20.9p Medications Affecting the Coagulation Cascade

coagulation system

One of the most significant medical advances over the last decade or so is the ability to attenuate or modify the human (?).

coagulation

Our normal coagulation pathway represents a balance between (?) (thrombosis), the pathway that is responsible for clot formation, and the mechanisms that inhibit or reverse coagulation (thrombolysis).

disease processes

Many (?) involve the coagulation pathway.

thrombotic or embolic

The formation of a clot (?) can cause multiple significant problems such as heart attack, stroke, pulmonary embolism, deep venous thrombosis, and similar problems.

bleeding and blood loss

Disorders that inhibit the blood’s ability to clot (coagulate) can lead to (?).

clotting cascade

The (?) is complex with multiple clotting factors that function in an intrinsic pathway (initiated by trauma within the vascular system) or extrinsic pathway (initiated by external trauma—tissue damage).

common pathway

Both pathways end in a (?).

medications

We now have multiple (?) that can modify the coagulation cascade.

Platelet aggregation inhibitors

(?) decrease the formation of platelet plugs.

true anticoagulants

They are not (?).

aspirin

The prototype antiplatelet medication is (?).

cyclooxygenase

It inhibits (?), an enzyme needed for the synthesis of thromboxane A2(TXA2).

TXA2

Remember that (?) causes platelets to aggregate and promotes local vasoconstriction.

platelet plugs

By inhibiting TXA2, aspirin decreases the formation of (?) and potential thrombi.

existing thrombi

Aspirin, as well as other antiplatelet and anticoagulant medications, has no effect on (?); it only curbs the formation of new thrombi.

myocardial infarction

Aspirin is indicated in the acute treatment of developing (?).

ischemic stroke

It is also useful in preventing the recurrence of myocardial infarction (MI) and of (?) following transient ischemic attacks (TIAs).

bleeding

One of aspirin’s primary side effects is (?).

gastric ulcers

It also can lead to an increase in (?), which are a frequent source of gastrointestinal hemorrhage.

dangerous blood loss

By both stimulating the development of a potential source of bleeding and blocking an important mechanism for stopping that bleeding, aspirin can cause (?).

dipyridamole (Persantine)

Other antiplatelet medications include (?).

ADP and glycoprotein IIB/IIIA inhibitors

A major class of medications in this family includes the (?) such as ticlopidine (Ticlid), abciximab (ReoPro), clopidogrel (Plavix), ticagrelor (Brilinta), eptifibatide (Integrilin), tirofiban (Aggrastat), and ticlopidine (Ticlid).

Anticoagulants

(?) interrupt the clotting cascade.

parenteral and oral

The two main types of anticoagulants are (?).

heparin

The prototype parenteral anticoagulant is (?), a substance derived from the lungs of cattle or the intestines of pigs.

antithrombin III’s ability

Its primary mechanism of action is to enhance (?) to inhibit the clotting cascade.

parenterally

Because heparin is very polar, it is very poorly absorbed and must be given (?).

deep vein thrombosis

Heparin injections and infusions are indicated in treating and preventing (?) (also called venous thromboembolic disease [VTE]), pulmonary embolism, and some forms of stroke.

fibrinolytics

Heparin also is used frequently in conjunction with (?) to treat MI and stroke.

bleeding

As you would expect, (?) is heparin’s primary side effect.

thrombocytopenia

Other untoward effects include (?) (decreased platelet counts) and allergic reactions.

units

Heparin is measured in (?) rather than milligrams.

unit

A (?) is that amount of heparin necessary to keep 1 mL of sheep plasma from clotting for one hour.

potency

Using this measurement is necessary because heparin’s (?) varies greatly when measured in milligrams.

Low-molecular-weight heparin (enoxaparin [Lovenox])

(?) has become increasingly popular in emergency medicine.

molecular weight

Normal heparin has a (?) of 5,000 to 30,000 Da whereas low-molecular-weight heparin has a molecular weight of 1,000 to 10,000 D; because of this, it has greater bioavailability, is easier to dose, and has fewer effects on platelet function.

Low-molecular weight heparin

(?) is administered subcutaneously.

Protamine sulfate

(?) is available as a heparin antagonist; it can reverse the effects of heparin in the presence of dangerous and unintended bleeding by binding with heparin.

antithrombin III

This prevents heparin from binding with (?) and enhancing its anticlotting abilities.

warfarin (Coumadin)

The prototype oral anticoagulant is (?).

primary side effect

Its history serves as a useful reminder of its (?).

rat poison

Warfarin was first developed as a (?) that killed through uncontrolled bleeding.

clinical use

After noticing that a patient who attempted suicide by ingesting warfarin did not, in fact, die, its (?) was investigated.

bleeding

Needless to say, this medication’s primary side effect is (?).

vitamin K

Warfarin prevents coagulation by antagonizing the effects of (?), which is needed for the synthesis of multiple factors involved in the clotting cascade.

chronic use

It is prescribed for (?) to prevent thrombi in high-risk patients such as those who have hip replacements or artificial heart valves or those who are in atrial fibrillation.

placental barrier

Because warfarin easily crosses the (?) and has dangerous teratogenic properties (capable of causing malformations), it is contraindicated in pregnant patients.

many other medications

It also interacts adversely with (?).

bleeding

Like heparin, warfarin can lead to (?).

biweekly

Warfarin therapy must be closely monitored (usually (?)) to ensure adequate levels.

Vitamin K

Unlike other anticoagulants, warfarin’s effectiveness varies based on the amount of (?) in the diet.

prothrombin time (PT)

Warfarin therapy can be monitored by measuring the patient’s (?), which is used to calculate the international normalized ratio (INR).

vitamin K

Excessive warfarin levels can lead to bleeding, which can be reversed with injections of (?) (if the bleeding is not critical).

fresh frozen plasma

If the bleeding is life threatening, (?) (which contains clotting factors) can be administered.

prothrombin complex concentrate (4-factor unactivated) (KCentra)

The most effective therapy for severe bleeding (e.g., intracerebral hemorrhage) is (?) that is derived from human plasma.

early 2000s

Newer oral anticoagulants were introduced in the (? and are now widely utilized.

directly acting oral anticoagulants (DOACs)

They are referred to by several names including (?), novel oral anticoagulants (NOACs), and non-vitamin K antagonist oral anticoagulants.

dabigatran (Pradaxa]

These agents include the direct thrombin inhibitor (?) and the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa).

fewer serious side effects

They have been shown to be as good or possibly better than coumadin with (?).

routine blood testing

They do not require (? (PT/INR or PTT).

improved safety profile

Because of an (?), these medications are commonly prescribed.

fresh frozen plasma (FFP)

Reversal of these agents is difficult although (?) is commonly used for that purpose.

idarucizumab

Two reversal agents, (?) and andexanet alfa, have been approved as a reversal agent for selected DOACs.