Neoplasia/Hematology - Pharmacology - Antianemia Agents; Hemostatic Agents Flashcards
Name the most relevant vitamins, minerals, or stimulating factors inducing proper erythropoeisis.
Vitamins B12 and B9
Fe2+
Erythropoeitin
What medication(s) can be given to stimulate platelet production?
Oprelvekin
(IL-11)
What medication(s) can be given to stimulate granulocyte production?
Filgrastim (G-CSF);
sargramostim (GM-CSF)
Vitamins B12 and B9 are necessary for synthesis of what in red blood cells?
dTMP
(due to proper activity of dihydrofolate reductase)
G-CSF stimulates production of what?
Neutrophils
GM-CSF stimulates production of what?
Granulocytes + other myeloid cells
What is the most common type of anemia?
Microcytic, hypochromic anemia
(due to iron deficiency)
Although most of the iron in the body is bound in hemoglobin, a significant portion is bound to ________, a transport protein, and ________, a storage protein.
Although most of the iron in the body is bound in hemoglobin, a significant portion is bound to transferrin, a transport protein, and ferritin, a storage protein.
What transporter in the duodenum allows for iron uptake?
DMT1
In what clinical scenarios should iron be given to a patient with hemolytic anemia?
It should not!
(Iron stores are elevated in hemolytic anemia)
What dietary forms of iron can be administered to a patient with iron deficiency anemia?
Ferrous sulfate;
ferrous gluconate;
ferrous fumarate
What parenteral forms of iron can be administered to a patient with iron deficiency anemia?
Iron dextran;
sodium ferric gluconate;
iron sucrose
Hemochromatosis occurs most often in patients with an __________ disorder of iron __________ and in patients receiving frequent __________ for treatment hemolytic anemia.
Hemochromatosis occurs most often in patients with an inherited disorder of iron absorption and in patients receiving frequent transfusions for treatment of hemolytic anemia.
How can acquired hemochromatosis be treated?
Chelation therapy (deferasirox or deferoxamine)
How can inherited hemochromatosis be treated?
Phlebotomy
True/False.
Folate (B9) is involved in the metabolism of both the following: methylmalonyl-CoA, homocysteine.
False.
Cobalamin (B12) is involved in the metabolism of both the following: methylmalonyl-CoA, homocysteine.
A deficiency of cobalamin leads to elevated serum levels of what?
A deficiency of folate leads to elevated serum levels of what?
Methylmalonic acid, homocysteine;
homocysteine
What is the typical scenario in which iron poisoning occurs?
A child finding/ingesting supplements
What are the signs/symptoms of iron poisoning?
Necrotizing gastroenteritis;
shock;
metabolic acidosis
The iron stored in intestinal mucosal cells is complexed to / stored in what?
Ferritin
(forming apoferritin)
What is the most common type of vitamin B12 deficiency anemia?
Pernicious anemia
Anticoagulants are generally used to prevent what?
Venous clots
Antiplatelet medications are generally used to prevent what?
Arterial clots
What medication class is used to prevent venous clots?
Anticoagulants
What medication class is used to prevent arterial clots?
Antiplatelets agents
The hemophilias are disorders of __________ hemostasis.
von Willebrand is a disorder of __________ hemostasis.
The hemophilias are disorders of secondary hemostasis.
von Willebrand is a disorder of primary hemostasis.
Primary hemostasis mostly involves what?
Platelet adhesion
_________ hemostasis mostly involves inactive circulating proteins primarily made in the ________.
Secondary hemostasis mostly involves inactive circulating proteins primarily made in the liver.
What glycoprotein binds platelets to exposed von Willebrand factor?
gp Ib
What glycoprotein binds platelets to each other via fibrinogen?
gp IIb/IIIa
Arterial clots are mainly composed of what?
Platelets
Venous clots are mainly composed of what?
Fibrin
What is the main trigger for arterial clots?
Atherosclerosis
What is the main trigger for venous clots?
Stasis
Venous clots can bypass the lungs and become arterial if what if present?
A patent foramen ovale
True/False.
DVTs and PEs typically result due to atherosclerosis and are clots composed mainly of fibrin.
False.
DVTs and PEs typically result due to stasis and are clots composed mainly of fibrin.
