The influence of the intensity of heparinization on bleeding risk is controversial.

Although an elevated aPTT has historically been considered a risk factor for

bleeding complications, several investigators have been unable to substantiate a

relationship between supratherapeutic aPTT values and hemorrhagic effects.

3

In

addition, bleeding episodes can occur when coagulation test results are within the

therapeutic range. These conflicting results may be explained in part by the influence

of additional risk factors for bleeding and by the effect of heparin on platelet function

and vascular permeability.

J.T. has developed hematuria despite an acceptable intensity of anticoagulation.

He should be questioned and examined for the presence of nose bleeding (epistaxis),

increased tendency to bruise (ecchymosis), bright red blood in the stool

(hematochezia), black or tarry stool (melena), or coughing up of blood (hemoptysis).

Blood pressure and pulse, both sitting and standing, should be obtained to determine

whether orthostasis representing blood loss is present. A thorough evaluation of the

urinary tract may reveal a previously unknown abnormality that will explain the

bleeding episode. Although his concurrent low-dose aspirin therapy may increase the

risk of minor bleeding complications, aspirin therapy would not be discontinued due

to his history of coronary artery disease.

CASE 11-1, QUESTION 12: What other side effects of heparin should be considered in J.T.?

Osteoporosis

The development of osteoporosis has been associated with administration of more

than 20,000 international units/day of heparin for 6 months or longer.

32 Various

mechanisms have been suggested, but the underlying pathophysiology of this rare

adverse effect remains unclear. Affected patients may present with bone pain and/or

radiographic findings suggestive of fractures. The possibility of osteoporosis should

be considered in patients receiving long-term, high-dose heparin therapy such as

pregnant patients, postmenopausal women, and elderly patients.

Hypersensitivity Reactions

Other rarely occurring adverse effects associated with heparin include generalized

skin reactions that can progress to necrosis, alopecia, and hypersensitivity reactions,

resulting in hypotension, nausea, and shortness of breath. In 2007, an increase in

hypersensitivity reactions to heparin was attributed to oversulfated chondroitin

sulfate in the heparin manufacturing process.

33

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p. 187

Reversal of Effect

CASE 11-2

QUESTION 1: K.G. is a72-year-old woman with a DVT that occurred during her hospital stay. On day 4 of

heparin therapy, she received a full bag of 25,000 units of heparin during a 1-hour period as a result of an

infusion pump malfunction. The infusion was stopped and within 30 minutes, she became diaphoretic and

hypotensive. Bright red blood was evident on rectal examination, and a large retroperitoneal mass was noted.

How should the excessive heparin effect be reversed?

K.G. has definite signs of hemorrhage from the GI tract, a site of bleeding

associated with considerable mortality. Heparin should be discontinued immediately,

and treatment should include maintenance of fluid volume and replacement of clotting

factors with whole blood, fresh frozen plasma, or clotting factor concentrates. If

hemorrhage had not been present and the only manifestation of overdose had been a

prolonged aPTT, administration of heparin simply could have been discontinued,

permitting the effects to clear within a few hours.

Protamine can be used to neutralize heparin by forming an inactive protamine–

heparin complex.

3 Protamine has a rapid onset of action, with effects lasting about 2

hours. Protamine sulfate is infused slowly over 3 to 5 minutes, as a 1% solution at a

dose of 1 mg for each 100 international units of heparin administered in the last 2 to 3

hours. The maximum single recommended dose of protamine is 50 mg, but doses may

be repeated if bleeding persists. Response to protamine therapy can be assessed by a

return of the aPTT to baseline. Adverse effects associated with protamine include

systemic hypotension secondary to rapid administration; anaphylaxis characterized

by edema, bronchospasm, and cardiovascular collapse; and catastrophic pulmonary

vasoconstriction

34

(see Chapter 32, Drug Hypersensitivity Reactions).

Outpatient Treatment of DVT

CASE 11-3

QUESTION 1: N.C. is a 32-year-old woman who presents to the emergency department (ED) complaining of

right leg pain behind the right knee of 2-day duration. She denies recent injury, but her medication history

reveals that she recently started combination oral contraceptive tablets. She has no significant medical history

and has no family history of clotting disorders. A duplex ultrasound is positive for DVT and immediate

anticoagulation is indicated. What therapeutic alternatives to hospitalization for IV UFH are available for this

patient?

