Hematologic meds Flashcards
Prothrombin time is screening for the function of the _______ pathway.
INR is a standardize PT designed to account for differences in _________
APPT: is a screening test for the ________ pathway
Extrinsic
Thromboplastin
Intrinsic
Oral anticoagulants include what drug categories and what drugs?
Indirect Thrombin Inhibitors: Warfarin
Direct Oral Factor Xa inhibitors: ApiXAban, RivaroXAban, EdoXAan
Direct Thrombin inhibitors: Dabigatran mesylate
Injectable anticoagulants include what drug categories and what drugs?
Indirect Thrombin Inhibitors : Heparin, LMWHs (Enoxaparin and Dalteparin), Fondaparinux
Direct Thrombin Inhibitors: Bivalirudin, Argatroban
In general, what is the clinical use of an Anticoagulant?
Venous thrombosis (DVT) Venous thromboembolism Artificial Heart Valves A-Fib Protein C and S bleeding disorders Prophylaxis after surgery
What kind of drug is Warfarin? What part of the cascade does it inhibit? What is its mechanism of action?
Oral Indirect Thrombin inhibitor
II (prothrombin), **VII (extrinsic pathway), IX, X
Inhibit VITAMIN K cofactors. (clot stuff needs VIT K)
Why use warfarin?
Prophylaxis and Tx of DVT, PE, Thromboembolic complications of A-fib and valve replacement
Prevent death following Stroke and MI
Protein C and S def.
Is anticoagulation based on the half life of warfarin? What if we need rapid effect?
No, it is based on half life of coagulation factors (2-7 days)
Combine with Heparin or LMWH until therapeutic INR reached
Describe INR in terms of monitor schedule, normal range, and goal catagories.
Measure INR bi-weekly at first hen Q4-6 as dosing is stabilized.
Normal = 0.8-1.2
Goal of 2-3 if = Prophylaxis of DVT and Tx of thrombotic disease
Goal of 2.5-3.5 if = artificial valve or medical condition w/ signs and symptoms of elevated INR??
What is the dose for Warfarin
It depends on the individual.
Ditrate does to therapeutic INR. @ 1 week you will see initial adjustment in PT, then adjust q2-3 days to get goal.
What are the hallmark adverse reactions of Warfarin?
Purple toe
Also skin necrosis and bleeding stuff.
Dont give it to preggos…. EVER.
If a warfarin patient presents with a high INR, what should you do?
Follow the table.
If it is high but under 4.5 –> Reduce or skip dose. Resume when INR is normal.
If between 4.5-10 –> Hold 1-2 doses and return when normal. If **URGENT SURGERY needed, give Vitamin K (Phytonadion).
If over 10 –> Hold warfarin and give Vitamin K (oral or IV)
If a warfarin patient presents with Major Bleeding, what should you do?
Give PCC (as opposed to FFP) Administer vitamin K slow IV
What is prothrombin complex concentrate used for? What are our two agents?
Urgent reversal of acquired coagulation factor deficiency (IE warfarin)
Kcentra - Prothrombin and factors + protein C and S
Profilnine - Factors
What is the reversal agent for Warfarin? Is this rapid push?
Phytonadion (vitamin K)
Give slow to avoid anaphylactic reactions (IV and PO) only)
This medication is extracted from porcine intestinal mucosa, binds to Anti-thrombin III to inhibit coagulation factors faster and is used to reduce thrombi expansion and prevent thrombin formation
Heparin (subq or IV only)
**BTW acts in minutes not hours and days like warfarin
Heparin crosses the placenta and travels via breast milk so it is totally contraindicated in pregnant patients right?
No. It does not do those things and is pregnancy cat C
What four major adverse reactions do you get with Heparin
Bleeding
Osteoporosis
Hyperkalemia
Heparin Induced Thrombocytopenia (plate below 150k) bleeding occurs under 50k
Who doesn’t get heparin?
Pts with or with Hx of HIT Active bleeding or hemophilia Thrombocytopenia or purpura HTN or IC hemm Recent surg or upcoming lumbar puncture
What do we use to monitor Heparin.
aPTT (activated partial thromboplastin time)
Hemoglobin, Hematocrit, platelets, bleeding
Because LMWH binds to anti-thrombin III and inactivates factor Xa, what test is unnecessary?
aPTT
LMWH is pregnancy catagory _______ as opposed to heparin which is _______
B
C
What are the two LMWHs? What makes them different?
Enoxaparin and Daltaparin
Both can be used in prophylaxis of DVT, but only ENOXAPARIN can be used in prophylaxis of ischemic complications of angina and MI.
Enoxaparin is also used in acute DVT tx, Inpatient and outpatient with warfarin and STEMI.
Dateparin - VTE and prev VTE in CANCER patients
Protamine is the reversal agent for heparin. Does this work the same for Enoxaparin and Daltaparin?
