Deep-VenousThrombosis and Pulmonary Thromboembolism¶

Chapter 290 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 290

Key Clinical Points¶

VTE encompasses deep-venous thrombosis (DVT) and pulmonary embolism (PE), leading to death, disability, and distress.
Virchow's triad (stasis, hypercoagulability, endothelial injury) plus inflammation drives VTE development.
Massive PE is defined by systemic hypotension and extensive pulmonary involvement (at least half of the vasculature).
D-dimer serves as a critical 'rule-out' tool for PE in low/moderate clinical probability cases.
Age-adjusted D-dimer (age imes 10) is used to rule out PE in patients >50 years old.
Anticoagulation options include UFH, LMWH, Fondaparinux, and DOACs (Rivaroxaban, Apixaban, Dabigatran, Edoxaban).
Post-PE syndrome affects ≈ 50% of patients with persistent dyspnea and fatigue.
CTEPH is a less frequent but serious complication causing exertional breathlessness.
S1Q3T3 and T-wave inversions in V1-V4 are key ECG indicators of right heart strain from large PE.
DVT diagnosis is confirmed by non-compressible veins on ultrasound (homogeneous, central thrombus).

DEFINITION & CLASSIFICATION¶

• Venous Thromboembolism (VTE): encompasses both deep-venous thrombosis (DVT) and pulmonary embolism (PE). • Clinical Impact: leads to cardiovascular death, chronic disability, and emotional distress.

EPIDEMIOLOGY¶

• Mortality Trends: ◦ US: Plateaued at ≈ 4.5 per 100,000 in 2017. ◦ Europe: Continued to decrease linearly since 2000. • Socioeconomic Impact: PE hospitalizations increased in both disadvantaged and nondisadvantaged communities (2003-2019). • Readmissions: 30-day all-cause readmission rate is 11%; 90-day rate is 15% for PE patients. • COVID-19 Impact: Associated with a high incidence of DVT and PE.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Inflammatory Trigger: Inflammation is the central trigger for acute PE and DVT. • Virchow's Triad: ◦ Venous stasis ◦ Hypercoagulability ◦ Endothelial injury → Combined with inflammatory triggers, these lead to recruitment of activated platelets. • Prothrombotic States: ◦ Factor V Leiden: Causes resistance to protein C. ◦ Prothrombin gene mutation: Increases plasma prothrombin concentration. • Inflammation-Linked Conditions: Risk factors include cancer, obesity, and autoimmune diseases. • Atherothrombosis Interaction: VTE (red clot) and arterial thrombotic (white clot) events share similar drivers: inflammation, hypercoagulability, and endothelial injury.

CLINICAL FEATURES¶

• Pulmonary Embolism (PE): Often called 'the great masquerader'; most common symptom is unexplained breathlessness. • Deep-Venous Thrombosis (DVT): Most common symptom is a persistent, intensifying calf cramp or 'charley horse' over several days. • Post-PE Syndrome: Affects ≈ 50% of patients; characterized by persistent dyspnea, chronic fatigue, and reduced exercise capacity. • Postthrombotic Syndrome (PTS): Damages venous valves; causes ankle/calf swelling and leg aching; can lead to skin ulceration (Figure 3). • Upper Extremity DVT: Often linked to pacemakers, internal cardiac defibrillators, or indwelling central venous catheters. • What to Look For (Diagnostic Clues): ◦ Massive PE: Dyspnea, syncope, hypotension, and cyanosis. ◦ ECG Signs: S1Q3T3 sign (S in I, Q in III, inverted T in III) and T-wave inversions in V1-V4 (Figure 7). ◦ Chest X-ray: Westermark's sign (focal oligemia), Hampton's hump (peripheral triangular density/pulmonary infarction), Palla's sign (enlarged right descending pulmonary artery). ◦ Other Signs: McConnell's sign (hypokinesis of RV free wall), Urschel's sign (visible superficial veins in chest wall). ◦ May-Thurner Syndrome: Right proximal iliac artery compression of the left proximal iliac vein; presents as recurrent left thigh edema in young women.

