XI, and XII. LMWH is prepared from unfractionated

• When the international normal ized ratio (INR) is

supratherapeutic in a patient who is not bleeding, a cau ­

tious approach to vitamin K administration is important.

Administering excess vitamin K may overcorrect the INR,

leaving the patient refractory to further anticoagulation.

heparin and includes only short chains. LMWH binds to

antithrombin III but inhibits only factor X. LMWH is

advantageous because it has a more predictable dose

response and greater bioavailability. Heparin-induced

thrombocytopenia (HIT) is due to immunoglobulin G (IgG)

antibody that binds platelets and results in their activation,

creating both thrombocytopenia and thrombosis. Typically,

the onset of HIT is generally 5-12 days after onset of

therapy. The incidence of HIT is 1-3% in patients treated

with unfractionated heparin, but is much less common in

patients taking LMWH.

Warfarin inhibits the cofactor of vitamin K, which normally allows for the production of anticoagulants (protein C

and S) and coagulants (factors II, VII, IX, and X). Because

protein C has a half-life that is much shorter than the halflife of factors II, VII, IX, and X, a hypercoagulable state is

seen first, necessitating the coadministration of unfractionated or LMWH until warfarin has reached its full anticoagulant potential after 5 days. Dabigatran etexilate directly and

competitively binds to free and clot-bound thrombin, which

prevents further clot formation.

CLINICAL PRESENTATION

..... History

Consider the reason the patient has presented to the ED as

it relates to their anticoagulant use.

308

ANTICOAGU LANT THERAPY AND ITS COMPLICATIONS

Gastrointestinal ( GI) bleeding is a common complication

and may not be noticed by the patient; therefore, inquire

about blood in the stool or melena. Any history of trauma,

especially head trauma, should be taken very seriously in

the patient on anticoagulant medications. Intracranial

bleeding is the most common fatal bleeding complication

related to anticoagulation therapy.

If a bleeding complication is occurring, make sure to

have investigated why the patient is taking anticoagulant

therapy. Patients who have had a recent VTE or a prosthetic

heart valve have a greater need for anticoagulation than a

patient with isolated AF. This information is extremely useful when there is a severe bleeding complication that

requires reversal of anticoagulation.

Consider coadministration of additional medications

to patients already taking warfarin that will either increase

or decrease the anticoagulant effects. Medications that

increase the international normalized ratio (INR) include

several antibiotics, nonsteroidal anti-inflammatory drugs,

prednisone, cimetidine, amiodarone, and propanolol. A

decrease in INR is induced by carbamazepine, barbiturates,

haloperidol, and ranitidine. Additionally, several herbal

medications may also increase or decrease the INR.

Lastly, assess for risk factors that increase the patient's

chance of bleeding. For patients on warfarin, risk factors

include INR >4.0, age >75 years, prior history of GI bleed,

hypertension, cerebrovascular disease, renal insufficiency,

alcoholism, and known malignancy. Risk factors for bleeding

in patients on heparin or LMWHs include increasing dose,

degree of elevation of partial thromboplastin time (PTT),

recent surgery or trauma, renal failure, use of another anticoagulant (aspirin, glycoprotein inhibitor), and age >70 years.

..... Physical Examination

Abnormal vital sign that suggest hypovolemia and shock

should be addressed immediately in a patient with a bleed ­

ing complication. Look for any evidence of head trauma.

Sublingual or neck hematomas are airway emergencies,

especially if they are expanding. During the cardiovascular

exam, listen for murmurs or an irregular heart rhythm that

suggests AF. Tenderness during the abdominal exam may

suggest intraperitoneal hemorrhage. A rectal examination

is indicated to diagnose GI bleeding. Conduct a thorough

skin assessment because patients recently started on warfarin may develop warfarin skin necrosis due to capillary

thrombosis in the subcutaneous tissues. Patients with HIT

may also develop similar skin lesions. Ecchymosis and

hematomas should be noted.

DIAGNOSTIC STUDIES

...,_. Laboratory

General laboratory studies include a complete blood count

(to detect anemia and thrombocytopenia) and a

prothrombin time, INR, and PTT. In addition, get a basic

metabolic panel to assess renal function.