In the past, UFH was the initial treatment of choice for acute DVT; however,

LMWHs and fondaparinux are now becoming more convenient and practical

treatment alternatives to UFH.

15 These agents, administered SC and without the need

for routine coagulation monitoring, allow patients to be treated at home while

transitioning to therapeutic warfarin. In addition, meta-analysis data suggest that

LMWH therapy for acute VTE results in fewer deaths, major hemorrhages, and

recurrent VTE when compared to UFH.

35 Based on these advantages, outpatient use

of LMWH has become the most common approach to treatment of uncomplicated

DVT in patients that transition to warfarin. Home treatment is safe and effective and

improves the overall physical and social functioning of patients being treated for

DVT.

36 The drug costs associated with LMWH treatment are much higher than the

costs of IV UFH, but overall costs to healthcare systems are significantly reduced

when patients can be treated at home rather than in the hospital.

37,38 Fondaparinux can

also be considered as an alternative treatment as it has been shown to be as effective

and safe as LMWH in the treatment of DVT.

39 Additionally, weight-based SC UFH

(initial dose of 333 international units/kg followed by 250 international units/kg

every 12 hours) without routine aPTT monitoring while patients become therapeutic

on warfarin is an alternative for the treatment of acute VTE.

40 Vials of UFH at a

concentration of 20,000 international units/mL are used by the pharmacy or the

patient to draw up the weight-based dose. Although routine aPTT monitoring is not

necessary, platelet count monitoring during the first 2 weeks is required to evaluate

the possible development of HIT.

For N.C. to be treated at home with LMWH, she or a family member must be

willing and able to administer SC injections, and she must be able to return for

frequent follow-up visits, particularly during the first few weeks while warfarin

therapy is initiated. In addition, her healthcare insurance should cover the cost of the

drug, or she must be able to pay out of pocket. Contraindications to outpatient

treatment of VTE include a preexisting condition that requires hospitalization,

clinical symptoms of PE with hemodynamic instability, and recent or active bleeding.

N.C. meets the eligibility requirements for home treatment of her DVT. She is also

a suitable candidate for a DOAC and prefers to not have to perform self-injections of

medication. Currently, there are two DOACs, rivaroxaban and apixaban, approved in

the United States for monotherapy and do not require an initial period of parenteral

anticoagulant. Advantages to the use of a DOAC compared to warfarin include the

lack of routine monitoring for assessing drug efficacy, fewer drug and food

interactions, and a lower rate of major bleeding compared to warfarin. Currently,

only dabigatran has an FDA-approved agent for reversal, idarucizumab, and there are

several other reversal agents in clinical trials. The lack of reversal agent leaves

some providers and patients apprehensive to their use. When selecting a DOAC, it is

important to know the patient’s renal function because these agents have varying

doses based on current renal function. A baseline CBC should also be checked,

because all anticoagulants have the potential for bleeding, and it is important to know

the baseline hemoglobin level in case bleeding occurs on treatment. In this case, N.C.

received an injection of LMWH while in the emergency department, and rivaroxaban

is selected for monotherapy, at 15 mg twice daily with food for 21 days, followed by

20 mg daily with food for the remainder of her 3-month duration of treatment. N.C.

should be advised to follow up with her primary care provider regarding her new

diagnosis, and it should be stressed to the patient the importance of proper

transitioning of the dose from the twice a day to the once a day schedule.

Anticoagulation clinics may also be involved in N.C.’s care to follow up and make

sure she was able to obtain the medication without insurance barriers, that the DOAC

dose was appropriate, that her DVT symptoms are improving, that she is tolerating

the medication, and that she transitions to the correct dose appropriately.

41 Higher

risk patients, such as those with lower health literacy and multiple medical problems,

may benefit from face-to-face clinical visits if this information cannot be obtained by

telephone. Centralized anticoagulation services are expanding beyond traditional

monitoring to include patients on DOACs by prospectively following them to ensure

optimal therapeutic outcomes. There are some cases where it may be necessary to

test whether the DOAC is present, such as in a patient with acute stroke, need for

urgent surgery, or in the case of major bleeding.

42 There is no current consensus on

how best to do this, because the tests that correlate the best are not often readily

available. Of those that are readily available, aPTT or thrombin time are often used

to detect dabigatran presence, and the prothrombin time or anti-factor Xa calibrated

for the factor Xa inhibitors.

