Hemostasis Flashcards
The stages of hemostasis?
Primary
Secondary
Fibrinolysis
What is primary hemostasis?
Formation of the platelet plug
What is secondary hemostasis?
Coagulation
When the actual clot forms
What is fibrinolysis?
Clot is dissolved
What is the vessel itself’s initial response to injury?
Vasospasm
What stimulates the vasospasm of the injured vessel to occur?
Disrupted endothelium
What stage includes formation of the platelet plug?
Primary
What initiates formation of the platelet plug?
Injury to vessel exposes endothelial collagen
What coagulation factor is required for adhesion of platelets?
Von Wilebrand
vW
What factor(s) activate platelets for the platelet plug?
Thrombin and tissue factor
What is meant by platelet activation?
Platelets change shape
What prostaglandin promotes platelet aggregation?
Thromboxane
What substances are also included in the platelet plug?
Fibrinogen and thrombin
Aggregation of platelets triggers further?
Attraction of more platelets
Platelet activation
What kind of bleeding/injury do platelet plugs control?
Minute vessel breaks that occur constantly
-full clot not required
Platelet counts under what allow spontaneous bleeding to occur?
< 20,000
Intercerebral hemorrhage can occur from just a platelet count below?
< 20,000
Thrombocytopenia means what? And what can you see with this as evidence of someone unable to form platelet plugs?
Low platelet count
Petechia
Production of thromboxane requires what?
Cyclooxygenase (COX)
What inhibits the production of the prostaglandin thromboxane?
Cox inhibitors interferes with the enzyme cyclooxygenase, which means it interferes with the production of thromboxane
COX inhibitors interfere with what part of hemostasis?
Function of the platelets
- platelet aggregation
- formation of a platelet plug
What COX inhibitor has temporary interference on hemostasis?
NSAIDs
How long do NSAIDs interfere with platelet function?
1-2 days
What cox inhibitor has permanent interference on platelet function?
Aspirin
Why is ASA interference considered permanent?
It lasts the life of a platelet
What is the life of a platelet?
8-12 days
-1-2 weeks
How long does ASA interfere with platelet function?
1-2 weeks
What lab tests will tell platelet function, NOT count?
Bleeding time
What bleeding time may indicate bleeding risk?
Over 7-8 minutes
What platelet count constitutes thrombocytopenia?
< 100,000
What platelet count constitutes surgical bleeding risk?
< 50,000
What platelet count constitutes spontaneous bleeding?
< 20,000
What are the 4 A’s of platelet plug?
Activation
Adhesion
Aggregation
Attraction
What changes the platelet plug into a clot?
Fibrin
What is the inactive form of fibrin?
Fibrinogen
What factor converts fibrinogen into fibrin?
Thrombin
What is the inactive form of thrombin?
Prothrombin
What factor converts prothrombin into thrombin?
Factor X
What constitutes the chain of events that occur from factor X > fibrin formation?
The common pathway
The formation of fibrin requires what substances?
Fibrinogen
Calcium
Thrombin
The formation of thrombin requires what substances?
Prothrombin
Calcium
Factor X
What (old) 2 pathways were described to get to factor X?
Extrinsic and Intrinsic pathway
What factors are involved in the extrinsic pathway and what lab test would show abnormalities?
III
VII
PT
What factors are involved in the intrinsic pathway and what lab test would show abnormalities?
VIII IX XI XII PTT
What has replaced the intrinsic/extrinsic pathways?
The cell based theory
-tissue factor theory
What factor does the cell based theory say triggers coagulation?
Factor III
What are the many names for factor III?
Tissue factor
Thromboplastin
Tissue thromboplastin
What are the phases of cell based theory?
Initiation
Amplification
Propagation
Describe initiation phase
Triggered by vessel injury to endothelial surface exposing tissue factor
Tissue factor and factor VII activate factor X
How much thrombin is created due to initiation phase
Only a small amount
Describe the amplification phase
XXX
How much thrombin is created from the activation stage?
Thrombin generation is gaining momentum
Describe the propagation phase
XXXX
This propagation phase is also the?
The common pathway
What is thromboelastogram?
Lab test: TEG
-follows clot through initiation, complete formation, strength and lysis
What can TEG not detect?
vW disease or ASA effects
What is the R time on TEG?
Time to begin forming clot
What is the problem if R is prolonged in a TEG?
Coagulation factors
What is the K describe on a TEG?
Time of clot strengthening
What is the problem if K is prolonged on TEG?
Fibrinogen
What is MA on a TEG?
Measures the clot’s strength
What is the problem in the MA on a TEG?
Platelets
What is the determined by the time period after the MA?
Fibrinolysis
TEG waveforms
TEG waveforms
What is responsible for clot lysis?
Plasmin
How does plasmin dissolve the clot?
It removes the fibrin
What activates the plasminogen?
Tissue plasminogen activator
-tPA
What inhibits plasmin?
Anti plasmin
-supports clot
What class of drugs dissolve clots?
Thrombolytics
Name 3 plasminogen activators
TPA and analogues
Streptokinase
Urokinase
Name 3 plasmin inhibitors
Aprotinin
Amicar amiocarproic acid
Transexamic acid
What is the most common inherited bleeding disorder?
