This document provides an overview of deep vein thrombosis (DVT) and pulmonary embolism (PE), including their epidemiology, risk factors, pathophysiology, clinical presentation, diagnosis, and differential diagnosis. Some key points include: - VTE, which includes DVT and PE, is a major cause of death. PE can be fatal if large or recurrent. DVT survivors may develop post-thrombotic syndrome. - Risk factors for VTE include genetic thrombophilias, cancer, trauma, surgery, and prolonged immobility. - PE occurs when clots from DVT embolize to the lungs, potentially causing right heart strain or failure. Symptoms range from mild to severe

1. Pulmonary
Thromboembolism
Shime c2

2. DVT & Pulmonary Thromboembolism: Introduction
Epidemiology
VTE, which encompasses DVT and PE, is one of the 3 major
cardiovascular causes of death, along with MI & stroke.
 VTE can cause death from PE or, among survivors, chronic
thromboembolic pulmonary HTN & postphlebitic syndrome.
DVT of the lower extremity is subdivided into two categories:
• Distal (calf) vein thrombosis, in which thrombi remain
confined to the deep calf veins
• Proximal vein thrombosis, in which thrombosis involves the
popliteal, femoral, or iliac veins
~3/4th of symptomatic VTE events occur in the community,
and the remainder are hospital acquired.

3. DVT & Pulmonary Thromboembolism: Introduction…
 The long-term effects of nonfatal VTE lower the quality of life.
 Chronic thromboembolic pulmonary HTN is often disabling and
causes breathlessness.
 Postphlebitic syndrome
 Also known as postthrombotic syndrome or chronic venous
insufficiency
 Is a late effect of DVT & eventually occurs in >1/2 of DVT patients.
 Causes the venous valves of the leg to become incompetent and
exude interstitial fluid.
 Patients complain of chronic ankle or calf swelling and leg aching,
especially after prolonged standing.
 In its most severe form, postphlebitic syndrome causes skin
ulceration, especially in the medial malleolus of the leg.
 There is no effective medical therapy for this condition.

4. Prothrombotic States
 Thrombophilia(hypercoagulability) contributes to the risk of
venous thrombosis.
The 2 most common autosomal dominant genetic mutations are:
 Factor V Leiden mutation, which causes resistance to activated
protein C (which inactivates clotting factors V and VIII), and
 The prothrombin gene mutation, which increases the plasma
prothrombin concentration.
 Antithrombin, protein C, and protein S are naturally occurring
coagulation inhibitors.
Deficiencies of these inhibitors are associated with VTE but are
rare.

5. Prothrombotic States…
 Antiphospholipid antibody syndrome(APS) is the most common
acquired cause of thrombophilia
 APS is associated with venous or arterial thrombosis.
 Other common predisposing factors include :
 Cancer,
 Systemic arterial HTN ,
 COPD ,
 Long-haul air travel, Air pollution,
 Obesity,
 Cigarette smoking,
 Eating large amounts of red meat,
 Oral contraceptives, Pregnancy, Postmenopausal hormone
replacement,
 Surgery, and trauma.

6. Antiphospholipid syndrome
• The diagnostic criteria require:
- one clinical event, i.e. thrombosis or pregnancy
complication, and
- two antibody blood tests spaced at least three
months apart that confirm the presence of either
lupus anticoagulant, or anti-β2-glycoprotein-I
(since β2-glycoprotein-I antibodies are a subset of
anti-cardiolipin antibodies, an anti-cardiolipin
assay can be performed as a less specific proxy)

7. • Antiphospholipid syndrome can be primary or
secondary. Primary antiphospholipid
syndrome occurs in the absence of any other
related disease. Secondary antiphospholipid
syndrome occurs with other autoimmune
diseases, such as systemic lupus
erythematosus (SLE).

8. Pathophysiology - VTE
Embolization
 When venous thrombi are dislodged from their site of formation,
they embolize to either:
 The pulmonary arterial circulation or,
 Paradoxically, to the arterial circulation through a patent foramen
ovale or atrial septal defect.
 ~1/2 of patients with pelvic vein thrombosis or proximal leg DVT
develop PE, which is often asymptomatic.
 Isolated calf vein thrombi pose a much lower risk of PE but are
the most common source of paradoxical embolism.
 Upper extremity venous thrombi rarely embolize and cause PE.

