VENOUS THROMBO-EMBOLISM

PERIPHERAL VENOUS DISEASE

and
PULMONARY EMBOLISM
PERIPHERAL VENOUS DISEASE

DEEP VEIN THROMBOSIS (DVT)

and
SUPERFICIAL THROMBOPHLEBITIS
 DEEP VEIN THROMBOSIS
(TROMBOZA VENOASA PERIFERICA)
 Definition
• is a blood clot that forms in a deep vein in
the body.
• Most deep vein clots occur in the lower leg or
thigh.
• often resulting in potentially life-threatening
emboli to the lungs or debilitating valvular
dysfunction and chronic leg swelling (Post-
thrombotic syndrome)
• DVT is one of the most prevalent medical
problems today, with an annual incidence of
80 cases per 100,000.
• Lower-extremity DVT is the most common
venous thrombosis.
anatomic predisposition to left leg
ileofemoral DVT

“obstruction” that occurs where the

right iliac artery crosses the left iliac
vein
 Pathophysiology
Over a century ago, Rudolf Virchow described 3
factors that are critically important in the
development of venous thrombosis:
immobilization
(1) venous stasis Postoperative
(2) hypercoagulability Thrombophilia (eg: ATIII, f.V Leyden,
pr.S, pr.C)
(3) vein damage oral contraceptives
Trauma, surgery

These factors have come to be known as

the Virchow triad.
 Etiology (Clinical risk factors for DVT)
1. major surgeries (eg: hip or knee replacement, pelvic surgery)
2. Fractures
3. Immobility
4. Cancer ± chemotherapy

risk factors can be subdivided by duration:

 Transient (eg: leg fracture, surgery, long-distance air travel,
use of oral contraceptives, pregnancy)
 Long-term (eg: congenital antithrombin deficiency, cancer)

Distal (below knee) DVTs are more frequently related to transient situations while proximal
ones to chronic conditions.
In 25–50% of first DVT episodes, no predisposing factor is identified.
Clinical Manifestations
1. Spontaneous Pain
2. Induced Pain (walking, compression, balancing the ms. of
the leg, positive Homans' sign (calf pain on dorsiflexion of the
foot)
3. Edema
 pretibial >leg, swelling level, white skin
 phlegmasia alba dolens
 phlegmasia cerulea dolens = painful blue
appearance of the leg, occurs due to massive
thrombosis involving major and collateral veins of
the leg (superficial vein sistem is closed)
Imaging Diagnosis (1)

• Compression venous ultrasonography (VUS)

± Doppler imaging
 the most widely used noninvasive test for suspected
DVT
 accuracy in detection of thrombus involving the
popliteal or more proximal veins
 Noncompressibility of the veins is diagnostic of DVT
Imaging Diagnosis (2)
• Magnetic Resonance Venography
 high sensitivity and specificity for proximal DVT
 expensive and not readily available in most centers
Imaging Diagnosis (3)
• Contrast Venography
 remains the gold standard for diagnosis
 expense, discomfort to the patient and potential for
adverse experiences
LABORATORY FINDINGS

• D-Dimer elevated levels in plasma,

numerous nonthrombotic conditions (sepsis,
pregnancy, surgery, and cardiac or renal failure) also can cause
elevated levels = nonspecificity
exclude VTE when levels are not raised
The signs and symptoms are calf or thigh pain, tenderness,
swelling, or superficial venous dilatation. None of these signs is
specific for DVT. Even the well-known Homan's sign (i.e., calf pain
with dorsiflexion of the foot) is unreliable; its accuracy is only
50%.

Doppler ultrasound (US) examination (duplex scanning) detects

DVT proximal to the calf veins with >95% accuracy; unfortunately,
it is not as sensitive in detecting calf vein DVT.

Ascending venography is still the reference standard.

DIAGNOSIS
• Clinical prediction rule (two-level modified Wells
score)

• ELISA D-dimer measurement is recommended in

‘unlikely’ clinical probability patients to exclude DVT.

