Global Blood Resources LLC The Use of the Hemobag® to Improve Clinical Outcomes in any Blood Management Program Keith A. Samolyk CCP, LCP Global Blood Resources LLC WWW.MYBLOODFIRST.COM

Roadmap Factors affecting transfusion decisions Blood conservation techniques Ways to reverse hemodilution Ultrafiltration / Hemoconcentration The Hemobag® – how it works Clinical trial of the Hemobag® Flagship cases

What drives transfusion decisions? LVEDP, EF, LM stenosis, # diseased vessels, lowest Hct on CPB vs. adverse outcomes 6,980 CABG patients Significant association: Hctlowest & death IABP & return to CPB No association: Hctlowest and stroke Disease Variables (9%) Surgeon (56%) Age, sex, BSA, comorbidity score Patient Variables (35%) NNECDSG 1998

Lowest Hct on CPB vs Adverse Outcomes 6,980 CABG patients Significant association Hctlowest & death IABP & return to CPB No association Hctlowest & stroke Adjusted Mortality Lowest Hct on CPB NNECDSG(Defoe 2000)

Managing anemia with transfusion after CPB increases mortality 10,178 CABG patients If Hct < 22% & raised with transfusion... Mortality directly influenced by transfusion NNECDSG

Minimum Accepted Hematocrit Levels During ECC 18- 21% { normal risk patients } 21- 25% { high-risk patients during bypass } Post-Operatively Adequate oxygen delivery decreases morbidity & mortality 22-25% { normal risk patients } 25-30% { high-risk patients } Jehovah's Witness patients Remarkable tolerance of severe acute normovolemic anemia Tight adherence to specific guideline Most cases can be performed without using allogeneic blood and a HCT above min.

Typical Blood Conservation Techniques Used Today Acute Normovolemic Hemodilution (ANH) Hemodilution with crystalloid solutions Intraoperative Autologous Donation (IAD) Cell Saver for Shed Blood and Conservation Apheresis / Platelet Gel / PRP Ultrafiltration (Hemoconcentration), Hemobag® Autotransfusion of unprocessed Shed Blood from chest tube collection drains

Blood Conservation Techniques for ECC Minimize circuit prime by Condensing circuit to accommodate priming volume of ~1100 mL – 1400 mL Smaller volume increases risk of micro-air, poor air handling qualities, and less reaction time Retrograde Autologous Prime (RAP)*** Displace crystalloid prime with patients own whole blood slow controlled exsanguination (1000 mL or more) team support of Anesthesia short acting vasoconstrictors like Neosynepherine Can be done for free and is very cost effective Closed Biocompatible/Heparin Coated Systems/SMC Reduce surface activation of blood Air is foreign surface

It’s not just ECC that contributes to hemodilution Anesthesia may give 1-4 L perioperatively For every 1L of crystalloid given only 250 mL remain intravascular Total Body Water Increase leads to: Tissue edema & cellular/organ dysfunction Prolonged ventilatory support Pulmonary hypertension Decreased lung compliance Coagulopathy It’s not just ECC that contributes to hemodilution

Average Circuit Volume is ~ 1200–1600mL Retrograde Auto Priming for free can reduce circuit prime volume to ~ 500–800 mL or less while maintaining a safe and trusted circuit helping to eliminate hemodilution How else can we reverse Hemodilution ?

Answer: Hemoconcentraters

Positive Effects of Ultrafiltration/Hemoconcentration Removes noncellular H20 Decreases total body H20  concentrating WB Increases Hct platelets & clotting factors albumin & plasma proteins Removes cytokines & anaphylatoxins C3a, C5a IL6, IL8, TNF-A ET-1, bradykinins adhesion molecules sE-Selectin Improves organ fcn myocardial fcn cerebral oxygenation pulmonary compliance Reduces post-op blood loss  reduces transfusions Reduces perioperative morbidity Naik, 1991, Hospital for the Sick, Great Ormond St. UK

Benefits of MUF MUF increases Post CPB Hct Systolic and diastolic pressure Cardiac Index Myocardial contractility Red cell mass Pulmonary compliance Arterial oxygenation Cerebral oxygenation Left ventricular function Diastolic compliance Plasma proteins

Ultrafiltration combats Hemodilution MUF decreases Heart rate & PVR Myocardial wall thickness Pulmonary hypertension Incidence of effusions Intrapulmonary shunt fraction 24 hr blood loss Inotrope requirement Blood product usage TBW content Hospital stay

How does it happen?

