hemostasis/ clotting Flashcards
hemostasis
process aimed at closing a leak in vascular system, prevent loss of blood
3 phases
hemostasis 3 phase and time
rest of process and time
1) vasoconstriction (immediate)
2) plt plug (in secs)
3) fibrin clot (in mins)
clot retraction 20min-1h
healing 1-2wks
what is Vasoconstriction
- Vascular spasm, SM contract
- Initiated by sympathetic nerves
- Mediated by vascular smooth muscle cells
- Correlate with damage
- Lasts for 30min ~ hrs
vasoconstriction function
○ Provide time for PLT and coagulation phase
○ Endothelial cells of opp side stick tgt
○ Reduce blood loss, most times not suff
○ Endothelial cells contract, expose basal lamina
PLT phase
Damage to endothelial wall exposes collagen
○ Plt stick
○ Plt secrete contents
○ More plt stick
○ Plt plug (+VE feedback cascade)
1. Plt adhere to exposed collagen fibers, activated 2. Release granules with PLT agonists 3. Plt aggregates to form plug, release more plt, attract subs
PLT main function
○ Closure of leak by formation of temp patch
○ Release chemical mediators, regulate blood clotting
○ Contraction of blood clot
how to prevent unintentional PLT activation/ aggregation
(endo cells)
Intact endothelial cells release NO, Prostacyclins
Inhibit unintentional PLT activation/ aggregatiom
how does PLT adhesion occur
Von Willebrand’s Factor (vWF)
○ Plasma protein produced by PLT
○ Allow PLT bind to exposed collagen through glycoprotein receptors
- Adhesion leads to Plt activation
□ Morphological change
- Trigger release of granules for aggregation
how does PLT aggregation occur
PLT agonists
ADP
□ Attract, activate more plt
Thromboxane A2
□ Promote aggre & further vasoconst
Fibrinogen links plt through glycoprotein receptors
□ Fibrinogen links stabilise by factor XIII
3) Formation of fibrin mesh steps
- Thrombin converts
○ Fibrinogen –> fibrin - Crosslink to form fibrin mesh
○ Pulls PLT tgt, mesh over PLT plug over wound - Factor 13 to make plug stronger
Thrombin activities ** key regulator of hemostasis
○ Enhance own generation (+ve feedback loop)
○ Factor XIII activation (stabilise fibrin mesh)
○ PLT activation
○ Release PF3 from PLT (activate intrinsic pathway)
coagulation cascade EXTRINSIC
- Vessal injury
- Exposed molecules of vessel wall release TISSUE FACTOR/ THROMBOPLASTIN
1) Allow Factor 7 (VII) activation to VIIa
2) VIIa activates factor X (with Ca2+)
3) Xa activates prothrombin –> thrombin (with Ca2+, Va)
extrinsic requires
tissue factor (thromboplastin)
VII
Ca2+
intrinsic pathway (slows - mins, involves many enzymes)
Various pathway, chains reaction, activation cascade
Form complex with additional cofactor to activate factor 10
1) exposed to collagen fibers - damage inside blood vessels/ foreign surfaces (glass)
2) plt phospholipids conformational change (activates XII –> XIIa)
3) XIIa activate XI –> XIa
4) XIa activate IX –> IXa (with ca2+)
5) IXa activate X –> Xa (with Ca2+, VIIIa)
intrinsic pathway need
plt phospholipid
XII (12)
XI (11)
IX (9)
Ca2+
VIIIa, Va
common pathway
x – > Xa (Ca2+, Va or VIIIa)
by Xa: prothrombin –> thrombin +Ca2+ + Va
by thrombin: fibrinogen –> fibrin
fibrin + XIIIa + thrombin
clotting factors
foolish people try climbing fast
I,II,III,IV,XIII
I – fibrinogen
II – prothrombin
III – tissue factor
IV – Ca2+
V –
VII –
VIII –
IX – plasma thromboplastin
X –
XI – plasma thromboplastin
XII –
XIII – fibrin stabilising
clotting factors feature
clotting factors require vit K (II, VII, IX, X)
all produced by liver
Clot retraction
Stabilise clot by squeeze serum from fibrin clot
