Mechanism of Heparin in Pulmonary Embolism Treatment
Primary Mechanism of Action
Heparin works by binding to antithrombin III, causing a conformational change that dramatically enhances antithrombin III's serine protease activity, which then inhibits activated coagulation factors—particularly Factor Xa and Factor IIa (thrombin)—thereby preventing further clot formation and extension while allowing the body's natural fibrinolytic system to gradually dissolve existing pulmonary emboli. 1
Specific Molecular Actions
Small amounts of heparin primarily inhibit Factor Xa, while larger therapeutic doses inhibit both Factor Xa and thrombin (Factor IIa). 1
Heparin prevents stable fibrin clot formation by inhibiting activation of the fibrin stabilizing factor. 1
Critically, heparin does NOT have fibrinolytic activity and will not lyse existing clots—it only prevents new clot formation and extension of existing thrombi. 1, 2
Clinical Rationale for Use
The primary therapeutic goal is immediate anticoagulation to prevent further clot formation and extension, allowing endogenous fibrinolysis to gradually resolve the pulmonary emboli over time. 2
Heparin should be initiated immediately when there is high or intermediate clinical suspicion of pulmonary embolism, even before diagnostic confirmation, unless contraindicated. 3, 2
Without anticoagulation, untreated pulmonary embolism carries a high mortality rate, making rapid anticoagulation essential. 3
Pharmacokinetic Considerations
Heparin is highly bound to antithrombin, fibrinogens, globulins, serum proteases, and lipoproteins, with a volume of distribution of 0.07 L/kg. 1
Peak plasma concentration and onset of action occur immediately after intravenous administration. 1
The plasma half-life is dose-dependent, ranging from 0.5 to 2 hours, with biphasic clearance involving rapid saturable clearance followed by slower first-order elimination. 1
Important Limitations
Unfractionated heparin has nonspecific binding to plasma proteins (fibrinogen, factor VIII, vitronectin, fibronectin), which limits its anticoagulant effect and causes high intersubject variability in response. 4
This nonspecific binding is responsible for heparin resistance observed in some patients with pulmonary embolism and necessitates frequent laboratory monitoring with aPTT. 4
Heparin does not undergo enzymatic degradation and is mainly cleared by liver and reticuloendothelial cell-mediated uptake. 1