Bleeding disorders Flashcards
what are the 3 components of the “hemostasis tripod”?
- Primary Hemostasis, mediated by platelets
- Coagulation, a chemical process
- Vasoconstriction, a mechanical process
Platelets adhere to disrupted vessel wall via:
A) Platelet surface membrane glycoprotein receptor Ib
B) vonWillebrand factor
Platelets adhere to one another via:
– surface receptor glycoprotein IIb/IIIa
– fibrinogen
what are the 2 Arachidonic acid vasoconstrictors?
– thromboxane A2
– prostaglandins (PGs).
Platelet surface provides a site for what to occur?
– generation of thrombin
– subsequent fibrin formation
what are the steps in the “extrinsic pathway” for clotting?
tissue factor- factor VII pathway
A) tissue factor exposed to blood
B) tissue factor forms complex with factor VII
C) factor VII activated- Factor VIIa
D) whole complex binds to factor X
E) Xa converts prothrombin (factor II) into Thrombin (IIa)
- this step requires factor V as a c-factor
what happens in the “secondary”/alternate clotting pathway?
A) factor IX activated by tissue-factor/VIIa complex
B) factor IXa and cofactor VIII activates factor X
C) thrombin formation proceeds
what is the 3rd coagulation pathway?
A) Thrombin itself activates factor XI
B) Factor XIa activates factor IX
C) Pathway proceeds to additional thrombin formation
____________ is essential for the conversion of fibrinogen into fibrin
Thrombin
what are the 4 main roles of thrombin?
1) conversion of fibrinogen into fibrin
2) Activates coagulation factors and cofactors, facilitating its own formation
3) Strong activator of platelet aggregation
4) Mediates Fibrinogen cleavage
what are the 3 main anti-coagulation mechanisms?
1) Tissue factor pathway inhibitor (TFPI)
2) Protein C
3) Antithrombin III
how does Protein C work?
1) Circulating protein C activated by endothelial cell-bound enzyme thrombomodulin in association with thrombin
2) Activated protein C degrades the important cofactors V and VIII
3) Activation requires an essential cofactor: protein S
____________ will inhibit both Thrombin and factor Xa
Antithrombin III
Antithrombin III is Strongly enhanced by presence of what molecule?
Heparin
Fibrinolysis is mediated by what molecules? what causes their activation?
A) tPA and uPA found in endothelial cells
B) Released by several stimuli, including hypoxia, acidosis
what are the 2 ways in which Fibrinolysis is inhibited?
1) Activator inhibitors (PAIs)
2) Circulating protease inhibitors, e.g. α2-antiplasmin
____________ is the most common CONGENITAL coagulation DISEASE
von Willebrand Disease
what are the 3 subtypes of von Willebrand disease?
1) Type I: reduced concentration (10-45% normal levels)
2) Type II: dysfunctional vWF
3) Type III: absent vWF (homozygous for gene defect)
Desmopressin (DDAVP) is used to treat what types of von Willebrand disease?
Type 1
Type 2a
how are severe forms of von Willebrand disease treated?
replacement with transfused factors
For von Willebrand disease, treatment must continue for _______ days after surgery
4 to 7 days
_____________ is the most commonly INHERITED coagulation DISORDER
how is this disease inherited?
Hemophilia A
- Sex-linked recessive, 1 of 10,000 male births
Hemophilia A is caused by a reduction in what molecule?
Factor VIII
Patients with factor VIII levels greater than ___% rarely bleed spontaneously, but will have bleeding problems after surgery or trauma
5%
Mild Hemophilia A patients can have Factor VIII levels of ___% or less, while severe forms have less than ___%
Mild = 40%
severe = less than 1%
how is Hemophilia A treated?
Mild cases: DDAVP (desmopressin)
Severe cases: transfusion
Hemophilia B is similar to Hemophilia A but affects _________
factor IX
what are the 2 types of Hypercoaguable diseases?
A) Protein C Deficiency, Protein S Deficiency
B) Factor V Leiden
what causes Factor V Leiden syndrome?
Polymorphic factor V which resists inactivation by activated protein C
All Hypercoaguable conditions put the patient at risk for __________
thrombosis
what clotting-related compounds are produced by the liver?
