Full information about DVT

1. Deep vein thrombosis and
pulmonary embolism.
Etiology, clinic, diagnosis,
treatment, prevention.
K.L. Lonskii, 2022

2. 2. Heit JA, et al ASH Annual Meeting Abstracts. 2005;106:910.
3. Cohen AT, et al. Thromb Haemost. 2007;98:756−764.
4. Cohen AT. Poster ISPOR 8th, 2005.
The relevance of the thromboembolism
• Each year pulmonary embolism (PE)
causes death 300 thousands patients
in the United States and more than
500 thousands in the EU 2,3
• The risk of post-thrombotic syndrome
(PTS) in drug therapy is up to 80%
• The total cost of thromboembolism
treatment is € 3.1 billion per year4

3. Venous thromboembolism includes:
 deep vein thrombosis of the lower
extremities (DVT)
 pulmonary embolism (PE)
 combination or each disease
separately
Venous thromboembolism is a
"silent killer"

4. The annual incidence of venous
embolism varies from 100 to 200 cases
per 100 000 population
(Heit J.A., 2008;Cohen A.T. et al., 2007).

5. Thrombosis and embolism are reported in
2 million people in the United States and
700 000 in Europe. (International Consensus
Statement. Prevention and treatment of venous
thromboembolism 2013)
The annual incidence of DVT in Europe is
1 case per 1000 people. (V. Perederyi, 2003)

6. Venous embolism and it’s complications
DVT
PTS
PE
Death Pulmonary
hypertension
Recurrent episodes (relapses)

7. Deep vein thrombosis (DVT)
The annual incidence of
DVT in Europe is 1 in 1000
people.
Chronic form of the
disease occurs in 85-90% of DVT
cases with drug therapy
Retrombosis occurs in 10-
80% cases after surgery.

8. After 5 years treatment with anticoagulants
• 95% of patients show chronic vein
insufficiency
• 15% have progression of symptoms up to
venous ulcers
• 15% have symptoms of venous lameness.
(Comerota A.J., Gale S.S., 2006; Akesson
H. et al., 1990)

9. In some patients with common proximal
acute DVT lasting less than 14 days with a
low risk of bleeding, catheter-directed
thrombolysis (CDT) is recommended (level
of evidence 2B).
(Guidelines of American Venous Forum 2012; Scientific
Statement From the American Heart Association 2014)

10.  About 80% of
DVT are
asymptomatic
20%
80%
Venous thrombosis features
Turpie AGG. State of the art: solutions for thromboprophylaxis. VTE Experts Meeting, 2005. Seville,
Spain

11. Diagnostic algorithm
Clinical probability
D-dimer test:
• Negative (anticoagulants denial);
• Positive (compression ultrasound);
DVT is excluded (next examination in 7
days);
DVT diagnosed (start treatment).

12. Wells score for DVT diagnosis
(Wells P.S., Anderson D.R., Bormanis J., et al. Value assessment of pretest probability of deep-vein thrombosis in clinical management.
The Lancet. 1997;351:1795-8.)
Present Score
Lower limb trauma or surgery or immobilisation in a plaster cast +1
Bedridden for more than three days or surgery within the last four week +1
Tenderness along line of femoral or popliteal veins (NOT just calf
tenderness)
+1
Entire limb swollen +1
Calf more than 3cm bigger circumference,10cm below tibial tuberosity +1
Pitting oedema +1
Dilated collateral superficial veins (non-varicose) +1
Past Hx of confirmed DVT +1
Malignancy (including treatment up to six months previously) +1
Intravenous drug use +3
Alternative diagnosis as more likely than DVT -2
Pre-test Clinical probability of a DVT with score:
DVT "Likely" if Well's > 1
DVT "Unlikely" if Wells< 2

