1) Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common cardiovascular disease among hospitalized patients, especially critically ill patients in the ICU. 2) Risk factors for VTE include surgery, trauma, cancer, immobilization, and factors related to the underlying critical illness. Several clinical prediction models can assess a patient's risk. 3) Diagnosis involves blood tests, imaging like ultrasound and CT, and assessment of right ventricular function. Treatment involves supportive care, anticoagulation with heparin or low molecular weight heparin, and consideration of thrombolysis for hemodynamically unstable patients.

1. VENOUS THROMBOEMBOLISM
By: Dr. Ram Gopal Maurya

2. Introduction
• VTE is defined as pathologic formation of a
thrombus within the venous system;
• It includes DVT and pulmonary embolism (PE).
• VTE is the third most common cardiovascular
disease after myocardial infarction and stroke.
• The estimated incidence ranges between 1 to
2 per 1,000 person-years.

3. EPIDEMIOLOGY
• VTE commonly complicates the course of hospitalized
patients, especially those in the ICU and sometimes
despite VTE prophylaxis.
• A study of mechanically ventilated patients,
undergoing chest CT unrelated to suspected PE, found
PE in 18.7% of examined individuals.
• In autopsy studies of critically ill patients, PE was found
in 7% to 27%.
• PE continues to have a high mortality rate, most deaths
due to PE within the first 3 months of follow-up occur
during the first week after diagnosis.

4. RISK FACTORS

5. • One or more of these conditions is present in
almost all ICU patients, and thus VTE is
considered a universal risk in critically ill patients.
• Incidence of VTE increases correspondingly with
the number of risk factors present.
• Risk factors can be subgrouped into..
1. High risk
2. Moderate risk
3. Low risk

6. • High risk factors
1. Hip or leg fracture
2. Hip or knee replacement
3. Major general surgery
4. Major trauma, including spinal cord injury

7. • Moderate risk
1. Arthroscopic knee surgery
2. Central venous
catheterization
3. Congestive heart or
respiratory failure
4. Hormone replacement
and oral contraceptive
therapy
5. Malignancy (active or
recently treated)
6. Pregnancy
7. Paralytic stroke
8. Prior VTE
9. Thrombophilia (inherited
or acquired
• Low risk
1. Bed rest > 3d
2. Prolonged immobility due
to sitting (e.g.,car or air
travel)
3. Increasing age
4. Laparoscopic surgery
5. Obesity
6. Varicose veins

8. Venous Thrombo-embolism Risk
Assessment

9. Padua prediction score
• The Padua Prediction Score was developed to estimate
risk of venous thromboembolism (VTE) in hospitalized
medical patients.
• In the derivation study, 1180 patients were followed
for up to 90 days after admission to monitor for the
development of VTE.
• The percent of subjects developing VTE was as follows:
• “Low risk” patients (711) (score <4): 0.3 percent
• “High risk” patients receiving adequate in-hospital
thromboprophylaxis (186) (score ≥4): 2.2 percent
• “High risk” patients not receiving adequate in-hospital
thromboprophylaxis (283) (score ≥4): 11.0 percent

11. The IMPROVE risk-assessment model
Risk factor point
Prior venous thromboembolism 3
Diagnosed thrombopholia 2
Current lower limb paralysis 2
Current cancer 2
Immobilised for at least 7 days 1
Stay in ICU or coronary care unit 1
More than 60 years old 1
Note: a total score of 0 or 1 as low risk and
not needing anticoagulant prophylaxis
score of 2 or more as high risk and need
prophylaxis.

12. • The IMPROVE risk score was used to determine
VTE risk in 15,156 medical patients enrolled in
the observational International Medical
Prevention Registry on Venous
Thromboembolism (IMPROVE) study .
• The observed rate of VTE within 92 days of
admission was 0.4 to 0.5 percent if none of these
risk factors was present, and was in the range of
8 to 11 percent in those with the highest risk
score.

13. Revised Geneva score
RISK FACTORS POINT
Predisposing factors
• age >65 years
• Previous DVT or PE
• surgery or fracture within 1 month
•Active malignancy
1
3
2
2
Symptoms
•Unilateral lower limb pain
•Haemoptysis
3
2
Clinical signs
•Heart rate 74-94 bpm
•Heart rate >95 bpm
•Pain in respone to LL deep vein palpation and unilateral
edema
3
5
4
Note: low risk
intermidiate
high
0-3
4-10
>11

14. Modified Well Criteria

15. limitation
• Require validation from independent, prospective
studies before they can be used in routine
practice.
• In general, VTE prophylaxis should be considered
in medical patients older than age 40 who have
limited mobility for ≥3 days, and have at least one
thrombotic risk factor .
• All patients admitted to intensive care units are
considered high risk for VTE , even after routine
prophylactic anticoagulation .

