Heparin Season Heparin & Direct Factor X Inhibitors

1.1 "Heparin Season": Heparin & direct Factor X inhibitors Normally, thrombin-aka Factor II (beaver with II-shaped teeth)-cleaves fibrinogen to form active fibrin, which crosslinks to form a clot (throm-beaver is crosslinking sticks to build a dam). Prothrombin is activated to thrombin by Factor Xa complexing with... TSII (Factor X is represented by the fox). Unfractionated heparin is a glycoprotein produced endogenously that polymerized to various lengths. When administered clinically in its unfractionated form, there are a variety of lengths of polymer chains. Indirectly inhibits Factor X and ergo thrombin, by activating the antithrombin III complex, which in turn irreversibly inactivates Factor X. (The Heppy Heparin Hunter standing in the stream is carrying a cage with 3 bars in the middle for antithrombin III. The cage inhibits a thrombin beaver and a Factor X fox.) Prevents clot formation but does not lyse extant clots (the hunter can't destroy the dam the beaver had already built PTT levels need to be monitored continuously with UFH (woodpecker making PTTTTTT sound is being monitored by a second heppy hunter, with a second woodpecker in the tree to remind us of intrinsic pathway testing). Administration is IV (ivy around the tree) Clinical indications include acute management of clot conditions: DVT, commonly in iliofemoral & popliteal veins (iliofemoral river) PE, with ischemia distal to the clot (woodpecker sitting in the lung-shaped tree, with leaves off the ranch distal to the bird) Acute MI (heart-shaped banjo with broken stings) Safe for use in pregnancy because does not cross the placenta, although LMWH is preferred d/t ease of use (pregnant woman is standing next to LMWH girl) Toxicity: & Heparin-induced thrombocytopenia (HIT): antibodies produced against heparin:PF4 complex widespread platelet activation via Fc component of IgG antibodies. This results in a paradoxical hypercoagulable state & thrombosis (hunter is skeet shooting, and broken clay plates lie around. Despite the hunter, the beaver continues to build a sheltering dam around him). If this process results in a thrombotic event, may be referred to as heparin induced thrombocytopenia thrombosis (HITT) or HIT type 2. Tx: immediate removal of all heparin products and administration of alternative rapid-acting anticoagulation, e.g. direct thrombin inhibitors like bivalirudin ("no intruding" sign), argatroban or dabigatran (gators in the water); Bleeding (no duh) Hypoaldosteronism hyperkalemia (depleted mineral mine boarded up in the shape of a K) Osteoporosis (bone shaped tree branch weakened by termites) Low molecular weight heparin (LMWH) (enoxaparin & others) is a smaller molecule-only the smaller polymers are delivered. As such, while it has the same MOA as UFH, only inhibits Factor X, not thrombin (girl hunting is smaller than the adult heppy hunter. She carries a similar antithrombin III cage, but only inhibits a fox; no beaver here!) Has a longer half-life than UHF (white flag that looks like an exponential decay plot). Doesn't require PTT monitoring, as dose is based on pt. weight rather than PTT. Eliminated renally. As such, renal insufficiency can prolong half-life (girl standing flag on a fractured, or insufficient, kidney shaped rock). Less likely to cause HIT (young girl skeet shooting is missing) Fondaparinux acts similarly to heparin, except binds to antithrombin III with greater specificity (Fido has a pair of antithrombin III cages, because he's so good at binding them). Has the lowest risk of HIT (Fido cannot even pick up the gun) Protamine sulfate can be used to reverse heparin action, decreasing bleeding risk. It is a positively charged molecule that binds to the negatively charged heparin, preventing its action ("Protected Area" fence that is positively charged keeps the hunters out). Most effective against UFH, not so much against LMWH or fondaparinux (girl hunter and dog are able to avoid the fence). Direct factor Xa inhibitors include rivaroxaban, apixaban, darexaban, (-Xaban suffix) act in a self-explanatory fashion (guy directly grabbing fox without needing a trap). Do not require monitoring. Oral administration. Ease of use makes more appealing in managing A-fib & flutter (TV screen) In cases of life-threatening bleeding, may administer andexanet alfa, a biologic that shares homology with Factor Xa but has no proteolytic effects. Functions as a decoy, binding to Xa receptors & enabling intravascular coagulation by increasing availability of endogenous factor Xa. Associated with significant thrombosis risk.