What are the smallest form elements in the blood
Platelets
What are platelets
Fragments of megakaryocytes
What do platelets not contain
A nucleus
What are thrombocytes
Another name for platelets
What is the function of platelets
Hemostasis
What is Hemostasis
Prevent blood loss through clot formation
What is Thrombopoietin
Hormone that regulates platelet production
Where is thrombopoietin produced
The liver
What organelles are within platelets (3)
ER
Mitochondria
Golgi
What contractile proteins are within platelets
Actin and Myosin
What clotting factor is produced by platelets
13 XIII (Fibrin)
What chemicals do the platelets produce (5)
Fibrin
Thromboxane A2 (TxA2)
ADP
Polyanions
Platelet Factor 4 (PF4)
Where are the platelet chemicals stored
Granules
What is the function of Polyanions
Activate coagulation cascade
What is the purpose of the glycoproteins GP11b and GP111a present on
the platelet membranes
Drug targets for anti-platelet therapy
Hemostatsis Steps
1. Vasoconstriction TXA2
2. Primary Hemostasis - Loose platelet plug is formed
3. Secondary Hemostasis- Coagulation cascade --> unyielding plugs
4. Fibrinolysis
What protein in located within the basement membrane
Collagen
What is the first step in the activation of platelets
The platelets exposure to collagen
Once the platelets are activated my collagen exposure what happens
Polyanions trigger coagulation cascade
What do platelets release once the Polyanions have triggers the
cascade (2)
Factor XIII
Thromboxin A2
What is required for fibrin formation
Factor XIII
What does Thromboxin A2 cause
Vasoconstriction --> decreases the blood flow
What is Von Willebraud Factor (vWF)
A protein
Where is vWF released from
Endothelial cells
When do endothelial cells release vWF
When collagen is exposed to blood
What is the function os vWF
Activate platelets and makes them sticky
How many clotting pathways are there
2
-Intrinsic
-Extrinsic
How many clotting factors are there
13
Where are clotting factors secreted from
The liver
What form are the clotting factors secreted in
zymogens
How are activated clotting factors annotated
With a lowercase a
ex: Ia IIa IIIa
What is Fibrin fiber
The mesh that stops the bleeding
What is the extrinsic factor called
Tissue injury pathway
What is the extrinsic pathway
Injury to the underlying tissue
Releases Tissue Thromboplastin factor 3
Factor 3 act 7 act 10
What is the intrinsic factor called
Contact activation pathway
What is the intrinsic pathway
Exposure to collagen to platelets
Activates Polyanions
Polyanions activate factor XIIa (12)
12 act 11 act 9 act 8 (9+8 act 10)
What is the goal of the intrinsic and extrinsic pathway
To produce Prothrombin Activator
What does Prothrombin activator do
Converts prothrombin to thrombin
What does thrombin activate
Platelets
What does thrombin cleave
Fibrinogen
Where does fibrinogen get released from
The liver
Fibrinogen is cleaved into
Fibrin
What type of Fibrin is fibrinogen cleaved into
Soluble Fibrin
How are Soluble Firbin strengthen into insoluble fibrin
Factor XIII
What is Factor XIII also known as
Fibrin stabilizing factor
Platelet Activators (5)
vWF
TxA2
ADP
Collagen
Thrombin
Platelet Suppressors (4)
PGI2
Prostacyclins
PGE2
NO
What are PGE2, NO, Prostacyclins
Vasodilators
What is the purpose of Fibrinolysis
Breakdown fibrin in a clot
What is the purpose of Tissue plasminogen Activator (TPA)
Dissolving blood clots
What does TPA do
Converts plasminogen into plasmin
What does plasmin do
dissolved fibrin fibers
What is the purpose of anticoagulants
Prevent frequent clot formation
What are the natural anticoagulants (3)
Heparin
Antithrombin III
Protein C
What factors activate Protein C
Thrombomodulin + Thrombin
What does Protein C inactivate
Factor 5
Factor 8
Why does Protein C inactivate factor 5 and 8
Induction anticoagulation
What does a deficiency of Protein C cause
Clot formation
What are the clinical assessments for hemostasis
Platelet count
Prothrombin time (PT) test
aPTT test
What is the normal platelet count range
150- 400
What pathway is associated with the PT test
Extrinsic Pathway
Which factor is associated with Pt test
7
Which factors can be tested with aPPT test
12, 11, 9, 8
Factor that lead to bleeding disorders (3)
1. Vessel wall abnormalities
2. Deficiency in platelets
3. Deficiency in coagulation factors
What factors can lead to the deficiency in platelets
1. Decrease in the productions of platelets
