Coagulation Lecture Mauro Flashcards
What is the vascular response to damage?
vasoconstriction to cause narrowing to reduce blood flow
What occurs during primary hemostasis?
the formation of the platelet plug
What occurs when endothelium is damaged
when endothelium is damaged it exposes collagen, VWF, and tissue factor
What is the first step in primary hemostasis
platelets will undergo platelet adhesion and combine the GP1b/IX to the vWF that is incorporated into the subendothelium
What occurs after the platelets undergo a shape change?
release granules = ADP, TXA2, serotonin, fibrinogen
How do platelets undergo adhesion?
as other platelets get recruited they expose GP11b/IIIa complex and link to fibrinogen to form the platelet plug
What does secondary hemostasis do?
Forms fibrin scaffolding that will help bind the platelet plug to keep it on the site of injury
Where is tissue factor release from
the subendothelium at the site of injury
What starts the coagulation cascade
release of the TF from the subendothelium in the extrinsic pathway and TF will also help start the intrinsic pathway by activating 9 to 9A
- once you have a small amount of thrombin produced by extrinsic pathway and this will go back and help activate the intrinsic pathway with 9, 11, cleaving of 8 from VWF
What does increased production of thrombin lead to
more intrinsic pathway activation
Which factor helps with platelet activation?
Factor Xa and it also helps with exposure of phospholipids on platelet surface
What does anti-thrombin do
circulating plasma protease inhibitor that neutralizes factors
Activated protein C
in the presence of protein S, can help neutralize 8a and 5a
TFPI
circulating in blood, inhibits and neutralizes Xa and TF:VIIa
What increases when heparin is given?
concentration of TFPI
What does fibrinogen do?
Finds to the fibrin clot via exposure of lysine residues
and gets converted to plasmin
What does plasmin do
starts breaking up fibrin clots and release degradation products including D-dimer
PAI
Plasminogen activator inhibitor
- released by the endothelium
- inhibits plasminogen to plasmin actiation
Alpha 2 antiplasmin
released by some of the platelets
- inhibits plasmin activation
TAFI (thrombin activatible fibrinolysis inhibitor)
removes lysine residues
What is a normal platelet count
normal 150,000-400,000 microL
Thrombocytopenia with prolonged bleeding
when platelets drop below 100,000
When are platelets below 50,000 a concern?
before surgery
What is the platelet count at which we are worried about spontaneous bleeding
below 10,000
*hemorrhage
What does PT test look at
looks at extrinsic and final common pathway
- see how well the factors in the extrinsic and final common pathway are acting
- factor VII, X, V, thrombin, fibrinogen
What does PTT test look at
looks at intrisic and final common pathway
Mixing studies
- take part of patients blood and add it to normal blood and remeasure whatever test is prolonged
- if you’re only looking at a factor deficiency, the test will normalize
If you do mixing study and it doesn’t correct, what is the issue in the blood?
you have an inhibitor - an antibody that is preventing the factors from acting appropriately
- you can tell the strength of an inhibitor based upon how much normal blood you have to add to normalize your blood
What is a d-dimer
fibrin monomer, part of the fibrin degradation products
When is d-dimer elevated
presence of clot turnover, marker of fibrinolysis, and a marker of recent/ongoing blood coagulation
What is measured in the intrinsic pathway
PTT - partial thromboplastin time
What is measured in the extrinsic pathway
PT - prothrombin time
If you have a prolonged PT and the mixing study corrects then you have a deficiency in:
you have a factor deficiency (factor VII), vitamin K deficiency, or liver disease
What is vitamin k required for?