..... Imaging

Lower the threshold to obtain an imaging study in patients

on anticoagulant medications. Any patient taking oral

anticoagulation therapy who suffers minor or major head

trauma with or without a headache should have a head

computed tomography ( CT) scan to rule out intracranial

hemorrhage.

MEDICAL DECISION MAKING

History, physical examination, and laboratory studies may

be sufficient to arrive at a diagnosis of an anticoagulation

complication. However, when indicated, intracranial,

splenic, liver or retroperitoneal bleeding should be ruled

out with CT. If skin lesions are noted, consider the diagnosis of warfarin skin necrosis or HIT.

TREATMENT

For patients starting on heparin therapy due to VTE disorders, the therapy begins with an 80 IU /kg bolus followed by

continuous infusion of 18 IU/kg/hr. For patients receiving

treatment for acute coronary syndrome or on fibrinolytic

therapy or a glycoprotein inhibitor, the dose is reduced

60 IU/kg bolus, 12 IU/kg/hr infusion. PTT is measured

6 hours after initiation of the bolus, with a goal of 1.5-2.5 times

normal. When clinically significant bleeding is present, stop

the heparin infusion. Anticoagulation lasts up to 3 hours

after the infusion is stopped. If major bleeding occurs,

administer protamine (1 mg/100 IU heparin) intravenously (IV), given slowly over 5-10 minutes to a maximum

dose of 50 mg.

Enoxaparin is the most commonly prescribed LMWH

in the ED. The most common dosing regimen is 1 mg/kg

subcutaneously every 12 hours. Dosing will need to be

adjusted in morbidly obese patients or those in renal

failure. Protamine (1 mg/1 mg enoxaparin) can be

administered to a maximum dose of 50 mg when r eversal

is indicated, but reversal is not as effective as with unfractionated hepar in. If major or life-threatening bleeds

occur, consider giving blood products such as PRBC and

FFP.

If warfarin therapy is being initiated in the ED, the

usual starting dose is 5 mg by mouth daily. Lower doses are

usually required in the elderly, in patients with liver disease, or those with poor nutrition. The therapeutic range

for the INR depends on the indication. Patients with

mechanical valves are considered therapeutic at INR levels

of 2.5-3.5, whereas other patients ( eg, with AF or VTE) are

therapeutic at INR levels of 2-3 .

Management of bleeding complications or supratherapeutic INR with warfarin is outlined in Figure 73- 1.

CHAPTER 73

No bleeding

Warfa ri n

anticoagu lation

Red uce or omit

next dose of

warfarin

Recheck INR

in 24 hr

Hold warfarin

Recheck INR

in 24 hr

Hold warfarin

Vitamin K 3-5

mg PO

Recheck INR

in 24 hr

Hold warfarin

Vitamin K 10

mg IV Hold warfarin

Vitamin K 10

mg IV

FFP 3-4 units

FFP 3-4 units

• Figure 73-1. Anticoagulant therapy and its compl ications diagnostic algorithm for supratherapeutic INR

from warfarin. FFP, fresh-frozen plasma; INR, international normal ized ratio; IV, intravenous; PO, by mouth.

For reversal, N administration of vitamin K is most rapid,

with onset within 1 -2 hours, compared with 6-10 hours

for oral dosing. Administer N vitamin K over 30 minutes

to minimize the small risk of anaphylaxis. Higher doses

of vitamin K (10 mg) may result in warfarin resistance

(up to 1 week) when it is time to restart anticoagulation

therapy. FFP is used as the flrst-line agent for reversal of

bleeding due to warfarin. The initial dose is 2-4 units.

Consider giving other products such as prothrombin

complex concentrate (PCC) and recombinant factor

VIla.

The oral direct thrombin inhibitor dabigatran is not

routinely started in the ED. However, more patients are

presenting to the ED on dabigatran with bleeding

complications. Currently there is no antidote for the

reversal of bleeding complications associated with its use.

Therefore, clinical management consists of stopping the

medication, and if a major or life-threatening bleed occurs,

consider giving FFP, PRBC, or some in vitro studies suggest

PCC or recombinant factor Vlla.