(3-08-17) Bleeding Disorders and Assessments Flashcards
what makes up the hemostasis tripod?
- Primary hemostasis (platelets)
- coagulation (chemical process)
- vasoconstriction (mechanical process)
*all of these are balanced by ANTIcolagulant activity which prevents excessive coagulation and keeps blood flowing appropriately
what occurs in primary hemostasis?
- platelets adhere to disrupted vessel wall (glycoprotein receptor Ib)(von willebrand factor)
- platelets adhere to one another (glycoprotein IIb/IIIa)(fibrinogen)
what factors allow platelets to adhere to disrupted vessel wall in primary hemostasis?
glycoprotein IB
von willebrand factor
what factors allow platelets to adhere to each other ?
glycoprotein IIb/IIIa
fibrinogen
what two things do arachidonic acid vasoconstrictors release?
- thromboxane A2
- prostaglandins (PGs)
what two things do platelets surfaces provide?
- generation of thrombin
- subsequent fibrin formation
what is the extrinsic system of the coagulation cascade?
- TF exposed to blood
- TF then binds and activates factor VII to factor VIIa
- TF-VIIa then activates X to Xa
- Xa then converts prothrombin(II) to thrombin (IIa)
*this is most effective in the presence of phospholipid surface
what is the instrinsic (secondary) system of the coagulation cascade
- TF exposed to blood
- TF then binds and activates factor VII to factor VIIa
- TF-VIIa activate IX to IXa
- IXa uses cofactor VIII to activate X to Xa
- Xa then converts prothrombin (II) to thrombin (IIa)
*only small differences from extrinsic system
what is the 3rd pathway for the coagulation cascade?
- thrombin itself activates XI to XIa
- XIa activates IX to IXa
- IXa goes back into intrinsic pathway to make additional thrombin
*postitive feedback
what is essential for the conversion of fibrinogen to fibrin?
thrombin
- activates coagulation factors and cofacgtors, facilitating its own formation
- mediates fibrinogen cleavage
what are the 3 natural anticoagulation mechanisms?
- tissue factor pathway inhibitor (TFPI)
- protein C
- antithrombin III
what is the mechanism for the natural anticoagulation mechanism protein C?
- protein C activated by endothelial cell-bound enzyme thrombinomodulin
- activated protein C degrades the important co factors V and VIII
- activation requires cofactor protein S
what is the mechanism for the natural anticoagulation mechanism antithrombin III
- forms complex and inactivates thrombin and factor Xa
- strongly enhanced by presence of HEPARIN
what is fibrinolysis?
turning plasminogen into plasmin…. breaks down clots
-mediated by tPA and uPA (found in endothelial cells)
what two levels is fibrinolysis inhibited by?
- activator inhibitors (PAIs)
- circulating protease inhibitors
what is the most common congenital coagulation disease?
von Willebrand Disease
what is the prevalence of von Willebrand disease?
- mild (5:1,000)
- severe (1:25,000)
what are the 3 subtypes of von Willebrand disease?
- type 1: reduced conc (10-45% normal levels)
- type 2: dysfunctional vWF
- type 3: absent vWF (homozygous for gene defect)
what is used to correct types one and IIa vWB disease?
*mild
DESMOPRESSIN
- promotes release of vWF stored in endo cells
- inc vWF circulating 2-3x
- CONTRAINDICATED in type IIb vWB
what is used to correct type IIb and type III vWB disease?
replacement with transfused factors
*tx must continue for 4-7 days after surgery
what is the most commonly inherited coagulation disorder?
hemophilia A
deals with factor VIII deficientcy
what is mild and severe hemophilia?
mild = 40% of normal severe = less than 1%
*pts with factor VIII levels greater than 5% rarely bleed spontaneously, but will have bleeding problems after surgery or trauma
what is the treatment for mild to moderate hemophilia A?
Desmopressin
- releases endogenous factor VIII from liver and endo cells
- releases vWF which inc VIII levels
what is the treatment for severe hemophilia A
factor VIII transfusion
-very expensive
what is hemophilia B?
- similar to hemophilia A but affecting factor IX
- treated with factor transfusion when severe
what are the hypercoagulatable coagulation diseases?
- protein C deficiency, protein S deficiency
- factor V leiden
what is the link between coagulation and liver disease?