True/False.
MIs and strokes typically result due to atherosclerosis and are clots composed mainly of fibrin.
False.
MIs and strokes typically result due to atherosclerosis and are clots composed mainly of platelets.
Bleeding time is a measure of the time it takes for an incision to stop bleeding.
This is a measure of what process?
Primary hemostasis
How long is the average bleeding time?
1 to 9 minutes
An abnormal bleeding time indicates defects in either:
__________ or _________.
An abnormal bleeding time indicates defects in either:
platelets or vWF.
True/False.
Elevated bleeding times are seen in patients with pure clotting factor deficiencies.
False.
Normal bleeding times are seen in patients with pure clotting factor deficiencies.
(Bleeding time measures platelet function in primary hemostasis)
In pure clotting factor deficiencies, there is ________ bleeding time.
In pure clotting factor deficiencies, there is normal bleeding time.
What do PFAs measure?
Platelet function
What does the prothrombin time measure?
- (Primary or secondary hemostasis?)*
- (Extrinisic or intrinsic pathway?)*
- (Which factors?)*
Secondary hemostasis;
extrinsic pathway;
factors I, II, V, VII and X.
What does the partial thromboplastin time measure?
(Primary or secondary hemostasis?)
(Extrinisic or intrinsic pathway?)
(Which factors?)
Secondary hemostasis;
intrinsic pathway;
factors I, II, V, VIII, IX, X, XI, XII
Which factors are checked by either a partial thromboplastin or prothrombin time?
I, II, V, X
What is a normal prothrombin time?
10 - 15 seconds
What test(s) can be used to monitor the effects of unfractionated heparin?
Partial thromboplastin time
(PTT or aPTT)
What test(s) can be used to monitor the effects of warfarin?
Prothrombin time;
INR
What test(s) can be used to monitor the effects of antiplatelet drugs?
Bleeding time;
PFA
Name the respective drug or drug class that each of the following tests is used to monitor:
Prothrombin time (INR)
Partial thromboplastin time
Bleeding time (or PFA)
Warfarin
Unfractionated heparin
Antiplatelet medications
What is the equation for calculating international normalized ratios (INR)?
( PTtest / PTnormal )ISI
(ISI = the international standard index for that particular manufacturer’s test reagent)
What is the typical international normalized ratio (INR) range for healthy individuals?
0.8 - 1.2
For those on warfarin therapy, the INR should typically be ____ to ____.
For those on warfarin therapy, the INR should typically be 2.0 to 3.0.
True/False.
A therapeutic aPTT should be 1.5 to 2.5x control values.
True.
Prothrombin time and INR are used to measure the _________ clotting pathway and monitor the effects of _________.
Prothrombin time and INR are used to measure the extrinsic clotting pathway and monitor the effects of warfarin.
Partial thromboplastin times are used to measure the ________ clotting pathway and monitor the effects of ________.
Partial thromboplastin times are used to measure the intrinsic clotting pathway and monitor the effects of heparin.
Bleeding times and PFAs are used to measure the effectiveness of _________ hemostasis and monitor the effects of _________ medications.
Bleeding times and PFAs are used to measure the effectiveness of primary hemostasis (platelets) and monitor the effects of antiplatelet medications.
An elevated bleeding time/PFA would indicate that the patient is receiving medication that may interfere with which of the following?
A. Factor II
B. GPIIb/IIIa.
C. Factor VII
D. Factor XII
E. Vitamin K
B. GPIIb/IIIa.
Heparin activates __________ to inhibit factors _____________.
Heparin activates antithrombin III to inhibit factors II, IX, X, and XII.
Unfractionated heparin is highly _______ and also has an especially high affinity for factors ____ and ____.
Unfractionated heparin is highly acidic and also has an especially high affinity for factors II (thrombin) and X.
How is unfractionated heparin administered?
IV or subcutaneous
Name the medication that can be used in treating in all the following:
Venous thrombosis
PE
Peripheral arterial thrombosis
Heparin
What medication is useful in prevention of post-operative DVT and PE?
Heparin
What medication is useful in treatment and prophylaxis of thromboembolic events related to atrial fibrillation?
