DIAGNOSTIC TESTING IN PATIENT BLOOD MANAGEMENT PROGRAMSThe Role of Diagnostic Point-of-Care Testing

“Diagnostic testing is an essential component of

Patient Blood Management. The accurate assessment

of the true causes of bleeding dysfunction facilitates

the employment of evidence based, goal directed

therapy to rapidly prevent and treat excess blood loss.”

Sherri Ozawa RN Clinical Director, Institute of Patient Blood

Management, Englewood Hospital Medical Center, Englewood, NJ

Supported by a grant from Tem Systems, Inc. (ROTEM ®)

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What Is the Issue? Blood transfusion is the most common procedure performed in US hospitals 1

• Every year, approximately 14 million units of packed red blood cells are used2

• One in ten hospitalized patients who undergoes an invasive procedure is transfused3

• It is estimated that 40-60% of transfusions are administered without appropriate clinical justification4

Modifiable risks that can reduce patient exposure to blood products 5

94% of transfusions in surgical patients can be attributed to modifiable events.

• Low preoperative hemoglobin levels

• Excessive surgical blood loss

• Inappropriate transfusion practices

What Factors Impact Bleeding Related Complications?

Evolving technology in health care can predispose patients to bleeding complications.6

• Progressive widespread use of anticoagulant and antiplatelet therapeutics

• Technological advances that enable complex and lengthy surgical procedures

• Advancing age of the general population with associated comorbidities that predispose to bleeding related complications

Why Should I Care?Unanticipated surgical bleeding is expensive and associated with poor outcomes7

• Rate of bleeding-related complications was almmost 30% in commonly performed operating procedures

• Incremental length of stay associated with bleeding-related complications or transfusions was 6 days

• Incremental cost per hospitalization associated with bleeding-related complications and adjusted for covariates was: $1,279 -$2,805 depending on type of surgery

“Achieving hemostasis in surgical patients is finding that fine balance between perioperative bleeding and pathological thrombosis; the two extremes of preventing a patient from bleeding to death while also preventing them from clotting to death.” – SHERRI

OzAWA RN

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Goals of Diagnostic Testing in Patient Blood Management

Rapid diagnosis and arresting blood loss by accurately assessing true causes of bleeding dysfunction8

• Use both quantitative and qualitative measures to assess true coagulation status

• Recognize the major mechanism of a developing coagulopathy

• Use goal directed diagnostic testing to direct and establish treatment goals

Conventional Coagulation Testing - What Do We See?Blood tested almost one hour after it is drawn

Blood is drawn. It’s transported to the laboratory. It’s centrifuged. The cells are removed. Calcium and activators are added. Clot initiation (ATT and PTT) is measured.

Routine plasma coagulation tests only reflect 1-2% of the entire coagulation process9

• Only 5% of total thrombin has been generated when the coagulometer stops

• Only plasma is analyzed

• Interaction of platelets (or any other cells) are not assessed

• Interaction with the coagulation system, fibrinolysis or FXIII is not assessed

Time (sec)

Coagulation

PTAPTTFibrinogenClauss

Final clot

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Mildly abnormal test results are associated with hemostatically adequate coagulation factor concentrations10

Below is a graph comparing the percentage of available clotting factors with INR values.

• 25-30% of factors are required to produce a clot (INR ≈ 1.7)

• INR may be elevated, but patient is still able to clot

New Insights: Viscoelastic Diagnostic TestingBasic principles of rotational thromboelastometry (ROTEM™)11

A citrated blood sample is placed is a stationary cup with calcium chloride and a coagulation activa-tor. The rotating pin is lowered into the blood. Clot formation changes the torque between the pin and the cup.

Lightdetector

Diode

Blood

100

60

20

10 20 30Time (min)

Clot

�rm

ness

(mm

)

40 50 60

Dataprocessor

Pin

ML

CT Closing timeCFT Clot forming timeAlpha Alpha angleA10 Amplitude 10 min after CTMCF Maximum clot �rmnessML Maximum XXXX

CFT

CT

MCFA10Alpha

100 %

50 %

30 %

1INR 1.3

60 ml/kg FFP = 4 L ‘fresh’ plasmaCL

OTT

ING

FAC

TORS zone of normal

hemostasis

zone of normalanticoagulation

15 ml/kg FFP

1.7 2.0 2.2 3.0

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Measurements include coagulation time (CT;sec), clot formation time (CFT; sec), -angle (degrees), amplitude at 10 minutes after CT (A10; mm), maximum clot firmness (MCF; mm), and maximum lysis (ML; % decrease decrease 60 min after MCF).

Morphology and clot formation changes are dependent on clotting defect11

Below are examples of ROTEM™ traces using the EXTEM test.

normal test result

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20 40 60 80 100 120

4020

2040

60

80

prolongued CTand reduced MCF

60

20 40 60 80 100 120

4020

2040

60

80

reduced MCF

60

20 40 60 80 100 120

4020

2040

60

80

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20 40 60 80 100 120

4020

2040

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hyper�brinolysis

delayed initiationof coagulation

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20 40 60 80 100 120

4020

2040

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Allows assessment of clotting defect and replenishment of what is needed without additional blood components

Below is an algorithm using the results of viscoelastic testing and a summary of therapeutic options.