9. Physiology : PE
 The most common gas exchange abnormalities are
 Hypoxemia (decreased arterial PO2) and
 An increased alveolar-arterial O2 tension gradient
 Other pathophysiologic abnormalities include the following:
 Increased pulmonary vascular resistance
 Impaired gas exchange
 Alveolar hyperventilation due to reflex stimulation of irritant
receptors.
 Increased airway resistance due to constriction of airways distal to
the bronchi.
 Decreased pulmonary compliance due to lung edema, lung
hemorrhage, or loss of surfactant.

10. Right-Ventricular Dysfunction : In PE
 Progressive right heart failure is the usual cause of death from PE.
 Increased pulmonary vascular resistance RV wall tension rises
further RV dilation and dysfunction.
 RV contraction continues even after the LV starts relaxing at end-
systole.
 The interventricular septum bulges into and compresses an
intrinsically normal LV.
 Diastolic LV impairment develops, attributable to septal
displacement, & results in:
 Reduced LV distensibility and
 Impaired LV filling during diastole.

11. Right-Ventricular Dysfunction : In PE…
 Increased RV wall tension :
 Compresses the right coronary artery,
 Diminishes subendocardial perfusion,
 Limits myocardial oxygen supply, and
 May precipitate myocardial ischemia and RV infarction.
 Underfilling of the LV may lead to a fall in LV CO and systemic
arterial pressure, thereby provoking myocardial ischemia due to
compromised coronary artery perfusion.
 Eventually, circulatory collapse and death may ensue.

12. Differential diagnosis:-
• Chronic venous insufficiency
• Cellulitis / abscess
• Lymphedema—
• Arthritis
• Trauma
• Compartment syndrome (chronic)
• Calf muscle pull or tear
• Superficial thrombophlebitis
• Drug-induced edema or heart failure

13. Diagnosis : VTE
Clinical Evaluation
 VTE mimics other illnesses, and PE is known as "the Great
Masquerader," making diagnosis difficult.
 In DVT the most common history is a cramp in the lower calf
 The most common history in PE is unexplained breathlessness.
 In evaluating patients with possible VTE, the initial task is to decide on
the clinical likelihood of the disorder.
 Low likelihood of DVT or a low-to-moderate likelihood of PE initial
diagnostic evaluation with d-dimer testing alone with out obligatory
imaging tests.
 If the d-dimer is abnormally elevated, imaging tests are the next step.

14. Wells criteria for DVT probability
Active cancer (treatment ongoing or within the
previous 6 months or palliative)
1
Paralysis, paresis, or recent plaster
immobilization of the lower extremities
1
Recently bedridden for more than 3 days or
major surgery, within 4 weeks
1
Localized tenderness along the distribution of
the deep venous system
1
Entire leg swollen 1
Calf swelling by more than 3 cm when
compared to the asymptomatic leg (measured
below tibial tuberosity)
1
Pitting edema (greater in the symptomatic leg) 1
Collateral superficial veins (nonvaricose) 1
Alternative diagnosis as likely or more likely
than that of deep venous thrombosis
-2

15. Score:
High probability 3 or greater
Moderate probability 1 or 2
Low probability 0 or less
Modification:
This clinical model has been modified to take one other clinical feature into account: a previously
documented deep vein thrombosis (DVT) is given the score of 1. Using this modified scoring
system, DVT is either likely or unlikely, as follows:
DVT likely 2 or greater
DVT unlikely 1 or less

16. Wells criteria and modified Wells
criteria
Clinical symptoms of DVT (leg swelling, pain with
palpation)
3.0
Other diagnosis less likely than pulmonary embolism 3.0
Heart rate >100 1.5
Immobilization (≥3 days) or surgery in the previous
four weeks
1.5
Previous DVT/PE 1.5
Hemoptysis 1.0
Malignancy 1.0

17. Score:
Probability Score
Traditional clinical probability assessment (Wells criteria)
High >6.0
Moderate 2.0 to 6.0
Low <2.0
Simplified clinical probability assessment (Modified Wells criteria)
PE likely >4.0
PE unlikely ≤4.0

