pharm blood clotting ch 48

the body's protective mechanisms to prevent excess blood loss.

hemostasis

3.1 Hemostasis: how your body stops bleeding

Hemostasis = the body's protective mechanisms to prevent excess blood loss. Think of fixing a leaky pipe in 3 steps:

1 Vascular constriction (0 seconds): the injured vessel squeezes down. The injured lining releases factors, and blood

flow decreases.

2 Platelet plug (seconds to minutes): platelets stick (adhere) to the injured wall, release granules, and clump

together (aggregate), forming a plug.

3 Coagulation cascade and fibrin clot (minutes): the clotting cascade is switched on and a blood clot (platelets +

fibrin mesh) forms.

the injured vessel squeezes down. The injured lining releases factors, and blood flow decreases.

Vascular constriction

how long does Vascular constriction take

0 sec

immediate

platelets stick (adhere) to the injured wall, release granules, and clump together (aggregate), forming a plug.

platelet plug

how long does platelt plug take

seconds to minutes

the clotting cascade is switched on and a blood clot (platelets and fibrin mesh) forms.

Coagulation cascade and fibrin clot

how long does Coagulation cascade and fibrin clot take

minutes

both feed into the common clotting pathway.

the intrinsic pathway and the extrinsic pathway

a clot where u dont want one

thrombosis

thrombi (clots) form, decreasing blood flow or fully blocking a vessel, causing hypoxia, anoxia, necrosis. These are the common ones.

• Thromboembolic disorders:

: excess bleeding. Less common than clots, but can be highly fatal.

Hemorrhagic disorders:

. Anti-clotting drugs cause ;

bleeding

pro-clotting drugs cause

.

thrombosis

Alter platelet aggregation and the platelet plug

Antiplatelets

Antiplatelets prototype drug

Aspirin, clopidogrel

Interfere with the clotting cascade and thrombin formation

Anticoagulants

anticoagulant prototype drug

Heparin, warfarin

Break down a clot already formed by stimulating the

plasmin system

Thrombolytics

Thrombolytics prototype drug

Alteplase

which step of hemostasis does antiplatelets work on

step 2

which step of hemostasis does anticoagulants work on

step 3

which step of hemostasis does thrombolytics work on

reverses a finsihed clot

Antiplatelet agents

: abciximab (ReoPro), anagrelide (Agrylin), aspirin (generic, prototype), cilostazol, clopidogrel (Plavix),

dipyridamole (Persantine), eptifibatide, ticagrelor (Brilinta), ticlopidine, tirofiban (Aggrastat), vorapaxar (Zontivity).

antiplatelte action

inhibit platelet adhesion and aggregation by blocking receptor sites on the platelet membrane.

Anagrelide - antiplatelet action

it is different: it blocks platelet production in the bone marrow.

Antiplatelet agents used for

CV diseases prone to blocked vessels; keeping venous and arterial grafts open; preventing

cerebrovascular blockage; peripheral artery disease; adjuncts to thrombolytics in MI and preventing reinfarction

after MI.

pharmacokinetic antiplatelets

generally well absorbed, highly bound to plasma proteins, liver metabolism, urine excretion, tend to enter

human milk.

contraindication/caution antiplatelet

allergy, plus agent-specific ones.

: bleeding disorder or active bleeding, recent surgery, closed head injury, pregnancy and lactation.

adverse effect antiplatelet

bleeding, headache, dizziness, weakness, GI distress, skin rash.

inhibits prostaglandin synthesis by inactivating cyclooxygenase-1 (COX-1), which prevents

arachidonic acid from becoming thromboxane A2. No thromboxane A2 means platelets can't aggregate.

ASPIRIN

uses aspirin

: reduce risk of death and MI in chronic coronary artery disease (history of MI, unstable angina, chronic

stable angina); reduce death and recurrent stroke after ischemic stroke or TIA; peripheral artery disease; also a

pain and fever reducer.

pharmokokinetic aspirin

oral. Onset 5-30 min, peak 0.25-2 h, duration 3-6 h. T1/2 15 minutes to 12 hours. Liver metabolism, urine

excretion.

aspirin adverse effect

acute aspirin toxicity (hyperpnea, possibly fever, coma and CV collapse), nausea, dyspepsia,

heartburn, epigastric discomfort, GI bleeding, occult blood loss, dizziness, tinnitus (ringing in the ears), difficulty

hearing, anaphylactoid reaction.

avoid aspirin in

active bleeding, recent surgery, closed head injuries.

