APEX Coagulation
What 7 things are found inside the platelet?
- actin and myosin -thrombosthenin -ADP -calcium -fibrin stabilizing factor -serotonin -growth factor
Name the procoagulants.
-Factors I - XIII -Fibrinogen -vWF -Fibronectin
Name the antifibrinolytics.
-a-antiplasmin -plasminogen activator inhibitor
Name the anticoagulants.
-antithrombin III -protein C -protein S -Tissue pathway factor inhibitor
Name the fibrinolytics.
-plasminogen -tPA -urokinase
What is the functions of glycoproteins?
-repelled by healthy vascular endothelium -adhere to injured endothelium, collagen, and fibrinogen --GPIb attaches activated platelet to vWF --GPIIb-IIIa complex links platelets together to form plug
What is the normal INR value in health patients?
1
What are four reasons why blood remains a liquid?
1) coagulation proteins circulate in an inactive form 2) the endothelium is smooth and the glycocalyx repels clotting factors 3) undamaged endothelium does not express tissue factor or collagen. This prevents activation of platelets and the coagulation cascade 4) Activated factors are removed by brisk blood flow through the vessels as well as anticoagulants in circulation
What are the 3 steps in the formation of the platelet plug?
1. Adhesion 2. Activation 3. Aggregation
What are the steps in the intrinsic pathway?
1. Blood trauma exposure to collagen activates factor XII 2. Factor XI Activation 3. Factor IX Activation 4. Factor X Activation 5. Prothrombin Activator
What are the three phases of the contemporary cell-based coagulation cascade?
1. Initiation phase - TF/VIIa activate the final common pathway 2. Amplification - platelets are activated 3. Propagation - a large amount of thrombin is produced
What two functions does vascular spasm serve?
1. It reduces blood loss 2. It helps procoagulants remain in the affected area, so they can do their jobs
What is INR?
A calculation that standardizes PT results. It is based on the ratio between the patient's PT and the standard mean PT.
What factors should be associated with platelet activation and aggregation?
ADP Thromboxane A2
What is the process in which the body breaks down the clot after it is no longer needed?
Fibrinolysis
Is the extrinsic pathway slow or fast?
Fast, requiring only 15 seconds
What is Fibrin broken down into?
Fibrin degradation products
What is the extrinsic pathway measured by?
PT and INR
What is the intrinsic pathway measured by?
PTT and ACT
How does fibrinolysis work?
Plasminogen circulates in the blood and whenever tPA (tissue plasminogen activator) and urokinase is released from vascular endothelial cells then the plasminogen is converted to plasmin and that essentially breaks down fibrin.
What pathway is activated when coagulation is initiated outside of the intravascular space?
extrinsic
What two things are on the external membrane of platelets?
glycoproteins and phospholipids
What is the intrinsic pathway inhibited by?
heparin
What organ can sequester up to 1/3 of call circulating platelets for later use?
spleen
What do phospholipids do?
substrates for prostaglandin synthesis --produce thromboxane A2 (activates platelets)
What happens to a vessel immediately following vascular injury?
the vessel contracts to reduce blood flow to the area.
What does the heparin-AT complex neutralize?
thrombin and activated factors X, XII, XI, IX
R-time on TEG?
time to begin forming clot Normal Value: 6 - 8 minutes Problem area: coagulation factors Treatment: FFP
What does platelet count monitor?
The number of platelets , not how well the platelets function
What does aPTT measure?
The time is takes to form a clot using PHOSPHOLIPID, CALCIUM, ACTIVATOR
What does PT measure?
The time it takes to form a clot using TISSUE FACTOR, CALCIUM
What factors make up the final common pathway?
Think Dollar Denominations 10 5 2 1
What are the 3 steps fo the extrinsic pathway?
1. Tissue Factor Release 2. Factor X Activation 3. Prothrombin Activator
What are the 4 steps of hemostasis?
1. Vascular spasm 2. Formation of the platelet plug (primary hemostasis) 3. Coagulation and the formation of fibrin (secondary hemostasis) 4. Fibrinolysis when the clot is no longer needed
What four mechanisms limit the size of the clot?
1. Vasodilation washing out ADP and TxA2 2. Antithrombin inactivating thrombin 3. Tissue factor pathway inhibitor neutralizing tissue factor 4. protein C and S, inhibiting 3, 5, 8
What are the 6 steps in drawing the coagulation cascade?
1. count backwards from 12 2. 3, 4, and 6 don't exist 3. 10 is the front man in the band - it's the only one out of order 4. 5 and 8 are co-factors, so they go above the line 5. 7 is lucky, so it goes in your pocket (below the line) 6. 2 is prothrombin and 1 is fibrinogen
What are the steps of the final common pathway?
1. injury activates the coagulation cascade by activating the extrinsic or intrinsic pathway 2. the final common pathway begins where prothrombin activator changes prothrombin to thrombin 3. thrombin is a proteolytic enzyme that changes fibrinogen to fibrinogen monomer. In the presence of calcium, fibrin fibers are created. 4. after the platelets aggregate, fibrin is incorporated into the platelet plug. Activated fibrin-stabilizing factor facilitates cross-linkage of the fibrin fibers, and this completes the clot. 5. the clot stays in place until the underlying vascular tissue has repaired itself
What are the vitamin K dependent factors
10 9 7 2
What is the normal value for PT?
12 - 14 seconds
What factors make up the intrinsic pathway?