Heparin
Does enoxaparin have a higher or lower molecular weight than unfractionated heparin?
Lower
(it is a low molecular weight (LMW) heparin)
Heparin is dosed based on what?
Enoxaparin is dosed based on what?
aPTT;
body weight
Which has a better bioavailability and half-life, heparin or enoxaparin?
Enoxaparin
Which of the following has less activity at factor II (thrombin) and more activity at factor X?
Heparin
Enoxaparin
Enoxaparin
Is enoxaparin useful in DVT / PE prophylaxis or treatment?
Both!
A patient begins bleeding after heparin sulfate is administered. What do you do to reverse the effects of the heparin?
Administer protamine sulfate
(note: often not useful in reversing enoxaparin)
What are some of the potential negative side effects of heparin use?
Hemorrhage;
heparin-induced thrombocytopenia;
osteoporosis
Why is heparin-induced thrombocytopenia associated with a paradoxical thrombosis?
Platelet activation
(in response to the thrombocytopenia)
Name a few examples of alternatives to heparin.
Hirudin, lipirudin, bivalirudin,
argatroban, fondaparinux
Relative to regular heparin, enoxaparin:
a) can be used without monitoring aPTT
b) has a shorter duration of action
c) is less likely to produce a teratogenic effect
d) is more likely to be given intravenously
e) is more likely to cause thrombosis and thrombocytopenia
a) can be used without monitoring aPTT
Warfarin is generally administered as a sodium salt and has ____% bioavailability.
Warfarin is generally administered as a sodium salt and has 100% bioavailability.
There is an ___ to ___ ____ delay before warfarin takes effect and a ___ to ___ ____ lag until complete effect due to long half life of factor II.
There is an 8 to 12 hour delay before warfarin takes effect and a 2 to 3 day lag until complete effect due to long half life of factor II.
___% of warfarin is protein bound with a T1/2 of ___ hours (in plasma).
99% of warfarin is protein bound with a T1/2 of 36 hours (in plasma).
Warfarin blocks synthesis of which factors?
II, VII, IX, and X;
proteins C and S
Warfarin is indicated in prophylaxis and treatment of:
- ______ thrombosis and ____.
- _____________ events related to MI, stroke and atrial fibrillation.
Warfarin is indicated in prophylaxis and treatment of:
- Venous thrombosis and PE.
- Thromboembolic events related to MI, stroke and atrial fibrillation.
A patient on warfarin has an INR of 17.0. To prevent hemorrhage, the warfarin should be discontinued and the patient should be treated with (in addition to PCCs):
a) Alteplase
b) Aminocaproic acid
c) Factor VIII
d) Protamine
e) Vitamin K.
e) Vitamin K.
A pregnant woman with a history of heparin induced thrombocytopenia is diagnosed with a DVT. The most appropriate therapy is
A. Warfarin
B. Enoxaparin
C. fondaparinux
D. Clopidigrel
E. Aspirin
C. fondaparinux
What are some signs of warfarin overdose?
(including INR)
Hematuria;
bleeding gums;
INR > 6
How should warfarin overdose be treated?
Fresh frozen plasma
+
vitamin K
What are some contraindications to warfarin use?
Pregnancy;
hemorrhagic tendencies;
warfarin-induced skin necrosis
What enzyme does warfarin inhibit?
Epoxide reductase
Patients with what disorder are more at-risk for hemorrhagic skin necrosis upon administration of warfarin?
Protein C deficiency
(remember, warfarin also inhibits protein C!)
__________ is an oral medication that can be administered to treat GI bleeding.
Thrombin is an oral medication that can be administered to treat GI bleeding.
Name a few medications that can be used as coagulants.
Fresh frozen plasma (FFP);
cryoprecipitate (fibrinogen, fVIII, VwF, fXIII);
factor VIII concentrate/Factor IX;
factor VIIa;
prothrombin complex concentrates (PCCs)
Name the characteristics of the ideal anticoagulant medication in terms of the following:
Route of administration
Timeframe
Monitoring requirement
Reversibility
Drug/diet interactions
Oral
Short-acting
No monitoring required
Easily reversible
No drug/diet interactions
What is the mechanism of dabigatran etexilate?
How can it be reversed?