2. Decrease in the survival of platelets
What is caused by the decrease in the number of platelets
Aplastic Anemia
What is the most common cause of platelets deficiency
Decrease int he survival in platelets
What is thrombocytopemia
The decline in platelets due to reduced production or survival
What is the platelet count in
Less than 100,000
What happens when the platelet count is low
Spontaneous bleeding (below 20,000)
Decrease in platelet production is seen in
Aplastic anemia
What conditions impede on platelets ability to survive
ITP
TTP
HIP
How many days do platelets usually last in the blood
10 days
What is Chronic Throm. Purapura (ITP)
Autoimmune condition that attack the platelet membrane receptors
In what way are the membrane receptors impacted
Antibodies against glycoproteins are present on the platelet membranes
What causes Thrombotic Thromb purapura (TTP)
A defect in plasma enzyme ADAMTS13
What is the purpose of ADAMTS13 enzyme
Cleaves vWF and makes it less reactive
What happens in the absence of ADAMTS13
vWF is reactive and causes all the platelets to be used up
-Increases clot formation (even when not needed)
What is Heparin induced thrombin (HIT)
Drug induced thromb
What is the most common Thrombocytopenia
HIT
What happens in HIT
Immune response against Heparin-Platelet Factor 4 complex
What is the result of HIT immune rxn
Aggregation of platelets = thrombosis
What is the most common inherited bleeding disorder and what Isis prevalence
von Willebrand Disease
~1% prevalence
What is von Willebrand Disease
Inherited bleeding disorder
How heavy is the bleeding
Mild bleeding
What defects cause bleeding in von WIllebrand Disease
Platelet adhesion (stickiness)
Which vitamin activates prothrombin II and factors 7 9 10
Vitamin K
What can occur in Vitamin K deficiency
Bleeding disorders
How common is Vitamin K deficiency
Not common
How does Warfarin (Coumarin) impact vitamin K
Inhibits enzyme VKORc1 which decreases vitamin K levels
What does a deficiency in Factor 8 cause
Hemophilia A
What does deficiency in Factor 9 cause
Hemophilia B
Which form a hemophilia is the most common
Hemo A
Which hemophilia is called Christmas disease
Hemo B
What clotting pathway is impacted by the deficiency in factor 8 and 9
Intrinsic pathway
What kind of diseases are Hemorrhages A and B
X-linked recessive
What are the aPTT and PT levels in Hemorrhages A and B
Prolonged elevation of APTT and normal PT
Which hemophilia type may be helped by Vitamin K
Hemo B
What is Thrombosis
Formation of a blood clot
What are the (2) types of Thrombosis
Red
White
Which type of thrombosis leads to deep vein thrombosis (DVT)
Red thrombosis
What does White thrombosis lead to
Aggregation of platelets
Where is white thrombosis seen
Arteries
Where is red thrombosis seen
Veins
Which specific veins contain deep veins
Femoral
Iliac Veins
Pophiteal Veins
Where in the body does DVT form
The legs
Which thrombosis can and cannot form a embolus
Red- can
White- cannot
What is an embolus
A clot circulating in the blood
What needs to be activated for the red thrombus to form clots
Platelets and coagulation cascade need to be activated
thrombusWhat is needed to be activated for white thrombis to form clots
Platelets only
What are the risk factors for DVT (6)
Venous Stasis
Hypercoagulationability
Vessel wall injury
Cancer
Increased use of estrogen
Family history and age
What are the Vischows Triad risk factors
Venous Stasis
Hypercoagulationability
Vessel wall injury
What is Venous Stasis
Limited movement causing blood to sit
(ex- truck driver)
What is Vessel Wall Injury
Tissue to injury that triggers DVT
What is pulmonary embolism
Blood forms in the lungs
What are the consequences of a pulmonary embolism (6)
1. Hypertension
2. Right Heart failure
3. Hypoxia
4. Decreased partial pressure for CO2 and O2
5. Alveolar Collapse (where gas exchange takes place)
6. Partial lung collapse
What is the most common test for pulmonary embolism
D-dimer test
What is the D-dimer test
A highly sensitive, non specific test that rules out thromboembolism
by D-dimers
What does a negative test indicate
Individual does not have an embolism
What does a positive test indicate
Individual has a thromboembolism but additional testing is needed to
confirm DVT or PE
Why is a D-dimer test no specific
D-dimer levels increase in pregnancy and with age and may not be due
to DVT or PE