pharm: platelet disorders

week of 9/24

platelet disorders

Thrombocytosis (too many -> thrombosis)

Thrombocytopenia (too few -> bleeding)

Von Willebrand’s disease (defective adhesion)

thrombocytosis

Treatment:

Treat underlying cause

Antiplatelet

Hydroxyurea or anagrelide (in high-risk patients)

Platelet-pheresis

antiplatelet therapies

Used to decrease risk of stroke, MI, vascular disease

Aspirin (ASA)

P2Y 12 receptor blockers

• 1. Thienopyridines like Clopidrogel (plavix) and prasugrel (Effient)

• 2. Non-Thienopyridies like Ticagrelor (Brilinta) and Cangrelor (Kengreal)

Vorapaxar (Zontivity)

GPIIb/IIIa inhibitors

• Abciximab (Reopro), Tirofiban (Aggrastat), and Eptifibatide (Integrilin)

Dipyridamole

Cilostazol

aspirin (antiplatelet) dose

DOSE: 81 mg po QD typical

SALICYLATE

aspirin (ASA) indication

NSAID, antipyretic (treats fever), anti-inflammatory (in higher doses), antiplatelet (in higher doses)

aspirin MOA

MOA: irreversibly inhibits COX-1, reduces prostaglandin and thromboxane A2, produces analgesic, antipyretic, reduces platelet, anti-inflammatory

aspirin se

SE: tinnitus, N/V, GI bleed, Reye’s syndrome, prolonged bleeding time, thrombocytopenia, bruising, angioedema

prevents GI side effects of aspirin

PPI’s such as Prilosec (omeprazole), nexium (esomeprazole)

H2 blockers such as Pepcid (Famotidine), Nizatidine (Axid)

Misoprostol (Cytotec) -> inhibits gastric acid secretion (Rx)

EC ASA (enteric coated ASA, it’s a protective thing over ASA so it doesn’t dissolve until it gets to the stomach later on and that will reduce GI) - Ecotrin

PPI

• prevents GI side effects of ASA

• ONCE A DAY DOSING

• Omeprazole, esomeprazole, pantoprazole (least amount of CYP activity, if you have someone on clopidogrel, this is the one to use), lansoprazole (THESE BLOCK CYP ENZYMES)

PPI MOA

MOA: binds to H+/K+ (ATPase enzyme system) which suppresses the secretion of hydrogen ions in stomach

PPI adverse effects

Adverse effects: diarrhea, C.diff, hypomagnesemia, increased incidence of pneumonia, possible acute renal impairment

clotting cascade

if you’re on PPI too long, your magnesium will go low, so you can prescribe a magnesium supplement. together → diarrhea so you add anti-diarrhetic med = clotting cascade

PPI interactions

clopidogrel (an antiplatelet, a prodrug which needs to be metabolized by CYP enzymes), vitamin B12, calcium carbonate, FeSo4

H2 Receptor antagonist

Famotidine (pepcid): 10, 20, 40 mg QD/BID IV/PO (dose based on renal function)

Nizatidine (Axid): 150 mg, 300 mg QD/BID IV/PO (dose based on renal function)

Cimetidine (Tagamet) QD/BID IV/PO (dose based on renal function)

H2 Receptor antagonist MOA

MOA: selectively antagonizes histamine H2 receptors

H2 Receptor Antagonist SE

SE: diarrhea, constipation, dizziness, HA, B12 def after long term use

Misoprostol (Cytotec) MOA

PGE1 analog

MOA: interacts with prostaglandin receptors on parietal cells in stomach. Results in reduced acid secretion

Misoprostol (Cytotec) dose

DOSE: 100 mcg to 200 mcg PO qid

Misoprostol (Cytotec) adverse effects and contraindication

Adverse effects: diarrhea, abdominal pain

CONTRAINDICATED DURING PREGNANCY (can increase uterine contractions)

P2Y-12 ADP receptor blockers

Clopidogrel (Plavix)

Ticagrelor (Brilinta)

Ticlopidine (Ticlid)

Prasugrel (Effient)

Cangrelor (Kengreal)

P2Y-12 ADP Receptor Blocker MOA

MOA: inhibits binding of ADP to its receptors on plts -> inhibits activation of GPIIb/IIIa receptors required by plts to bind to fibrinogen and to each other

Clopidogrel (Plavix) MOA

• antiplatelet

• MOA: P2Y-12 ADP Receptor Antagonist (irreversible binding). Inhibits plt-fibrinogen binding -> inhibit plt aggregation

Clopidogrel (Plavix) dose

Maintenance dose: 75 mg PO daily

Clopidogrel (Plavix) metabolism

Metabolism: PRODRUG!! Extensively by liver, half life = 8 hours

Plt aggregation returns to normal 5 days after drug is stopped

Clopidogrel (Plavix) adverse effects and BBW

BBW: poor metabloizers of CYP450 can experience more CV events following acute coronary syndrome or percutaneous coronary intervention

Adverse effects: bleeding, SJS, TTP

aspirin dose for cardioprotective properties

81 mg

Prasugrel (Effient) MOA

Antiplt, faster acting

MOA: P2Y-12 ADP Receptor Antagonist (irreversible binding)

Prasugrel (Effient) adverse effects

Adverse effects: angioedema, bleeding, HA, hyperlipidemia, HTN, TTP

Don’t give stroke pts or MI!!!! Not preferred if over >75 and <60 kg due to bleeding

Prasugrel (Effient) interaction

anticoag and other antiplts

Ticagrelor (Brilinta)

Ticagrelor (Brilinta) MOA

Antiplt

MOA: P2Y-12 ADP Receptor Antagonist (REVERSIBLE BINDING). Inhibits plt-fibrinogen binding -> inhibits plt aggregation

