Hematologic Flashcards
What does an endothelial cell normally secrete to repel circulating thrombocytes? (Two things)
- Prostocyclin (PG12)
2. Nitrous oxide (NO)
This proteolytic enzyme converts fibrinogen to fibrin:
Thrombin
What are the three phases of clotting?
- Platelet Adhesion
- Platelet Activation
- Platelet Aggregation
How do NO and PGI2 affect platelets?
They induce cAMP synthesis, which decreases intracellular Ca++ and INHIBITS GPIIb/IIIa activation
Damaged endothelial cells expose what?
Von Willebrand factor (vWF) and collagen
Name the top three chemical mediators secreted by adhered/activated platelets:
- ADP (Adenosine diphosphate)
- TXA2 (thromboxane A2)
- 5HT (Serotonin)
What action does local 5HT released by activated platelets have in the area of the endothelial damage?
Vessel spasm, reducing blood loss
Primary actions of TXA2?
- Stimulate activation and aggregation of platelets
2. Potent vasoconstrictor
What is thrombin’s job?
To convert fibrinogen to fibrin
What is the function of the GPIIb/IIIa receptors on thrombocytes?
Facilitate platelet-platelet interaction; fibrin bridge connects the GPIIb/IIIA receptors of one platelet to another
This pathway is shorter, and measured by PT/INR:
Extrinsic pathway
This pathway in longer, and measured by aPTT:
Intrinsic pathway
Which pathway is vitamin K dependent? Extrinsic or intrinsic?
Extrinsic, because it starts with Factor VII (which is Vitamin K dependent)
Name three natural anticoagulants:
- Protein C
- Protein S
- Anti-thrombin III
Which pathway is prothrombin time (PT) used to monitor?
Which factor is involved?
What does that factor need in order to be synthesized?
Extrinsic pathway
Factor VII
Vitamin-K dependent
Which factors are Vitamin K-dependent?
Which has the shortest life-span?
Which has the longest?
Factors II, VII, IX, X
Shortest: VII
Longest: II (thrombin)
Which pathway does the aPTT test assess?
The intrinsic pathway
What are the elements of Virchow’s Triad?
- Vascular wall injury
- Stasis
- Hypercoagulable state
MOA for ASA?
IRREVERSIBLY inhibits COX-1 and 2
Stops conversion of AA to prostaglandin, leading to less TXA2
Leads to inhibition of platelet aggregation, decreased inflammation
ASA dose range for prevention of cardiovascular events:
50mg to 160mg
Top risk of ASA use:
GI bleeding
Rare SE of ASA?
Reye’s Syndrome - swelling of the liver and brain (peds)
Avoid use of salicylates in children
ASA pregnancy category?
C/D —> avoid in 3rd trimester
*APAP —> preferred for pregnancy
Dipyrimadole MOA?
- Stimulates PGI2 synthesis
- Stimulates cAMP
- Inhibits platelet aggregation
Dipyrimadole use?
- Combined with ASA to prevent CVA (ischemic)
2. Post-heart valve replacement thrombus prevention
Dipyrimadole SE’s?
Coronary steal phenomenon: unstable angina patients
Caution when used with anticoagulants
Aggrenox (ASA and Dipyridamole) - use?
Reduce risk of stroke in pt’s who have already experienced TIA or CVA
Aggrenox - CI’s?
Reye’s Syndrome
Cilostazol - MOA?
PDE3 inhibitor
Inhibits cAMP breakdown
Inhibits platelet aggregation
Vasodilatory in vascular smooth muscle
Cilostazol - use?
Intermittent claudication (muscle pain) symptom relief
Cilostazol - SE’s?
Cardiac (palpitation, tachyarryhthmias)
HA
Diarrhea
Cilostazol - CI’s?
BLACK BOX: HF
Vorapaxar - MOA?
PAR-1 antagonist
Inhibits thrombin-induced platelet aggregation
Does NOT inhibit platelet aggregation via ADP, vWF, etc
Vorapaxar - use?
Prevention of thrombotic events in pt’s with hx of MI or PAD
Vorapaxar - CI’s?
Not for use in ACS
Avoid use with strong CYP3A inhibitors or inducers
Avoid use with anticoagulants
Clopidogrel (Plavix) and Prasugrel (Effient) - MOA?
IRREVERSIBLY inhibits ADP from binding to P2Y12 receptor - leads to inhibition of GPIIb/IIIa expression (required for platelet aggregation)
Ticagrelor - MOA?
