Hemostasis and Thrombosis Flashcards
purpose of hemostatic system
- helps to ensure that blood is confined to and flows freely within the circulatory system
how the normal hemostatic system limits blood loss
- precisely regulated interactions between components of vessel wall, circulating blood platelets, and plasma proteins
common clinical manifestations of many diseases
- hemorrhage
- intravascular thrombosis
- embolism
the two mechanisms underlying the arrest of bleeding
- vasoconstriction
- formation of a hemostatic plug
vasoconstriction
- narrowing of blood vessels to help prevent further blood loss
formation of a hemostatic plug
derived from
- thrombus or clot
- derived from platelets and fibrin strands in which RBCs and WBCs are trapped
hemostasis is
- the arrest of bleeding following vascular injury
hemostasis is dependent on interactions between
- platelet adhesion and aggregation
- endothelial cell function
- blood coagulation system
- clot lysis (fibrinolysis) system
primary hemostasis
secondary hemostasis
tertiary hemostasis
- aggregation/endothelium
- coagulation
- fibrinolysis
components of primary hemostasis
- blood vessels
- platelets
blood vessels designed for
- smooth movement of blood from the heart to the tissues and back
the surface of blood vessels is considered to be
- an anticoagulant surface
the purpose of blood vessels being an anticoagulant surface
- prevents a clot from forming on their surface
platelets help to
- maintain the integrity of the vessel lining
- plug any rupture in the circulatory vessels
normal intimae that suppress hemostasis
- prostacyclin
- heparan sulfate
- tissue factor pathway inhibitor
- nitric oxide
- thrombomodulin
to suppress hemostasis you need Pretty Huge TNT
platelets are formed from
- the cytoplasm of bone marrow megakaryocytes
size of platelets
- smallest of the blood cells
normal platelet count
- 150-450x10^9 per liter
normal platelet lifespan
7-10 days
shape of platelets
- disc shaped
structure of platelets
that reflects?
- complex internal structure
- reflects the specific hemostatic functions of the platelet
flow of hemostasis
- vascular integrity breached
- procoagulation (initiate)
- anticoagulation (stop)
- fibrinolysis (clear out)
- vascular integrity restored
consequences of either abnormal or uncontrolled hemostasis
- bleeding (hemorrhage)
- thrombosis (venous or arterial)
blood coagulation system composed of
and they are called
- a series of specific plasma proteins
- coagulation factors
how coagulation factors interact
- in a highly ordered sequence
ultimate object of coagulation factors
- convert soluble fibrinogen into insoluble fibrin
- stabilize primary hemostatic plug
coagulation factors referred to by
- Roman numerals
coagulation factors named by
- order of discovery
coagulation factor 1
- fibrinogen
FOOLISH
coagulation factor 2
- prothrombin
PEOPLE
coagulation factor 3
- tissue thromboplastin (factor)
TRY
coagulation factor 4
- calcium
CLIMBING
coagulation factor 5
- labile factor
LONG
coagulation factor 6
- not used
coagulation factor 7
- stable factor
SLOPES
coagulation factor 8
- anti hemophilic factor
AFTER
coagulation factor 9
- Christmas factor
CHRISTMAS
coagulation factor 10
- stuart factor
SOME
coagulation factor 11
- anti hemophilic factor C
AWFUL HUMANS
coagulation factor 12
- hageman factor
HAVE
coagulation factor 13
- fibrin stabilizing factor
FALLEN
secondary hemostasis composed of
- zymogens/active enzymes
- cofactors
- non-protein cofactors
- fibrinogen and factor XIII
zymogens/active enzymes
- vitamin K dependent
- vitamin K independent
vitamin K dependent factors
- 2
- 7
- 9
- 10
vitamin K independent factors
- 11
- 12
- 13
cofactors
- factor 5
- factor 7
- tissue factor
- von Willebrand factor
non protein factors
- calcium