Capillary "Type" Permeability varies with type of capillary Capillary type varies with organ function 1. Tight (brain) 2. Continuous (skeletal muscle, skin) 3. Fenestrated (secretory glands, kidney, gut) 4. Discontinuous (liver, spleen, bone marrow)

Edema: Most common clinical manifestation of an imbalance of forces at the capillary wall Excess accumulation of fluid in the interstitial space that has not been readsorbed into capillaries or taken up by the lymphatics Causes include Obstruction Permeability or change in reflection coefficient Increased protein permeability results in an imbalance Occurs in trauma, thermal injury, inflammation Life threatening manifestations - endotoxic shock, ARDS Plasma Protein Reduction in circulating plasma proteins, especially albumin Liver dysfunction, malnutrition, or acute alteration of fluid status Albumin attenuates extravasation of fluid out of intravascular space to interstitial space Capillary pressure

How can we get these positive effects of HEMOCONCENTRATION? Removes noncellular H20 Decreases total body H20  concentrating WB Increases Hct Platelets & clotting factors Albumin & plasma proteins Removes cytokines & anaphylatoxins Improves organ fcn myocardial fcn cerebral oxygenation pulmonary compliance Reduces post-op blood loss  reduces transfusions Reduces perioperative morbidity Naik, 1991, Hospital for the Sick, Great Ormond St. UK

A New Technology for Blood Management is the HEMOBAG® A Universal Blood Reservoir for Salvaging Autologous Whole Blood from ECC’s Specially designed for quickly Filling Hemoconcentrating Transfusing All in the same Hemobag® Doubles use of any Hemoconcentrator

TS3 Tubing Set doubles the use of any Hemoconcentrator For use both during the case

And at the end of the case for Whole Blood Salvaging of the ECC Circuit

HEMOBAG® SUMMARY HEMOBAG® SUMMARY

“Your Body Your Choice” pg. 26, S.Farmer and D. Webb

The Big Picture Choices/ Alternatives Publication Vol 4 Issue 2, Center for Bloodless Medicine and Surgery, University of Miami / Jackson Med Ctr.

Salvaged Blood with a Cell Saver

Blood Salvaged with the Hemobag® Everything that’s Autologous is Concentrated and given back for stability and Homeostasis

Data from 40 Patients’ ECCs chased with 2.0 L of crystalloid filling the Hemobag® Average time to Fill the Hemobag®: 60 sec +/- 20 sec Hemoconcentrate contents of the Hemobag® (2L1L): 10.5 min +/- 1 min (total = 11.5 min +/- 80 sec) Average change in blood parameters: Pre-Hemobag Post-Hemobag HCT 21.4% 53.1% Total Protein 2.6 g/dL 8.2 g/dL Fibrinogen 92 mg/dL 305.8 mg/dL Platelet Conc. 186 K/uL 266 K/uL Salem Hospital, Salem Oregon Ave. volume returned = 820 mL

Results represent what is possible with the Hemobag® FLAGSHIP CASE #1:Over 80y/o female, AVR case, post-op bleeding: 300mL, left ICU post-op Day #1, no blood products given Reinfused 900 mL Conc. Autologous Whole Blood from CPB circuit with: Hct = 57% Platelets = 364 K Fibrinogen = 740 mg Albumin = 6.6 g/dL Total protein = 11.7 g/dL Time: 12 minutes Extracorporeal circuit kept viable & ready to go back emergently Results represent what is possible with the Hemobag®

FLAGSHIP CASE #2:60 yr old CABG x 3, post-op bleeding was 290 mL, left ICU on Post-op Day #1, no blood products given Reinfused 1150 mL Conc. Autologous Whole Blood from CPB circuit with: Hct = 56% Platelets = 430 K Fibrinogen = 972 mg Albumin = 5.7 g/dL Total protein = 13.6 g/dL 300% increase in FVII 73% activity to 223% Time: 10 minutes Extracorporeal circuit kept viable & ready to go back Illustrates capabilities of the Hemobag® when used for Whole Blood Salvaging in CV Surgery

Both the Hemobag® and TS3 tubing set come 5 to a box and are sold together

Sterile Peel Pouches

Easy to Understand Directions

Benefits Overview CELL SAVER VS HEMOBAG® If you were the patient wouldn’t you want all your own AUTOLOGOUS CELLS back first?

Conclusion about the Hemobag® The Hemobag® system effectively Concentrates Extracorporeal Circuit contents Produces Autologous Whole Blood high in RBC’s and plasma proteins Offers advantages over current technology quick, easy, enhanced end product “The Hemobag® is the Missing Piece in the Big Picture of Blood Salvaging and Conservation”

Bottom Line Life is related to blood and anything you can do to save more of a patient’s Own Whole Blood is better than anything else … Period ! Patients transfused with allogeneic blood products are exposed to a host of new potential complications No one is exempt from resultant immunosuppression The least of these is a mild form of TRALI which leads to longer and delayed time to extubation & discharge from the ICU increased risk of Morbidity and Mortality Autologous whole blood is jugular for perfect natural homeostasis We should be doing everything we can to conserve more of this precious substance It’s in the Patient’s Best Interest - It’s the Right of all Patients

Thank You for listening ! Global Blood Resources LLC WWW.MYBLOODFIRST.COM WWW.HEMOBAG.COM