Not completely.
What is the boxed warning for LMWHs?
Spinal/epidural hematomas which may result in long term or permanent paralysis.
What is Fondaparinux? What is it used for?
Anticoagulant the binds to ANTITHROMBIN III and inhibits Factor Xa.
Prophylaxis DVT in surgery
Treate acute DVT w/ Warfarin
Treat acute PE w/ Warfarin
What side effects and boxed warnings does Fondiparinux and LMWH share
Almost all of them
Epidural shit, less likely to cause HIT than heparin. Bleeding. No monitoring.
Protamine is from _______. It is the reversal agent for what? Do we push it fast? What drugs does it interact with?
Fish sperm
Heparin
SLOW
ABX (beta lactams)
What do Direct Oral Factor Xa inhibitors do?
What drugs are in this class?
What are the black box warnings?
Selectivly block Xa (doesn’t need cofactor)
RivaroXAban, ApiXAban, EdoXAban
Spinal/epidural Hematoma and d/c without adequate anticoagulation causes stroke.
What makes Oral Factor Xa inhibitors better than Warfarin? What makes them worse?
Better: “non inferior” but APIXABAN is better, less drug interactions. Has an antidote (AndeXXA). No monitor
Worse: More expensive. Cant use in PROSTHETIC VALVES.
What are the clinical uses of Rvaroxaban, Apixaban and Edoxaban?
All - Stroke prevention and systemic embolism in Non valvular A-Fib
Riva and Api - Also Prophylaxis of DVT following surgery
All - DVT/PE tx
What is the only direct Xa inhibitor that is preg cat B?
Apixaban
Who shouldnt get Direct Xa inhibitors?
Liver patients and no Edoxaban w/ <15 CrCl
What 3 drugs are Direct Thrombin inhibitors?
Bivalirudin, Argatroban, Dabigatran (prodrug)
What are the clinical indications for Bivalirudin and Argatroban (direct thrombin inh)?
Bivalirudin - PCI, PTCA, **PCI w/ risk of HIT or HITTS
Argatroan - prophylaxis and tx of pt with HIT and **PCI w/ risk of HIT
Bivalirudin and argatroban are Direct thrombin inhibitors but get metabolized differently. How?
B - Renal
A - liver
Are we required to monitor Direct thrombin inhibitors? Do we need bridging?
Yes. if HIT then aPPT. IF PCI or similar than ACT.
Yes, bridge with warfarin as opposed to just stopping.
What is dabigatran? What is it used for?
Direct thrombin inh. PRODUG
Prevent stroke or systemic embolism in pt w/ non valve A-fib
DVT/PE treatment and proph.
Does Dabigatran have a black box warning? What is it?
What is Dabigatran’s reversal agent?
Spinal/epidural hematoma. D/c = stroke risk
Idrarucizumab (Paxbind)
What are the major interactions w/ Dabigatran
Aspirin and clopidogrel.
Take 2 hrs before antacids
Though Dabigatran is similar to Bivalrudin and Argatroban, what are the differences in terms of Monitoring, contraindications, and Warfarin conversion
No monitoring in Dabigatran
Don’t use dabigatran w/ mechanical heart valve
No bridge. Stop/start at specific INR.
List the anticoagulants with reversal agents and their corresponding drug .
Heparin - Protamine Sulfate LMWH - Consider PS but not complete Fondaparinux - PCC maybe Warfarin - Phyronadion (Vit K), PCC Dabigatran - Idarucizumab Xa's - Recomb factor Xa (Andexxa)
What do fibrinolytics do? What are there general clinical uses?
Dissolve clots by converting plasminogen to plasmin. This cleaves fibrin.
STEMI Acute Isch Stroke Acute PE Restoce CV cath flow Severe MASSIVE DVT
Urokinase is an example of what type of drug?
Thrombolytic enzyme. Convert uncomplexed plasminogen to plasmin.
What is tPA? What does it do? What drugs are found in this class?
Drug that activates BOUND plasminogen initiating fibrinolysis.
Alteplase (STEMI, PE, Acute Ischemic Stroke, CV cath reflow)
Reteplase and Tenecteplase (ACUTE STEMI)
Who should absolutely not get a Fibrinolytic?
Hx of Intracranial HEMORRHAGE Hx of CEREBROVASCULA lesion Known INTRCRANIAL Neoplasm ISCHEMIC STROKE < 3 months AORTIC dissection Head/facial trauma w/in 3 months Active bleeding
This drugs main effect is inhibition of prostaglandin synthesis
Aspirin
These drugs are ADP P2Y12 receptor inhibitors
Clopidogrel
Ticagrelor
Prasugrel
Cangrelor
These drugs are Glycoprotein IIB/IIA receptor inhibitors
Abciximab
Epitifabatide
Tirofiban