42

p. 187

p. 188

Table 11-13

Dosing of Low-Molecular-Weight Heparin and Fondaparinux for the Treatment

of Venous Thromboembolism

Dalteparin Enoxaparin Tinzaparin Fondaparinux

100 international units/kg

SC every 12 hours OR

200 international units/kg

SC every 24 hours

1 mg/kg SC every 12

hours OR 1.5 mg/kg SC

every 24 hours

175 international units/kg

SC every 24 hours

5 mg SC every 24 hours if

weight <50 kg

7.5 mg SC every 24 hours

if weight 50–100 kg

10 mg SC every 24 hours

if weight >100 kg

SC, subcutaneously.

CASE 11-3, QUESTION 2: During a follow-up call to N.C. from the anticoagulation clinic the next morning,

it is discovered that N.C. was not able to get the rivaroxaban filled at her pharmacy last night because her

insurance does not cover any DOAC therapy without first documenting a treatment failure to warfarin. What

alternative treatment is available for N.C?

Before the DOACs, treatment with self-injected LMWH bridging to warfarin at

home was the standard of care. Possible treatment options and doses for N.C. are

listed in Table 11-13. In this case, enoxaparin is the LMWH preferred by her

insurance because it is available generically. The usual dosing of enoxaparin for

treatment of DVT is 1 mg/kg total body weight SC every 12 hours, rounded to the

nearest 10-mg increment. Once-daily dosing at 1.5 mg/kg SC every 24 hours is also

an option, but this strategy is inferior to twice-daily dosing in patients with

malignancy or obesity.

43 N.C.’s medical history is suitable for the once-daily dose of

enoxaparin, which is more convenient for administration. At 65 kg, a dose of 1.5

mg/kg would be 97.5 mg, which will be rounded to the nearest 10-mg increment.

N.C. will therefore receive 100 mg SC every 24 hours. Warfarin therapy is initiated

concurrently to expedite the conversion to oral treatment.

Because LMWHs are eliminated renally, patients with significant renal impairment

require dose reductions to prevent drug accumulation and to minimize the risk of

bleeding complications.

44 The degree of drug accumulation can vary between the

various LMWH preparations, and thus specific guidelines for dose adjustments are

agent specific (Table 11-14).

45 Some experts suggest monitoring of anti-factor Xa

activity to rule out accumulation of LMWHs in patients with renal impairment who

are on treatment for extended periods of time (i.e., greater than 1 week).

45,46

Fondaparinux is also renally excreted and is contraindicated in patients with

creatinine clearance less than 30 mL/minute.

N.C. should be educated regarding the potential adverse effects of LMWH therapy

(bleeding, thrombocytopenia, pain and bruising at the injection site), required

laboratory monitoring, and the expected duration of anticoagulation. At baseline, Hgb

and/or Hct, INR, serum creatinine (SCr), and platelet count should be determined.

Platelets will continue to be monitored at least every 2 to 3 days while the patient is

receiving LMWH therapy, to a maximum of 10 to 14 days. N.C. can expect to

continue enoxaparin therapy for a minimum of 5 days. If by day 5 her INR is

therapeutic and stable, enoxaparin can be discontinued. Oral anticoagulation with

warfarin should be continued for 3 months.

15 N.C. should also be advised against

further use of estrogen-containing contraceptives.

47

To ensure the safety and efficacy of home treatment, N.C. should be provided with

the names and telephone numbers of the healthcare providers who will assume

responsibility for her care, including her primary physician and her anticoagulation

management team. No patient should be sent home with LMWH without an adequate

follow-up plan.

Table 11-14

Dosing of Low-Molecular-Weight Heparins in Patients with Renal Impairment

(CrCl < 30 mL/minute)

a

LMWH Dalteparin Enoxaparin Tinzaparin

Product information

recommendations

Use with caution Prophylaxis—30 mg SC

daily

Use with caution

Treatment—1 mg/kg SC

daily

Dosing suggestions based

on agent-specific

pharmacokinetic

observations

CrCl < 30 mL/minute

a

: no

dose adjustment needed

up to 1 week with

prophylactic doses

For use longer than 1

week, consider monitoring

of anti-Xa activity and

adjust dose if

accumulation is noted

CrCl 30–50 mL/minute: no

dose adjustment needed

CrCl <30 mL/minute

a

:

Consider a 40%–50%

dose decrease and

subsequent monitoring of

anti-Xa activity

CrCl 30–50 mL/minute:

Consider a 15%–20%

dose decrease with

prolonged use (longer than

10–14 days) and

subsequent monitoring of

anti-Xa activity

CrCl <30 mL/minute

a

:

consider a dose decrease

of 20% and subsequent

monitoring of anti-Xa

activity

CrCl 30–50 mL/minute: no

dose adjustment needed

a

In patients with a CrCl <30 mL/minute, data are very limited and use of unfractionated heparin is suggested.