• Venous US is recommended as first line imaging

method for DVT diagnosis
 The Wells score
Clinical variable Points

Active cancer (treatment ongoing or within previous 6 months or palliative) +1

Paralysis, paresis or recent plaster immobilization of the lower extremities +1

Recently bedridden for 3 days or more, or major surgery within the previous 12 weeks requiring general or regional anesthesia +1

Localized tenderness along the distribution of the deep venous system +1

Entire leg swelling +1

Calf swelling at least 3 cm larger than that on the asymptomatic leg (measured 10 cm below the tibial tuberosity) +1

Pitting edema confined to the symptomatic leg +1

Collateral superficial veins (non varicose) +1

Previously documented DVT +1

Alternative diagnosis at least as likely as DVT −2

Three-level Wells score

Low <1

Intermediate 1–2

High >2

Two-level Wells score

Unlikely ≤1

Likely ≥2
DIFFERENTIAL DIAGNOSIS
Muscle strain
Direct twisting injury to the leg
Leg swelling in paralyzed limb
Lymphangitis, lymphatic obstruction
Venous reflux
Muscle tear
Baker cyst
Cellulitis
Internal abnormality of the knee
TREATMENT

• Anticoagulation
• Thrombolysis/Thrombectomy Mechanical
thrombus removal alone is not successful and needs adjuvant
thrombolytic therapy.

• Vena cava filter

• Compression = Elastic compression stockings
Anticoagulation = “standard therapy”
 initial treatment + long term treatment
 does not lyse the clot, prevent clot formation/ extension

• Oral Direct Thrombin and Factor Xa Inhibitors

• Heparin
unfractionated heparin (iv)
Low Molecular Weight Heparin (LMWH) (sc)
Oral Direct Thrombin and Factor Xa
Inhibitors
initial treatment+ long term treatment

• Rivaroxaban (XareltoR): 15 mg twice daily for 3

weeks followed by 20 mg/day

• Apixaban (EliquisR): 10 mg twice daily for 7

days followed by 5 mg twice daily
Heparins does not lyse the clot, prevent clot formation/ extension

H= inhibition of factor Xa
 Heparins = initial treatment
• can be injected intravenously or subcutaneously
• Heparin sodium = unfractioned H
must be given as a continuous infusion (iv)
 Δt = 3 – 5 days >> 10 days
aPTT level should be monitored (x 2 initial aPTT)
If long-term anticoagulation is required, heparin is
often used only to commence anticoagulation
therapy until an oral anticoagulant takes effect.
Activated Partial Thromboplastin Time (aPTT or APTT)
(1,250 IU/ora)
 Low Molecular Weight Heparin
(LMWH)
• sc (once or twice daily)
• Give LMWH: dalteparin
enoxaparin
nadroparin
tinzaparin
fondaparinux
• Dosages depend on the patient’s weight,
no aPTT needed !!
• Ex: Fondaparinux:
5 mg/day if weight is < 50 kg;
7.5 mg/day if weight is 50 to 100 kg;
10 mg/day if weight is > 100 kg
Transition to Oral Treatment (1)

1 2 3 4 5 6 7 8 9 10

HEPARIN
for aPTT x 1,5-2,5

AntiVitamin K AC for INR 2 – 3………………………........3 months

At least 2 days overlap H + Sintrom for INR 2-3

DOAC ......................................3 months

AntiVitamin K Anticoagulants
1. Acenocumarol initiate 4 -6 mg/day
2. Warfarine initiate 5 – 10mg/day

• Action mecanism: inhibit the production of

clotting factors II (prothrombin), VII, IX, and X
• the drug should be started within 24 to 48
hours of initiation of heparin with a goal of
achieving international normalized ratio (INR)
results between 2.0 and 3.0
 Transition to Oral Treatment (DOAC)
• Dabigatran at 150 mg twice daily
• Apixaban 5 mg twice daily
• Rivaroxaban 20 mg/day
• Edoxaban 60 mg/day

DOAC = Direct acting Oral AntiCoagulants

NOAC = Non-antivitamin K Oral AntiCoagulants
DOAC

Apixaban is a direct inhibitor of factor Xa

Rivaroxaban is a competitive reversible
antagonist of factor Xa.

Dabigatran is a competitive
reversible antagonist of thrombin.
Side Effects of Anticoagulants
• Bleedings
• Major bleeding (e.g., intracranial,
gastrointestinal or retroperitoneal) leading to
hospitalization, transfusion, or death
DVT Prevention
• in different populations of patients:
surgery (particularly major hip and knee surgery, as well as
neurosurgery )
major trauma
prolonged bedrest or immobilization (>72 h)
previous episodes of VTE
presence of malignant disease
Paralysis
morbid obesity
increasing age.
• mechanical prophylaxis (antiembolic stockings and
intermittent pneumatic compression) should be used
as an adjunct to pharmacologic prophylaxis or in
patients with a high risk for bleeding

• low-dose fractionated heparin

• Low-dose Oral DOAC
PULMONARY EMBOLISM
(EMBOLIA PULMONARA)
• PE describes the blockage of a pulmonary
artery or one of its branches by a blood clot or
foreign material.
• Pulmonary thromboembolism is not a disease
in and of itself. Rather, it is a complication of
underlying venous thrombosis.
PE and DVT are part of the spectrum of VTE and share the same genetic and
acquired risk factors
Pathophysiology of pulmonary embolism

To reach the lungs, thromboemboli travel through

the right side of the heart.

