Hematology -coagulation cascade Flashcards
What are the steps for coagulation?
- vessel spasm
- platelet activation
- Coagulation
- Clot retraction and repair
- fibrinolysis
What causes vascular spasm when there is an injury?
- damaged endothelial cells release endothelin, causes myogenic contration (pain reflex) causing smooth muscle contraction and resulting in vessel constriction
- serotonin and TXA2 cause smooth muscle to contract
What causes the increase of megakaryocytes?
stromal cells produce thrombopoetin (TPO) which increases the production of MKC
What are the surface proteins on platelets?
- GP 1b-1X-V (vWF binds here)
- GP 2b/3a (fibrinogen binding site)
- P2Y12 ( ADP binding side)
- TPa (TXA2 binding site)
- GP 1a, GP6 (collagen binding site)
What are the steps for platelet activation?
- vWf and collagen are released from the damaged endothelium
- vWf binds to GP 1b-1x-V on platelet surface activating the platelet
- Activated platelets secret ADP and TXA2 which binds to P2Y12 and TPa respectively, recruiting more platelets to to bind to them. Also activates GP 2b/3a to bind fibrinogen and create cross links with other proteins and aggregating them to form a platelet plug
What step of platelet activation does aspirin block?
- blocks the activation/formation of TXA2
What step of platelet activation does clopidogrel block?
- blocks the ADP receptor, preventing the activation of ADP and further platelet recruitment
What step of platelet activation does Abciximab block?
- blocks GP 2b/3a receptor therefore preventing fibrinogen cross link with other platelets
What contractile proteins are used in clot retraction and repair?
- myosin
- actin
- released by local tissue macrophages
What initiates fibrinolysis?
- endothelium releases tPA (tissue plasminogen activator) some of which is inhibited by PAI (plasminogen activator inhibitor). The tPA activates plasminogen and plasmin formation which breaks down blood clot. The break down product of blood clot is FDP (fibrin degradation product).
What test evaluates the coagulation of the intrinsic pathway?
- Activated partial thromboplastin time (aPTT)
- evaluates coagulation factors (12, 11, 10, 9, 8, 5, 2, 1)
What test evaluates the coagulation of extrinsic pathway?
- prothrombin time (PT) (time it takes for fibrin clot to form)
- evaluates factors 7, 10, 5, 2, 1
What is the bleeding time test?
- evaluates the time it takes for someone’s cut blood vessel to constrict and how long it takes for platelets to clot
What pathways do the heparin and warfarin affect?
- heparin affects intrinsic pathway
- warfarin/coumadin affects the extrinsic pathway
How does vitamin K affect the coagulation cascade?
Vitamin K is necessary for the extrinsic pathway. Factor 7 is vitamin K dependent. Without vitamin K, there will be no activation of the extrinsic pathway
In what kind of blood disorder would you expect to see petechiae in?
- disorders of platelets or vessels
In what blood disorder would you expect to see deep dissecting hematomas?
- disorders of coagulation
In what blood disorder would you expect to see hemarthrosis?
- hemarthrosis (bleeding into the joint)
- would be seen in disorders of coagulation
Can coagulation disorders be hereditary?
some coagulation disorders such as hemophilia A and B and vwf disease are hereditary
What clotting factors abnormality can prolong PTT?
- Factors 11, 9 and 8
What clotting factors abnormality can prolong PT/INR?
- Factor 7
What clotting factors abnormality can prolong PT and PTT?
- Factor 10, 5, 1, 2
What is the difference between thrombophilia and hemophilia?
- thrombophilia = increased tendency to form clots
- hemophilia = increased tendency to bleed
What are some of the causes for inherited thrombophilias?
- deficiency of coagulation inhibitors (protein S or C deficiency, antithrombin deficiency)
- Dysfunction of coagulation factors (dysfibrinogenemia/abnormal form of fibrinogen, factor V leiden, prothrombin gene mutation)
What are some of the causes of acquired hyper-coagulable states?
- malignancy
- surgery
- immobilization
- trauma
- pregnancy
What proteins inhibit platelet activation?
- PG12 (prostacycline)
- NO (nitric oxide)
What proteins inhibit thrombin?
- thrombomodulin
- heparin sulphate
What inhibits fibrin and other clotting factors?
- tissue plasminogen activator
What proteins/factors inhibit blood clot formation in healthy blood vessel?
- CD39 (inhibits ADP)
- PG12 and NO
- thrombomodulin
- C-protein (inhibits thrombin)
- Heparin sulphate (inhibits Xa and thrombin)
- plasmin (inhibits fibrin)
