Treatment of venous thrombosis and pulmonary embolism

1. By
Mahmoud ElhosinyAbou Elmagd
Assistant lecturer of pulmonary and critical care medicine

2. OBJECTIVES
 Prevent death from PE
 Prevent post-thrombotic syndrome
 Prevent recurrent venous thromboembolism
(VTE)
 Achieve these objectives with minimal side
effects and inconvenience

3.  Anticoagulants
 Thrombolytic therapy
 Caval interruption
 Surgical removal

4.  Initial treatment with heparin is necessary.
 LMWH can replace heparin and is now
treatment of choice
 Continued treatment following hospital
discharge is necessary.
Established Anticoagulants

5.  Massive PE with shock or syncope
 Major PE with right-ventricular dysfunction
 Major PE with normal right-ventricular
function
 Minor PE

6.  Massive PE with shock or syncope
 Thrombolysis or surgery
 Major PE with right-ventricular
dysfunction
 Anticoagulants
 Thrombolysis
 Major PE without right-ventricular
dysfunction
 Anticoagulants
 Minor PE
 Anticoagulants

7. SuspectedVTE
1.Obtain baseline APTT,PT,CBC count.
2.Check for contraindication to heparin
therapy.
3.Order imaging study.
4.Start either:
UFH 5000 IU IV or
LMWH.

8. I. Heparinization:(Started on clinical suspicion)
Heparin is a sulphated mucopolysaccharide obtained
from animal lung and gut mucosa. It combines with
naturally occurring clotting factor activator
antithrombin III, improving the inhibitory effect of
this substance on factor IIa (thrombin ) and Xa
The objective of therapy is to prevent extension or
recurrence of thrombus while avoiding haemorrhagic
complications
It‘s clearance is unaffected by renal or hepatic
diseases.

9. Heparin does not cross the placenta and is
safe during pregnancy.
Failure to achieve full anticoagulation within
24 hours increases risk of recurrent venous
thrombosis by 15 times.

10. 1. Continuous I.V.I.
Adjust dose to achieve APTT = 1.5 - 2.5
times control (ie 60-105 seconds) .
Check APTT every 6 hr. until APTT is
between 60 and 105 then check APTT
once Daily; check APTT 6 hours after
any dose change

11.  Check platelet count between day 3 &
5 and again between day 7 & 10 of
heparin therapy and stop heparin if
the platelet count falls below 100,000
 Plasma heparin levels may be
preferable to the APTT but are
generally not widely available -
therapeutic levels are 0.2-0.4 IU/mL

12. 2. Intermittent S.C.I.
 As an alternative to 5 day administration
of IV heparin in acute PE
 Probably more effective and at least as
safe as continuous infusion

13.  Osteopenia has been reported with unfractionated
heparin administered for more than 6 months.
 No information is available about the beneficial effects
of concomitant multivitamins, calcium, or vitamin D
supplementation.
 The problem of osteopenia and osteoporosis might be
less with low molecular weight heparin, but providing
optimum calcium and vitamin D supplementation is
reasonable for all patients receiving long-term heparin
administration.

14. - Caused by an antibody directed against the heparin-
platelet factor 4 complex which binds to Fc receptors on
platelet surfaces.
-It occurs in 3-4% of patients receiving un fractionated
heparin for 7-10 days
-Less likely in patients treated with low molecular weight
heparin

15.  Bleeding from over dose of heparin
is treated by Protamine sulphate
 One mg protamine sulphate IV
,neutralizing 100 units of heparin
within 15 minutes.

16. ▪ Longer half life.
▪ Greater ease of administration
▪ Less hemorrhagic complication.
▪ Less anti-heparin antibody.

17. 1. For inpatient treatment of DVT or PE
i. Enoxaparin 1 mg/kg SC BID
ii. Or Enoxaparin 1.5 mg/kg SC
iii. Tinzaparin 175 u/kg SC
2. For outpatient treatment of DVT
i. Enoxaparin 1 mg/kg SC
ii. Tinzaparin 175 u/kg SC
3. Precautions in use:
i. Half life can be prolonged in renal insufficiency.
ii. Bleeding can occur in obese patients in whom
correct dosing can be difficult to estimate.

