In disseminated intravascular coagulation (DIC), both thrombosis and bleeding occur simultaneously. The fibrinolytic inhibitor PAI-1 (plasminogen activator inhibitor type 1) paradoxically contributes to the coagulopathy by:

• A Activating thrombin to generate more fibrin
• B Directly activating protein C, consuming natural anticoagulants
• C Inhibiting tPA and uPA, suppressing fibrinolysis and causing microvascular thrombosis and end-organ failure despite bleeding from factor consumption ✓
• D Activating factor XII to generate bradykinin and excess fibrinolysis

Explanation

In DIC triggered by sepsis/endotoxin, cytokines (particularly TNF and IL-1) upregulate PAI-1 expression massively, suppressing fibrinolysis. This creates a paradox: simultaneous coagulation activation (via TF pathway) generates fibrin microthrombi causing end-organ ischemia, while PAI-1 prevents fibrinolytic clearance of these thrombi, worsening microvascular thrombosis. Meanwhile, factor consumption and platelet trapping cause bleeding. The net outcome is a prothrombotic-fibrinolytic imbalance. In septic DIC specifically, the PAI-1-dominated phenotype causes more organ failure than bleeding (unlike obstetric DIC which is hyperfibrinolytic).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.