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Prevention of Venous Thromboembolism

CASE 11-4

QUESTION 1: M.G., a 63-year-old obese man, is to undergo elective abdominal surgery for treatment of an

umbilical hernia. He has a medical history significant for hypertension, currently controlled by enalapril 10 mg

daily (blood pressure, 130/80 mm Hg), and gout, controlled with allopurinol 300 mg daily. What therapeutic

interventions might decrease the risk of DVT or PE in M.G.?

Surgical procedures represent a significant risk factor for DVT formation.

However, all hospitalized patients, including both surgical and nonsurgical/medical

patients, should be stratified for risk of VTE based on the presence of various

factors.

12,48–50 Risk stratification is used to select the most appropriate therapeutic

interventions to prevent DVT and thereby reduce the risk of fatal PE. These

interventions include both mechanical and pharmacologic strategies.

NONPHARMACOLOGIC MEASURES

Mechanical interventions aimed at preventing venous stasis and increasing venous

return include the use of elastic compression stockings, as well as leg elevation, leg

exercises, and early postoperative ambulation. Intermittent pneumatic compression

(IPC) of the leg muscles, using inflatable cuffs applied to the calf and thigh,

represents another alternative for the prevention of DVT.

12 Because it is generally

less effective than pharmacologic prophylaxis, mechanical prophylaxis is most

commonly used in patients at high risk of bleeding, or as an adjunct to pharmacologic

prophylaxis in patients at very high risk for VTE.

PHARMACOLOGIC MEASURES

Fixed, low-dose unfractionated heparin (LDUFH), administered as 5,000 units SC

every 8 to 12 hours depending on the indication, is an inexpensive and effective

pharmacologic approach to DVT prevention in the setting of venous stasis in patients

with acute medical illness, or after certain surgical procedures. Because LDUFH

inactivates factor Xa without a direct effect on factor IIa, the aPTT is not prolonged,

and therefore aPTT monitoring is unnecessary. Bleeding complications are

minimized using this dosing regimen.

Fixed-dose SC LMWH and fondaparinux are alternative approaches for preventing

DVT. Enoxaparin 30 mg SC every 12 hours or 40 mg SC once daily, dalteparin 2,500

to 5,000 international units SC once daily, and fondaparinux 2.5 mg SC once daily

are effective strategies, although enoxaparin has been studied for a larger number of

indications. The DOACs rivaroxaban, apixaban, and dabigatran have been FDAapproved for DVT prophylaxis in orthopedic surgery patients. Betrixaban 160 mg as

a single dose followed by 80 mg daily is approved for VTE prophylaxis in adult

patients hospitalized for an acute medical illness. Current recommendations for

prevention of VTE based on risk stratification are presented in Table 11-15.

12,48,49

M.G. is at high risk for DVT and PE, not only because of general surgery but also

because of his age (older than 40 years) and the presence of other risk factors for

VTE (obesity, and probable postoperative immobilization). Options for DVT

prevention include SC heparin at 5,000 international units every 8 hours or a LMWH

(enoxaparin 40 mg SC daily, or dalteparin 2,500 international units initial dose

followed by 5,000 international units SC daily). The first dose should be

administered several hours preoperatively, and dosing should continue

postoperatively until he is fully ambulatory. If bleeding risk is of concern, IPC could

be used as an alternative. VTE prophylaxis is typically continued until hospital

discharge, but may be continued for up to 30 days in certain high-risk populations,

including patients with cancer, orthopedic surgery, bariatric surgery, or with a prior

history of VTE.