19. Clinical Decision Rules - DVT
Low Clinical Likelihood of DVT if Point Score <=0 ; Moderate if Score Is 1 to 2;
High if Score Is >=3
Clinical Variable Score
Active cancer 1
Paralysis, paresis, or recent cast 1
Bedridden for >3 days; major surgery <12 weeks 1
Tenderness along distribution of deep veins 1
Entire leg swelling 1
Unilateral calf swelling >3 cm 1
Pitting edema 1
Collateral superficial nonvaricose veins 1
Alternative diagnosis at least as likely as DVT –2

20. Clinical Decision Rules for PE
High Clinical Likelihood of PE if Point Score Exceeds 4
Clinical Variable Score
Signs and symptoms of DVT 3.0
Alternative diagnosis less likely than PE 3.0
Heart rate >100/min 1.5
Immobilization >3 days; surgery within 4 weeks 1.5
Prior PE or DVT 1.5
Hemoptysis 1.0
Cancer 1.0

21. Clinical Syndromes & dDx - VTE
 Sudden, severe calf discomfort suggests a ruptured Baker's cyst.
 Fever and chills usually herald cellulitis rather than DVT, though
DVT may be present concomitantly.
 P/E may consist only of mild palpation discomfort in the lower
calf.
 In massive DVT , the patient presents with marked thigh swelling
and tenderness during palpation of the common femoral vein.
 In extreme cases, patients are unable to walk or may require a
cane, crutches, or a walker.

22. History of symptoms:
DVT
-Swelling or edema
-Pain
-Warmth of the affected extremity
-Sympoms of PTE
PTE
-Shortness of breath (commonest)
-Rapid breathing
-chest pain of a "pleuritic" nature (worsened by
inspiration)
-Cough
-Hemoptysis (coughing up blood)
-Orthopnea
-Symptoms of DVT

23. PHYSICAL EXAMINATION
DVT
• Dilated superficial veins
• Unilateral edema or swelling with a difference in calf or thigh
diameters
• Unilateral warmth, tenderness, erythema
• Pain and tenderness along the course of the involved major veins
• Local (e.g., inguinal mass) or general signs of malignancy
• “Homan’s sign” -calf pain on passive dorsiflexion of the foot.
However, it’s negative predictive value is quite low and it is not used
in modern clinical medicine for diagnosis of DVT
• Look for physical findings of PTE (DVT embolises to the pulmonary
circulation resulting in PTE)

24. PTE
-Fever
-Tachypnea (commonest)
-Tachycardia
-Rales
-Decreased breath sounds
-Wheezing
-Jugular venous distension
-Accentuated pulmonic component of the
second heart sound
-Calf or thigh swelling, erythema, edema,
tenderness, palpable cords (concomitant DVT)
-Physical findings of complications can also
be present (see complications above)

25. Differential Diagnosis – VTE…
DVT
Ruptured Baker's cyst
Cellulitis
Postphlebitic syndrome/venous insufficiency
PE
 Pneumonia, asthma, COPD
 Congestive heart failure
 Pericarditis
 Pleurisy: costochondritis, musculoskeletal discomfort
 Rib fracture, pneumothorax
 Acute coronary syndrome
 Anxiety

26. Clinical syndromes – VTE…
 Upper extremity venous thrombosis may present with asymmetry in
the supraclavicular fossa or in the circumference of the upper arms.
 A prominent superficial venous pattern may be evident on the anterior
chest wall.
 Patients with massive PE present with:
 Systemic arterial hypotension &
 Usually have anatomically widespread thromboembolism.
 Those with moderate to large PE have:
 RV hypokinesis on echocardiography but
 Normal systemic arterial pressure.
 Patients with small to moderate PE have both:
 Normal right heart function and
 Normal systemic arterial pressure.
 They have an excellent prognosis with adequate anticoagulation.

27. Clinical syndromes – VTE…
The presence of pulmonary infarction
 Usually indicates a small PE
Is exquisitely painful because it lodges
peripherally, near the innervation of pleural
nerves.
 Pleuritic chest pain is more common with
small, peripheral emboli.