VonWillebrands disease
What is vonWillebrand’s needed for?
Adhesion of platelets
What medication can exacerbate vW symptoms?
ASA
-should be avoided
What lab results are seen with vW?
Prolonged bleeding time
PT/PTT may be normal
PLT count may also be normal
What is the first line treatment for vW? Why?
DDAVP
It treats the most common form of vW
What is DDAVP?
Analogue of vasopressin
What is given if vW patient does not respond to DDAVP?
FFP
Non-recombinant factor VIII
Why must non-recombinant factor VIII be used?
Recombinant factor VIII is artificially created and does not contain vW
Where is factor VIII made?
In the liver
Where is vW synthesized?
By vessel endothelial cells
What is the relationship between vW and factor VIII?
vW with factor VIII combine to take part in coagulation
-VIIIc is without vW
Hemophilia is an abnormality on which chromosome?
X
What lab value would show hemophilia?
Prolonged PTT
What is hemophilia A?
Deficiency of factor VIIIc
-treatment is factor VIII
What is hemophilia B?
Deficiency of factor IX
What can treat both types of hemophilia?
FFP
What type of hemophilia can cryoprecipitate treat?
Hemophilia A
-though controversial
Which type of hemophilia is more common?
Hemophilia A
What is the most common inherited defect in secondary hemostasis?
Hemophilia A
What is the most common inherited cause of abnormal bleeding?
VW disease
What is the most common inherited cause of abnormal secondary coagulation?
Hemophilia A
What is the most common cause of abnormal bleeding?
ASA
What is more common acquired bleeding problem or inherited?
Acquired
What are examples of acquired bleeding problems?
Liver disease Decreased function VIII, IX, XI RA Colitis Aging Systemic lupus erythematous
What factors are NOT made by the liver?
VW: endothelium
Calcium: factor IV from diet
III: from damaged tissue
Liver disease causes what lab abnormalities?
Elevated PT and PTT
Vitamin K is required for the liver to synthesize what factors?
II
VII
IX
X
What contains all coagulation factors except platelets?
FFP
What does FFP also contain?
Anticoagulation factors like antithrombin III
What is in cryoprecipitate?
Factor VIII
Fibrinogen
XIII
What is stored banked blood deficient in?
Platelets
Factor V
Factor VIII
What factor has the shortest half life?
Factor VII
Why does stored banked blood has deficiencies?
Because of the process of removing the plasma
What is dilutional coagulopathy?
So much banked blood has been giving which doesn’t have factors V, VIII and platelets
What is usually the biggest problem with dilutional coagulopathy?
Low platelets
Platelets may be need if how much banked blood has been given?
10-15 units
With dilutional coagulopathy a patient’s factors have to fall below what % for coagulation to no longer be normal?
< 30%
What can be given with dilutional coagulopathy after platelet transfusion and bleeding still a problem?
FFP
Name some anti-coag factors
Antithrombin (antithrombin III)
Protein S
Protein C
Thrombomodulin
What drug class inhibits further clot formation?
Anticoagulants
What does Heparin augment?
Antithrombin III
Heparin interferes with which pathway?
Intrinsic
So what factors are affected by Heparin?
I II V VIII IX X XI XII By interfering with intrinsic pathway, it also interferes with the common pathway
How is the activity of Heparin monitored?
PTT
What explains heparin resistance?
Low antithrombin III
How is low antithrombin III treated?
FFP
-so heparin resistance is treated with FFP
What is the most common cause of drug induced thrombocytopenia?
Heparin Induced Thrombocytopenia (HIT)
What is a risk of using direct thrombin inhibitors?
Increased risk of bleeding
-it can not be reversed
Name direct thrombin inhibitors
Bivalirudin
Argatroban
Hirudin
Dabigatran
What direct thrombin inhibitor has the shortest half life?
Bivalirudin
Name direct factor X inhibitors
Fondaparinux
Rivaroxaban
Apixaban
What are the advantages of low molecular weight heparin?
Longer half life More predictable Less monitoring needed Less platelet inhibition Less HIT
What are the disadvantages of LMWHeparin?
Not reversible
How does Coumadin work?
Competes with vitamin K at the liver
What factors are affected by this vitamin K competition with Coumadin?
II
VII
IX
X
What pathway does Coumadin interfere with?
Extrinsic pathway
What test does Coumadin affect?
PT
What test is Coumadin monitored for therapeutic levels?
INR
-ratio that tells you how much longer clotting takes
What is disseminated intravascular coagulation?
Uncontrolled coagulation activation
Widespread thrombosis of small vessels
Consumes clotting factors and platelets
What type of things can DIC be a secondary complication of?
Sepsis Shock Post op Transfusion reaction OB complications Others
What are the symptoms of DIC?
Spontaneous diffuse hemorrhage Decreased platelets Decreased fibrinogen Elevated PT Elevated PTT Elevated fibrin degradation products
What is the distinctive characteristic of DIC? (2 names)
Elevated fibrin degradation products
AKA fibrin split products
What is the treatment of DIC?
Platelets and FFP
Treat underlying cause
Heparin is a controversial treatment