Introduction
Pulmonary embolism is more fatal than acute myocardial infarction.
The main diagnostic test is CT chest, not lung scanning anymore.
PE is more fatal in the elderly.
PE is more fatal in blacks.

Causes
In half of cases of venous thromboembolism (VTE), no evident cause is present.
Polymorphisms associated with VTE are factor V Leiden, ADRB2 and LPL.
VTE increases chance of atherosclerosis.
Risk factors for PE are old age, arterial diseases, smoking, COPD, VTE, immobility, acute infection, long air travel, malignancy, pregnancy, oral contraceptives, HRT, pacemakers and central venous catheters.

Mechanism
Virchow’s triad for coagulation are trauma to vessel wall, hypercoagulability and stasis.
Prothrombin gene mutation 20210 can cause VTE.
Deficiencies of antithrombin III, protein C and protein S can cause VTE.
Acquired causes of VTE are APLA syndrome and hyperhomocysteinemia.
Factor V Leiden causes activated protein C resistance.
Factor V Leiden can cause abortion.
Heparin decreases AT III level while warfarin decreases protein C and protein S levels.
Pregnancy and OC pills decrease protein S level.
Best way to identify a predisposition to VTE is a positive family history.
Saddle embolus lodges at MPA bifurcation.
Massive pulmonary embolism can cause RV infarction by decreasing of RCA flow and increasing RV oxygen demand.

Diagnosis

Normal plasma d-dimer rules out PE.

Best imaging test for PE is CT chest.

Commonest symptom is dyspnoea and commonest sign is tachypnoea.

Syncope and cyanosis suggest that the PE is massive; pleuritic chest pain suggests that it is small.

Low grade fever and tachycardia are common.

Loud P2 and PSM of TR can occur.

Acute cor pulmonale means acute RV failure. This is manifested by RV S3 and elevated JVP.

ECG may show RV ischemia, incomplete RBBB or S1Q3T3.

Massive PE is the term used when there is hemodynamic deterioration. This needs to be treated by embolectomy or thrombolytic therapy. The term submassive PE is used when there is RV hypokinesia, but no hemodynamic deterioration. This may or may not need embolectomy or thrombolysis.

Pulmonary infarction occurs at 3 to 7 days after PE.

Paradoxical embolism usually occurs through a PFO.

In paradoxical embolism, usually VTE is not found as it has already embolised.

In PE, usually ABG will be normal.

In PE, RV dysfunction is suggested by T inversion in v1 to v4.

Inferior T inversion can occur.

Right axis deviation can occur.

Severe dyspnoea with normal CXR suggests PE.

Massive PE can cause focal oligemia. This is called Westermark’s sign.

Hampton hump indicates pulmonary infarction.

In pregnancy and in renal failure, lung scan is preferred to CT chest.

In half of PE cases, echo will be normal.

McConnell sign means free wall hypokinesis with sparing of the apex.

D shaped LV can occur.

IVC will be dilated and will not show inspiratory collapse.

DVT is mainly diagnosed by loss of vein compressibility.

In PE, DVT imaging will be negative in half.

The most accurate diagnostic test is chest CT.

There is a clinical decision rule score for PE.

If the score is more than 4, there is a high probability of PE and CT chest is warranted. If the score is 4 or less d-dimer is to be done and if it turns out to be positive, CT chest is to be done.

Management

Clinical predictors of increased mortality are old age, hypotension, tachycardia, heart failure, chronic lung disease and malignancy.

Investigation predictors of increased mortality are (1) elevated tropinins or BNP and (2) RV hypokinesia (echo) or RV enlargement (CT).

High risk patients need thrombolysis or embolectomy while low risk patients need only anticoagulation.

Unfractionated heparin is a sulfated glycosaminoglycan with an average molecular weight of 15,000 (3,000-30,000). It activated antithrombin III which inactivates thrombin and other clotting factors (9 to 12). Antithrombin III cannot inactivate clot bound thrombin. Thus heparin does not dissolve clots.

Heparin is given to keep the aPTT at 1.5 to 2.3 times control (usually 60-80 secs). This is usually attained by giving UFH as a bolus of 80 U/kg followed by an infusion of 18 U/kg with further dose adjustments made according to the Raschke Nomogram.
Enoxaparin has an anti Xa to anti IIa ratio of 3.9 (maximum of all LMWHs) and can be given BD at 1 mg/kg or OD at 1.5 mg/kg. The therapeutic anti Xa level is 0.5-1.0 U/ml. The dose must be reduced in renal failure.
LMWH is accepted for DVT, but not for PE.
Fondaparinux binds to ATIII leading to inactivation of factor X, but not thrombin. It does not cause thrombocytopenia. There is no specific antidote if bleeding occurs. The dose has to be reduced in renal failure.
Fondaparinux is accepted for PE. The dose depends on body weight and is given OD S/C. <>100 kg – 10 mg. For prevention, 2.5 mg.
Warfarin inhibits clotting factors 2, 7, 9 and 10. The full effect occurs only at 5 days (half life of thrombin) even though PT increases earlier (because half life of factor 7 is only 6 hrs). There is an initial procoagulant response due to depletion of proteins C and S. Patients with CYP 2C9 variant alleles have low warfarin dose requirement. VKORC1 gene variations also affect the dose (vitamin K epoxide reductase complex 1). Green leafy vegetables and rifampicin decrease INR while antibiotics and acetaminophen increase INR.

Protamine immediately reverses UFH effect, but only partially reverses LMWH effect. It is given over 10 to 30 mins at a dose of 1 mg per 100 units of heparin. In patients with prior exposure to the protamine in NPH insulin, allergic reactions can occur.

HIT is 10 times more common with UFH than with LMWH. It occurs at 5 to 10 days and occurs when IgG antibodies bind to heparin-platelet factor 4 complex, leading to platelet activation. This causes thrombosis and consumption thrombocytopenia. Stop heparin and give a DTI like bivalirudin.