Patient Blood ManagementMinh-Ha Tran, DO, FASCPUC Irvine HealthTransfusion Medicine Service

Agenda State the guiding principles of Patient Blood Management

Name the three phases of perioperative blood conservation

Discuss examples of modalities relevant to each phase

Define “restrictive” hemoglobin threshold

Discuss transfusion risks

Name three transfusion alternatives

Become acquainted with basic principles of platelet and plasma transfusion practice

Patient Blood ManagementA series of ‘rights’

◦ Right Patient Right Product

Right Reason Right Time

Who defines ‘right’?◦ Clinical decision informed by evidence

Not all hypotension is due to anemia Not all hypoxia is due to reduced red cell mass

Not all who are anemic require red cell transfusion

Perioperative Management

Preoperative Intraoperative PostoperativeMedication review and targeted bleeding history

Acute normovolemic hemodilution when appropriate

Iron supplementation

Management plan for congenital bleeding disorders

Use of antifibrinolytics when appropriate

Reduction of iatrogenic blood loss

Evaluation and treatment of preoperative anemia

Application of minimally invasive surgical techniques

Medical optimization Intraoperative cell salvage

Utilization of restrictive transfusion strategies throughout the perioperative period

Anemia tolerance, utilization of transfusion alternatives when possible

A word about PADPreoperative Autologous Donation

◦Induces Preoperative Anemia Increases risk for allogeneic transfusion

Generates waste as most units wind up discarded A waning practice…

Restrictive Transfusion Strategies

Emphasize clinical, not just laboratory indicators Whenever possible: single unit transfusion, then reassess

StudyPatient Population

Arms Primary Outcome

TRICC

NEJM 1999

838 Critical Care

patients [RCT]

7 g/dL (n=418) vs

9 g/dL (n=420)

30 Day ACM: (18.7% vs 23.3%, p = 0.11)

TRACS

JAMA 2010

502 Cardiac Surgery

with Cardiopulmonary

Bypass [RCT, NI study]

8 g/dL (n=249) vs 10

g/dL (n=253)

NI margin for 30 day ACM predefined at -8%: Observed

between group difference 1% [95% CI, -6% to 4%], p =

0.85.

FOCUS

NEJM 2011

2016 Patients with

CAD/Risk of CAD after

Hip Fracture Surgery

[RCT]

< 8 g/dL (n=1009) vs

10 g/dL (n=1007)

Death or inability to walk across room unassisted at 60

days: Abs Risk Difference 0.5 percentage points [95% CI, -

3.7 to 4.7]

Acute UGI Bleed

NEJM 2013

921 Patients with severe

Upper GI bleeding

[RCT]

< 7 g/dL (n=461) vs

< 9 g/dL (n=460)

45 Day ACM: 91% restrictive vs 95% liberal; HR for death

with Restrictive Strategy 0.55 [95% CI: 0.33 to 0.92], p =

0.02.

Transfusion Risks

(Allergic)

Anemia Management Strategies

Anemia Tolerance – General Guidelines◦Acute bleeding, hypovolemic shock

Transfuse as needed Surgical management

◦Chronic anemia, stable patient Assess for symptoms

…and comorbidities Determine cause

…and anemia treatment options Establish timeline for correction

…is the patient preoperative?

Iron Deficiency Anemia

Iron Deficiency AnemiaAnemia severity

◦Endogenous erythropoietic drive

Likelihood of response◦Assess for malabsorption, continued

losses, anemia of inflammation, renal anemia

Slope of response◦Reduced if continued ongoing losses or

malabsorption

Treatment ConsiderationsEnteral Formulations

Iron Salts Unit Dose (mg) Elemental Iron (mg) Notes

Ferrous Sulfate 325 65 Iron salts are similarly tolerated; adverse effects generally attributable to elemental iron content.