28. .
 Nonthrombotic PE may be easily overlooked.
 Possible etiologies include:
 Fat embolism after pelvic or long bone fracture,
 Tumor embolism,
 Bone marrow, and air embolism.
 Cement embolism and bony fragment embolism can occur after
total hip or knee replacement.
 IV drug users may inject themselves with a wide array of substances
that can embolize such as hair, talc, and cotton.
 Amniotic fluid embolism occurs when fetal membranes leak or tear
at the placental margin.
18

29. C/Fs PE
 Dyspnea is the most common symptom of PE, and
 Tachypnea is the most common sign.
 Dyspnea, syncope, hypotension, or cyanosis indicates a massive
PE
 Whereas pleuritic pain, cough, or hemoptysis often suggests a small
embolism situated distally near the pleura.
 On P/E, young and previously healthy individuals may appear
anxious but otherwise seem well.
 They may have dyspnea only with moderate exertion.
 Often lack "classic" signs such as tachycardia, low-grade fever, neck
vein distention, and an accentuated P2.

30. Nonimaging Diagnostic Modalities
 Blood Tests
 The quantitative plasma d-dimer rises in the presence of DVT or PE
because of the breakdown of fibrin by plasmin.
 The sensitivity of the d-dimer is >80% for DVT and >95% for PE.
 The d-dimer is a useful "rule out" test
 But d-dimer assay is not specific.
 Levels increase in patients with myocardial infarction, pneumonia,
sepsis, cancer, and the postoperative state and pregnancy.
 Arterial blood gases lack specificity for PE, even though both PO2
and Pco2 often decrease.
 PO2 & alveolar-arterial O2 gradient may help asses severity of
PE.
20

31. PE & DVT - Dx…
 Elevated Cardiac Biomarkers
 Serum troponin levels increase b/ce of RV microinfarction.
 Myocardial stretch results in elevation of BNP or NT-pro-BNP.
 Biomarkers predict an increase in complications and mortality from PE.
 Electrocardiogram
 Sinus tachycardia is the most common
 The S1Q3T3 sign: an S wave in lead I, a Q wave in lead III, and an inverted T
wave in lead III.
 This finding is relatively specific but insensitive.
 Perhaps the most common finding is T-wave inversion in leads V1 to V4.
 Noninvasive Imaging Modalities
 Venous Ultrasonography DVT
• lack of compressibility, homogenous thrombus with low echogenicity,,
abnormal Doppler flow dynamics (flow blunted by calf compression))

32. PE & DVT - Dx…
 Because DVT and PE are so closely related and are both treated
with anticoagulation, confirmed DVT is usually an adequate
surrogate for PE.
 In contrast, a normal venous ultrasound does not exclude PE.
 About one-half of patients with PE have no imaging evidence of
DVT
 For patients with nondiagnostic venous ultrasound, one should
consider alternative imaging modalities for DVT, such as CT and
MRI.

33. CXR & Chest CT In PE
Chest Roentgenography
 A normal CXR often occurs in PE.
 Well-established abnormalities include
 Focal oligemia (Westermark's sign),
 A peripheral wedged-shaped density above the diaphragm (Hampton's hump),
 An enlarged right descending pulmonary artery (Palla's sign).
Chest CT
 Spiral chest CT( CT- pul. Angiography = CT-PA) with IV contrast is the
principal imaging test in PE.
 RV and LV enlargement can also be seen on CT and can be used for risk
stratification
 In PE, RV enlargement indicates an increased likelihood of death in the next 30 days.
 Lung parenchyma can be evaluated for alternative Dx such as pneumonia,
emphysema, pulmonary fibrosis, pulmonary mass, and aortic pathology.
 Sometimes asymptomatic early-stage lung cancer is diagnosed incidentally.

34. Large bilateral proximal PE
On a coronal chest CT image in a 54/M with lung ca & brain metastases.
There are filling defects in the main & segmental pulmonary arteries bilaterally (white
arrows).
Only the left upper lobe segmental artery is free of thrombus.