18. II. Coumadin strategies:
 Start at the same day heparin begins.
 Check PT/INR once daily until stable
 Adjust to achieve INR of 2.0 - 3.0
 The INR must be checked frequently (every 1-2
weeks) while patients are receiving coumadin.
 Patients must be cautioned about common foods
and drugs which can alter coumadin's effect
 Need minimum of 4 - 5 days overlap with heparin

19. II. Coumadin strategies:
Duration of anti-coagulation
 4-6 w  DVT without risk factors.
 3 m  non postoperative DVT.
 6m  second DVT/PE.

20. II. Coumadin strategies:
Indication of life anticoagulantion
 Cancer.
 Anti phospholipid antibody.
 Deficiency of anti thrombin III,
protein C or Protein S.

21. Onset of action: : 24-72 hours
Peak effect: Full therapeutic effect: 5-7
days;
INR may increase in 36-72 hours
(clearance of circulating prothrombin )
Absorption: Oral: Rapid, complete
Time to peak, plasma: Oral: ~4 hours

22. Dosing:
Oral: Start 2-5 mg daily for 2 days or 5-10 mg daily for 1-
2 days)
Oral: Administer with or without food.Take at the same
time each day
Dosing: Renal Impairment
No adjustment required,.
Dosing: Hepatic Impairment
Monitor effect at usual doses.The response to oral anticoagulants
may be markedly enhanced in (obstructive jaundice, hepatitis,
and cirrhosis. INR should be closely monitored.

23. MECHANISM OF ACTION
Warfarin inhibits clotting by limiting hepatic
production of the biologically active vitamin K-
dependent clotting factors (activated factors II,
VII, IX, and X).
.

24. (INR >4)
age (≥65 years)
history of GI bleeding, hypertension, malignancy
cerebrovascular disease, serious heart disease, vasculitis
anemia, severe diabetes,, trauma, hepatic ,renal
insufficiency, polycythemia vera,, open wound.
drug-drug interactions.
long duration of therapy
(

25. WARFARIN Side Effect
cardiovascular: Angina, chest pain, edema, hemorrhagic shock,
hypotension, pallor, syncope, vasculitis
Central nervous system: Coma, dizziness, fatigue, fever,
headache, lethargy, malaise, pain, stroke
Dermatologic: Alopecia, bullous eruptions, dermatitis, rash,
pruritus, urticaria
Gastrointestinal: Abdominal cramps, abdominal pain, anorexia,
diarrhea, flatulence, gastrointestinal bleeding, mouth ulcers,
nausea, taste disturbance, vomiting
Genitourinary: Hematuria, priapism

26. Hematologic: Agranulocytosis, anemia, leukopenia, retroperitoneal
hematoma, unrecognized bleeding sites (eg, colon cancer) may be
uncovered by anticoagulation
Hepatic: Cholestatic jaundice, hepatic injury, hepatitis,
transaminases increased
Neuromuscular & skeletal: Joint pain, muscle pain, osteoporosis
(potential association with long-term use), paralysis, paresthesia,
weakness
Respiratory: Dyspnea, tracheobronchial calcification
Miscellaneous: Anaphylactic reaction, cold intolerance,
hypersensitivity/allergic reactions, skin necrosis, gangrene,
“purple toes” syndrome

27.  Hypersensitivity to warfarin
 Condition with risk of hemorrhage
 Hemorrhagic tendency
 Inadequate laboratory techniques
 Vitamin K deficiency
 Intramuscular injections

28. Potentiate warfarin
Levofloxacin
Nonsteroidal anti-
inflammatory drugs
Omeprazole
Tramadol
Trimethoprim-
sulfamethoxazole
Acetaminophen
Allopurinol
Amiodarone
Amoxicillin-clavulanate
Ciprofloxacin
Erythromycin
Fluconazole

