expressed on intact endothelial cells. Binds with thrombin to make it able to activate Protein C.
Inhibitor of coagulation by cleaving active factor 5 and 8.
Tissue-type plasminogen activator, turns plasminogen into plasmin so it can break down fibrin.
von Willebrand Factor produced by platelets and endothelium. Binds to exposed ECM, and polymerizes to bind to platelets in blood, to bind them to ECM.
Also carried in blood bound to factor 8, thrombin will cleave vWF/F8 and activate 8.
PAI (plasminogen activator inhibitors)
secreted by damaged endothelium, to prevent fibrin breakdown.
released from endothelium immediately after damage, potent vasoconstrictor to limit immediate blood loss.
the initial clot formed from platelets bound to vWF and the ECM.
the clot formed from fibrin polymerization.
produced in arachidonic acid pathway of platelets, facilitates platelet aggregation.
adhesion of platelets to leukocytes.
Buccal-mucosal bleeding time. Evaluates platelet function, but not very sensitive. > 4-5 min in dogs is prolonged, > 3min in cats. Elevated with vWF disease, thrombocytopenia, thrombocytopathia.
C/S of vWD
NO PETECHIAE!! Otherwise bleeding from mucosal surfaces (gingiva, hematuria, epistaxis, GI bleeding), post-sx bleeding. Sometimes no hx of bleeds.
Decreased platelets <20 x 10(9) /L get spontaneous bleeding. DO see PETECHIAE, suffusive hemorrhage, bleeding into body cavities, hematomas.
Causes: rare for inherited, acquired include increased destruction (ie: immune-mediated) or decreased production (ie: virus affecting bone marrow).
Tests: low platelet count, prolonged BMBT, normal PT/PTT.
Disorder of platelet function.
Similar C/S and tests to thrombocytopenia.
Inherited rare (ie: Chediak-Higashi syndrome, def'c of dense granules). More common are acquired (ie: drugs like aspirin).
"things that help coagulation and repair"
Platelet and transforming growth factors.
"things that help aggregation"
Disseminated intravascular coagulopathy
Dx: CBC see low platelets. BMBT/PT/PTT all prolonged, FDP-D dimer present, Antithrombin III decreased.
Made in liver, VitK dependent.
Activated upon exposure to tissue factor.
Activates factor 9 and 10.
Made in liver, VitK dependent.
Activated from F7a/TF complex.
With factor 5, Ca2+ and phospholipid from platelets will convert prothromin to thrombin.
From platelet granules, combines w/ F10a and Ca2+ (also needs platelet phospholipid) will turn prothrombin into thrombin.
TF exposed, F7 binds. Activates F9 and 10. F10a activates F5 (and Ca2+/PLipid), makes a bit of thrombin.
Thrombin does "lots of stuff!"
- will activate a whole bunch more platelets, so get more F5 and F8 secreted from platelet granules.
- Activate F11.
- Cleaves vWF from F8 and activates 8.
- Activates more F5.
In platelet alpha granules, also in circulation bound to vWF.
Activated by thrombin.
Binds to F9 and activates more F10 (also needs Ca2+ and platelet PLipid) to greatly increase the amount of thrombin made.
Activated by F7 and F11.
Binds to F8 and together activates more F10 to make lots of thrombin.
Churning out TONS of thrombin, b/c every activated platelet can make lots!
F11 that was activated by thrombin can go and activate more F9, with the F9a from initiation, now lots of F9a that can bind with F8a on platelet surface. The F9a/F8a activates more F10, and along with F5a get WAY more thrombin.
activated partial thromboplastin time. Uses F12 (Hegeman factor) to initiate the "intrinsic" system.
One-step prothrombin time. Uses tissue factor to initiate the "extrinsic" system.
Converts fibrinogen to fibrin.
Activates other clotting factors (F11, F5, F8)
Activates endothelium to secrete growth factors for healing.
Activates endothelium to express leukocyte adhesion factors.
Don't forget the "forgotten factor". Cross-links the fibrin polymers to stabilize the fibrin clot.
Tissue-factor pathway inhibitor: expressed by endothelial cells, binds TF/F7 when it is activating F10, limits coagulation to area it is needed.
Produced by endothelium and liver. Inactivates majority of thrombin as well as F9-12. Enhanced by interaction w/ heparin (endothelial or exogenous). Defc'n makes animal hypercoagulable, results from loss (protein-losing nephropathy/enteropathy), decreased production (liver dz), or consumption (DIC).
Protein C/Protein S
Thrombomodulin on intact endothelium binds with thrombin, activates PC. This joins w/ PS to inactivate F5 & F8.