Anticoagulants ex

: antithrombin III (Thrombate), argatroban, bivalirudin (Angiomax), dalteparin (Fragmin), desirudin (Iprivask),

enoxaparin (Lovenox), fondaparinux (Arixtra), heparin (prototype), warfarin (Coumadin), dabigatran (Pradaxa),

rivaroxaban (Xarelto), apixaban (Eliquis), betrixaban (Bevyxxa), edoxaban (Savaysa), protein C concentrate

(Ceprotin).

anticoagulant action

: interfere with the normal cascade of the clotting process. Exact action varies by drug.

maintains a state of anticoagulation in patients prone to dangerous clots (oral).

warfarin

(oral) reduces risk of stroke and systemic embolism in nonvalvular atrial fibrillation, and treats and

prevents recurrence of DVT and PE.

Dabigatran

Anticoagulants contraindications

Contraindications: allergy; conditions that bleeding could make worse; warfarin: pregnancy

safer anticoagulant in preganncy

heparin

caution anticoagulatnt

renal or hepatic disease

adverse effect anticoagulant

bleeding; : heparin-induced thrombocytopenia (HIT).

anticoaggulant interaction

: other drugs or substances that increase bleeding risk; warfarin interacts with a vast number of

drugs; check each agent before use.

because of the size of the molecule, they

do not greatly affect thrombin, clotting or PT, so they cause fewer systemic adverse effects.

Low molecular weight heparins (LMWH) such as enoxaparin and dalteparin:

preferred anticoagulant in children at many institutions.

Low molecular weight heparins (LMWH)

mechanism heparin

: inhibits thrombus and clot production by blocking conversion of prothrombin to thrombin and

fibrinogen to fibrin.

heparin uses

: prevention and treatment of venous thrombosis and PE; atrial fibrillation with embolization; DIC;

preventing clotting in blood samples and heparin lock sets; adjunct in MI and stroke.

pharmokinetic heparin

IV: immediate onset, peak minutes, lasts 2-6 h. Subcutaneous: onset 20-60 min, longer duration (about

8-12 h; slide text slightly blurry on the peak). T1/2 30-180 minutes. Metabolized in cells; excreted in urine.

adverse effects:heparin

bleeding, epidural or spinal hematoma, heparin-induced thrombocytopenia (HIT),

hypersensitivity, hair loss, bruising, chills, fever, osteoporosis (long-term use), suppression of renal function

(long-term use).

heparin antidote

protamine sulfate.

Thrombolytics ex

alteplase (Activase, prototype), reteplase (Retavase), tenecteplase (TNKase).

thrombolytic action

activate the body's natural anticlotting system by activating tissue plasminogen. Only work if the patient

has plasminogen in the plasma.

thrombolytic used for

: dissolving an already-formed clot in acute MI, PE, or ischemic stroke; also unblocking occluded central

venous access devices.

pharmokinetic thrombolytic

cleared after liver metabolism; cross the placenta; unknown if they enter human milk.

Contraindication:thrombolytic

allergy. Cautions: any condition that could be worsened by dissolving clots (recent surgery,

closed head injury, active bleeding), pregnancy and lactation.

adverse effect/intercation thrombolytic

EXTREME bleeding risk, cardiac arrhythmias, hypotension, mental status changes, GI

bleeding, hypersensitivity.

• Interactions: any anticoagulant or antiplatelet drug.

ALTEPLASE mchanism

: an enzyme that converts plasminogen to plasmin, which breaks down fibrin clots, fibrinogen and

other plasma proteins; lyses thrombi and emboli.

pharmokinetic thromolytic

PK: IV, onset immediate, peak end of injection. T1/2 72 minutes. Metabolized in plasma/liver.

reverses warfarin.

• Vitamin K

reverses factor Xa inhibitors (rivaroxaban, apixaban, etc.).

Andexxa (coagulation factor Xa)

reverses dabigatran.

Praxbind (idarucizumab)

adjunct for anticoagulant

Prothrombin complex concentrate

• Decreases platelet aggregation and decreases fibrinogen in the blood.

3.8 Hemorrheologic agent: pentoxifylline

3.8 Hemorrheologic agent: pentoxifylline result

less clot formation and more blood flow through narrowed or damaged vessels.

what can Hemorrheologic agent: pentoxifylline do

Can induce hemorrhage; associated with many CV stimulatory effects.

genetic lack of specific clotting factors, so any injury is dangerous.

Hemophilia:

clotting factors and proteins aren't produced.

liver disease

: not enough platelets.

bone marrow disorders

replace missing clotting factors. Goal: BUILD the clot.

Antihemophilics:

: inhibit plasminogen-activating substances (antiplasmin activity). Goal: PROTECT the clot (stop it

from breaking down).

Hemostatics

Antihemophilic Names:

antihemophilic factor (Elocate, Obizur, ReFacto), coagulation factor VIIa (NovoSeven), factor IX (BeneFix,

Profilnine SD), factor IX complex, anti-inhibitor coagulant complex (Feiba NF), factor XIII (Corifact).

Antihemophilic action

: replace clotting factors that are genetically missing or low. Which drug depends on the type of hemophilia.

