Reversing Medications That Cause Bleeding

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1 Reversing Medictions Tht Cuse Bleeding Dine M. Birnbumer, M.D., FACEP Professor of Medicine University of Cliforni, Los Angeles Senior Fculty Deprtment of Emergency Medicine Hrbor-UCLA Medicl Center The Agony nd The Ecstsy of Pltelets nd Clotting The Ecstsy We cn chnge how people clot We cn prevent strokes We cn prevent DVT nd PE We cn improve crdic outcomes in ACS The Agony nd The Ecstsy of Pltelets nd Clotting The Agony Vrible efficcy Nrrow therpeutic index Potentil drug / food interctions Need for monitoring Bleed risk Antidotes nd reversibility The Agony nd The Ecstsy of Pltelets nd Clotting We need better drugs nd guess wht! We hve them! But better HOW???? Newer is Better Right? Depends on wht color glsses you re looking through As crdiologist? As neurologist? As n emergency physicin? Or s ptient? Issues with the New Agents For emergency prctitioners Cn we mesure their ctivity if we need to? Cn we reverse their effects in cses of bleeding requiring emergency cre? 1

2 Will NOT cover Dltprin (Frgmin) Fondprinux (Arixtr) Aspirin Tried nd true Poisons pltelet for life of the pltelet 5-10 dys Cn reverse with (nd/or) Pltelet concentrte DDAVP ( µg/kg) Reversl in minutes Clopidigrel nd Prsugrel Thienopyridine derivtives Block ADP receptor on pltelet Cn be effectively combined with spirin in some cses Increses bleeding risk signficntly Therefore, in some cses the combintion overll is not worth the risk Clopidigrel nd Prsugrel Clopidigrel (Plvix ) vs. Prsugrel (Effient ) Prsugrel hs stronger ntipltelet effect In generl More effective thn clopidigrel More mjor bleeding events thn clopidigrel Clopidigrel nd Prsugrel Cn reverse with (nd/or) Pltelet concentrte (15-30 minutes) Mybe dd DDAVP ( µg/kg) Reversl in minutes 2

3 ETRINSIC Binds to ntithrombin Potentites inhibition of thrombin nd fctor (by 1000-fold) Hlf-life of minutes If stopped, hemostsis restored in 3-4 hr Reversed with protmine sulfte Dosing is 1 mg protmine per 100 units heprin given in lst 2-3 hours Usully mg effective Mximum dose 50 mg Hlf-life 10 minutes Reversl is immedite My cuse llergic rection Low Moleculr Weight Low dose vs. high dose hve differing hlf-lives Both, however, lst longer thn regulr unfrctionted IV heprin Low Moleculr Weight If stopped, hemostsis restored in hours Prtilly reversed by protmine sulfte 1 mg protmine per 100 units LMWH given in the lst 8 hours Mximum dose 50 mg Hlf-life 10 minutes; infusion my be needed Reversl, when effective, is immedite Vitmin K Antgonists 3

4 ETRINSIC Vit K Antgonists: Long experience with its use Blocks production of vitmin K dependent cogultion fctors (II, VII, I, ) Induces fctor deficiency stte Mens we my be ble to replce these fctors to reverse it Risk of mjor bleeding 0.5% per yer Risk of ICH is 0.2% per yer Vit K Antgonists: Risk of bleeding directly relted to height of INR Over 3.0, incidence doubles when compred to INR of Risk of bleeding increses with codministrtion of ntipltelet gents Elderly hve two-fold incresed risk of ICH Vit K Antgonists: Hemostsis fter cesstion: hours Reversl Vitmin K (dose depends on INR nd body wgt) IV: Reversl in hours PO: Reversl in 24 hours FFP lrge mounts needed my be prohibitory PCCs reversl is immedite Wht is PCC? Complex Concentrte Briplex, Octplex 4 fctors Profilnine, Bebulin 3 fctors Contin multiple fctors, including prothrombin Hve more prothrombin thn FFP Fctor Inhibitors The xbns 4

5 ETRINSIC Fctor Inhibitors Orl Fctor inhibitors relto (pproved 7/11/11) Eliquis (pproved 12/30/12) Cnnot mesure nticogulnt effect Fctor Inhibitors relto (pproved 7/11/11) Surgicl DVT prophylxis Stroke prevention in nonvlvulr AF DVT/PE tretment ACS coming down the pike? Eliquis (pproved 12/30/12) Stroke prevention in nonvlvulr AF Edoxbn - Lixin Fctor Inhibitors relto Hlf-life 5-13 hours Eliquis Hlf-life 9-14 hours Edoxbn - Lixin Hlf-life 9-10 hours Fctor Inhibitors Generl efficcy / sfety dt (so fr) Compred with LMWH (DVT prophylxis) Lower bleeding risk Similr efficcy Compred with wrfrin (stroke in AF) Noninferior to wrfrin Lower rte of bleeding (2.1 % vs 3%) Fctor Inhibitors Reversl in bleeding Cesstion of mediction will reverse nticogulnt effect How long it tkes depends on hlf-life All re too long in cses of serious bleeding Immedite reversl No ntidotes found to dte Fctor inhibitor ntidotes would be useful, being investigted but not vilble to dte 5

6 ETRINSIC Direct Thrombin Inhibitors Hirudin ws prototype (leech spit) Prdx (ppr. Oct 2010) Competitive, direct thrombin inhibitor Approved for Stroke prevention in A Fib (2010) DVT prophylxis fter surgery (ACS coming soon?) Hlf-life hours Prdx Benefits over wrfrin Anticogultion immedite No trnsient hypercogulble stte Does not require blood testing to monitor Miniml interctions with food/drugs Not recommended in renl filure or in ptients with impired heptic function Prdx For stroke prevention As effective s wrfrin Risk of mjor bleeding sme or less thn wrfrin (round 3%) Older ptients hd higher risk of bleeding Issues for emergencies Cnnot follow blood testing for nticogultion effect (non-liner effect) Cogultion studies re elevted, but do not correlte with bleeding risk (Note: These rtes were in trils; we ll see wht hppens in the rel world ) 6

7 Issues for emergencies Tretment of bleeding Supportive cre prbcs, IV fluids, stopping bleeding by direct mens Activting thrombin Removing dbigtrn Not highly protein bound 4 hours of dilysis removes 68% of dbigtrn Direct Thrombin (II)Inhibitors Issues for emergencies Tretment of bleeding Activting thrombin My be impossible FFP hs miniml prothrombin not likely useful PCCs my be useful but poorly studied to dte rvii not dequtely studied nd unlikely useful Not useful: Cryoprecipitte, protmine, DDAVP, trnexmic cid, minocproic cid Time to hemostsis fter stopping tking mediction Antidote Time to reversl 3-4 hr Protmine sulfte Immedite LMW hr Protmine (prtil) Immedite Pentscchrides Fond: hr Idrpr: 5-15k Recomb VII Vit K Antg : hr Vit K IV Vit K orl PCCs Orl thrombin nd fctor inhibitors Usully within 12 hr Recomb fct Thrombin???? Immedite thrombin genertion hr 24 hr Immedite Unknown Thnk You For Your Attention! Any Questions? Aspirin 5-10 dys DDAVP, pltelets minutes Clopidogrel Prsugrel 1-2 dys Pltelets, mybe DDAVP minutes 7

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