- phospholipid surfaces
calcium found where
- in blood
phospholipid surfaces found where
- from cells
purpose of thrombin
- fibrinogen -> fibrin
purpose of activated factor XIII
- cross link fibrin
plasma concentration of factor 7
0.5
half life of factor 7
3-6 hours
plasma concentration of factor 8
0.1-0.2
half life of factor 8
8-12 hours
trauma to blood vessel exposes
- collagen and tissue factors
trauma to blood vessel triggers
- platelet adhesion and aggregation
primary hemostasis process
- injury exposes collagen
- vWF
- initial hemostatic plug
activated platelets release
- granule contents
granule contents examples
- ADP
- TXA2
purpose of ADP, TxA2
- recruit more platelets
- promote aggregation
platelet glycoprotein IIb/IIIa type of receptor
- integrin receptor
platelet gycoprotein IIb/IIIa function
- adheres to fibrinogen
- enhances aggregation
- stabilizes thrombus
activated platelets also release
- coagulation factors
- promote coagulation process
growing platelet thrombus stabilized by
- fibrin
what is trapped in the thrombus
- RBC/WBC
what do endothelial cells release
- prostacyclin
- nitric oxide
purpose of releasing prostacyclin and nitric oxide
- inhibit further platelet aggregation
critical role of platelets in
- primary hemostasis
critical role of blood coagulation proteins
- secondary hemostasis
extrinsic pathway of coagulation cascade
- VII activates TF(Tissue Factor)+VIIa
- TF+VIIa -> X
- X->Xa+Va
- Xa+Va activates Prothrombin-> Thrombin
- Thrombin activates Fibrinogen->Fibrin
intrinsic pathway
- XIa activates IXa and VIIIa
- IXa and Vllla -> Xa+Va
- Xa+Va activates Prothrombin-> Thrombin
- Thrombin activates Fibrinogen->Fibrin
other part of pathway
- HMWK/Prekallikrein activates XII->XIIa
- XIIa activates XI->XIa
- XI activates IX->IXa for intrinsic pathway
what activates Va
- V
platelets primary stage
- subendothelial collagen
- vWF -> platelet adhesion
- platelet adhesion -> platelet activation
- platelet activation -> platelet aggregation by ADP TxA2
Fibrinolysis tertiary pathway
- plasminogen-> plasmin by tPA
- fibrin -> fibrin degradation products by plasmin
the end of blood coagulation result
- thrombus (clot)
- “hemostatic plug”
thrombus formation following vessel wall injury
- vascular injury
- platelet activation
- activation of coagulation
- thrombin forms thrombus
initiation steps
- vascular injury
- platelet activation
- activation of coagulation
amplification steps
Thrombin feedback to amplify and create a lot more thrombin!
burst steps
Creates massive amount of thrombin to cleave fibrinogen.
factor VIII inheritance
- X-linked
factor IX inheritance
- X-linked
fibrin monomer polymerizes
- end to end
- side to side
- in nonenzymatic process
stable fibrin clot formed when
- fibrin-stabilizing factor (13) covalently links the adjacent domains of three fibrin monomers through gamma chains
what type of molecule is fibrin stabilizing factor
- factor XIII
What activates XIII to XIIIa
- Thrombin
fibrinogen molecule formed from
- three protein molecules present in the molecule in pairs
three protein molecules
- A alpha
- B beta
- gamma
the central part of the fibrinogen molecule is the
- E domain
the distant ends of the fibrinogen molecule are the
- D domain
thrombin action on fibrinogen
- cleaves two small activation peptides from fibrinogen to form fibrin
what is D dimer
- degradation product of cross linked fibrin
what does D dimer reflect
- ongoing activation of the hemostatic system
D dimer levels of healthy individuals
- low
elevated D dimer levels could indicate
- ongoing activation of hemostatic and thrombolytic system
coagulation complex that provides in vivo trigger to initiate blood clotting
- tissue factor/VIIa
anticoagulant property of thrombin
- complex with thrombomodulin