Further closure of leak
Repair
- PDGF stimulates vascular SM cells to build new vessel wall
- endothelial cells multiply and restore inner endothelial lining (Stimulated by VEGF)
Regulate blood clotting
anti-coagulants (prostacyclin, serotonin, blood clots)
(Smooth endothelial surface, antithrombin III, heparin, thrombomodulin, tissue plasminogen activator)
VS
pro coagulants (tissue factor EXT, collagen XIII INT, collagen)
Prostacyclin
PG produced by intact endothelial cells
- Inhibit plt activation
- Limit spread of blood clotting
Serotonin
High conc inhibits ADP activity (ADP is plt agonist, that attracts and activates more PLT)
Serotonin
High conc inhibits ADP activity (ADP is plt agonist, that attracts and activates more PLT)
Blood clot
Limit spread of thrombin, other procoagulants
artificial anticoagulants
Chelators (citrate, EDTA)
vit K antagonists (warfarin, coumarin)
DOAC - CLC
FIBRINOLYSIS is to __
- Dissolution of clots
- Constantly at low lvl (balanced with coagulation) by eqm of thrombin + plasmin
fibrinolysis steps
- Plasminogen trapped inside clot
i. Plasma protein and protease precursor made by liver - Surrounding tissue and vascular endothelial cells release
i. Tissue plasminogen activator tPA - Cleaves inactive plasminogen –> plasmin
i. Digest fibrin, dissolve clot - Macrophage remove remains of clot
Blood clotting disorders, unable to clot
hemophilia (X linked)
liver disease
vit K deficiency
thrombocytopenia
blood clotting disorders (too much clot)
thrombosis
thromboembolism
strokes & Afib
hemophilia (X linked)
○ Excessive bleeding after injury
○ Hereditary hemophilias, lack of clotting factors
- Hem A: lack factor VIII
□ Use recomb factor
- Hem B: lack factor IX (ext)
- Hem C: lack factor XI (ext)
Liver disease
Hepatitis, hepatocell carcinoma, liver cirrhosis = Inability to produce
- to synthesise procoagulant (tissue factors, collagen)
- Most clotting factors produced by liver
- Produce bile, absorb fat and vit K
Vit K deficiency
○ Essential for synthesis of several clotting factors
○ 1/2 from gut bact (methionine), 1/2 diet
○ LT Abx use results in vit K deficiency (cephalosporins) and bleeding disorders
Thrombocytopenia
○ Circulating PLT too low (<50 million/mL)
- Normal 200-500mil/mL
○ Spontaneous, widespread hemorrhage, visible by small purple spots on skin
○ Cause by:
-Damage to bone marrow (Malignancy, chemo)
= Tx with fresh whole blood / plt transfusion
Thrombosis
○ Inapp clotting
- Roughened surface of vessel, endothelial cell injury, disturbed blood flow
Thrombus: clot develops and persists in unbroken blood vessel
Thrombi can block circ, result in tissue death
- Coronary: thrombus in heart = Lead to HA
- Cerebral: thrombus in brain = Lead to stroke
Thromboembolism
○ DVT. Embolus: thrombus free float in blood stream
-Impair body ability to obtain O2
-Cerebral: stroke
-Cardiac: HA
○ Tx: tPA, heparin + vit K antagonist
○ Risk factors: Smoke, dehydration, oral contraceptives, polycythemia, surg, immobility
Freq: 1 in 1000, mortality 1-5%
Strokes and Afib
○ Afib: cause blood to collect in heart, clot formation, incr risk of strokes
○ Hemorrhagic stroke: need blood to clot
○ Ischemic stroke: need dissolve the clot
blood coagulation tests
1) partial thromboplastin time – INT and COMMON
2) prothromnin – citrated plasma + Ca + tissue factor (EXT and COMMON)
3) INR: ratio of PT/ population
norm = 0.9-1.3
PTT measures
I, II, V
intrinsic: VIII, IX, X, XI, XII
monitor heparin
range: 25-39s
PT measures
factors: I, II , V
EXT: VII, X
monitor warfarin
range: 12-15s
