Clotting & Blood flow I&II Flashcards
can platelet activation alone stop a large bleed?
no - need help from activation of coagulation cascade
role of fibrinolysis
removes the blood clot to restore blood flow to the repaired blood vessel
collagen
plays a role in platelet aggregation and activation
-normally hidden under endothelial lining
hemostasis
prevents blood loss from broken blood vessel
- primary –> vascular spasm, platelet plug
- secondary –> blood coagulation (clotting)
platelets
formed from megakaryocytes in bone marrow
- no nuclei, have mitochondria for ATP
- removed by tissue macrophages
prostacyclin (PGI2) and NO
inhibit platelet activation and aggregation
- inhibited by COX2
- vasodilate to increase laminar blood flow or directly prevent platelet aggregation
heparan sulfate
activate antithrombin preventing blood clot
thrombomodulin
inhibit thrombin activation preventing coagulation
tissue factor inhibitor
inhibit tissue factors preventing coagulation
2 ways to inhibit platelet aggregation?
- endothelial integrity - collagen hidden
2. laminar flow by PGI2 and NO
role of ADP in platelet aggregation
needed for aggregation
- ectonucleotidases –> break nucleotides –> no ADP or platelet aggregation
- adenosine –> compete w/ ADP binding spot –> inhibit aggregation
GP 1b-5-6
receptor on platelet - binds to vWF attached to collagen
-do not recognize free vWF
GP 1a/2a and GP 6
bind collagen directly
-target for therapy
GP 2b/3a
most important - cannot be active all the time
-bind FREE vWF and fibrinogen to begin platelet aggregation
thromboxane A2
secreted from activated platelets but also activates platelets (+ feedback)
-made from COX –> NSAIDs inhibit synthesis and coagulation
alpha vs. dense granules
release contents when platelets are activated
- alpha = release fibrinogen, vWF, coagulation factor 5
- dense = release ADP, Ca++
von willebrand factor
made in multimers
- deficient in ADAMTS13 –> outoaggregation of platelets leading to thrombosis and thrombotic thrombocytopenia purpura (TTP)
- binds collagen for GP 1a-5-9
- increase half life of factor 8
Ca++ during platelet activation
activation increases Ca++ levels –> myosin/actin interaction –> filopodial shape to clot easier and increase SA for binding
-do not coagulate without Ca++
what results in the binding of ADP (to P2Y receptor) or thromboxane A2?
activate GP 2b/3a –> bind fibrinogen and vWF –> meshwork for platelet aggregation (platelet plug)
-GP 2b/3a inactive form until needed
role of fibrinogen
connects the platelets together forming a weak plug
-GP 2b/3a binds the free fibrinogen and vWF to aggregate the platelets - does not need collagen
what is the goal of coagulation cascade?
convert fibrinogen to fibrin and cross-link to make stronger
- classical (intrinsic and extrinsic)
- contemporary
which factor combines with 11a to break 10 to 10a?
factor 8a
-8a + 11a forms intrinsic X-ase
which factor combines with 10a converting prothrombin to thrombin?
5a
5a + 10a forms prothrombin complex
what combines with tissue factor in extrinsic pathway?
7a
TF + 7a forms extrinsic X-ase which breaks 10 to 10a
hemophilia
occurs with tissue factor mutation
-cannot do intrinsic or extrinsic pathways –> no coagulation
what is required for platelet aggregation interconnecting with coagulation cascade?
- neg charge surface on platelets from phospholipids
- Ca2+ for linking together
role of thrombin
- covert fibrinogen to fibrin
- activate tissue factor 13 to cross link fibrin (strong)
- also activate tissue factor 5,8,11
- activates intrinsic mechanism
what forms intrinsic tenase (Xase)?
factor 9a and 8a
-activate 10a
what forms extrinsic tenase (Xase)?
tissue factor and 7a (factor 3)
-activate 10a
what forms prothrombinase?
factor 10a and 5a
-convert prothrombin to thrombin
contemporary model
-extrinsic (initiation) activates intrinsic (amplification) after producing thrombin
what does thrombin activate in the contemporary pathway?
- 11 –> 11a
- 8 –> 8a combining with 9a (intrinsic Xase)
- 5 –> 5a
- increase platelet activation, fibrinogen, vWF
difference b/w contemporary and classical model
- contemporary - form thrombin 1st through extrinsic model then activate intrinsic
- classical - do not need thrombin to activate intrinsic (have factor 12)
protein C
thrombin inhibition
- thrombomodulin (endothelium) binds with thrombin –> activate protein C –> inactivate 5a and 8a
- requires protein S cofactor
antithrombin
normal endothelium
-bind to heparan sulfate to inactivate thrombin, 9a, 10a, 11a –> stop coagulation
tissue factor pathway inhibitor
normal endothelium
-inhibit 10a and 12a tissue factor complex –> stop coagulation
role of Ca2+ in coagulation
- platelet aggregation, change shape, and forming complexes
- hemophilia with hypocalcemia
role of vitamin K in coagulation
coenzyme for synthesis for clotting factors
- deficiency –> bleeding
- warfarin can inhibit recycling
role of plasmin
degrades the blood clot by chewing off fibrin –> forms D dimers (high levels in DVT)
-recombinant plasminogen activators to prevent blood clots
petechiae
common platelet deficiency, not common coagulation deficiency
-platelet aggregation stops the bleeding for leaky capillary
thrombocytopenia vs. thrombocytosis
thrombocytopenia = bleeding tendency thrombocytosis = coagulation tendency
prothrombin time
tissue factor + phospholipids + Ca2+
- INR - standardization of plasma to see how good tissue factor is working
- fast coagulation
- use if on warfarin or suspected vit. K deficiency
partial prothrombin time
phospholipids + Ca2+ + silica
- no tissue factor or standardization –> rely on intrinsic pathway
- slower coagulation