16. Pathophysiology

17. • Thrombi may form in the veins, superficially
(superficial vein thrombosis, SFVT) or deep
(deep vein thrombosis, DVT).
• PE originates from thrombi in the deep veins
of the lower extremities in at least 90% of
patients, Mostly form the popliteal or more
proximal deep veins of the lower extremities.
•

19. DIAGNOSIS
• Clinical feature
• Investigation

21. Diagnostic Testing
• Chest Radiography: Typically described
findings are as follows: ipsilateral elevation of
the diaphragm on the affected side, wedge-
shaped pleural based infiltrate (Hampton
hump), focal oligemia (Westermark sign), or
enlarged right descending pulmonary artery
(Palla sign), atelectasis and cardiomegaly.
• Chest radiograph may be normal up to 25%.

23. Electrocardiography
• Sinus tachycardia occurs in most patients with PE.
• Classic findings on EKG of S1Q3T3 (S in V1, Q
wave in V3, and T wave inversion in V3) and right
bundle branch block do not occur in most
patients with PE, and they have low positive
predictive value when they do occur.
• Signs of RV strain that include right axis deviation
and right ventricle hypertrophy may suggest the
presence of PE

25. D-Dimer Assay

26. Venous Ultrasound
• Pulmonary emboli originate primarily from
thrombi in proximal leg veins, so the
evaluation of suspected PE can begin with a
search for thrombosis in the proximal leg veins
using ultrasound imaging at the bedside.
• two ultrasound methods: 1. compression
ultrasound and 2. color Doppler mode.
• The combination of compression and Doppler
ultrasound is known as duplex ultrasound.

27. • duplex ultrasound has a sensitivity ≥ 95%, a
specificity ≥ 97%, a positive predictive value as
high as 97%, and a negative predictive value as
high as 98%.
• If venous ultrasound shows evidence of proximal
leg vein DVT, no further evaluation for PE is
necessary (since the treatment of DVT and PE is
essentially the same).
• However, a negative evaluation for DVT does not
exclude the diagnosis of acute PE.

29. CT Angiography
• This is a specialized method of CT that uses a spiral or
helical scanner that rotates around the patient to
produce a “volumetric” two-dimensional view of the
lungs. When spiral CT is combined with the peripheral
injection of a contrast agent, the central pulmonary
arteries can be visualized. Pulmonary emboli appear as
filling defects.
• multidetector CT scans, CT angiography (CTA) has a
sensitivity of 83%, a specificity of 96%, a positive
predictive value of 92% to 96% and a negative
predictive value of 96% for the diagnosis of PE.

31. Radionuclide Lung Scan
• Ventilation-perfusion lung
scans are widely used in the
evaluation of suspected PE.
• secure the diagnosis in only
about 25% to 30% of cases .
• The problem is the
presence of lung disease
(particularly infiltrative
disease), which produces an
abnormal scan in about 90%
of cases.

32. • A normal lung scan excludes the presence of a
pulmonary embolus, whereas a high-
probability lung scan carries a 90% probability
that a pulmonary embolus is present.
• A low-probability lung scan does not reliably
exclude the presence of a PE.
• An intermediate-probability or indeterminate
lung scan has no value in predicting the
presence or absence of a pulmonary embolus.

33. Pulmonary Angiography
• considered the most accurate method for
detecting pulmonary emboli.
• reserved for cases where the other diagnostic
tests are unable to confirm or exclude a
pulmonary embolism that is highly suspected.

34. Classification of PE
• MASSIVE ; SUBMASSIVE ; OTHER/MILD
1. MASSIVE PE : RV dysfunction with arterial
hypotension or cardiogenic shock.{ systolic
blood pressure <90 mm Hg or a drop >40 mm
Hg from baseline for at least 15 minutes that
remains present despite volume resuscitation
and vasopressor therapy}.
2. SUBMASSIVE PE : RV dysfunction without
arterial hypotension or cardiogenic shock.

