = sepsis, OB, malignancy, preeclampsia, placental abruption, AFE
- Tx = IVFs, FFP, PLTs, Cryo, IV heparin, LMWH
Protein C & S deficiency results in:
- hypercoagulability
- thrombosis
Coagulation d/o tx w/ desmopressin
- vWB Type I > II
- Hemophilia A
MOA Desmopressin/DDAVP
stimulates release of vWF & increases factor 8 activity