Haemostasis Basics Flashcards
Hemostasis
Physiological process that stops bleeding at the site of an injury while maintaining normal blood flow elsewhere in the circulation
How does intact endothelium prevent blood coagulation
Smooth
Expresses anticoagulants, tissue factor pathway inhibitor, thrombomodulin, heparin like proteoglycan, ectonucleotidase, platelet inhibitors, nitric oxide, prostacyclin
What are the stages of homeostasis
Primary
Secondary
Tertiary
What occurs in primary haemostasis
Vasoconstriction
Platelet plug formation
What happens in secondary haemostasis
Coagulation cascade
Deposition and stabilisation of fibrin
What happens in tertiary haemostasis
Dissolution of fibrin clot
Steps of haemostasis
Vascular spasm
Platelet plug formation
Clot formation
Clot retraction
Fibrinolysis
vascular spasm
trauma to vessel wall triggers smooth muscle contraction
Vascular spasm
Trauma to vessel wall triggers smooth muscle contraction
What causes smooth muscles to contract in vascular spasm
Local myogenic spasm
Endothelium and platelets release vasoconstrictor substances
Nervous reflexes
What are platelets derived from
Bone marrow megakaryocytes
What is the diameter of a platelet
1-4 um
What is the reference range for platelets in blood
140-450 x 10^9
What is the lifespan of a platelet
8-14 days
What system removes platelets from circulation
Reticuloendothelial system
What granules are part of a platelet
Alpha
Delta
Where does the activated coagulation cascade occur in secondary haemostasis
Platelet membrane
What do delta dense granules in platelets do
Facilitate platelet adhesion
Facilitate vasoconstriction
What type of platelet granules contain ADP and serotonin
Delta dense granules
Which platelet granules contain vWF, factor v, platelet derived growth factor, and high molecular weight kininogen
Alpha granules
What processes are platelet contractile proteins involved in
Platelet activation
Platelet aggregation
Clot retraction
Stages of platelet plug formation
Adhesion of platelets to damaged surface
Activation of platelets
Aggregation of platelets
What do platelets bind to in primary haemostasis
Exposed subendothelial collagen in vessel wall
Subendothelial bound vWF
What mediates platelet adhesion
Platelet receptors
What molecule can platelets directly adhere to
Collagen
What does platelet receptor GP1A bind to
Collagen
What does platelet receptor GP1B bind to
Von willebrand factor
What does von willebrand factor do
Binds to platelets allowing the platelet to bind to collagen
Exposes GPIIB and GPIIIa
Complexes with factor viii preventing its degradation
What cells synthesise von willebrand factor
Endothelial cells
Megakaryocytes
Where is von willebrand factor stored
Subendothelial matrix
Plasma
Platelet alpha granules
What exposes GPIIB and GPIIIA on platelets
Von willebrand factor binding
What stages of haemostasis are apeffected by von willebrand disease
Primary
Secondary
How is von willebrand disease inherited
Autosomal
What does von willebrand disease cause
Deficient or defective von willebrand factor
What type of von willebrand disease creates a mild deficiency
Type 1
What type of von willebrand disease creates defective protein
Type 2
What type of von willebrand disease has absent protein
Type 3
What 3 things occur when platelets become activated
Shape change
Increase surface receptor expression
Release granule contents
What causes platelets to change shape when they activate
Release of intracellular Ca2+ stores
What are the cytoplasmic projections on activated platelets called
Pseudopods
What substances do platelets release when activated
ADP
Serotonin
Thromoxane A2
What receptors does ADP released from platelet granules bind to
P2Y1
P2Y12
Which receptor causes intracellular ca2+ store release, platelet shape change, and transient aggregation when ADP binds to it
P2Y1
What happens when ADP binds to P2Y12
Decreased adenyl cyclise -> decreased cAMP -> sustained aggregation
Sustained platelet aggregation involves which receptor? P2Y1 or P2Y12
P2Y12
What does thromoxane A2 do