Thrombin inhibition;
idarucizumab
________ is an orally active, selective Factor Xa inhibitor that has a rapid onset and good bioavailability.
Apixaban is an orally active, selective Factor Xa inhibitor that has a rapid onset and good bioavailability.
What is the reversal agent for factor Xa inhibitors?
Andexanet alfa
Name a few examples of thrombolytic medications.
Streptokinase (1st gen);
TPAs (2nd gen)
Name a few example medications that are in the TPA category.
What is the suffix on these medications?
Tenecteplase;
Reteplase;
alteplase
‘-plase’
The conversion of plasminogen to plasmin can be brought about by:
a) aminocaproic acid
b) heparin
c) aspirin
d) reteplase.
e) warfarin
d) reteplase.
Currently, there are four mechanisms by which drugs interfere with platelet function:
1. Prostaglandin–___________ inhibition
2. Inhibition of the ______ binding in platelets
3. Cyclic nucleotide phosphodiesterase inhibition
4. Receptor blockade of gpIIb/IIIa receptors, blocking the final pathway of platelet aggregation
Currently, there are four mechanisms by which drugs interfere with platelet function:
1. Prostaglandin–Thromboxane A2 (TXA2) inhibition
2. Inhibition of the ADP binding in platelets
3. Cyclic nucleotide phosphodiesterase inhibition
4. Receptor blockade of gpIIb/IIIa receptors, blocking the final pathway of platelet aggregation
Currently, there are four mechanismsby which drugs interfere with platelet function:
1. Prostaglandin–Thromboxane A2 (TXA2) inhibition
2. Inhibition of the ADP binding in platelets
3. Cyclic nucleotide ___________ inhibition
4. Receptor blockade of ___________, blocking the final pathway of platelet aggregation
Currently, there are four mechanismsby which drugs interfere with platelet function:
1. Prostaglandin–Thromboxane A2 (TXA2) inhibition
2. Inhibition of the ADP binding in platelets
3. Cyclic nucleotide phosphodiesterase inhibition
4. Receptor blockade of gpIIb/IIIa receptors, blocking the final pathway of platelet aggregation
Aspirin exerts its antiplatelet effects by inhibiting expression of what?
Thromboxane A2
Clopidogrel exerts its anti________ effects by inhibiting _____-binding within ________.
Clopidogrel exerts its antiplatelet effects by inhibiting ADP-binding within platelets.
___________ exerts its antiplatelet effects by inhibiting ADP-binding within platelets.
Clopidogrel exerts its antiplatelet effects by inhibiting ADP-binding within platelets.
Aspirin inhibits TXA2 production by _________ly acetylating COX, thereby inhibiting platelet aggregation.
Aspirin inhibits TXA2 production by irreversibly acetylating COX, thereby inhibiting platelet aggregation.
Name two antiplatelet medications that irreversibly block platelet ADP receptors.
Clopidogrel;
ticlopidine
As the antiplatelet effects of aspirin and clopidogrel are irreversible, how long will their effects last?
~8 - 10 days
(lifespan of a platelet)
Dipyridamole is an antiplatelet medication that inhibits _________, thus increasing platelet cAMP and decreasing _________ uptake.
Dipyridamole is an antiplatelet medication that inhibits phosphodiesterase, thus increasing platelet cAMP and decreasing adenosine uptake.
__________ is an antiplatelet medication that inhibits phosphodiesterase, thus increasing platelet cAMP and decreasing adenosine uptake.
Dipyridamole is an antiplatelet medication that inhibits phosphodiesterase, thus increasing platelet cAMP and decreasing adenosine uptake.
What are the indications for clopidogrel usage?
Recent MI, stroke, acute coronary syndrome or peripheral artery disease
What medication blocks gpIIb/IIIa?
What is its main indication?
Abciximab;
percutaneous coronary intervention (PCI)
The mechanism of eptifibatide anticlotting action is:
a) activation of antithrombin III
b) blockade of posttranslational modification of clotting factors
c) inhibition of thromboxane production
d) irreversible inhibition of platelet ADP receptors
e) reversible inhibition of glycoprotein IIb/IIIa receptors
e) reversible inhibition of glycoprotein IIb/IIIa receptors
(similar to abciximab)