13. Diagnosis
CT Phlebography
Echocardiography

14. Floating clot

15. Anticoagulants treatment
Виды и интенсивность традиционной противосвертывающей терапии
Initial therapeutic dose
Early maintenance therapy /
secondary prophylaxis.
Low-molecular-weight heparin (LMWH)
Unfractionated heparin (UFH)
international normalized ratio (INR) 2,0–3,0
INR 2,0–3,0 or 1,5–2,0
Min 5 days
Минимум 3 month
> 3 month*
Kearon C, et al. Chest. 2008;133:454-545.
Schellong S, et al. In: ESC Textbook of Cardiovascular Medicine. 2nd Edition. 2009. Ch.37, pp1348-1349.
Long-term maintenance therapy
/ secondary prophylaxis

16. Schulman S et al. N Engl J Med 2009;361:2342–52; Schulman S et al. Circulation 2014;129:764–72;
EINSTEIN Investigators. N Engl J Med 2010;363:2499–510; EINSTEIN–PE Investigators. N Engl J Med 2012;366:1287–97;
Agnelli G et al. N Engl J Med 2013;369:799–808; The Hokusai-VTE Investigators. N Engl J Med 2013;369:1406–15
Anticoagulation for the treatment of acute VTE
Treatment protocols
Day 1 Min 3 month
Days 5–11
Current treatment standard
Vitamin K antagonists (VKA)
Dabigatran
RE-COVER + RE-COVER II
Edoxaban HOKUSAI-VTE
DABIGATRAN 150 mg b.i.d.
LMWH
8‒11 days
Rivaroxabanum 20 mg q.d.
раз/сутки
Apixaban 5 mg b.i.d.
LMWH
Edoxaban 60 mg q.d.
LMWH
≥ 5 days
Rivaroxabanum
EINSTEIN-DVT + EINSTEIN-PE
Apixaban
AMPLIFY
Rivaroxabanum 15 mg b.i.d.
3 weeks
Apixaban 10 mg b.i.d.
1 week

17. Treatment and prevention of the VTE
17
Xarelto 15 mg b.i.d. 21 day, later 20 mg q.d.

18. Reference CHEST(ACCP) 2016
VTE without malignant tumor – preference oral
anticoagulants before VKA (grade 2В), preference VKA
before LMWH (grade 2С)
CHEST 2016; 149(2):315-352 Copyright 2016 American College of Chest Physicians.

19. Combined analysis EINSTEIN DVT and PE: The same
efficacy profile at lower risk of major bleeding in the
rivaroxaban group
Частота клінічно значущих кровотеч була співставна в обох групах (9,4% в групі ривароксабану й 10,0% в групі еноксапарину / АВК [ОР=0,93;
95% ДИ 0,81–1,06]). *Рецидив ВТЕ підраховується в популяції ITT (пацієнти, яким було призначено лікування); # Великі кровотечі
підраховувалися в популяції безпеки (пацієнти, які прийняли хоча б одну дозу досліджуваного препарату). ВР – відношення ризиків, ДІ–
довірчий інтервал, ЗВР – зниження відносного ризику, АВК - антагоніст вітаміну К, ВТЕ - венозний тромбоемболізм.
1. Prins MH et al, Thromb J 2013;11:21
0,5
3,0
2,5
2,0
1,5
1,0
0,0
Ривароксабан (n=4150)
Еноксапарин/АВК (n=4131)
0 30 60 90 120 150 180 210 240 270 300 330 360
Час до події (дні)
Кумулятивна
частота
події
(%)
ВР 0,89
95% ДІ 0,66–1,19
p<0,001
Час до події (дні)
0,5
3,0
2,5
2,0
1,5
1,0
0,0
Ривароксабан (n=4130)
Еноксапарин/АВК (n=4116)
0 30 60 90 120 150 180 210 240 270 300 330 360
46%
ЗВР
Кумулятивна
частота
подій
(%)
ВР 0,54
95% ДІ 0,37–0,79
p=0,002
Relapse of VTE Major bleeding

