Coagulation Overview Flashcards
primary hemostasis requires ___, ____ ___ componenets and ___ ___ factor
platelets, blood vessel components, and von willebrand
they form a platelet plug which adheres to blood vessel walls.
temporarily stops bleeding immediately.
what is secondary hemostasis
clotting factor take part in a cascade of chemical reactions that eventually create a mesh of fibrin within the blood
- coagulation cascade.
the fibrin mesh (activated by coagulation cascade) strengthens the underlying platelet plug.
all coagulation factors are made in the liver except ____
except factor 8
3 main mechanisms to stop clot formation (preventing coagulation from happening everywhere)
tissue factor pathway inhibitor (TFPI)– inhibits factor 7, TF, and 10
antithrombin: degrades thrombin, factor 9, 8, 11, 12 –> intrinsic pathway
activated protein C- degrades factor 5 and 8 (needs protein S)
function of antithrombin– which clotting factors does it affect?
degrades thrombin, factor 9, 10, 11, 12 –> intrinsic pathway
primary vs secondary hemolysis
both happen to remove the clot to restore the patency of the blood vessel as part of the wound healing process.
primary: intrinsic processes: plasmin activates and cleaves and degrades insoluble fibrin
seconday: acquired process: breakdown of clots due to a medication, medical disorder ex/ DIC
most common congenital cause of excess bleeding
con willebrand disease
most common acquired cause of excess bleeding
medications like NSAIDS and antiinflammatories and ginkobiloba
first line lab investigations when worried about a coagulation disorder
CBC, aPTT, INR, ferritin
Vwf antigen, factor 8, and concentration of Vwf.
measuring disorders of primary hemostasis
primary hemostasis= bleeding in platelet function disorders (not the clotting cascade per se)
therefore: cbc and pbs (measure the number of platelets
platelet function test/closure time, platelet aggregation studies, flow cytometry, VWF:ag and WVF activity with factor 8(since Vwf is part of primary hemostasis)
Why is it possible that VWF may be a false negative despite a person having a primary hemostasis disorder?
because VWF and factor 8 are acute phase reactants and can increasing during stressful situations.
If suspicious history is obtained, repeated testing may be
required to ensure diagnosis is not missed
measuring disorders of secondary hemostasis
secondary hemostasis uses the clotting cascade.
- primary hemostasis is unaffected therefore temporary platelet plug is formed so bleeding may stop temporarily.
PT/INR, PTT, TT, fibrinogen.
additional testing for specific coagulation factor levels, 13.
what factors does the PTT inherently measure?
intrinsic pathway
12, 11, 9, 8
what factors does PT inherently measure?
extrinsic pathway
7, TF.
what are causes for prlonged PT/INR
PT = extrinsic pathway affected.
therefore, assuming PTT is normal (and intrinsic pathway not affected),
factor 7 deficiency, plus maybe some common pathway factor deficiencies.
- usually due to coumadin or vitamin K deficiency (which can affect aPTT too)
what is your differential for an isolated prolonged aPTT?
isolated prolonged PTT= extrinsic normal and intrinsic pathway is affected.
12 deficiency if no bleeding (and HMWK, prekallekrien)
11
9 (hemophilia) deficiency
8 (hemophilia B) deficiency.
probably not vit K deficiency or liver since that would also affect extrinsic pathway.
deficiencies in inhibitors like APLA, factor 13.
could be heparin
- Heparin produces its major anticoagulant effect by increasing AT-mediated inhibition of synthesis and activity of factors Xa (FXa) and IIa (FIIa, thrombin).
is prolonged PTT is identified and there are no bleeding symptoms:
bleeding symptoms since childhood:
What tests to do next?
is prolonged PTT is identified and there are no bleeding symptoms: APLA, FACTOR 12 DEFICIENCY
bleeding symptoms since childhood: FACTOR 8 OR 9 ISSUE (HEMOPHILIA)
next step is to do mixing study with pt plasma and normal plasma
- if PTT corrects, it indicates a factor deficiency which has been replaced by normal plasma added.
- if PTT remains prolonged, it indicates an inhibitor in patient plasma (ex/ APLA/lupus inhibitor)
3 major contributors to VTE (Virchow’s triad)
- venous stasis (immobility, heart failure, varicose veings)
- endothelial injury (surgery, trauma/car accident)
- hypercoagulable state. (acute phase post op, cancer, thrombophilia)