29. Inhibit warfarin
Azathioprine
Barbiturates
Carbamazepine
Haloperidol

30. Foods High inVitamin K Green leafy vegetables
Broccoli, brussels sprouts, cabbage, collard
greens, endive, green scallion, kale, spinach,
turnip greens, watercress SaladOils canola, salad,
and soybean oils mayonnaise ,Liver, green tea
‫بعض‬‫األطعمة‬‫عانية‬‫في‬‫فيتامين‬‫ك‬:‫بعض‬‫األطعمة‬
‫عانية‬‫في‬‫انخضروات‬‫انخضراء‬‫فيتامين‬‫ك‬‫انىرقية‬
‫انقرنبيظ‬،‫وبراعم‬،‫بروكسم‬‫وانمهفىف‬،،‫وانخضر‬
‫انهندباء‬،‫انكرنب‬‫انبصم‬،‫األخضر‬،‫انهفث‬،‫انسبانخ‬
،‫انهفث‬‫انجرجير‬‫زيىت‬‫سهطة‬‫انكانىال‬‫وفىل‬‫انصىيا‬
‫وانسيىت‬‫انمايىنيس‬‫انكبد‬ , ‫انشاي‬‫االخضر‬

32. III. ThrombolyticTreatment:
Indications:
1. P.E. with hemodynamic compromise.
2. P.E. with hemodynamic stability but
dysfunction by cardiac echo.
Contraindication:
-Absolute:
-Internal bleeding
-C.V. ,intracranial , intraspinal ,surgery
for last 2.m.
-Intracranial neoplasm.

33. Relative(major):
 Surgery, obstetrical delivery, organ biopsy, within the previous 10 days.
 Trauma,GI bleeding, or CPR within the previous 10 days.
 Cerebrovascular disease.
 Severe uncontrolled hypertension.
Relative (minor):
 Recent minor trauma.
 Diabetic hemorrhagic retinopathy.
 Probable left ventricular or left atrial thrombus.
 Coagulopathy.
 Pregnancy .
 Septic thrombo phlebitis.

 Endocarditis.

 Age > 75

34.  Types of thrombolytic agents:
-Steptokinase.
-t-P A.
 Intrapulmonary a. thrombolytics.
1.Urokinase.
2. t-PA.
 Unlike the case with myocardial infarction,
thrombolytics do not result in complete clot lysis.
 Intrapulmonary artery infusions of thrombolytics are
not superior to systemic infusions.

35. IV. Inferior vena caval interruption:
Indications:
 Absolute contraindication to
anticoagulation.
 Complications developing during
anticoagulation(e.g severe internal
bleeding)

36. V. Emergency surgical embolectomy :
 Angiographically-proven massive PE with
hemodynamic compromise and, availability
of experienced thoracic surgical team.
 Failure of ,or contraindication to
thrombolysis.
 Operative mortality = 35%.
VI. Catheter techniques:
1. Transvenous extraction of emboli results in an
improvement in 61% of patients.
 mortality = 28%.
2. Rotational catheter fragmentation

37.  Age: Over 40
 History of DVT/PE
 Varicose Veins
 Previous
Immobilization
(>72 hours)
 Myocardial Infarction
 Congestive Heart
Failure
 Obesity
 Stroke
 Pelvic Abdominal &
Urological Surgeries
 Orthopedic Operations
 Malignancy
 Trauma & acute SCI
 Neurosurgery

38. Moderate Risk
* Abdominal, Pelvic and
Urological surgeries, in
patients over 40 years,
lasting over 30 minutes
Enoxaparin 20mg/0.2ml S.C.
every 24 hours,
with the first dose given 2
hours pre-operatively
* Surgery in patients over 40
years plus DVT with:
* Extensive Malignant Disease
* Major Orthopedic Surgery
* Stroke
Enoxaparin 40mg/0.2ml S.C.
every 24 hours,
with the first dose given 12
hours pre-operatively
Regimen
Very High Risk
Regimen

39.  Continue Prophylaxis Until Discharge.
 Consider Continuing Prophylaxis After
Discharge in Patients at High Risk.
 PREVENTION IS FAR SUPERIOR...
TOTREATMENT