DIFFERENTIAL DIAGNOSIS¶

• DVT Differentials: Ruptured Baker's cyst, muscle strain/injury, cellulitis, acute postthrombotic syndrome/venous insufficiency. • PE Differentials: Pneumonia, asthma, COPD, congestive heart failure, pericarditis, pleurisy (viral syndrome), costochondritis, musculoskeletal discomfort, rib fracture, pneumothorax, acute coronary syndrome, anxiety, vasovagal syncope.

DIAGNOSTIC APPROACH¶

• Clinical Decision Rules: ◦ DVT: Low likelihood if score ≤ 0; Moderate if 1-2; High if ≥ 3. ◦ PE: High likelihood if score >4. ◦ Variables for DVT: Active cancer (1), Bedridden >3 days/surgery <12 weeks (1), Tenderness, Entire leg swelling, Unilateral calf swelling >3 cm, Pitting edema, Collateral veins. • Blood Tests: ◦ D-dimer ELISA: Rises due to fibrin breakdown by plasmin. ◦ Rule-out: Normal d-dimer rules out PE in low/moderate probability cases. ◦ Age Adjustment: Use age imes 10 for patients >50 years old to rule out acute PE. • Imaging Modalities: ◦ CT Pulmonary Angiography: Primary imaging test for PE. ◦ Venous Ultrasound: Primary test for DVT; diagnosis is secure if thrombus is homogeneous, central, and low echogenicity (Figure 8). • What Excludes the Diagnosis: ◦ D-dimer Rule Out: Normal d-dimer in low pretest probability cases. ◦ DVT Imaging Security: Non-compressible, homogeneous, central thrombus. ◦ PE Unlikely: If scan is normal or nearly normal. ◦ Alternative Diagnosis: Subtracts 2 points from the Wells score if an alternative is as likely as DVT.

Diagnostic Pathway¶

Assess clinical likelihood (Wells Score).
If low/moderate probability, perform d-dimer.
If d-dimer is normal → Rule out PE.
If high likelihood or d-dimer is high → Proceed to imaging (CT Pulmonary Angiography for PE; Venous Ultrasound for DVT).
If ultrasound is non-diagnostic → Consider MR, CT, or Phlebography.

MANAGEMENT & TREATMENT¶

• Anticoagulation Strategies: 1. Parenteral: UFH (bolus/continuous), LMWH (Enoxaparin, Dalteparin, Tinzaparin), or Fondaparinux. 2. Transition to DOACs after 5 days: ◦ Rivaroxaban: 15 mg BID for 3 weeks → 20 mg daily; (CrCl 15-50 mL/min → 10 mg BID). ◦ Apixaban: 10 mg BID for 1 week → 5 mg BID. (For age >80, weight <60 kg, or serum Cr >1.5 mg/dL → 2.5 mg BID). ◦ Dabigatran: 150 mg BID (CrCl >30 mL/min); 75 mg BID (CrCl 15-30 mL/min). ◦ Edoxaban: 60 mg daily (normal renal, weight >60 kg); 30 mg daily (CrCl 15-50 mL/min). 3. Heparin-Induced Thrombocytopenia (HIT): Use Argatroban (liver metabolized) or Bivalirudin (kidney metabolized), or Fondaparinux. 4. Compression Stockings: For swelling; use graduated compression 30–40 mmHg or 20–30 mmHg. 5. Advanced Therapy: Fibrinolysis or catheter-directed therapy for advanced cases.