- liver is the source of coagulation factors
- liver is also the source of protein C, protein S, and fibringogen
- if diseases, thrombocytopenia may exist
- thrombocyte function is impaired in cirrhotic pts
what is the best way to determine if your liver is diseased?
model for end-stage liver disease score
*may be more useful predictor of bleeding complications than INR alone
what is the link between coagularion and renal disease?
- renal failure pts often present with coagulation abnormalities and are at risk for inc bleeding
- low hematocrit in pts with renal failure may contribute to impaaired fxn of primary hemostasis
*desmopressin has been shown to correct prolonged bleeding time in pts with uremia
what are the anti-platelet drugs?
- aspirin
- clopidogrel (plavix)
- Dipyramidole
- glycoprotein receptor IIb/IIIa inhibitors
how does aspirin work?
- irreversible inhibitor of platelet membrane associated cyclooxygenase
- may be associated with sig impairment of primary hemostasis and mild enhancement of bleeding
what are the adverse effects of aspirin?
- excess bleeding and the occurrence of hemorrhagic gastritis or even gastric ulceration
- for most dental procedures, discontinuing aspirin is NOT indicated and may pose greater risks than benefits
how does clopidogrel work?
- blocks the ADP receptor on the platelet
- more expensive than aspirin
- results in more clinical bleeding than aspirin
- generally safe to continue through oral surgery like aspirin
how does dipyramidole work?
- antiplatelet effect by inhibition of phosphodiesterase
- a potent inhibitor of platelet aggregation but has not seen many clinical trials
how does glycoprotein receptor IIb/IIIa inhibitors work?
- MOST POTENT inhibitor of platelet aggregation
- competitive inhibitor of fibrinogen binding to the IIb/IIIa site
- intravenous forms more effective than oral
what are the anticoagulation drugs/
- coumadin
- factor Xa inhibitors
- heparin
- low molecular weight heparins
- pentasaccharides
how does coumadin work?
- given orally
- blocks the essential vit K-dependent carboxylation of coagulation factors II, VII, IX, and X
- dose effect relationship vaires considerably between pts and in individuals
what is used to monitor coumadin?
PT/INR
what is the most important side effect of coumadin?
bleeding
*it is rare but coumadin induced skin necrosis may occur
how do factor Xa inhibitors work?
NOACs, TSOACs, DOACs = synonyms
- first new drugs for stroke or DVT prophy since coumadin
- do not require lab monitoring
- reatively rapid onset (2-3 hrs) and short half-life
- STROKE prevention comparable to coumadin
- risk of extracranial bleeding same (or possibly higher)
how does heparin work?
- given parenterally
- binds to antithrombin III which potentiates inhibition of factors IIa and Xa more than 1000 fold
- effect after IV admin is immediate
- heparin has a dose depentdent half life
how do low molecular weight heparins work?
- given parenterally
- in some situations have a more favorable antithrombitic effects and induce fewer bleeding complications
- more predicatable and longer half-life
how do pentsaccharides work/
- parenteral
- indicated DVT prophy or DVT/PE tx
- synthetic compounds that exert antithrombin-dependent exclusive inhibition of factor Xa
- Xa inhibition is indirect
what are the complications with heparin and its derivatives?
- BLEEDING
- heparin induced thrombocytopenia
- long term use of heparin has been associated with osteocytopenia
what are the steps to ID a pt with a risk of bleeding
- med history (ask about previous surgeries)
- NEVER advise a pt to hold or discontinue any prescribed anticoagulation, even aspirin, without consulting the prescriber first
- physical exam (look for abnormal bruising, petechiae, splenomegaly)
- lab exam
- PT/INR (normal is 12 +/- 2 seconds
- activated partial thromboplastin time (PTT)(measures “intrinsic” pathway
what does a prolonged PTT time indicate?
- use of heparin
- antiphospholipid antibody, which inc the risk of thrombosis
- coagulation factor (hemophilia)
- sepsis
- presence of antibodies agains coagulation factors
what is the deal with measuring platelet function - bleeding time
- was the standard method for assessing primary hemostasis for many years
- is subject to many problems
- is not sensitive and poorly reproducible
- can be affected by aspirin
IT SUCKS
what is considered the GOLD STANDARD for platelet function analysis?
-platelet affregometry