Ferrous Gluconate 325 36

Ferrous Fumarate 325 106

Non-Salts

Carbonyl Iron 45 45

Carbonyl iron microspheres derived by heating gaseous iron pentacarbonyl; absorption dependent on solubilization by gastric acid

Parenteral Formulations

Dextran Stabilized Concentration(mg elemental iron/mL) Vial Notes

LMW Iron Dextran(INFed) 50 100 mg/2 mL Watson Pharma, Inc, Corona, CA

Iron Sucrose(Venofer) 20 100 mg/5 mL;

200 mg/10 mL American Regent, Inc, Shirley, NY

Sodium Ferric Gluconate Complex in Sucrose solution

(Ferrlecit)12.5 62.5 mg/ 5 mL Watson Pharma, Inc, Corona, CA

Ferumoxytol(Feraheme) 30 510m g/17 mL AMAG Pharmaceuticals, Lexington, MA

Ferric Carboxymaltose(Injectafer) 50 750 mg/15 mL Luitpold Pharmaceuticals, Shirley, NY

Erythroid Stimulating Agents

Erythroid Stimulating Agents

Sun Mon Tues Wed Thurs Fri Sat

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

300 U/Kg

Sun Mon Tues Wed Thurs Fri Sat

600 U/kg

600 U/kg

600 U/kg

600 U/kg

Malabsorption

Celiac DiseaseInflammatory

Bowel DiseaseRoux en Y

Gastric Bypass[vegan/

vegetarian]

General CommentsOral Iron

◦ Hb will rise slowly, beginning 1-2 weeks after initiation of treatment

◦ 2 g/dL over ensuing 3 weeks

◦ Hb deficit typically halved by 1 month, normal by 6-8 weeks

Parenteral Iron◦ In those unresponsive or intolerant to oral iron, or in those whose iron

losses exceed absorptive capacity, IV iron is an option

◦ Calculate an iron deficit and replenish the deficit

ESA◦ If ESA’s are administered for renal anemia, coordinate care with the

nephrologist

◦ In noncancer patients, ESA’s may be used to augment the erythropoietic response to iron – particularly in mild anemia or when IDA is complicated by inflammation

◦ Always co-administer with iron to avoid functional iron deficiency

Calculating Iron DeficitExample: 82 kg woman with heavy uterine

bleeding presents with H/H of 6.3 g/dL and 18.9%

Total Blood Volume◦ 70 mL/kg x 82 kg = 5740 mL (57.4 dL)

Hemoglobin Deficit◦ 12 g/dL – 6.3 g/dL = 5.7 g/dL

◦ 5.7 g/dL x 57.4 dL = 327 g

Iron Deficit◦ 3.34 mg Fe/g Hb

◦ 327 g Hb x 3.34 mg Fe/g = ~1000 mg Fe

From the LiteratureIDA treatment:

◦ A higher and more rapid hemoglobin response with parenteral iron

◦ Risk of infection increased with parenteral iron

Preoperative anemia: ◦ Oral iron alone ineffective for preoperative purposes, particularly

when anemia is mild◦ Treatment most effective with ESA containing regimen

Critical Care Patients:◦ ESA alone has minimal impact in transfusion avoidance among

critical care patients, particularly when restrictive transfusion strategies are in place

The anemia we cause…

PlateletsUsual Adult Dose

is 1 Apheresis Platelet Unit

Platelets

Platelets

Plasma

Plasma

PCC – first view – Tran, et al.

0 1 2 3 4 5 6 7 8 9 10 11 12 13-1.00

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

10.00

11.00

12.00

f(x) = 0.87265707126853 x − 1.21662810391693R² = 0.93037900284288

PreTreatment INR vs Delta INR in PCC Group

Delta INR Linear (Delta INR)

PreTreatment INR

Delt

a I

NR

(P

re-P

ost)

Tran MH, Gayatinea R, Albicker P, Baje M.PCC and NovoSeven for Critical Bleeds and Coagulopathy Reversal

PBM PI Project

PMID: 24919540

EBM GI Bleed Protocol

Utilization Review

Utilization Review

Summative CommentsPatient Blood Management

◦ Protect the patient from unnecessary or excessive transfusions

◦ Inform transfusion decisions not simply by hemoglobin, but by patient symptoms and comorbidities

◦ Utilize restrictive transfusion strategies◦ Reduce iatrogenic anemia through reduction in both the

volume and frequency of blood draws◦ Avoid arbitrary 2 unit transfusions◦ Consider transfusion alternatives for anemia

management