20. Treatment of “fragile*” patients with VTE - similar efficacy
with less risk of massive bleeding
Relapse of VTE (fragile)
Relapse of VTE
(commonі)**
Massive bleeding (fragile)#
Massive bleeding
(commonі)#
n=10 n=35 n=30 n=37
Rivaroxaban
Enoxaparine/VKA
p=0,011
* Patients who meet one or more of the following criteria: age> 75 years, CrCl (creatinine clearance) <50 ml / min, low body weight (≤50 kg)
1. Prins MH et al, Thromb J 2013;11:21
Rivaroxabane
preference
Enoxa[arine/VKE
preference

21. Treatment of DVT / PE in patients with mild to moderate
renal insufficiency - similar efficacy at lower risk of massive
bleeding
Recurrence VTE (mild
RI)
Recurrence VTE
(moderate RI)
Recurrence VTE
(normal renal function)
Massive bleeding
(moderate RI)
Massive bleeding (mild
RI)
Massive bleeding
(normal renal function)
CrCl (мл/хв)
pinteraction=0,034
1. Bauersachs RM et al, Thromb J 2014;12
n=12
n=3
n=30
n=14
n=29
n=23
≥80 50–79 30–49
Rivaroxabane
preference
Enoxa[arine/VKE
preference
Rivaroxabane
Enoxaparine/VKA

22. Pradaxa (dabigatran etexilate)
Prevention of strokes and systemic embolism in patients with atrial
fibrillation
Direct thrombin inhibitor
Primary prevention of venous thromboembolism in patients who
have undergone extensive orthopedic surgery
Treating deep vein thrombosis and pulmonary embolism and
preventing recurrence
75 мг, 110 мг, 150 мг

23. The recommended dose of dabigatran for DVT / PE treatment relapse
prevention is 150 mg b.i.d.
• The same recommended dose as for the prevention of cerebrovascular
accident in atrial fibrillation - 110 mg b.i.d. approved for special patient
populations
• The duration of therapy should be individualized after careful evaluation of the
relationship between the benefits of treatment and the risk of bleeding
• A decision on a short duration (minimum 3 months) should be made based on
temporary risk factors (e.g. recent surgery, trauma, immobilization)
• Decisions on longer duration should be made based on persistent risk factors
or idiopathic DVT or PE
Pradaxa®: EU SmPC, 2014
150 mg b.i.d.
After treatment with parenteral
anticoagulant for at least 5 days

24. Ascending thrombophlebitis

25. In cases of floating
thrombosis for more
than 10 days in 5 cases
when fixing blood clots
to the vein wall, only the
floating part of the clot
was removed.

26. Floating clot of the vena cava
inferior

29. In some patients with common proximal
acute DVT lasting less than 14 days with a
low risk of bleeding, catheter-directed
thrombolysis (CST) is recommended (level
of evidence 2B). (Guidelines of American Venous
Forum 2012; Scientific Statement From the American
Heart Association 2014)

30. Method for regional thrombolytic therapy of DVT
The scheme of regional thrombolysis according to the
described method:
1-catheter
2-clot
3-direction of blood flow in the vessel, the introduction
of thrombolytics and catheter movement
4-scheme of catheter movement
5-level clot, on which the catheter is installed as the
thrombotic masses dissolve

31. A catheter inserted into the posterior tibial
vein on a phlebogram
Supply of the catheter to the distal
margine of thrombotic masses
Access to the posterior tibial vein with inserted catheter for
regional thrombolysis.
View immediately after catheter
placement
View 1 day after regional thrombolysis

32. Indications for catheter-directed
thrombolysis
Proximal nature of thrombosis
Terms of development of
phlebothrombosis up to 7 days
No contraindications to thrombolysis

33. Thrombectomy and regional
thrombolysis in patients with DVT
Condition of the limb before surgery, 1st
and 10th day after surgery

