Hematology Week 1: Hemostasis Flashcards
Hemostasis Definition
The stopping of a flow of blood
3 things that can kill the patient in seconds that are hemostatic disorders
Massive Stroke
Massive MI
Massive pulmonary embolism
Disseminated Intravascular Coagulation
The importance of balance in hemostasis

Vasoconstriction

Primary hemostasis
Platelet adhesion to injury sites
Secondary Hemostasis
formation of a fibrin clot

Fibrinolysis
enzymatic breakdown of fibrin clot

The stages of hemostasis
4 listed
- Vasoconstriction
- Primary hemostasis
- secondary hemostasis
- Fibrinolysis
Platelets
made in?

Platelets
Lifespan?

Platelets
The amount in circulation?

Platelets
where are they?

Functions of Platelets
4 Listed
- Stick to damaged epithelium
- Store ADP, Ca2+, proteins for coagulation
- Stack aggregate
- Surface phospholipids for coagulation reactions

Anatomy of a platelet
Membrane Receptors
3 listed
- glycoprotein 1b
- Glycoprotein 2b-3a
- Platelet agonist receptors

Anatomy of a platelet
Granules
- Alpha Granules
- Dense Granules

Glycoprotein 1b
Surface receptor on platelets that binds Von Willebrand Factor (vWF)
Glycoprotein 2b-3a
Surface receptors on platelet that bind fibrinogen
Glycoprotein 6
Surface receptor on platelet that binds collagen
Thromboxane A2
Surface receptor on platelet that binds

ADP Receptor on platelets

Platelet Alpha Granules Proteins
3 listed
Von Willebrand Factor
Fibrinogen
Factors 5, 8, 13
Platelet Dense Granule chemicals
3 listed
- ADP/ATP
- Calcium
- Serotonin
How are platelet granules released?
released upon platelet activation aiding hemostasis
Platelet adhesion and aggregation inhibition
endothelium secretes
NO
PGI2
ADPase
to inhibit platelet adhesion and aggregation

Endothelium secretes what to inhibit platelet activation
3 listed
NO
PGI2
ADPase

Platelet receptor that binds to von Willebrand Factor
Glycoprotein 1b
Platelet receptor that binds to collagen
Glycoprotein VI
Platelet receptor that binds fibrinogen and vWF
Glycoprotein IIb-IIIa
mainly binds Fibrinogen but binds some to vWF
Coagulation cascade
a series on enzymatic reactions that amplifies until there is a thrombin burst that overcomes the natural anticoagulants present and polymerizes fibrinogen into an insoluble fibrin clot sealing injured vessels

The receptor that allows platelets to:
initial attachment and activation
GPIb

The receptor that allows platelets to:
Activation and spreading
GPVI

The receptor that allows platelets to:
Aggregation
GPIIb-IIIa

Formation of a fibrin clot steps
Platelet surface
fibrinogen interacts with thrombin to form a fibrin clot

Fibrinogen is cleaved by?
the enzyme thrombin
releases fibrinopeptides and forms fibrin monomer
What crosslinks fibrin monomers to form fibrin polymers?
Factor 13
Fibrinogen polymerization to fibrin

What clotting factors need to work?
4 listed
- Clotting factor (FI-XIII)
- Phospholipids
- Calcium
- Co-factors (if necessary)

Thrombin generation common pathway
- the intrinsic and extrinsic thrombin generation pathways converge on the common pathway
- Factor X is where the extrinsic and intrinsic pathways converge
- Factor X and cofactor Factor V activate prothrombin to thrombin which cleaves fibrinogen to fibrin

Thrombin actions

Factor IIa
Thrombin
Factor II
Prothrombin
Factor VIIa Cofactor
Tissue Factor
The extrinsic pathway
Factor VII

Tissue factor is a?
Transmembrane receptor on cells outside of the circulation that binds Factor VIIa to activate the extrinsic pathway of coagulation
Are platelets needed for the extrinsic pathway?
No only need Factor VII to come in contact with Tissue Factor
The Intrinsic Pathway of Coagulation

Procoagulant proteins

Anti-coagulant Proteins
Also Anti-thrombin!!!

Anti-thrombin function
inactivate thrombin

Fibrinolysis
dissolution of fibrin clot

tPA function
Endothelial cells release tissue plasminogen activator after stimulation by thrombin
tPA binds tightly to fibrin
tPA AKA
Tissue plasminogen activator (tPA)
tPA & Factor XII activates
Plasminogen into plasmin
Plasminogen is cleaved into
Plasmin
Plasminogen is cleaved by?
tPA and Factor XII
Production of plasmin

Plasmin Function
cleaves fibrin into breakdown products
- fibrin degradation products
- D-dimers

D-dimers are formed by?
Plasmins cleavage of a fibrin clot
tPA is inactivated by?
Plasminogen activator inhibitor (PAI-1)

PAI-1 AKA
Plasminogen activator inhibitor
PAI-1 is released from?
The endothelium
The primary site of synthesis for most proteins involved with hemostasis?
Liver

Hemostatic proteins synthesized by the live
Procoagulants 2, 5. 7, 9, 10. 13
Anticoagulants: Protein C, Protein S, Anti-thrombin
Fibrinogen
Plasminogen
Chronic liver disease hemostatic consideration
can result in both bleeding and thrombosis
Vitamin K dependent facotrs and proteins for hemostasis
SNoTT Factors: Factor 7, 9, 10, 2
Protein C and S

GLA domain requires
- Vitamin K for carboxylation of the enzyme GLA domain
- GLA domains on factors bind Ca2+ which allows enzyme to bind phospholipid
What is a GLA domain
on clotting factors bind calcium and phospholipids
Intrinisic pathway relates to what test?
Partial Thromboplastin Time (PTT)

Extrinsic Pathway relates to what test?
Prothrombin Time

Prothrombin Time (PT)
evaluates the extrinsic pathway and common pathway
time it takes to take prothrombin to thrombin

Warfarin is monitored by this test
PT
PT reagent
Thromboplastin
Thromboplastin
Reagent for PT made of tissue factor and phospholipid
INR

INR is not designed for?
Patients with liver disease
PTT AKA
PArtial Thromboplastin Time
PTT
evaluates intrinsic pathway and common pathway

hypercoagulable state considerations
4 listed
- increased procoagulant factors
- decreased anticoagulant factors
- reduced fibrinolysis
- increased fibrin degradation products
Neonates hemostatic considerations
3 listed
- lower levels of procoagulant factors compared to adults
- lower amount of intrinsic pathway factors
- Vitamin K factors also lower (prophylactic Vitamin K is given at birth)
Why is vitamin K given to neonates?
Vitamin K factors are lower at birth
Coagulation in different life stages

Three parts of the circulatory system
3 listed

Arterial hemostatic considerations
Platelets are more active here
antiplatelet agents for preventing arterial thrombosis (Myocardial infarctions)
Venous hemostatic considerations
2 listed
Clotting factors are more active here
anticoagulants targeting clotting factors for preventing venous thrombosis
Microcirculation hemostatic considerations
2 listed
- Large endothelial surface
- Platelet dysfunction is observable here