1. April 23, 2015 Mini-Lecture Nathan King M.D. Anticoagulation Reversal Part 2: UFH & LMWH

2. Objectives

3. A 52 year old woman with is in the CCU for an NSTEMI. Cardiac catheterization did not reveal significant stenosis. While on a heparin drip she had an acute alteration in mental status and CT head revealed an intracranial hemorrhage with midline shift. Neurosurgery is preparing decompressive craniotomy. What is the next most appropriate next step? A. Treat with FFP B. Treat with Recombinant Factor VIIa C. Treat with Protamine Sulfate D. Treat with Vitamin K1 Case Vignette #1

4. Case Vignette #2 A 67 year old woman with history of a right lower extremity DVT on 40mg BID Lovenox, presents with acute altered mental status after 3 days of watery diarrhea and one day of decreased urine output. She last received medications more than 12 hours ago. On exam, she is confused, mucous membranes are dry, and her left thigh is much larger than her right. Labs 7 days ago: Hgb 9.3, BUN/Cr 12/1.1 Labs show now: Hgb 7.4, BUN/Cr 55/2.3 CT now: new enlargement muscles in the medial left thigh compared to prior CT What is the most appropriate next step? A. Call Interventional Radiology, treat with IV NovoSeven B. Call Nephrology consult, place HD catheter for emergent dialysis C. Call ACS surgery consult, treat with IV Vitamin K1 D. Call ACS surgery, treat with IV protamine

5. Mechanism of UFH and LMWH and Reversal LMWH Primarily acts on Xa Longer Half-life (3-6 hrs) Protamine Reversal agent for Heparinoids Heparinoids: Potentiate Antitithrombin III (AT) UFH (Unfractionated Heparin) Half-life shorter (30-60 minutes) Elevates PTT

6. Indications for anticoagulation reversal Supportive Measures / Monitoring: Support renal function with IVF and avoid nephrotoxins Monitor CBC and coags at lease Q12 hours Clinical Assessment: anticoagulation exposure possible medication interactions laboratory assessment: CBC, renal function, LFTs, and DIC screen

7. UFH and LMWH Reversal Protamine Dosing 25mg to 50mg boluses usually sufficient Based on timing, dose, and route of heparinoid to reverse Reactions Anaphylaxis can occur after previous exposure Special considerations Incompletely arrests anti-Xa activity of LMWH

8. UFH Reversal Time since UFH stopped(D) Protamine Dose to Neutralize 100 units of UFH Immediate1 – 1.5 30-60 minutes0.5 – 0.75 >2 hours0.25 – 0.375 Copyright 1978-2015 Lexicomp, Inc. All rights reserved.

9. LMWH Reversal Administer 1mg of protamine per 1mg enoxaperin Elevation of PTT or continued bleeding at 2-4 hours post dosing Administer 0.5mg of protamine per 1mg enoxaperin Repeat Dosing Copyright 1978-2015 Lexicomp, Inc. All rights reserved.

10. A 52 year old woman with is in the CCU for an NSTEMI. Cardiac catheterization did not reveal significant stenosis. While on a heparin drip she had an acute alteration in mental status and CT head revealed an intracranial hemorrhage with midline shift. Neurosurgery is preparing decompressive craniotomy. What is the next most appropriate next step? A. Treat with FFP B. Treat with Recombinant Factor VIIa C. Treat with Protamine Sulfate D. Treat with Vitamin K1 Case Vignette #1

11. A 52 year old woman with is in the CCU for an NSTEMI. Cardiac catheterization did not reveal significant stenosis. While on a heparin drip she had an acute alteration in mental status and CT head revealed an intracranial hemorrhage with midline shift. Neurosurgery is preparing decompressive craniotomy. What is the next most appropriate next step? A. Treat with FFP B. Treat with Recombinant Factor VIIa C. Treat with Protamine Sulfate D. Treat with Vitamin K1 Case Vignette #1

12. Case Vignette #2 A 67 year old woman with history of a right lower extremity DVT on 40mg BID Lovenox, presents with acute altered mental status after 3 days of watery diarrhea and one day of decreased urine output. She last received medications more than 12 hours ago. On exam, she is confused, mucous membranes are dry, and her left thigh is much larger than her right. Labs 7 days ago: Hgb 9.3, BUN/Cr 12/1.1 Labs show now: Hgb 7.4, BUN/Cr 55/2.3 CT now: new enlargement muscles in the medial left thigh compared to prior CT What is the most appropriate next step? A. Call Interventional Radiology, treat with IV NovoSeven B. Call Nephrology consult, place HD catheter for emergent dialysis C. Call ACS surgery consult, treat with IV Vitamin K1 D. Call ACS surgery, treat with IV protamine

13. Case Vignette #2 A 67 year old woman with history of a right lower extremity DVT on 40mg BID Lovenox, presents with acute altered mental status after 3 days of watery diarrhea and one day of decreased urine output. She last received medications more than 12 hours ago. On exam, she is confused, mucous membranes are dry, and her left thigh is much larger than her right. Labs 7 days ago: Hgb 9.3, BUN/Cr 12/1.1 Labs show now: Hgb 7.4, BUN/Cr 55/2.3 CT now: new enlargement muscles in the medial left thigh compared to prior CT What is the most appropriate next step? A. Call Interventional Radiology, treat with IV NovoSeven B. Call Nephrology consult, place HD catheter for emergent dialysis C. Call ACS surgery consult, treat with IV Vitamin K1 D. Call ACS surgery, treat with IV protamine

14. IF Suspected of bleeding or bleeding risk on UFH or LMWH: Determine if emergent reversal needed: ICH, emergent surgery, and major bleeding Initiate Supportive Measures and Clinical Assessment Reverse with Protamine: Incomplete arrest of LMWH Protamine treatment guided by route, timing, and dosage Summary