35. 3. OTHER/MILD PE : Patients who do not have
symptoms and signs of massive or submassive PE
have been grouped into the “other” category.
ASSESSSMENT OF RV DYSFUNCTION;
Echocardiography
On spiral CT
Elevated cardiac marker ; Troponin I > 0.9 ng/mL or
troponin T > 0.1 ng/mL
BNP > 90 pg/mL or pro-NT BNP > 500 pg/mL

36. European Society of Cardiology
guidelines
• an early mortality risk-based classification system
• uses four key risk assessment
• (1) hemodynamic instability (i.e., shock or hypotension present),
• (2) imaging-detected (echocardiogram or CT) signs of RV dysfunction,
• (3) elevated clinical risk score (by Pulmonary Embolism Severity Index
[PESI] or simplified PESI,
• (4) abnormal cardiac laboratory biomarkers (i.e., troponin, BNP).
1. High-risk PE patients have hemodynamic instability with imaging-
detected signs of RV dysfunction, with or without an elevated clinical risk
score and with or without abnormal cardiac laboratory biomarkers.
2. Intermediate-risk PE patients do not have hemodynamic instability, but
they have an elevated clinical risk score, and they may or may not have
imaging-detected signs of RV dysfunction and or abnormal cardiac
laboratory biomarkers.
3. Low-risk PE patients do not have abnormalities in any of the four key risk
assessments

37. PROGNOSTIC ASSESSMENT AND
SEVERITY INDICES
• Indicators of a poor prognosis or adverse
outcomes for patients who have PE..
1. hemodynamic instability/hypotension,
2. signs of RV dysfunction,
3. elevated troponin and/ or BNP,
4. coexisting DVT,
5. right ventricular thrombus

38. Pulmonary embolism severity index

41. Treatment
• Prevention Management
PREVENTION
• Primary prophylaxis —carried out using either
drugs or physical methods that are effective for
preventing deep vein thrombosis (DVT).
• Secondary prevention — Secondary prevention
involves the early detection and treatment of
subclinical venous thrombosis by screening
medical patients with objective tests that are
sensitive for the presence of DVT

42. THROMBOPROPHYLAXIS

43. Heparin
• Unfractionated Heparin: Heparin is an
indirect-acting drug that must bind to a
cofactor (antithrombin III or AT) to produce its
anticoagulant effect. The heparin-AT complex
is capable of inactivating several coagulation
factors, but the strongest interactions involve
the inhibition of factor IIa (thrombin) and
factor Xa (3). The anti-IIa (antithrombin)
activity is 10 times more sensitive than the
anti-Xa activity.

44. • Low-Dose Unfractionated Heparin: LDUH
• The standard regimen of low-dose
unfractionated heparin (LDUH) is 5,000 units
given by subcutaneous injection twice daily
(every 12 hours) or three times daily (every 8
hours.
• LDUH can be used for thromboprophylaxis in
most conditions except hip and knee surgery.

45. • No significant difference in the overall rate of
VTE between BID (5.4/1000 patient-days) and
TID (3.5/1000 patient-days) UFH heparin
dosing.
• The risk for major bleeding was significantly
greater with TID than with BID UFH dosing
(BID 0.35/1000 patient-days, TID 0.96/1000
patient-days).

46. Low-Molecular-Weight Heparin
• ENOXAPARIN: first LMWH approved for use.
• dose for thromboprophylaxis is 40 mg given by
subcutaneous injection once daily.
• with a very high risk of VTE (e.g., major
trauma, hip and knee surgery), the dose is 30
mg by subcutaneous injection twice daily.
• The prophylactic dose of enoxaparin in renal
failure (i.e., creatinine clearance < 30 mL/min)
is 30 mg once daily by subcutaneous injection.

47. • DALTEPARIN: two advantages over enoxaparin
1. given only once daily, even in high-risk.
2. can be continued without dose reduction in
patients with renal failure.

49. LMWH vs. Low-Dose
Unfractionated Heparin
1. LMWH is equivalent to LDUH for most conditions
encountered in the ICU, including acute medical
illnesses, major, non-orthopedic surgery, and
cancer-related surgery.
2. LMWH is superior to LDUH for major orthopedic
procedures involving the hip and knee.
3. The incidence of heparin-induced
thrombocytopenia with LMWH (0.2%) is less than
10% of the incidence with LDUH (2.6%).

50. Mechanical Thromboprophylaxis
1. Graded Compression Stockings: designed to
create 18 mm Hg external pressure at the ankles
and 8 mm Hg external pressure in the thigh.
2. Intermittent Pneumatic Compression: Bladder
inflation promotes venous outflow from the legs
by creating 35 mm Hg external compression at
the ankle and 20 mm Hg external compression at
the thigh.
• The IPC method is more effective than graded
compression stockings and can be used alone for
thromboprophylaxis

51. TREATMENT OF PE
• Objectives and Principles of Treatment
(1) supportive care (e.g., treatment of
hypotension and respiratory failure),
(2) facilitating the resolution of PE
(3) prevention of recurrent VTE,
(4) avoidance of complications from therapy.