Prophylaxis in Hospitalized Patients¶

High-risk nonorthopedic surgery: UFH 5000 units SC bid/tid; Enoxaparin 40 mg daily; Dalteparin 2500 or 5000 units daily.
Cancer surgery (incl. gynecologic): Enoxaparin 40 mg daily, consider 1 month of prophylaxis.
Medically ill (immobilized, prior VTE, central line, or cancer): UFH 5000 units bid/tid; Enoxaparin 40 mg daily; Dalteparin 2500 or 5000 units daily; Fondaparinux 2.5 mg daily.
Contraindicated Anticoagulation: Use intermittent pneumatic compression and/or graduated stockings.

COMPLICATIONS & PROGNOSIS¶

• Low-risk PE: 65–75% of cases; excellent prognosis. • Post-PE Syndrome: ≈ 50% of patients experience persistent dyspnea, fatigue, and reduced exercise capacity. • CTEPH: Less frequent complication; causes breathlessness especially with exertion. • Postthrombotic Syndrome (PTS): Damages venous valves; leads to chronic swelling and skin changes.

SPECIAL POPULATIONS¶

• Pregnancy: Risk factor for VTE; D-dimer levels increase in 2nd/3rd trimesters. • Upper Extremity DVT: Linked to pacemakers, ICDs, or central venous catheters.

KEY PEARLS & HIGH-YIELD POINTS¶

• Clinical Distinction: Not all leg pain is DVT (e.g., ruptured Baker's cyst); not all dyspnea is PE. • Infection vs. DVT: Fever and chills often indicate cellulitis rather than DVT. • D-dimer Utility: Primary role is as a 'rule-out' test in low/moderate probability scenarios. • S1Q3T3 Sign: Classic indicator of right ventricular strain from large PE (Figure 7). • Risk of Recurrence: ◦ Low risk (<3% per year): Major surgery or trauma. ◦ High risk (>8% per year): Active cancer, Antiphospholipid syndrome.

Reference Tables¶

TABLE 290-1 Inflammation-Linked Conditions That Can Trigger PE or DVT Ulcerative colitis Crohn’s disease Rheumatoid…¶

Harrison's 22e, p.2157

Ulcerative colitis
Crohn’s disease
Rheumatoid arthritis
Psoriasis
Diabetes mellitus, type 2
Obesity/metabolic syndrome
Hypercholesterolemia, especially elevated LDL cholesterol
Lipoprotein(a)
Pneumonia
Acute coronary syndrome
Acute stroke
Cigarette smoking
Sepsis/septic shock
Erythropoiesis-stimulating agents
Blood transfusion
Cancer

TABLE 290-2 Clinical Decision Rules Low Clinical Likelihood of DVT if Point Score Is Zero or Less; Moderate Likelihood…¶

Harrison's 22e, p.2159

Low Clinical Likelihood of DVT if Point Score Is Zero or Less; Moderate Likelihood if Score Is 1 to 2; High Likelihood if Score Is 3 or Greater
CLINICAL VARIABLE	DVT SCORE
Active cancer	1
Bedridden for >3 days; major surgery <12 weeks	1

TABLE 290-3 Differential Diagnosis of DVT and PE DVT Ruptured Baker’s cyst Muscle strain/injury Cellulitis Acute…¶

Harrison's 22e, p.2159

DVT
Ruptured Baker’s cyst
Muscle strain/injury
Cellulitis
Acute postthrombotic syndrome/venous insufficiency
PE
Pneumonia, asthma, chronic obstructive pulmonary disease
Congestive heart failure
Pericarditis
Pleurisy: “viral syndrome,” costochondritis, musculoskeletal discomfort
Rib fracture, pneumothorax
Acute coronary syndrome
Anxiety
Vasovagal syncope
Entire leg swelling	1
Pitting edema	1
Alternative diagnosis at least as likely as DVT	–2
High Clinical Likelihood of PE if Point Score Exceeds 4
CLINICAL VARIABLE	PE SCORE
Alternative diagnosis less likely than PE	3.0
Immobilization >3 days; surgery within 4 weeks	1.5
Hemoptysis	1.0

TABLE 290-5 Take-Home Points from the European Society of Cardiology 2019 Pulmonary Embolism Guidelines 1. Terminology…¶