Activates other platelets to induce platelet aggregation
Increases cytosolic calcium levels
Diffuses out of cell to enhance vasoconstriction
What molecule mediates platelet aggregation
Fibrinogen
How does fibrinogen form the platelet plug
Binds to GPIIb/IIIa on adjacent platelets
Where is fibrinogen released from for platelet aggregation
Alpha granules
How is primary haemostasis tested
Bleeding time
What is a normal bleeding time result
1-3 mins
What platelet count shows thrombocytopenia
<150000 cells/um
Petechiae
Tiny purplish spots of blood in skin or mucosa
What causes thrombocytopenia
Decreased platelet production
Increased platelet destruction
Increased platelet sequestration
Bernard soulier syndrome
Quantitative or qualitative defects of platelet GPIb
Glazmann’s thrombasthenia
Deficiency/ defective platelet GPIIB/IIIa
What occurs in secondary haemostasis
hemostasis plug formed by trapping RBCs in loose mesh of fibrin
How many pathways are involved in thrombin formation
3 - extrinsic intrinsic common
What does thrombin do
Activates fibrinogen to fibrin
Which vitamin is needed for maturation of factors 2, 9, and 10
Vitamin K
Which pathway extrinsic coagulation
Intrinsic
What is tissue factor
Integral Membrane protein in sub-endothelial tissue released in response to tissue injury
When is tissue factor releases
Tissue injury
What does FVII become when it binds to tissue factor
FVIIa
What substances from the extrinsic pathway act on factor X to activate it
Factor VIIa, thromboplastin, calcium, phospholipids
Where does factor Xa form a prothrombinase complex to generate thrombin
Extravascular tissue
How is the extrinsic pathway dampened
Inhibiting factor VII
Which factors are in the extrinsic pathway
7, 3(tissue factor)
What factors are involved in the intrinsic pathway
12, 11, 9 8
What molecule activates factor viii
Thrombin
What molecules activate factor x from the intrinsic pathway
Factor IXa, factor VIIIa, platelet phospholipids, calcium
What is factor VIII found in a complex with
Von willebrand factor
What is required for sustained thrombin activation
Activation of intrinsic pathway
Which pathway activates the intrinsic pathway
Extrinsic pathway
What do factor V, factor X, and tissue phospholipids combine to form in the common pathway
Prothrombin activator
What does the prothrombin activator do in the common pathway
Splits prothrombin to thrombin
Which ion is needed for prothrombin activator to split prothrombin to thrombin
Calcium
What molecule does thrombin act on to form fibrin
Fibrinogen
What molecules does thrombin act on
Fibrinogen
Factor VIII
Which molecule activates factor VIII
Thrombin
What prevents aggregation of fibrinogen molecules
Fibrinogen molecules have Strong negative charge
What causes blood to coagulate
Soluble fibrinogen converted to insoluble fibrin by thrombin
What bonds form between fibrin monomers to form a soft clot
Hydrogen bonds
What molecule mediates formation of a hard clot
Factor XIII
What bonds form in a soft clot to make it a hard clot
Covalent bonds
What pattern of inheritance is haemophilia
X linked
Which factor is affected in haemophilia a
Viii
What factor Is affected in haemophilia B
Factor IX
What happens to a clot after formation
Contraction
What causes clot contraction
Platelet contractile proteins
What do platelet contractile proteins do
Compress fibrin mesh work to retract clot
Pulls edges of cut together
What molecule breaks down fibrin to fibrin degradation products
Plasmin
What activates plasminogen to plasmin in the fibrolite pathway
Plasminogen activator
What measurement is uses to diagnose thrombosis
D-dimer concentration
What is the D dimer reference range
0-300 ng/ml
What tests are used to asses haemostasis
Blood count/ platelet count
Bleeding time
Clotting time
Prothrombin time
Activated partial thromboplastin time
What is the expected result for clotting time
3-10 minutes
What is the expected result for prothrombin time
12-15 secinds
What is the expected result for activated partial thromboplastin time
30-50 seconds