1. PE most commonly arises from the calf veins 2. The venous thrombi originate in venous
valve pockets and at other sites of presumed
venous stasis.
Clinical Manifestations
• The clinical impact of PE depends on the extent of reduction in
pulmonary blood flow, the time frame over which vascular obstruction
occurs, and the absence or presence of underlying cardiopulmonary
disease.
• Non-specific

• abrupt onset of pleuritic chest pain

• shortness of breath (tachypnea)
• Hemoptysis
• fever
• Syncope and seizures
• Cardiogenic shock
• New-onset atrial fibrilation
• Tachicardia >100beats/min, cyanosis, hypoxemia
• Distended jugular veins (=right heart failure)
• Pulmonary rales
PARACLINICAL INVESTIGATIONS

• D-Dimer testing in plasma

• Thoracic radiography
• Ecg
• Echocardiography
• Computed tomography pulmonary angiography
• Magnetic resonance imaging
• Pulmonary angiography
D-Dimer testing in plasma

• A plasmin-derived degradation product of fibrin

• an indirect index of ongoing activation of the
coagulation system
• False-positive D-dimer elevations can occur
• value of the D-dimer assay resides with its high
negative predictive value
Thoracic radiography
• Nonspecific findings
• Common radiographic abnormalities:
atelectasis,
pleural effusion
parenchymal opacities
elevation of a hemidiaphragm
decreased vascularity (Westermark sign)
dilatation of pulmonary vessels
triangular opacity with an apex pointing
toward the hilus (pulmonary infarction)
peripheral wedge-shaped infiltrate caused by
pulmonary infarction
Electrocardiogram
Acute cor pulmonale
• Tachycardia
• atrial fibrillation
• Nonspecific ST/T wave abnormalities: T(-) V1-V3
• S1 Q3 T3 sensitive in the presence of clinical
suspicion for pulmonary embolism
• tall, peaked P waves in lead II (P pulmonale)
• right QRSaxis deviation
• right bundle-branch block
Echocardiography
• dilated right atrium and ventricle
• moderate tricuspid regurgitation
• Elevated PA pressure <55 mmHg
Computed tomography pulmonary
angiography

Pulmonary CT angiography (CTA) is the imaging

modality of choice in suspected acute pulmonary
embolism (PE).

• spiral (helical) CT scanning

• shows emboli directly
Pulmonary angiography
• Gold standard
• Filling defects within pulmonary arteries
and/or branches
TREATMENT
Medical treatment
• Fibrinolytic Therapy
• Anticoagulation Therapy

Mechanical reperfusion = percutaneous

catheter embolectomy

Surgical reperfusion
Fibrinolytic Therapy
• Thrombolytic therapy should be used in patients with acute
PE associated with hypotension (systolic BP <90 mm Hg)
• preferably within 48 hours of the onset of symptoms

AGENTS RECOMMENDED REGIMENS

250,000 IU as a loading dose over 30 min,
Streptokinase
followed by 100,000 IU/hr over 12 to 24 hr
Tissue plasminogen activator
100 mg over 2 hr
ACTILYSE
Anticoagulation Therapy
(see DVT Anticoagulatiuon Therapy)

 Anticoagulation therapy is the cornerstone of PE treatment

and should be initiated immediately, even while patients with
suspected PE are awaiting the results of confirmatory tests.

• Oral Direct Thrombin and Factor Xa Inhibitors

• Heparin
 unfractionated heparin (iv)
 Low Molecular Weight Heparin (LMWH) (sc)

 Duration of oral anticoagultion = 6 months

 DIFFERENTIAL DIAGNOSIS OF PE
I. AFECŢIUNI PULMONARE SAU PLEUROPULMONARE ACUTE
Pneumonia
Obstrucţie bronşică acută
Atelectazie
Edem pulmonar acut
Astm bronşic sever
Pleurezie sau pleuropericardită
Abces pulmonar
II. ACUTE RIGHT CARDIAC FAILURE
Infarct acut de miocard
Tamponadă cardiacă
Miocardită
Cord pulmonar cronic decompensat
Embolie pulmonară nontrombotică
III. CARDIOVASCULAR COLAPSE – CARDIOGENIC SHOCK
Infarct acut de miocard
Tamponadă cardiacă acută
Anevrism disecant de aortă
Pneumotorax spontan sever
Septicemie cu germeni gram negativi

Gherasim L, Medicină internă, 2006