Harrison's 22e, p.2163

Non-Warfarin Anticoagulation
Unfractionated heparin, bolus and continuous infusion, to achieve aPTT 2–3 times
the upper limit of the laboratory normal, or
Enoxaparin 1 mg/kg twice daily with normal renal function, or
Dalteparin 200 U/kg once daily or 100 U/kg twice daily, with normal renal
function, or
Tinzaparin 175 U/kg once daily with normal renal function, or
Fondaparinux weight-based once daily; adjust for impaired renal function
Direct thrombin inhibitors: argatroban or bivalirudin (with suspected or proven
heparin-induced thrombocytopenia)
Rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg once daily with the
dinner meal thereafter. For CrCl 15–50 mL/min: 10 mg twice daily.
Apixaban 10 mg twice daily for 1 week, followed by 5 mg twice daily thereafter.
In patients with at least 2 of the following characteristics: age >80 years, body
weight <60 kg, or serum creatinine >1.5 mg/dL, the recommended dose is 2.5 mg
orally twice daily.
Dabigatran: 5 days of unfractionated heparin, LMWH, or fondaparinux followed
by dabigatran 150 mg twice daily with CrCl >30 mL/min. For CrCl 15–30 mL/min:
75 mg twice daily.
Edoxaban: 5 days of unfractionated heparin, LMWH, or fondaparinux
followed by edoxaban 60 mg once daily with normal renal function, weight
>60 kg, in the absence of potent P-glycoprotein inhibitors. For CrCl 15–50 mL/
min: 30 mg once daily.
Warfarin Anticoagulation
Requires 5–10 days of administration to achieve effectiveness as monotherapy
Use full-dose unfractionated heparin, LMWH, or fondaparinux as “bridging
agents” when initiating warfarin. Continue parenteral anticoagulation for a
minimum of 5 days and until two sequential INR values, at least 1 day apart,
achieve the target INR range.
Usual start dose is 5 mg
Titrate to INR, target 2.0–3.0

TABLE 290-5 Take-Home Points from the European Society of Cardiology 2019 Pulmonary Embolism Guidelines

1. Terminology such as “provoked” versus “unprovoked” PE/DVT is no longer
  supported by the guidelines, as it is potentially misleading and not helpful for
  decision-making regarding the duration of anticoagulation.
  2. Extended oral anticoagulation without an end date should be considered for
  patients with a first episode of PE and:
  a. No identifiable risk factor
  b. A persistent risk factor
  c. A minor transient or reversible risk factor

TABLE 290-6 Risk of Recurrent Venous Thromboembolism After Discontinuing Anticoagulation (European Society of…¶

Harrison's 22e, p.2163

RISK OF RECURRENCE	EXAMPLES
Low risk (<3% per year)	Major surgery or trauma
High risk (>8% per year)	Active cancer Antiphospholipid syndrome

TABLE 290-7 Prevention of Venous Thromboembolism Among Hospitalized Patients CONDITION High-risk nonorthopedic surgery…¶

Harrison's 22e, p.2164

CONDITION	PROPHYLAXIS STRATEGY
High-risk nonorthopedic surgery	Unfractionated heparin 5000 units SC bid or tid Enoxaparin 40 mg daily Dalteparin 2500 or 5000 units daily
Cancer surgery, including gynecologic cancer surgery	Enoxaparin 40 mg daily, consider 1 month of prophylaxis
Medically ill patients, especially if immobilized, with a history of prior VTE, with an indwelling central venous catheter, or with cancer (but without active gastroduodenal ulcer, major bleeding within 3 months, or platelet count <50,000)	Unfractionated heparin 5000 units bid or tid Enoxaparin 40 mg daily Dalteparin 2500 or 5000 units daily Fondaparinux 2.5 mg daily
Anticoagulation contraindicated	Intermittent pneumatic compression devices and/ or graduated vascular below-knee compression stockings