REVERSIBLY inhibits ADP from binding to P2Y12 receptor - leads to inhibition of GPIIb/IIIa expression (required for platelet aggregation)
Clopidogrel/Prasugrel - use?
Prevention of atherosclerotic events for pt’s with:
Recent stroke or MI, or PAD
Post-PCI patients
Ticagrelor - use?
ACS patients
Clopidogrel - active or prodrug?
Prodrug
Prasugrel- active or prodrug?
Prodrug
Ticagrelor - active or prodrug?
Active
Cangrelor - MOA?
Inhibits binding of ADP to P2Y12 receptor
Cangrelor - use?
Adjunct to PCI
Abciximab - MOA?
Monoclonal antibody GPIIb/IIIa receptor inhibitor
Abciximab - use?
Adjunct to PCI
Ebtifibatide - MOA?
GPIIb/IIIa receptor inhibitor - prevents binding of fibrin to GPIIb/IIIa, preventing platelet aggregation
Eptifibatide - use?
ACS, PCI
Tirofiban - MOA?
GPIIb/IIIa receptor inhibitor - prevents binding of fibrin to GPIIb/IIIa, preventing platelet aggregation
Tirofiban - use?
ACS, PCI
Eptifibatide and Tirofiban - considerations?
Renal insufficiency
Pharmacological management of unstable angina?
- Antiplatelet (P2Y12, GP)
2. Anticoag (UFH, LMWH, etc)
Clinical use for anticoagulants?
Reduce existing thrombi expansion (STEMI, CVA, PE) and prevent formation of new thrombi (a-fib)
What does UFH complex with to accelerate anticoagulation in the body?
Antithrombin III
Which factor(s) does UFH bind to and inhibit?
IIa (thrombin)
Xa
Onset of UFH?
Minutes
Adverse reactions UFH?
Heparin-Induced Thrombocytopenia with paradoxical embolization
Antidote for UFH?
Protamine sulfate
UFH - CI’s?
- Hx of HIT
- Hypersensitivity
- Recent surgery (increased bleeding risk)
- Intracranial hemorrhage
What laboratory test do we use to evaluate UFH response and adjust dosage (titrate to effect)?
Activated partial thromboplastin time(aPTT)
An aPTT of longer than ___ may indicate bleeding:
70 seconds
UFH - pregnancy category?
C (recommended for certain situations)
LMWH - MOA?
Similar to heparin - binds anti-thrombin III, but only inactivates Xa rather than IIa AND Xa
Which is more preferable in pregnancy - UFH or LMWH?
LMWH
Enoxaparin - uses?
- DVT prophylaxis
- Unstable angina
- STEMI
Dalteparin - uses?
- DVT prophylaxis
2. Preferred Rx for tx of recurrent VTE in cancer patients
Monitoring considerations for LMWH?
Not necessary to monitor aPTT, but LMWH does have a longer half-life than UFH
LMWH advantages over UFH?
- No need to monitor aPTT
- Less incidence of HIT
- Longer T1/2
- Pregnancy-safe
Protamine sulfate - CI’s?
Fish allergy
Fondaparinux - MOA?
Binds with anti-thrombin III, SELECTIVELY inhibiting Xa
Fondaparinux - use?
- DVT prophylaxis
- Acute DVT (w/ warfarin)
- Acute PE (w/ warfarin)
Fondaparinux - black box warning?
Spinal/Epidural hematoma
Fondaparinux - AE?
Less likely to cause HIT, but still CI in pt’s with thrombocytopenia (<100K)
Warfarin - MOA?
Inhibits Vitamin K epoxide reductase (in the liver), reducing the available Vitamin K for cofactors II, VII, IX, and X, as well as Proteins C and S
Warfarin - uses?
- DVT, PE, a-fib - treatment and prophylaxis
- Post-MI / CVA
- Protein C and S deficiency
What factor is “half-life” of warfarin actually based on?
The lifespan of the Vitamin K-dependent clotting factors and Protein C and S
First to die - VII (6 hours)
Last to die - II (3 days)
Warfarin monitoring?
PT (prothrombin time)
INR (international normalized ratio)
Target INR for DVT prophylaxis?
2 to 3
Target INR for artificial valve thrombosis prevention?
2.5 to 3.5
Warfarin in pregnancy?
Category X
Warfarin AE?
Purple Toe syndrome (from cholesterol microembolization)
Foods that can disrupt target warfarin therapy?
Vitamin-K heavy foods (mostly dark, leafy-green veggies)
Actions to take if INR is above target but less than 4.5?
Skip a dose
Actions to take if INR is 4.5 to 10?
Skip 1 to 2 doses, monitor, lower dose
Actions to take if INR is >10?
