Objectives:
► Achieve the following objectives with minimal side effects and inconvenience.
► Risk Stratification.
► Prevent death from PE.
► Prevent post-thrombotic syndrome.
► Prevent recurrent PE or VTE.

Death prevention
► Oxygen supplementation.
► Pain relief.
► Temporary mechanical ventilation.
► Inotropic agents.
► Anticoagulation.
► Thrombolytic therapy.
► Surgical Embolectmy.

Anticoagulants:
► Heparin
► LMWH
► Vitamin K antagonists (warfarin)
► Hirudin
► Pentasaccharide
► Oral small-molecule direct thrombin inhibitor

Established Anticoagulants:
► Initial treatment with heparin is necessary.
► Induction period with heparin therapy for 10 days and can be reduced to 5 days.
► LMWH can replace heparin and is now treatment of choice.
► Optimal therapeutic range with warfarin is an INR of 2.0 to 3.0.
► Continued treatment following hospital discharge is necessary.
► Optimal duration of warfarin therapy still to be established.

LMWH: A Major Advance:
► Weight-adjusted subcutaneous dosing predictable.
► Once-daily subcutaneous dosing effective in DVT.
► Treatment of PE effective and safe.
► Less osteopenia than UFH.
► Less HIT than UFH.
► Outpatient treatment effective and safe.

Factors That May Influence Duration of Oral Anticoagulation:

Shorter Course	Longer Course
Bleeding risk	VTE presentation (eg, massive PE),Recurrent VTE
Unstable anticoagulant response	Poor cardiopulmonary reserve
Inconvenient anticoagulation	Severe post-thrombotic syndrome
Fear of recurrence or bleeding	Thrombophilia

Potential Indications for Indefinite Anticoagulant Therapy:
► Inherited Thrombophilia: AT (= antithrombin), protein C and S deficiency
► Antiphospholipid syndrome.
► Recurrent idiopathic VTE.
► Malignancy.
► Thromboembolic pulmonary hypertension.

New Anticoagulants for Treatment of DVT:
► Hirudin (recombinant;lepirudin) is effective for treating thrombosis associated with HIT.
► The new oral small-molecule direct thrombin inhibitor appears promising in multiple clinical trials.
► Pentasaccharide has been evaluated in phase 2 studies and is being tested in phase 3 studies.

Fibrinolysis:
Exogenously administered drugs:
► Streptokinase - bacterial product - continuous use - immune reaction
► Urokinase - human tissue derived - no immune response ( best for PE in Egypt)
► Tissue plasminogen activator (tPA) - genetically cloned - no immune reaction – (EXPENSIVE)

N.B: Angikinase( 500,00 I.U ) Available in Egypt

Management Strategy and Prognosis for Pulmonary Embolism (MAPPET):
► 719 patients without carcinogenic shock
► 169 received thrombolytic therapy: 30-day mortality 4.7%; recurrent PE 7.7%; major bleeding 21.9%
► 550 received heparin: 30-day mortality 11.1%; recurrent PE 18.7%; major bleeding 7.8%

Randomized Trial of Caval Interruption:
► Initial benefit in preventing PE offset by excess of recurrent DVT in the longer term in the absence of anticoagulant.
► Therefore, caval filter not recommended for this patient population in the long term.

Pulmonary Embolectmy:
► Can be life saving in patients with massive PE.
► In consecutive series of 96 patients, mortality was 37% (Meyer et al, 1991).
► Cardiac arrest and associated cardiopulmonary disease were independent predictors of death.
► Elective pulmonary embolectmy was life saving in selected patients with chronic thrombo-embolic pulmonary hypertension
    (Moser et al, 1990).

Recommended Treatment of Acute PE:
Massive PE with shock or syncope.
► Thrombolysis or surgery.
Major PE with right-ventricular dysfunction.
► Thrombolysis (Goldhaber).
Major PE without right-ventricular dysfunction.
► Anticoagulants.
Minor PE.
► Anticoagulants

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