PULMONARY EMBOLISM

Clinical Presentation

CASE 11-5

QUESTION 1: A.W. is a 52-year-old, 70-kg woman. She recently returned from a 12-hour car ride where

she only stopped to stretch twice. Yesterday she noticed a swollen right calf that is painful and warm. This

swelling gradually increased, affecting the entire right leg to the groin, and prompted her to seek medical

attention. In the ED, she also notes the recent onset of right-sided pleuritic chest pain without SOB or

hemoptysis. Her medical history includes a gastric ulcer 4 years ago, treated with proton pump inhibitor therapy,

that has not recurred. Physical examination reveals an enlarged right leg and moderate tenderness in the entire

leg. Chest examination reveals labored respirations, equal breath sounds, and no wheezing or crackles. Vital

signs include blood pressure, 160/90 mm Hg; heart rate, 100 beats/minute; and respiratory rate, 28

breaths/minute and regular. Laboratory data include the following:

Hct, 26.7%

SCr 1.1 mg/dL

Arterial blood gases (on room air)

PO2

, 72 mm Hg (normal, 75–100)

PCO2

, 30 mm Hg (normal, 35–45)

pH 7.48 (normal, 7.35–7.45)

Chest CT shows a pulmonary embolism in the distal right main pulmonary artery extending into the right

lower lobe. The electrocardiogram (ECG) shows sinus tachycardia. The lower extremity duplex ultrasound is

positive for acute occluding thrombus from the right femoral vein all the way down to the soleal vein.

Coagulation test results include the following:

PT, 11.2 seconds (INR, 1.0)

aPTT, 28 seconds

Platelet count, 248,000/μL

What subjective and objective evidence in A.W. is consistent with PE?

SIGNS AND SYMPTOMS

The clinical diagnosis of PE is often difficult to make because of the nonspecificity

of symptoms.

51,52 The most common symptoms of PE include tachypnea, cough,

substernal and pleuritic chest pain, dyspnea, hemoptysis, fever, and unilateral leg

pain. Signs and symptoms such as hypotension, tachycardia, presence of B-type

natriuretic peptides (BNP) or NT-pro-BNP (N-terminal pro-brain natriuretic

peptide), troponins (I or T), hypoxia, and electrocardiogram (ECG) changes

suggestive of right ventricular strain are important to recognize as these may indicate

more severe thromboembolism and increased risk for 30-day mortality.

53 DVT

precedes PE in 80% or more of patients. A combination of these signs and symptoms

provides further evidence for acute PE.

DEFINITIONS

There are varying ways to define the severity of a PE. Some define PE based on a

patient’s in-hospital or 30-day risk for mortality, whereas other literature will cite

terms such as massive and submassive PE.

53,54 Low-risk PE is classified as the

presence of thromboembolism without changes in hemodynamics, right ventricular

function, or cardiac biomarkers. These types of patients can also be classified as

small-to-moderate PE. High-risk PE is defined by the presence of shock (manifesting

as tissue hypoperfusion, and hypoxia, cool clammy extremities, alterations in

consciousness) or hypotension, specifically defined as: a systolic blood pressure <

90 mm Hg or a ≥ 40 mm Hg drop in systolic blood pressure for > 15 minutes which

is not attributed to new onset arrhythmia, hypovolemia, or sepsis. These patients can

also be classified as having massive PE.

54 Patients with right ventricular dysfunction

characterized by echocardiographic evidence or by positive cardiac biomarkers

(BNP > 90 pg/mLor NT-pro BNP > 500 pg/mL, Troponin I > 0.4 ng/mL, Troponin T

> 0.1 ng/mL) are classified as having submassive PE if they are hemodynamically

stable.

54

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p. 190

Table 11-15

Prevention of Venous Thromboembolism12,48

General and Abdominal–pelvic Surgery

a

Very low risk for VTE Early and frequent ambulation

Low risk for VTE IPC over no prophylaxis

Moderate risk for VTE not at high risk for MB LMWH and LDUFH over no prophylaxis. IPC over no

prophylaxis

Moderate risk for VTE & high risk for MB IPC over no prophylaxis

High risk for VTE and not at high risk for MB LMWH or LDUFH over no prophylaxis. IPC or elastic

stockings can be added

High risk for VTE undergoing surgery for cancer and

not otherwise at high risk for MB

Extended prophylaxis with LMWH (4 weeks) over

limited duration

High risk for VTE and high risk for MB IPC over no prophylaxis until bleeding risk diminishes

then initiate pharmacologic prophylaxis

High risk for VTE unable to receive LMWH or

LDUFH and not at high risk for MB

IPC over no prophylaxis

General and abdominal–pelvic surgery patients IVC filter should not be used for primary VTE

prevention

Periodic surveillance with venous compression

ultrasound should not be performed

Orthopedic Surgery

Hip or knee replacement Minimum of 10–14 days of one of the following:

LMWH (preferred), fondaparinux, apixaban,

dabigatran, rivaroxaban, LDUFH, warfarin (INR 2–3),

or aspirin.