34. Pharmaco-mechanical
thrombolysis
Using the TRELLIS device (Covidien, USA)
The use of lower doses of thrombolytics
(alteplase - 5 mg per 1 cycle)
Reduction of terms of treatment and
rehabilitation
Rapid restoration of venous patency, saving the
venous valves

35. TRELLIS (Covidien, USA)

42. May-Thurner syndrome

43. The results of treatment of iliac-
femoral DVT - 2 days

44. PE - the relevance of the problem
The incidence of fatal
PE according to autopsy
is 50 cases per 100 000
people per year
(Nicolaides A. N. et al., 2006)

45. In England, 0.9% of hospitalized patients die from
pulmonary embolism, in the United States
pulmonary embolism is the cause of death of
200 000 patients annually, in France - 20,000
(Prandoni P., Lensing A. W., 1996).
According to the multicenter project (PIOPED), the
mortality rate from pulmonary embolism is about
25%. In-hospital mortality in pulmonary
embolism is 12% (up to 1% of all patients
hospitalized in Western Europe). (Dalen J.E.,
2006; Nutescu E.A. et al., 2014) .

46. PE diagnosis

47. Wells score for PE diagnosis
Criteria Points
Clinical signs and symptoms of DVT 3
PE number 1 diagnosis 3
Heart rate > 100 1.5
Immobilization > 3 days or surgery in previous 4 weeks 1.5
Prior history of DVT or PE 1.5
Hemoptysis 1
Malignancy 1
Risk of PE:
low – 0–1 point; moderate – 2–6 points; high ≥7 points.

48. Instrumental diagnosis of
pulmonary embolism
electrocardiography (SIQIIITIII)
radiography
echocardiography
computed tomography
angiopulmonography

49. Recommendations of the European
Society of Cardiology 2014
The severity of pulmonary embolism is determined by the
risk of early mortality, not by the anatomical location and
prevalence of emboli.
High risk of early
mortality
Moderate risk of early
mortality
Low risk of early
mortality (Eur. Heart J. –
2014)

50. PE with a high risk of early
mortality.
• shock;
• hypotension <90 mm Hg or
sudden decrease in blood
pressure by 40 mm Hg or more
for more than 15 minutes;
• markers of right ventricular
dysfunction: dilatation of the
right ventricle, increased
pressure in the right ventricle
with echocardiography,
tricuspid valve insufficiency

51. Pulmonary embolism with an
intermediate risk of mortality

52. Масивна тромбоемболія дольових гілок легеневої артерії за
даними СКТ

53. The results of treatment of a patient with massive
thromboembolism of the lobular branches of the pulmonary
artery using systemic thrombolytic therapy

54. Treatment of PE: recommendations ESC/ACCA 2013
Unstable
hemodynamics
Alteplasa IV 100 mg per 2 hours or 0,6 mg/kg/15 min (max.
50 mg.)
Urokinase IV 3 000 000 units per 2 hours
Streptokinase IV 1 500 000 units per 2 hours
Heparin IV 80 units/kg IV +18 mg/kg/hour.
Stable
hemodynamics
Enoxaparine
(SC)
1 mg/kg b.i.d. or 1,5 mg/kg q.d.
Tynzaparine
(SC)
175 units/kg q.d.
Fondaparinux
(per os)
7,5 mg (weight from 50 to 100 kg)
5 mg, weight ˂ 50 mg.
10 mg weight ˃ 100 мг.
Rivaroxabane
(per os)
15 mg b.i.d. 3 weeks, next 20 mg q.d.
www.escardio.org/ACCA

55. Evaluation of clots regression in
the study EINSTEIN PE
The first 400 patients enrolled in the EINSTEIN PE study
were evaluated separately for re-imaging of the lungs
after 3 weeks of therapy with CT or perfusion lung
scintigraphy.
Journal of Thrombosis and Haemostasis, 2013 .11: 679–685