12, 11, 9, 8
What is the normal value of platelets?
150,000 - 300,000
What is a normal platelet value?
150,000 - 300,000 mm3
What is a normal value for bleeding time?
2 - 10 minutes
What is the target INR value for patients on warfarin?
2 - 3 times the control
What is the normal range for aPTT?
25 - 32 seconds
What factors make up the extrinsic pathway?
3 and 7
In order to see a change in aPTT or PT, factors must be reduced by what percent?
30%
What is the range in Daltons of unfractionated heparin?
3000 - 30000
What activates factor 10?
7 activates 10 in the presence of 4 (Ca2+)
What is the life span of platelets?
8 - 12 days (1-2 wks)
What is a normal ACT value?
90 - 120 seconds
What platelet value increases spontaneous bleeding risk?
< 20,000 mm3
What platelet value increases surgical bleeding risk?
< 50,000 mm3
What should the ACT be before going on cardiopulmonary bypass?
> 400 seconds
What is TEG?
A "real time" visual representation of disorders of coagulation and fibrinolysis.
What should be considered if a patient fails heparin therapy?
AT deficiency
What does ACT stand for?
Activated clotting time
When is ACT measured?
Before heparin administration, 3 minutes after it is given, and every 30 minutes thereafter
How are fibrin degradation products measured?
By D-dimer
How are platelets cleared?
By macrophages in the reticuloendothelial system and spleen.
In the absence of vascular injury, how does the endothelium inhibit platelet function?
By secreting prostaglandin I2 (inhibits vWF adherence, TxA2 activation, and release of storage granules) nitric oxide (inhibits TxA2 receptors)
What is the extrinsic pathway inhibited by?
Coumadin
PT is associated with which pathway?
Extrinsic
Name the coagulation factors.
Foolish People Try Climbing Long Slope After Christmas Some People Have Fallen 1. Fibrinogen 2. Prothrombin 3. Tissue Factor 4. Calcium Ions 5. Labile Factor 7. Stable Factor 8. Antihemophilic Factor 9. Christmas Factor 10. Stuart-Prower Factor 11. Plasma thromboplastin antecedent 12. Hageman Factor 13. Fibrin Stabilizing Factor
What is the mnemonic for the extrinsic pathway?
For 37 cents you can purchase the extrinsic pathway
Name the platelet receptors.
GP1b ADP TxA2 Thrombin GpIIb - IIIa
What two glycoproteins do activated platelets express?
GpIIb and GpIIIa
What does the activation of factor XI require?
HMW kininogen
A60 (Amplitude at minutes after maximum amplitude) on TEG
Height of vertical amplitude 60 minutes after the maximum amplitude Normal Value: MA - 5 Problem Area: excess fibrinogen Treatment: TXA aminocaproic acid
Maximum amplitude (MA) on TEG
Highest vertical amplitude on the TEG. Measures clot strength. Normal Value: 50 - 60 mm Problem area: platelets treatment: platelets + / - DDAVP
What is the BEST predictor of bleeding during surgery?
History and physical
When does clotting to death occur?
If the procoagulants predominate, then the blood tends to clot. This increases the risk of stroke, myocardial infarction, or thrombosis elsewhere in the body.
What is the mnemonic for the intrinsic pathway?
If you can't buy the intrinsic pathway for $12, you can buy it for $11.98
PTT is associated with which pathway?
Intrinsic
How does heparin work?
It binds to antithrombin III accelerating its anticoagulant ability
What type of compound in heparin?
Large, negatively charge water soluble compound small volume of distribution
Where in the blood vessel are platelets located?
Near the vessel. Places them close to their site of action.
Alpha angle on TEG
Speed of fibrin accumulation Normal value: 50 - 60 degrees Problem area: fibrinogen Treatment: cryo
Is the intrinsic pathway slow or fast?
slow, requires up to 6 minutes to form a clot
What is the mnemonic for the final common pathway?
The final common pathway can be purchased at the five and dime for 1 or 2 dollars on the 13th of the month
K time on TEG
Time until clot has achieved fixed strength. Normal Value: 3 - 7 minutes Problem area: fibrinogen Treatment: cryo
What activates the extrinsic pathway?
Tissue factor
aPTT monitors the therapeutic response to __________________________.
Unfractionated heparin
What factor is missing in hemophilia a?
VIII
What factor should be associated with platelet adhesion?
Von Willebrand Factor
PT/INR measures the therapeutic response to _____________.
Warfarin
What state does blood exist in when there is no injury?
a viscous liquid
How long does it take to form a platelet plug?
about 5 minutes
Von Willebran Disease is a disorder of platelet _____________.
adhesion
What drugs prolong bleeding time?
aspirin and NSAIDS
What is endogenous heparin prodded by?
basophils, mast cells, liver
What is exogenous heparin derived from?
bovine lung and porcine GI mucosa
What is another name for the intrinsic pathway?
contact activation pathway
When does bleeding to death occur?
if the anticoagulants predominate, then the blood has a tendency not to clot. This increases the risk of bleeding.
What are platelets formed by?
megakaryocytes in the bone marrow
What does bleeding time monitor?
platelet function: the ability to form a platelet plug
What is missing in thrombocytopenia?
platelets
What accelerates factor XI activation?
prekallikrein
What is the primary goal of both pathways?
to produce prothrombin activator
What inhibits the extrinsic pathway?
warfarin