post-translational modification of factors II, VII, X, PC, PS
What is the first thing that drops with vitamin K deficiency
factor VII so you develop long PT first
coumadin
blood thinner
- inhibits vitamin K
- monitor with PT
What can lead to vitamin K deficiency
antibiotics, malnutrition, and coumadin
liver disease
all of the proenzymes are created in the liver
- decreased production of factors
- factor VII is the most sensitive
- pt will prolong
If you have a prolonged PTT and the mixing study corrects but you have no bleeding
then you have a deficiency in:
factor XII, pre-kallikrein, klinonogen
- body can compensate and go around the initial step of the intrinsic system
- tissue factor will activate lower down so you can bypass the upper step
If you have a prolonged PTT and the mixing study corrects but you have bleeding
then you have a deficiency in:
factor XI, IX, VIII, vWD (because it can lower factor VIII)
If you have a prolonged PTT and the mixing study doesn’t correct you have:
- factor inhibitor of VIII, IX, XI
- heparin
- lupus anticoagulant - prolongs PTT and causes clotting
lupus anticoagulant
prolongs PTT and causes clotting
- look for this in patient that is coming in with tons of clotting
prolonged PT and PTT
deficiencies of final common pathway
- severe vitamin K deficiency
- severe liver disease
- DIC (disseminated intravascular coagulation)
What sort of defect will give you mucocutaneous bleeding
platelet defect
- oral cavity, nasal, GI, GU bleeding
What sort of defect will give you excessive bleeding after cuts
primary hemostasis - platelet defect
- initial platelet cut is not forming
What sort of defect will give you petechaie
primary hemostasis platelet defect
What sort of defect will give you immediate bleeding with surgery
platelet defect, primary hemostasis
What sort of defect will you deep tissue bleeding and joint and muscle bleeding
coagulation disorder, secondary hemostasis
- can make initial platelet plug
What sort of bruising will you get with coagulation disorders and secondary hemostasis
large hematomas
What sort of defect will give you delayed bleeding with invasive surgery
coagulation disorder, secondary hemostasis
- not a stable clot after surgery
- need fibrin scaffolding and you don’t have that and then you have hemmorhaging
allo vs autoantibody
auto antibody - made it against your own body and allo antibody is making it against something foreign
What are the symptoms of a patient with a fVIII inhibitor
ecchymoses, epistaxis, GI, hematuria, intracranial
What is the treatment for a patient with FVIII inhibitor
give immunosuppression to suppress body’s response
- give FEIBA which is a bypassing agent
- give NOVO seven which ramps up the extrinsic system
What is caused by a deficiency in factor VIII
hemophilia A
what is caused by a deficiency in factor IX
hemophilia B
What is hemarthrosis a symptom of
hemophilia
- present first year of life
- muscle bleeds
- intracranial bleeds
- dental bleeding
- post surgery bleeding
What is the treatment of choice for hemophilia
give factor: factor VIII or IX concentrates
or DDAVP in mild hemophilia A to stimulate release of FVIII from endothelium
- prophylaxis for surgery and for children to prevent spontaneous bleeds
What does VWF do
helps bind the platelet to the subendothelium and carrier for FVIII and increases half life of FVIII
What is the most common type of VWD
type 1 - partial quantitative deficiency of vWF
- AD
- vWF antigen low and activity low
- fVIII low
What is the treatment for type 1 vWD
- DDAVP to release vWF and FVIII from endothelial cells
- intermediate purity FVIII concentrates
What is DIC
diffuse activation of thrombin which leads to consumptive coagulopathy and secondary fibrinolysis
- fibring degradation products can impact the whole clotting system
What can cause DIC
thromboembolism, sepsis, malignancy/leukemia, pregnancy complications (exlampsia, HELLP, placental abruption), severe liver failure, trauma
Symptoms of DIC
bleeding, renal and liver and pulm dysfunction, thromboembolism (arterial and venous)
What are symptoms of pulm embolism
pleuritic chest pain, SOB, tachychardia, cough
What does antiphospholipid antibody lead to
increases clotting and vascular tone
What is the clinical criteria for APLS
arterial or venous thrombosis or pregnancy morbidity: unexplained fetal death, premature birth due to preeclampsia, 3 or more unexplained miscarriages
What tests confirm lupus anticoagulant
- prolonged PTT that doesn’t correct with mixing
- proloned dRVVT assay that doesn’t correct with mixing
- correction of clotting time by adding phospholipid
What are the two syndromes that can cause both arterial and venous clotting
DIC and APLS
FVL mutation
abolishes cleaving site of APC
- FVL has 20 fold slower degradation time than normal FV so extended thrombin generation