Hip fracture surgery Minimum of 10–14 days of one of the following:

LMWH, fondaparinux, LDUFH, warfarin (INR 2–3),

or aspirin. LMWH preferred over warfarin or aspirin

Major orthopedic surgery Dual prophylaxis with antithrombotic and IPC during

hospitalstay. Extended prophylaxis up to 35 days

suggested.

Cardiac Surgery Uncomplicated course: IPC over no prophylaxis

Prolonged stay: add LDUFH or LMWH to IPC

Thoracic Surgery

Moderate risk for VTE & not at high risk for MB LMWH or LDUFH

High risk for VTE & not at high risk for MB LMWH or LDUFH ±IPC

High risk for MB IPC until bleeding risk diminishes, then pharmacologic

prophylaxis

Trauma

b LMWH or LDUFH.

Add IPC if high risk for VTE and use IPC if unable to

take LMWH or LDUFH

Acutely Ill Hospitalized Medical Patients

With increased risk of thrombosis LMWH, LDUFH BID, LDUFH TID, fondaparinux, or

betrixaban

With low risk of thrombosis No pharmacologic or mechanical prophylaxis

With bleeding or at high risk of MB No anticoagulant thromboprophylaxis

With increased risk of thrombosis and at high risk of

MB

GCS, IPC. When bleeding risk decreases, start

pharmacologic thromboprophylaxis instead of

mechanical thromboprophylaxis

a

includes gastrointestinal, urologic, gynecologic, bariatric, vascular, or plastic and reconstructive surgery.

b

includes traumatic brain injury, acute spinal injury, and traumatic spine injury.

BID, twice daily; GCS, graduated compression stockings; INR, international normalized ratio; IPC, intermittent

pneumatic compression; LDUFH, low-dose unfractionated heparin (5,000 international units subcutaneously every

8–12 hours); LMWH, low-molecular-weight heparin (enoxaparin 40 mg subcutaneously daily or 30 mg SC every

12 hours; dalteparin 2,500–5,000 international units subcutaneously daily); fondaparinux (2.5 mg subcutaneously

daily); VTE, venous thromboembolism; MB, major bleeding; AC, anticoagulation.

DIAGNOSIS

Because the clinical signs and symptoms of PE are difficult to distinguish from many

other medical conditions, further evaluation is necessary.

51,52 Chest radiograph, ECG,

and arterial blood gas

p. 190

p. 191

(alveolar-arterial oxygen gradient) abnormalities are often present in patients with

PE, but like clinical signs and symptoms, they are somewhat nonspecific. Pulmonary

imaging is necessary to diagnose or definitely rule out PE. Although many methods

are clinically available for chest imaging, the computed tomographic (CT) pulmonary

angiography and ventilation–perfusion lung scanning (V/Q scan) are the most

common tests used for the diagnosis of PE, with the multi-detector CT (MDCT) being

the imaging test of choice because of its ability to visualize the pulmonary arteries in

the greatest detail. Lung scans that incorporate an assessment of perfusion, or

regional distribution of pulmonary blood flow, and ventilation are referred to as V/Q

scans; they involve both the injection and the inhalation of radiolabeled compounds.

Test results are expressed as a high, intermediate, or low probability of PE. When

ventilation (air movement) is normal over an area that shows abnormal perfusion

(blood flow), a V/Q mismatch exists, and PE is highly probable. If a matched defect

is noted (abnormal ventilation over an area of abnormal perfusion), another disease

state, such as chronic obstructive airway disease, is more likely.

As in the case of DVT, clinical assessment of PE can improve the diagnostic

accuracy of noninvasive tests such as CT, MRI, or V/Q scanning. Validated

assessment tools can be used to stratify a patient’s probability of a PE

55–58

(Table 11-

16). In patients with a low clinical probability of PE, measuring a high-sensitivity Ddimer can be considered, and, if negative, PE can be ruled out, eliminating the need

of further imaging studies.