Viscoelastic POC Testing (TEG®) guided therapy was superior to conventional coagulation tests in trauma patients12

Holcomb (2012) evaluated a series of 1974 trauma patients, 25% of whom presented in shock and 28% of whom were transfused. The authors found that TEG®, Haemonetics®, predicted RBC transfu-sion and massive transfusion better than PT or PTT. TEG® was superior to fibrinogen in predicting plasma transfusion, and superior to platelet count in predicting platelet transfusion.

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Advantages compared to conventional coagulation testing11,13

• Conventional coagulation testing only provides limited information on the underlying coagulation disorder

• Whole-blood viscoelastic tests such as rotational thromboelastometry (ROTEM) or thrombelastography (TEG) offer a more comprehensive insight into the coagulation process in trauma

• Results are available within minutes and they provide information about:

• Initiation of coagulation, the speed of clot formation, and the quality and stability of the clot

• Viscoelastic tests have the potential to guide coagulation therapy according to actual needs of each patient and reducing the risks of over or under transfusion

• Goal-directed therapy with specific hemostatic drugs, coagulation factor concentrates, and blood components

• In several cohort studies, this POC-based management was associated with:

• Reduced transfusion requirements

• Reduced incidence of transfusion associated adverse events

• Improved patient outcomes

Summary

The superior information obtained with viscoelastic testing is critical to better direct effective thera-peutic interventions in patients with coagulation issues. Optimizing coagulation is a fundamental principle of Patient Blood Management and along with other evidence based interventions, can posi-tively impact patient outcome. Implementing organized PBM programs, which incorporate advanced capabilities such as viscoelastic testing result in better clinical decision making, cost savings, and optimal patient care.

What is Patient Blood Management?

“The timely application of evidence based medical and surgical con-cepts designed to manage anemia, optimize hemostasis, and minimize blood loss in order to improve patient outcomes.” - Society for the Advancement of Blood Management (SABM.org)

“Viscoelastic testing has the potential to guide us to the defect and allow the patient to receive only the appropriate blood component that will correct their defect.” – ARyEH SHANDER MD, CLINICAL

PROFESSOR OF ANESTHESIOLOGy,

MEDICINE AND SURGERy, ICAHN

SCHOOL OF MEDICINE AT MT SINAI,

NEW yORk

Interdisciplinary Blood Conservation

Modalities

ManagingAnemia

Patient-CenteredDecision Making

OptimizingCoagulation

IMPROVEDPATIENT

OUTCOMES

SABM©2013

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References1. Agency for Healthcare Research and Quality. Healthcare Cost Utilization Project Statistical Brief. #149.Most Frequent Proce-

dures Performed in Hospitals 2010. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb149.pdf - Accessed July 18, 2013.

2. Department of Health and Human Services, National Blood Utilization and Collection Survey, http://www.hhs.gov/ash/bloodsafety/nbcus/index.html

3. Agency for Healthcare Research and Quality. HCUP Facts and Figures: Statistics on Hospital-Based Care in the United States, 2007. Available at: http://www.hcup us.ahrq.gov/reports/factsand”gures/2007/ pdfs/FF_report_2007.pdf - Accessed June 16, 2013.

4. Shander A, Fink A, Javidroozi M, Erhard J, et al.Appropriateness of allogeneic red blood cell transfusion: the international consensus conference on transfusion outcomes. Transfus Med Rev. 2011 Jul;25(3):232-246.e53

5. Shander A, Javidroozi M, Perelman S, et al Mt Sinai J Med. Jan-Feb 2012.

6. Shander A, kaplan L, Harris M et al. Topical Hemostatic Therapy in Surgery: Bridging the knowledge and Practice Gap J Am Col Surg. 2014; in press.

7. Stokes ME, ye X, Shah M, Mercaldi k, Reynolds MW, Rupnow MF, Hammond J. Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients. BMC Health Serv Res. 2011; 11:135.

8. Armand R, Hess JR. Treating coagulopathy in trauma patients. Transfus Med Rev. 2003; 17(3): 223-31.

9. Mann kG, Brummel k, Butenas S. What is all that thrombin for? J Thromb Haemost. 2003 Jul;1(7):1504-14.

10. Dzik WH, in Mintz PC ed. Transfusion Therapy: Principles and Practice, 2nd edition. AABB 2005

11. Schöchl H, Maegele M, Solomon C, Görlinger k, Voelckel W. Early and individualized goal-directed therapy for trauma-induced coagulopathy. Scand J Trauma Resusc Emerg Med. 2012 24;20:15.

12. Holcomb JB, Minei kM, Scerbo ML, Radwan zA, Wade CE, kozar RA, Gill BAlbarado R, McNutt Mk, khan S, Adams PR, Mc-Carthy JJ, Cotton BA. Admission rapid thrombelastography can replace conventional coagulation tests in the emergen-cydepartment: experience with 1974 consecutive trauma patients. Ann Surg. 2012 Sep;256(3):476-86.

13. Lier H, Vorweg M, Hanke A, Görlinger k. Thromboelastometry guided therapy of severe bleeding. Essener Runde algorithm. Hamostaseologie. 2013;33(1):51-61.