Hold warfarin and give Vit-K
If major bleeding associated with Warfarin use is present?
PCC (prothrombin complex concentrate)
Or
FFP (fresh frozen plasma)
Phytonadione - MOA?
Fat soluble Vitamin K
Phytonadione - use?
Warfarin reversal agent
Bivalirudin - action and indication?
Direct thrombin inhibitor (factor IIa) // patients at risk for HIT
Bivalirudin - clearance?
Renal
Argatriban - MOA and use?
Direct thrombin inhibitor, used for treatment or prevention of HIT
Argatroban - clearance?
Liver
Dabigatran (Pradaxa) - MOA and use?
Direct thrombin inhibitor, DVT/PE/afib
Dabigatran (Pradaxa) - metabolized by?
P-glycoprotein
Dabigatran - pregnancy?
C
Dabigatran advantages over warfarin?
- Monitoring not required
- Lower risk of brain bleed
- More effective at preventing CVA
Dabigatran disadvantages over warfarin?
- Renal elimination
- Risk for dyspepsia
- Twice daily dosing
Idarucizumab (Praxbind) - MOA and use?
Monoclonal Ab fragment - binds dabigatran, neutralized anticoagulant effect
Reverses dabigatran effects
Suffix for direct oral factor Xa inhibitors?
-Ban (banning the factor Xa fox)
Oral direct Xa inhibitors - MOA?
Selectively blocks Xa, preventing conversion of prothrombin to thrombin
Major disadvantage for oral direct Xa inhibitors?
No antidote
Rivaroxaban and Apixaban - caution in which population?
Liver disease
Edoxaban - caution in which population?
Liver disease AND renal insufficiency
Which oral Xa direct inhibitor is best for pregnancy?
Apixaban
Fibrinolytics - MOA?
Activates conversion of plasminogen to plasmin that hydrolyzes (cleaves) fibrin
What classes are co-administered along with fibrinolytics?
Antiplatelet
Antithrombotic
Examples of two thrombolytic enzymes?
Streptokinase
Urokinase
Examples of tissue plasminogen activators?
Alteplase
Reteplase
Tenecteplase
Which TPA’s are only for STEMI?
Reteplase
Tenecteplase
Absolute contraindications for fibrinolytics? (Pneumonic - BD-HINT)
- Bleeding (any active bleeding)
- Dissection (aortic)
- Hemorrhagic CVA (ever)
- Ischemic CVA (< 3 months ago)
- Neoplasm (cranial)
- Trauma (head/face < 3 months ago)
Criteria for “massive” PE?
- SBP < 90 x15 minutes
- Loss of palpable pulse
- Requiring inotropic support
Alteplase - use?
CVA, STEMI, PE
Cryoprecipitate - what is it, what is it used for?
Plasma protein from whole blood, containing clotting factors, used to treat acute bleeding problems
Prothrombin Complex Concentrate (PCC) - what is it, what is it used for?
Blood coagulation factors, used to reverse effects of the “-bans” (Xa inhibitors) (bc there’s no actual antidote for the -ban’s)
Tranexamic Acid - MOA?
Displaces plasminogen from fibrin, resulting in inhibition of fibronolysis (promotes clotting)
Tranexamic Acid - AE?
Severe thrombotic events
Trsanexamic acid - elimination?
Renal
Tranexamic acid - caution with pt’s with…?
- Hx thrombotic events
2. Renal dysfunction
What are three essential nutrients for bone marrow hematopoiesis?
- Iron
- Vitamin B12
- Folic Acid
What percentage of orally administered iron actually gets absorbed?
25%
Antidote for iron overdose?
Deferoxamine - iron-chelating agent
What is required in the stomach for B12 absorption?
Intrinsic factor
Hepatic stores of Vit-B12 can last how long?
Up to 5 years
Folate, Folic Acid, Vitamin B9 - required for…?
DNA synthesis
Pt’s that may need folic acid:
- Pregnancy
- Alcoholics
- Hemolytic Anemia
- Dialysis
Leucovorin?
Folic acid antagonist (OD)
Where is eryhtropoietin produced?
Renal peritubular cells
Epoetin Alfa and Darbapoetin Alfa - MOA and use?
Increase the rate of proliferation and differentiation of erythroid precursor cells in the bone marrow
Used for anemia of chronic renal failure, chemotherapy-induced anemia
Filgrastim and Sargramostim - MOA and use?
Colony stimulating factors that cause the production, maturation, and activation of neutrophils
Chemotherapy, leukemia, stem cell transplant