52. Resuscitation
• Hemodynamic instability associated with PE
should lead to prompt resuscitation and
consideration for thrombolytic therapy.
1. Volume Administration.
2. Vasopressors
3. Supplemental Oxygen
4. Mechanical Ventilation and Sedation

53. Initial Anticoagulation Considerations
• Anticoagulation, the mainstay of treatment for
acute PE.
• Heparin is the corner stone of anticoagulation.
Bleeding Risk Assessment
All patients should undergo a bleeding risk
assessment and evaluation for
contraindications to anticoagulant therapy
before the initiation of such treatment.

54. • Absolute contraindications to anticoagulant
treatment include intracranial bleeding,
severe active bleeding, malignant
hypertension, or recent brain, eye, or spinal
cord surgery.

55. Heparin Therapy
• Unfractionated Heparin:

56. • The anticoagulant effect is monitored with the
activated partial thromboplastin time (PTT);
the target PTT is 46 –70 seconds, or a PTT
ratio (test/control) between 1.5 and 2.5.
• Heparin-Induced Thrombocytopenia: An
antibody-mediated thrombocytopenia can
appear 5–10 days after initiation of heparin
therapy.

57. Low-Molecular-Weight Heparin

58. • Enoxaparin : 1 mg/kg by subcutaneous injection every 12
hours. Reduce dose by 50% in patients with a creatinine
clearance <30 mL/min; e.g., 1 mg/kg once daily.
• Daltaparin: 100 unit/kg twice daily or 200 unit/kg once a
day.
• Although LMWH has several advantages over
unfractionated heparin, continuous-infusion unfractionated
heparin is preferred for treating VTE in the ICU because it is
rapidly acting, can be reversed promptly with protamine,
and does not require dose adjustment in patients with
renal insufficiency. LMWH is more appropriate for non-ICU
patients and outpatients

60. Oral anticoagulation
• Warfarin: Oral anticoagulation with warfarin
should be started as soon as possible after the
start of heparin anticoagulation.
• The initial dose is 5–10 mg daily for the first 2
days, with subsequent dosing tailored to the
international normalized ratio (INR). The target
INR is 2–3.
• When the INR reaches the therapeutic range,
anticoagulation with unfractionated heparin or
LMWH can be discontinued.

61. Why overlapping required

62. Other oral anticoagulant

63. Thrombolytic Therapy
• Thrombolytic therapy provides more rapid lysis of PE
and more rapid restoration of pulmonary perfusion
than anticoagulant treatment, with associated
reduction in pulmonary artery pressure and resistance
and an improvement in right ventricular function.
• Despite the belief that these drugs have life-saving
effects, thrombolytic agents have not convincingly
shown a mortality benefit in clinical trials.
• The primary risk of thrombolytic therapy is major
bleeding, which may include intracranial hemorrhage.

64. Thrombolytic agents
Agent FDA
approved for
PE
Direct
Plasminogen
Activator
Doses
Streptokinase Yes No 250,000-IU IV bolus over 30 min
followed by 100,000-IU/h for 24 h
Urokinase yes no 4,400-IU/kg bolus over 10 min
followed by 4,400 IU/kg/h for 12–
24 h
Alteplase Yes Yes 100-mg IV infusion over 2 h
Reteplase No Yes Double 10-U IV bolus over 2m in;
30 min apart
tenecteplase no yes Weight-adjusted IV bolus over 5 s
(30–50 mg with a 5-mg step every
10 kg from 􏰋60 to 􏰋 90 kg)

66. • The primary risk of thrombolytic therapy is
major bleeding, which may include
intracranial hemorrhage.

67. Nonpharmacologic Therapies
• Inferior Vena Cava Filter: indicated for
patients who have an acute VTE and an
absolute contraindication to anticoagulant
therapy.
• 2 types: 1) Permanent
2) Retrievable

68. Catheter Embolectomy
• Thrombus fragmentation 2) Rheolytic
thrombectomy 3) Suction thrombectomy 4)
Rotational thrombectomyC 5) Conventional
catheter-directed thrombolysis (CDT) 6)
Pharmacomechanical thrombolysis (PMT

69. SURGICAL EMBOLECTOMY
• Patients with massive PE and systemic arterial
hypotension or submassive PE with right
ventricular dysfunction in whom
contraindications preclude thrombolysis.
• Acute PE patients who require surgical excision
of a right atrial thrombus or closure of a
patent foramen ovale.
• Patients refractory to thrombolysis.