aminocaproic acid

**Class/Mechanism:** Synthetic lysine analog (6-aminohexanoic acid). It binds the lysine-binding sites on plasminogen and plasmin, which prevents their attachment to fibrin. This inhibits plasminogen activation to plasmin and blocks plasmin from degrading fibrin (at high concentrations it also directly inhibits plasmin). The result is stabilization of the fibrin clot. Tranexamic acid (TXA) has the same mechanism and is about 10x more potent, with a longer half-life.

**Physiology review:** Tissue plasminogen activator (tPA) and urokinase convert plasminogen to plasmin. Plasmin cleaves fibrin into fibrin degradation products (including D-dimer) and also degrades fibrinogen and factors V and VIII. Alpha-2 antiplasmin is the physiologic plasmin inhibitor. A deficiency of alpha-2 antiplasmin causes excessive fibrinolysis and bleeding. Aminocaproic acid works pharmacologically in the same direction as alpha-2 antiplasmin.

**Clinical uses:** - Reversal of excess fibrinolysis, including bleeding after thrombolytics (tPA, streptokinase) and **alpha-2 antiplasmin deficiency**. - Hyperfibrinolysis-associated bleeding: prostatic surgery (the prostate and urine are rich in urokinase), acute promyelocytic leukemia (APL) with DIC and hyperfibrinolysis, liver disease/cirrhosis, and cardiac surgery with bypass (reduces blood loss). - Mucosal bleeding in hemophilia and in patients with platelet disorders (e.g., dental extractions). Also used for heavy menstrual bleeding and postpartum hemorrhage (TXA is more commonly used). - Reduces rebleeding in subarachnoid hemorrhage (limited by thrombotic and ischemic risk). - Tranexamic acid is preferred in many settings today (trauma, postpartum hemorrhage, menorrhagia), as in the CRASH-2 and WOMAN trials.

**Adverse effects:** - **Thrombosis** (DVT, PE, stroke, MI). It is contraindicated in active intravascular clotting, especially **DIC**, unless the DIC is dominated by hyperfibrinolysis and heparin is given too. - **Upper urinary tract bleeding:** clots can form and cause **ureteral obstruction and renal colic or failure** (avoid in hematuria of upper tract origin). - **Skeletal muscle toxicity:** myopathy, rhabdomyolysis, and elevated CK. - Others: hypotension with rapid IV infusion, GI upset, nasal congestion, and dizziness.

**Pearls for boards:** - In a patient bleeding with elevated D-dimer and low fibrinogen from primary fibrinolysis, aminocaproic acid or TXA is the antidote. Do not give it in DIC with thrombosis. - It is the "antidote" for the thrombolytics (alteplase, reteplase, tenecteplase, streptokinase). Other reversal measures include cryoprecipitate (fibrinogen) and FFP. - Do not confuse with: **protamine** (reverses heparin), **vitamin K/PCC** (warfarin), **idarucizumab** (dabigatran), **andexanet alfa** (factor Xa inhibitors), and **desmopressin** (vWD, mild hemophilia A, uremic bleeding). - Renally excreted, so the dose must be reduced in renal impairment.