56. After 3 weeks of anticoagulant therapy in
patients with acute PE observed:
Complete clots disappearance in 41% of
patients
Reduction of clots size in 47% of patients
No changes in 12% of patientsПогрішення
обструкції судин не було
Journal of Thrombosis and Haemostasis, 2013 .11: 679–685
There was no difference in the rate of clots dissolution using
rivaroxaban or enoxaparin / AVK

57. Frequency of DVT depending on the
type of surgery
DVT rate(%)
0 10 20 30 40 50 60 70 80
Knee prosthesis
Hip fracture
Fracture of the femoral neck
Prostatectomy
Abdominal surgery
Gynecology
Neurosurgery
Prostate TUR
Inguinal hernia
Adapted from Bergqvist D et al. Br J Surg 1986

58. Congenital risk factors for
VTE
1.Antithrombin deficiency
2.Protein C deficiency
3.Protein S deficiency
4.Resistance to activated
protein C
5.Pathology of coagulation
factor V (Leiden factor)
6.Positive test with
prothrombin 20210A
1.Some dysfibrinogenemia
2.Disorders of the fibrinolytic
system
3.Increased homocysteine
blood levels
4.Increasing factors VIII, IX
and / or XI

59. Risk risk factors associated with
medical conditions
1.Acute myocardial infarction
2.Congestive heart failure
3.Acute respiratory diseases
4.COPD
5.Acute infectious diseases
6.Neurological lesions (stroke,
paralysis)
7.The presence of lupus
anticoagulant and / or
antiphospholipid antibodies
8.Nephrotic syndrome
9.Any acute medical conditions
requiring strict bed rest> 3 days
1.Diabetes mellitus
2.Malignant neoplasm
3.Cancer treatment (hormonal,
chemotherapy or radiation)
4.Some malignant
hemopathology (chronic
myeloproliferative syndromes,
nocturnal paroxysmal
hemoglobinuria, etc.)
5.Chronic inflammatory bowel
disease
6.Acquired
hyperhomocysteinemia

60. Dependence of VTE cases on age
Heit JA et al. Thromb Haemost 2001
0
100
200
300
400
500
600
700
800
900
1.000
0-14 20-24 30-34 40-44 50-54 60-64 70-74 80-84
Age (years)
Annual
cases
DVT
ТPE
Total VTE

61. General principles of VTE prophylaxis:
General preoperative prophylaxis includes rapid activation of patients,
fluid replenishment, limited blood transfusions, diagnostic control with
the detection of latent forms of DVT.
Recommended prophylactic doses of NFH and LMWH:
Moderate (in patients with moderate risk of thrombotic complications):
NFG - 5000 U x 2 times a day SC - control of APTT and platelet count
NMG <3400 U (enoxaparin - 20 mg, nadroparin - 0.3, dalteparin - 2500 U
once a day SC).
High (in high-risk patients):
NFG - 5000 U x 3 times a day SC - control of APTT and platelet count;
NMG> 3400 U (enoxaparin - 40 mg, nadroparin - 0.4, dalteparin - 3500 U for
one or 2 injections per day SC) - control of platelet count.

62. High risk of VTE
• age> 60 years
• DVT or PE in
anamnesis
• oncological pathology
• obesity III
• thrombophilia
DVT of a shin of 40-80%, DVT of an iliac and femoral segment of 10-
30%, fatal PE of 1-5%
40 mg SC q.d.

63. Modes of thromboprophylaxis start
Thromboprophylaxis start…
1.- Preoperative,12 hours before surgery
2.- Postoperatively,
12 hours after surgery
3.- Postoperatively,
24 hours after surgery
4.- Perioperatively,
2 hours before surgery
5.- Perioperatively,
6-8 hours after surgery
Good practice
Hemorrhagic risk
Suboptimal protocol
PROBABLY GOOD PRACTICE
Practice “Just in time”
Llau J.V., ESA, 2007.