A) Liver is the source of coagulation factors
B) Liver is also the source of Protein C, Protein S, and fibrinogen
Thrombocytopenia due to decreased liver function is the result of what conditions?
Result of portal hypertension and associated splenomegaly
- liver failure causes drop in thrombocytes (platelets)
T/F: Clinical bleeding in patients with liver disease is often worse than predicted by INR alone
True
what is a MELD score? what is it based on?
Model for End-Stage Liver Disease (MELD) Score
Formula based on:
– Serum bilirubin
– Serum creatinine
– INR
How do MELD scores correlate to mortality?
– 40 or more = 71.3% – 30–39 = 52.6% – 20–29 = 19.6% – 10–19 = 6.0% – less than 9 = 1.9%
how can renal disease effect coagulation?
attributed to impaired platelet adhesion, aggregation, and release
______________ has been shown to correct prolonged bleeding time in patients with uremia
DDAVP (Desmopressin)
___________ is a Irreversible inhibitor of platelet membrane-associated cyclooxygenase
Aspirin
- blocks the formation of thromboxane A2
- Less inhibition of other PG’s
_______ days are usually required after termination of aspirin use to restore adequate platelet function and effective hemostasis
5 to 7
what are the most important adverse effects of aspirin?
1) bleeding
2) the occurrence of hemorrhagic gastritis or even gastric ulceration
how does Clopidogrel (Plavix) function?
- Blocks the ADP receptor on the platelet
T/F: the combination of clopidogrel and aspirin was shown to be superior over aspirin alone
true
after an acute coronary event, percutaneous coronary interventions, and coronary stent placement
T/F: Clopidogrel results in MORE clinical bleeding than aspirin
true
how does Dipyramidole work?
antiplatelet effect by inhibition of phosphodiesterase
T/F: Glycoprotein Receptor IIb/IIIa Inhibitors are effective orally
False
Which vitamin-K dependent factors does Coumadin block?
factors II, VII, IX, and X
how long does it take for coumadin to reach its full effect? how long does it take for the effects of coumadin to dissipate after therapy has been stopped?
- the full effect of therapy is delayed for 2 or 3 days
- full restoration of normal coagulation after termination of Coumadin therapy requires at least 3 to 5 days
which tests are used to monitor the effects of coumadin?
PT/INR
T/F: factor Xa inhibitors do not require monitoring
true
what is the onset time for Factor Xa inhibitors? how long is their half life?
Relatively rapid onset (2-3 hours) and short half life (8-12 hours
what does Idarucizamab do?
acts as reversal agent for Dabigatran
what drug will act as a reversal agent for factor Xa inhibitors?
Andexanet Alfa
- Reverses anticoagultion in less than 5 minutes
Heparin binds to ___________
antithrombin III
T/F: The anticoagulant effect of heparin may be highly variable
true
what test is used to monitor the effects of heparin?
aPTT
what are the indications for the use of Pentasaccharides?
Indicated for DVT prophylaxis or DVT/PE treatment
what is heparin-induced thrombocytopenia?
– an immunological response to heparin characterized by thrombocytopenia and thromboedema
- occurs 5-7 days after first dose
what are some clinical signs that a patient may have a defect in their coagulation system?
– Abnormal bruising
– Petechiae
– Splenomegaly
normal PT averages ______ seconds
12 ± 2
T/F: PT times will not vary depending on laboratories
FALSE
- they can differ
The PT is prolonged by deficiencies in:
A) factor 7 B) factor 10 C) Factor 5 D) Prothrombin E) Fibrinogen
The PTT measures the slower “intrinsic” pathway: normal is roughly _______ seconds
25-40
Deficiencies in factors _____ or _____ will not be detected with the PTT test
VII or XIII
which lab test is used to monitor coumadin? which one is used to monitor heparin?
A) PT/INR is for Coumadin
B) aPPT is for heparin
Platelet Function Analyzer-100 (PFA-100) is used in place of what type of test?
bleeding time tests
__________________ is considered the gold standard for platelet function analysis
Platelet aggregometry (PAA)
how does dabigatran (Pradaxa) function?
direct thrombin inhibitor
name the factor Xa inhibiting drugs:
A) XARELTO (rivaroxaban)
B) ELIQUIS (apixaban)
C) SAVAYSA (edoxaban)
What deficiency causes the rare coumadin-induced skin necrosis?
protein C deficiency