35. Lung Scanning In PE
 Albumin labeled with a gamma-emitting radionuclide are injected
IV and are trapped in the pulmonary capillary bed for perfusion
scan.
 The perfusion scan defect indicates absent or decreased blood flow,
possibly due to PE.
 Ventilation scans, obtained with a radiolabeled inhaled gas such
as xenon , improve the specificity of the perfusion scan.
 Abnormal ventilation scans indicate abnormal nonventilated lung,
thereby providing possible explanations for perfusion defects other
than acute PE, such as asthma and COPD.
 A high-probability scan for PE is defined as :
 One that indicates segmental perfusion defects
 In the presence of normal ventilation.

36. -
 MRI (Contrast-Enhanced)
 When ultrasound is equivocal, MR venography with gadolinium contrast
is an excellent imaging modality to diagnose DVT.
Echocardiography
 Most patients with PE have normal echocardiograms.
 However, echocardiography can detect conditions that may mimic PE,
such as AMI , pericardial tamponade, and aortic dissection.
 Transthoracic echocardiography rarely images thrombus directly.
 The best-known indirect sign of PE on transthoracic echocardiography is
hypokinesis of the RV free wall.
 Transesophageal echocardiography when CT scanning facilities are not
available or when a patient has renal failure or severe contrast allergy.
 This imaging modality can identify saddle, right main, or left main PE.

37. Invasive Diagnostic Modalities - VTE
Pulmonary Angiography
Invasive catheter-based diagnostic testing is reserved
 For patients with technically unsatisfactory chest CTs and
 Those in whom an interventional procedure such as catheter-
directed thrombolysis or embolectomy is planned.
 A definitive diagnosis of PE depends on visualization of an
intraluminal filling defect.
Contrast Phlebography for DVT
Venous ultrasonography has virtually replaced contrast
phlebography as the diagnostic test for suspected DVT.

39. Treatment: Deep Venous Thrombosis
Primary Therapy versus Secondary Prevention
 Primary therapy consists of clot dissolution with thrombolysis
or removal of PE by embolectomy.
 Anticoagulation with heparin and warfarin or placement of an
inferior vena caval filter constitutes secondary prevention of
recurrent PE.
Risk Stratification
 High-risk patients:
 Hemodynamic instability,
 RV dysfunction, RV enlargement, or
 Elevation of the troponin level due to RV microinfarction.
 Predictors of an increased mortality rate from PE:
 RV hypokinesis on echocardiography, RV enlargement on chest CT, and
Troponin elevation
 Primary therapy should be reserved for patients at high risk of an
adverse clinical outcome.

40. Acute management of pulmonary thromboembolism.

41. Treatment: Massive Pulmonary Embolism
Anticoagulation
 Immediately effective anticoagulation is initiated with a parenteral
drug: UFH, LMWH, or fondaparinux.
 In patients with heparin-induced thrombocytopenia - A direct thrombin
inhibitor (argatroban, lepirudin, or bivalirudin )
 Parenteral agents are continued as a transition or "bridge" to stable,
long-term anticoagulation with a vitamin K antagonist (warfarin).
 Warfarin requires 5–7 days to achieve a therapeutic effect.
 During that period , overlap the parenteral and oral agents.
 After 5–7 days of anticoagulation, residual thrombus begins to
endothelialize in the vein or pulmonary artery.

42. Unfractionated Heparin
 UFH anticoagulates by binding to and accelerating the activity of
antithrombin.
 UFH is dosed to achieve a target activated partial thromboplastin
time (aPTT) that is 2–3 times the upper limit of the laboratory
normal.
 This is usually equivalent to an aPTT of 60–80 s.
 The major advantage of UFH is its short half-life.
 This is especially useful if the patient may undergo an invasive
procedure such as embolectomy.
 Patients are at risk of developing heparin-induced
thrombocytopenia.

43. Low-Molecular-Weight Heparins
These fragments of UFH have greater
bioavailability, a more predictable dose
response, and a longer half-life than does
UFH.
 No monitoring or dose adjustment is
needed unless the patient is markedly obese
or has chronic kidney disease.

44. Warfarin
This vitamin K antagonist prevents carboxylation
activation of coagulation factors II, VII, IX, and X.
Overlapping UFH, LMWH, or fondaparinux with
warfarin for at least 5 days can counteract the early
procoagulant effect of unopposed warfarin.
 In an average-size adult, warfarin usually is initiated
in a dose of 5 mg
The target INR is usually 2.5, with a range of 2.0–3.0.