Antihemophilic use

: prevent blood loss from injury or surgery; treat bleeding disorders.

Antihemophilic pharmokinetic

: replace normal factors, processed by the body normally.

Antihemophilic contraindication

: allergy; factor IX: liver disease with signs of intravascular coagulation or fibrinolysis;

lactation. Caution: pregnancy.

Antihemophilic adverse effct

risks of blood products; headache, flushing, fever, chills, lethargy; nausea and vomiting; stinging,

itching and burning at the injection site.

Treats classic hemophilia: temporary replacement of clotting factors to correct or prevent bleeding or allow surgery.

Prototype: ANTIHEMOPHILIC FACTOR

Prototype: ANTIHEMOPHILIC FACTOR mechanism

Mechanism: normal plasma protein needed for the conversion of prothrombin to thrombin, the final step in the

clotting pathway.

Prototype: ANTIHEMOPHILIC FACTOR PK

IV, immediate onset, T1/2 12 hours, cleared by normal protein metabolism.

Prototype: ANTIHEMOPHILIC FACTOR adverse effect

allergic reaction, stinging at site, headache, rash, chills, nausea.

3.11 Hemostatic agents ex

Systemic: aminocaproic acid (Amicar, prototype).

]Topical: absorbable gelatin (Gelfoam), human fibrin sealant (Artiss, Evicel), microfibrillar collagen (Avitene), thrombin

(Evithrom, Thrombostat), recombinant thrombin (Recothrom).

Hemostatic agent systemic action

: inhibits plasminogen-activating substances; has some antiplasmin activity

Hemostatic agents systemic indications

= prevent body-wide clot breakdown (hyperfibrinolysis) when serious systemic bleeding

could occur.

Hemostatic agents topical indication

= surface injuries with so much small-vessel damage that clotting doesn't occur and blood is

slowly, continually lost.

Hemostatic agents systemic PK

rapidly absorbed and widely distributed, excreted largely unchanged in urine.

Topical comes as sponges, sprays, solutions.

Contraindications Topical hemostatic agents

topical thrombin: allergy to bovine products.

Hemostatic agents Contraindications systemic

: : allergy, acute DIC.

Hemostatic agents caution systemic

): cardiac disease, renal or hepatic dysfunction, pregnancy and lactation.

Hemostatic agents topical adverse effect

infection

Hemostatic agents adverse effects systemic

excessive clotting, CNS and GI effects, weakness, fatigue, malaise, muscle pain,

intrarenal obstruction and renal dysfunction.

Hemostatic agents systemic intercations

: heparin, oral contraceptives or estrogen.

Hemostatic agents topical interactions

none reported

Treats excessive bleeding from hyperfibrinolysis; prevents recurrence of subarachnoid hemorrhage;

megakaryocytic thrombocytopenia management; decreases need for platelet administration; aborts and treats

hereditary angioneurotic edema attacks.

Prototype: AMINOCAPROIC ACID

PK Prototype: AMINOCAPROIC ACID

: oral: rapid onset, peak 2 h. IV: immediate onset, peak minutes, 2-3 h. T1/2 2 h. Excreted unchanged in urine.

adverse effect Prototype: AMINOCAPROIC ACID

: dizziness, tinnitus, headache, weakness, hypotension, nausea, cramps, diarrhea, fertility problems,

malaise, elevated serum creatine phosphokinase.

what to know for children on clotting drugs

institutions LMWH is the preferred anticoagulant; both

heparin and warfarin are also used. Monitor carefully for changes in GI or liver function and drug interactions. Teach

caregivers injury prevention.

what to know adults for clotting drugs

Injury prevention: electric razor, soft-bristled toothbrush, avoid contact sports. Teach what to do and when to

call for signs of bleeding.

• Wear MedicAlert identification in case of emergency.

• Tell all providers before using OTC drugs or alternative therapies (interaction risk); starting, stopping or changing

one drug may change how the body handles the others.

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• Regular blood tests are needed to check effectiveness (the newer oral anticoagulants don't need as much

monitoring).

• Pregnancy and lactation: high risk (bleeding or increased clotting during pregnancy; bleeding at delivery; risk of

altered clotting in the newborn). Don't use unless benefit outweighs fetal risk. Generally unsafe in lactation.

what to know elderly for clotting drugs

High risk of polypharmacy (CAD, CVA, peripheral vascular disease are common).

• Impaired liver and kidney function is common, changing metabolism and excretion.

• Start at the lowest possible dose and titrate carefully after checking response. Check liver and kidney function

before starting.

• Strictly evaluate whether the patient can follow through with regular blood testing.

• Watch for hidden bleeding: GI issues, severe bruising, altered mental status.

What is the effect of an antiplatelet drug?

Alters the formation of the platelet plug. (Anticoagulants