Jay Montgomery 3/13/12

From a surgical discharge summary at the VA: "On July 16 the patient was consented for guillotine amputation. The operation was discussed at length and he agreed that it was his best option."

Me: "In addition to her abdominal infection, it looks like she has also infarcted her left lobe of her transplanted liver.‖

Social Worker: "I hope it's not anything more serious."

large bruises. and bleeding gums. . 73 F with DM II. RA. and paroxysmal atrial fib s/p AV node ablation with pacemaker implantation presented to outpatient clinic with worsening fatigue for last several months that she states is due to daily episodes of atrial fib. She also reports some intermittent hematuria. Some loose stools over this time.

PMH: Parox AF DM RA HTN Social History: Married. Meds: Warfarin KCl Chlorthalidone Sotalol (recently increased from 80 to 120 BID) Losartan Amlodipine Sertraline Zolpidem Metformin Family History: M—CHF at age 83 F—Accidental death Brother—‖Open heart surgery‖ x 2 Sister—Unknown cardiac problems . No tobacco or ETOH. Retired. Rare caffeine.

Neck: No JVD. alert. No rash. Skin: Ecchymoses on both dorsal forearms and hands. RR 16. ND. NAD HEENT: Clear OP. Neuro: Non-focal. HR 60 BP 128/54.1 F. Mild conjunctival pallor. Abd: Soft.         T 98. NT. no M/R/G. SaO2 96% on RA Gen: Awake. No LAD. . RR. Lungs: CTAB CV: NR.

. EKG:  PM interrogation: normal PM function. 16 episodes of AF in last 8 months. longest 5 hours.

1 INR 4.4 Iron 22 Ferritin 17 TIBC 380 Fibrinogen 224 Smear: no schistocytes Prot 7.4 UA nl .4 103 28 11 1.2 AST 43 ALT 36 Alk P 108 TSH 3.4 Alb 4.8 MCV 75 Retic 2.1 24 187 136 4.4.0 91 9.

1. 2. 2.1. 3. recent  1.6.3. 1. 4.2.9.1. 1.4. 3.9.4. 5.1.7  Stools dark. 2. 3.8. INR history.3. 1. 2. 3. 1.5. 1.8.4. 1.6.4. borderline melanic Colonoscopy without identified discrete source of bleeding  .

Chest.  Coumadin stopped CHADS2 revisited: 2 (~4. . Epub 2009 Sep 17. 2010 Feb.0% risk of stroke/yr) *=part of CHADS2 score * * * * * Lip et al.137(2):26372.

 Decision was made to restart anticoagulation with a new medication Dabigatran (Pradaxa) Direct thrombin inhibitor .

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Verheugt.Relative risk reduction of stroke ~60% Absolute increase risk of bleeding to at least 1%/yr Brouwer. Circulation. 2003. . Olsen et al. 2002. Lancet.

  Coumadin stopped CHADS2 revisited: 2 (~4. .0% risk of stroke/yr) *=part of CHADS2 score * * * * * Lip et al. Epub 2009 Sep 17. Chest.137(2):26372. 2010 Feb.

 Dicoumarol discovered in 1939 at Wisconsin University  First hinted at by cattle hemorrhaging after eating spoiled hay  Modified slightly to make Warfarin in 1948   More potent Originally used a rodenticide  Used in humans in 50s The ―WARF‖ .

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INR 1.0 2 3 5 10 Therapeutic window Risk of thrombosis too high Risk of bleeding is prohibitive Hylek et al. NEJM. 2003. .

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antistatin.  1990: Tick anticoagulant peptide (TAP. was  1987: First factor Drug ClassHirudin. inhibitors hirudin Perzborn et al.  IIa Factor Potentiates antithrombin effect on Xa bivalirudin. indirect (Antistatin.isolated Vitamin K from leeches Antagonists Warfarin Xa inhibitor. another inhibitors + enoxaparin. first thrombin inhibitor Oral Parenteral  1950s: isolated from Mexican leech Factor Xa Heparin. . dalteparin Xa inhibitor) isolated Direct Xa  2001: inhibitors Approval of Fondaparinux. fondaparinux. TAP) parenteral Factor Xa inhibitor Argatroban. lepirudin.

66 (0.45 to 0.68 (0. Ann Intern Med 2004.75 to 3.19 to dose warfarin <0.04 0.37 to 1.46 to 0.06 1.88 (0.99) 0. p value 95% CI Major bleeding Odds ratio. 139:1018.0) p value 0. EB. JB.88 to 4. LJ.2 Conventional dose warfarin versus aspirin McNamara.61 (0.10 Conventional 0.44) >0.50) versus placebo Aspirin versus placebo 0.02) 0. Bass.78) >0.82 (0. RL.31 (0. 95 percent CI 1. Segal. .Comparison Stroke Odds ratio.2 1.001 0. Tamariz.

1.88)  Bleeding:    Olesen et al.55–1.95) 0.89–0. 0.81–0.86 if no treatment (1.0)    1.81 with ASA (1.84 (no treatment. Risk-adjusted registry—in those with high thromboembolic risk hazard ratios for thromboembolism (Coumadin=1.14 for coumadin + ASA (1. 0. Thromb Haemost 2011. 106: 739–749 .78-1.97) 1.90) 1.93 (ASA.23) 1.06-1.64 (VKA+ASA.73-1.74) 0.

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More basic= stronger inhibitor Less basic= increased oral bioavailability .

Factor Xa inhibitor candidate found through high throughput screening Rivaroxaban .

dalteparin . hirudin Heparin. enoxaparin. edoxaban Dabigatran. ximelagatran* Argatroban. apixaban. bivalirudin.Drug Class Oral Parenteral Vitamin K Antagonists Warfarin Factor Xa inhibitors + Direct Xa inhibitors Factor IIa inhibitors Rivaroxaban. fondaparinux. lepirudin.

80-2.75)* Major Bleeding Intracranial HR Hemorrhage HR .80-0.93)* 0.80)* 0.69 (0.79 (0.00) 0.66 (0.47-0.99)* Stroke HR 0.03) 0.35-0.89 62% (0.60-0.67 (0.04 (0.90-1.32 (0.88 64% (0.17) 0.16 (1.00-1.66-0.82-1.34) 1.77-1.66-0.20) 0.51 (0.92 55% (0.79 (0.53-0.Drug RE-LY Year Warfarin TTR* Dabigatran 9/2009 ROCKET AF Rivaroxaban 9/2011 ARISTOTLE Apixaban 9/2011 Death HR 0.82)* 1.96)* 1.95)* 0.

Efficacy and Safety Hazard Ratios vs Warfarin 1.6 0.0 * * * * Dabigatran * Rivaroxaban Apixaban Death Stroke Major Bleeding Intracranial Hemorrhage *statistically significant .8 0.4 1.2 0 * * Warfarin=1.2 1 0.4 0.

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Eerenberg E S et al. Circulation 2011.124:1573-1579 .

Cutoff= $50.000/QALY .

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   Dawood Darbar. MD Associate Professor of Medicine Division of Cardiology .

125:159-164 .Granger C B . Armaganijan L V Circulation 2012.