45. Complications of Anticoagulants
 Hemorrhage.
 For life-threatening or intracranial hemorrhage due to heparin or
LMWH, protamine sulfate can be administered.
 There is no specific antidote for bleeding caused by fondaparinux or
direct thrombin inhibitors.
 Major bleeding from warfarin is best managed with prothrombin
complex concentrate.
 With non-life threatening bleeding in a patient who can tolerate large
volume, fresh-frozen plasma can be used.
 Recombinant human coagulation factor VIIa (rFVIIa), is an option to manage
catastrophic bleeding from warfarin.
 For minor bleeding or to manage an excessively high INR in the absence of
bleeding, oral vitamin K may be administered.

46. Complications of Anticoagulants…
 HIT and osteopenia are far less common with LMWH than with
UFH.
 Thrombosis due to HIT should be managed with a direct thrombin
inhibitor:
 Argatroban for patients with renal insufficiency and
 Lepirudin for patients with hepatic failure.
 During pregnancy, warfarin should be avoided if possible because
of warfarin embryopathy,
 Most common during the 6th through 12th week of gestation.
 However, women can take warfarin postpartum and breast-feed
safely.
 Warfarin can also be administered safely during the second
trimester.

47. Duration of Anticoagulation
 Patients with PE after surgery, trauma, or estrogen exposure
ordinarily have a low rate of recurrence after 3–6 months of
anticoagulation.
 For DVT isolated to an upper extremity or calf that has been
provoked by surgery, trauma, estrogen, or an indwelling central
venous catheter or pacemaker, 3 months of anticoagulation
suffices.
 For provoked proximal leg DVT or PE, 3 to 6 months of
anticoagulation is sufficient.
 For patients with cancer and VTE, the consensus is to prescribe 3–
6 months of LMWH as monotherapy without warfarin and
 To continue anticoagulation indefinitely unless the patient is
rendered cancer-free.

48. Duration of Anticoagulation…
Among patients with idiopathic, unprovoked
VTE, the recurrence rate is high after
cessation of anticoagulation
It is recommended that anticoagulation be
considered for an indefinite duration with a
target INR b/n 2 and 3 for patients with
idiopathic VTE.

49. Maintaining Adequate Circulation
For patients with massive PE and hypotension, one
should administer 500 mL of normal saline.
Dopamine and dobutamine are first-line inotropic
agents for treatment of PE-related shock.
There should be a low threshold for initiating these
pressors.
Consider also norepinephrine, vasopressin, or
phenylephrine.

50. Fibrinolysis In VTE
Successful fibrinolytic therapy rapidly reverses right
heart failure and may result in a lower rate of death
and recurrent PE
The preferred fibrinolytic regimen is recombinant tPA
 Patients appear to respond to fibrinolysis for up to
14 days after the PE has occurred.
Contraindications to fibrinolysis include intracranial
disease, recent surgery, and trauma

51. Prevention of Postphlebitic Syndrome
Daily use of below-knee 30- to 40-mmHg vascular
compression stockings will halve the rate of
developing postphlebitic syndrome.
 These stockings should be prescribed as soon as DVT
is diagnosed
When patients are in bed, the stockings need not be
worn.
-
-

52. Prevention of Venous Thromboembolism
Condition Prophylactic strategy
High-risk general surgery Mini-UFH or LMWH
Thoracic surgery Mini-UFH + IPC
Cancer surgery, including
gynecologic cancer surgery
LMWH, consider 1 month of prophylaxis
Total hip replacement, total knee
replacement, hip fracture surgery
LMWH, fondaparinux 2.5 mg SC, once daily, or
(except for total knee replacement) warfarin
(target INR 2.5);

53. Prevention of Venous Thromboembolism…
Condition Prophylactic Strategy
Neurosurgery IPC
Neurosurgery for brain tumor Mini-UFH or LMWH, + IPC + predischarge
venous ultrasonography
Benign gynecologic surgery Mini-UFH
Medically ill patients Mini-UFH or LMWH
Anticoagulation contraindicated IPC