Ticagrelor (Brilinta) adverse effects and dosing

Give with aspirin, max 100 mg together with aspirin QD

Adverse effects: bleeding, dyspnea, HA, increased SCr

Ticagrelor (Brilinta) interactions

Interactions: strong CYP3A4 inhibitors -> decreased bleeding

Strong CYP3A4 inducers -> decreased efficacy

Dipyridamole (Persantine) MOA

MOA: increases adenosine (coronary vasodilator + plt aggregation inhibitor). Dilates coronary artery to help prevent clotting

Dipyridamole (Persantine) dosing and SE

more than ONCE a day

SE: dizziness, hypotention, HA, nausea, flushing

Dipyridamole (Persantine) interactions

more interactions compared to clopidegrol (main thing for clopidegrol is something that effects CYP enzymes). this drug has a LOT of interactions

Dipyridamole (Persantine) metabolism and warning

Metabolism: via liver, half life 10-12 hours

DO NOT USE IN PATIENTS WITH UNSTABLE ANGINA

Anagrelide (Agrylin)

Antiplt and phosphodiesterase inhibitor

Cilastazol (pletal)

• antiplt

  • contraindicated in heart failure!

Cilastazol (pletal) metabolism and SE

Metabolised by CYP3A4 and 2C19

Adverse effects: GI, headache

injectable antiplts

Eptifibatide and tirofiban are injectable antiplt

antiplt meds

often cause bleeding

aspirin

reye syndrome

GPIIb/IIIa inhibitors

Tirofiban (aggrastat)

Eptifibatide (Integrilin)

ARE GIVEN IV! With heparin and ASA (you need IMMEDIATE therapy, and warfarin takes 5 days to work, so you don’t want to use warfarin here)

Binds to GP IIb/IIIa, blocks binding of fibrinogen and vWF -> prevents aggregation

ITP treatment

Treatment: high dose steroids or IVIG when plts are less than 20k

First line: glucocorticoids raise plt count in approx 2/3 of patients, with most patients responding within 2-5 days

• Dexamethasone (no need to taper) and prednisone

• High dose steroids typically taper the medication

• Alternative: IVIG can raise plt count 24-28 hours, most useful for transient (pts who require rapid, temp increase in plt count) or who unable to tolerate glucocorticoids

IVIG: inc plt count by interfering with macrophage uptake with autoantibody-coated plts

TTP

Treatment: plasmapheresis or exchange transfusion

treating VWD

Demopressin (DDVAP): serves as ADH (antidiuretic hormone)

Weight based, IV and nasal spray

Useful in most pts with type 1, variable in type 2, and not useful in type 3

Watch out for anaphylaxis! Other SE: flushing, HA, rhinitis

coagulation disorders

Factor VIII deficiency: hemophilia A

Treatment: F VIII concentrate infusion

Factor IX Deficiency: Hemophilia B

Treatment: fresh frozen plasma/Factor IX concentrate

Factor XI deficiency

Treatment: daily infusion of fresh frozen plasma when bleeding is active or anticipated (surgery/childbirth)

Anticoags

Warfarin

UFH

LMWH

NOAC/DOAC (novel or direct oral anticoags)

Direct thrombin inhibitors

warfarin

 initially decreases protein C levels faster than it does with coag factors so can increase tendency to clot when treatment is first begum

Stopping bleeding

• Heparin reversal

Heparin reversal

protamine sulfate. protamine sulfate IV for every 100 IU of active heparin. Hypotension and anaphylaxis

Warfarin reversal

Vitamin K PO (Mephyton) or IM (Aquamephyton) will reverse its effects in a couple ofhours.

• DO NOT GIVE VIT K IV – will cause anaphylaxis!

Andexanet alfa (Andexxa)

is a modified recombinant factor

Xa molecule that reverses oral direct (e.g., apixaban, rivaroxaban) and injectable indirect (e.g., enoxaparin, fondaparinux) factor Xa inhibitors

dabigtran (pradaxa) reversal

praxbind (idarucizumab)

Treatment of Hyperfibrinolytic states

Tranexamic acid and Aminocaproic acid (amicar)

Unfractionated Heparin (UFH)

dosed without regard to renal function

rivaroxaban (xarelto)

selectively inhibits Coagulation Factor Xa

dabigatran (pradaxa)

direct thrombin inhibitor

clopidogrel (plavix)

irreversibly binds to ADP receptor

aspirin

irreversibly inhibits COX-1

alteplase (tPA)

binds to fibrin in thrombus and converts plasminogen to plasmin

ferrous sulfate 325 mg TID

• female presents with new diagnosis microcytic anemia with low ferritin of 10

  • include GI workup

fivaroxaban (xarelto)

• 58 y/o in ER with DVT

  • best ORAL option

ticagrelor (brilinta)

P2Y12 ADP receptor antagonist the reversibly binds to the receptor

warfarin

can induce paradoxical local thrombosis. This is usually seen in the first week of therapy, more common in patients with protein C or S deficiency

thrombolytics

activate plasminogen to plasmin resulting in degradation of fibrin

aspirin (anticoag)

81 mg PO qd

clopidogrel (plavix)

75 mg PO qd

ferrous sulfate (42 years old)

325 PO tid

warfarin starting dose

2-5mg PO qd (once a day)

folic acid

1 mg PO qd

apixaban (eliquis)

5 mg PO bid

dabigatran (pradaxa)

150 mg PO bid

contraindication to thrombolytic therapy

• suspected dissection of aorta

• previous hemorrhagic stroke

• active internal bleeding

HIGH blood pressure is NOT one