What is Patient Blood Management and How Is It Relevant to Medical Patients?

Definition

“Patient blood management incorporates patient-centered, evidence-based medical and surgical approaches to improve patient outcomes by relying on the patient’s own (autologous) blood rather than allogeneic blood. . . The emphasis on the approaches being ‘patient-centered’ is to distinguish them from previous approaches in transfusion medicine, which have been ‘product-centered’ and focused on blood risks, costs, and inventory concerns rather than on patient outcomes.”

Goodnough LT, Shander A. Anesthesia and Analgesia. 2013 Jan;116(1):15-34.

Retrospective cohort* study (n=504,208) pts hospitalized with cancer

Association between txn and increased risk of venous thromboembolism (VTE), arterial thromboembolism (ATE) and mortality in cancer patients.

*(discharge database of the University HealthSystem Consortium 1995-2003)

Multivariate logistic regression analysis:

Multivariate analysis ORs for Association between Transfusion and

VTE, ATE and In-hospital Mortality

RBC Plts P value

OR (95% CI) OR (95% CI)

VTE 1.60 (1.53-1.67) 1.20 (1.11-1.29) P<0.001

ATE 1.53 (1.46-1.61) 1.55 (1.40-1.71) P<0.001

Mortality 1.34 (1.29-1.38) 2.40 (2.27-2.52) P<0.001

494 studies analysed by international multidisciplinary panel of experts (15).

Used RAND/UCLA Appropriateness Method to determine appropriateness of allogeneic RBC txn in 450 typical clinical scenarios (surgery, trauma, medical, critical care) based on its impact on patient outcomes. - Appropriate = likely to improve health outcome - Inappropriate = not likely to improve health outcome, or even

likely to harm - Uncertain = more research required to make definitive decision

The analysis was confined to non-actively bleeding patients.

11.8%

59.3%

28.9%

AppropriateInappropriateUncertain

A systematic search of publications (Jan 1966 – March 2012) and meta-analysis to assess the benefit of blood transfusion in anaemic patients with MI

Studies comparing blood txn vs no blood transfusion or a liberal vs restricted blood txn strategy

10 studies including 203,665 patients

Results: Increased all-cause mortality associated with a strategy of

blood txn vs non blood txn (18.2% vs 10.2%, RR, 2.91; 95% CI, 2.46-3.44; P <.001)

Multivariate analysis - blood txn associated with a higher risk for mortality - independent of baseline Hb, nadir Hb , and change in Hb

during the hospital stay Significantly increased risk of subsequent MI (RR 2.04; 95% CI,

1.06-3.93;P=0.03)

Retrospective, pair-matched (ratio 1:1) cohort study Non-bleeding critically ill patients with moderate anemia

(Hb 70-90 g/L), admitted to the ICU over a 27-month period - Most were patients admitted following general, cardiothoracic,

transplant, vascular, or oncological surgeries. - Non-surgical admissions included patients presenting with coronary

disease, sepsis or decompensated COPD

Results: RBC txn did not improve clinical outcomes in terms of morbidity of mortality in critically ill anaemic patients. Transfused anaemic patients had poorer clinical outcomes compared

to matched non-transfused anaemic patients

Outcome Non-transfused anaemic patients

(N=214)

Transfused anaemic patients

(N=214)

P Value

In-hospital mortality

13.0% 21.0% <0.05

Nosocomial infections

6.7% 12.9% <0.05

Acute kidney injury 16.7% 24.8% <0.05

ICU re-admission 1.9% 7.4% <0.05

ICU LOS (days) 4 (3-7) 5 (3-9) <0.05

“Similar results were obtained in subgroup analysis where only more anemic patients (68 matched pairs) or patients with cardiovascular comorbidities (63 matched pairs) were considered.”

Leal-Noval SR. et al Intensive Care Med. 2013

The Medical Module contains clinical guidance in:

General medical Acute coronary syndrome Heart failure Cancer Gastrointestinal Chronic kidney disease Chemotherapy and haematopoietic stem cell

transplantation Thalassaemia and myelodysplasia Coagulopathy Thrombocytopenia

Restrictive transfusion thresholds Single unit RBC transfusion policy

In relation to transfusion practice there is a common theme throughout all Modules:

Decisions on whether to transfuse should take into account the absence of proven benefit, and should follow a precautionary principle

In medical patients the aetiology of anaemia is often multifactorial; where appropriate, reversible causes should be identified and treated

Due to the lack of evidence in the general medical population, evidence from other patient groups was applied to derive Practice Points

Red blood cell transfusion

RBC transfusion does not replenish iron stores

Depending on status of donor: one unit of RBC only delivers 100-200 mg elemental iron Average iron deficient adult may require 1000-2000mg

elemental iron to begin replenishing iron stores

Elderly patients with cardiovascular disease?

Does this patient group require a higher transfusion trigger?

19 RCTs with total of 6264 pts., comparing

restrictive vs liberal txn thresholds (<70/80 g/L vs <90/100 g/L)

Population: cardiac, vascular, orthopaedic, acute blood loss and/or trauma, ICU and leukaemia pts with chemo (1 trial).

Restrictive reduced the risk of receiving an RBC transfusion by 39% (RR 0.61, 95% CI 0.52 to 0.72)

No benefit from liberal transfusion in relation to any outcome measure, including functional recovery

Authors: “the evidence raises the possibility of harm associated with liberal transfusion.”

In-hospital mortality significantly higher in liberal (23% higher)

Infection significantly higher in liberal (19% higher)

In 1 trial significant increase in risk of re-bleeding (90%)

Acute Coronary Syndrome (ACS)

Chronic Heart Failure

Iron deficiency is common in patients with CHF, with

or without anaemia It is important to look for and treat iron deficiency in

patients with CHF to reduce symptoms and improve exercise tolerance and quality of life.

Iron deficiency is common in patients with CHF, and is usually associated with anaemia. A recent study has demonstrated reduced symptoms and improved submaximal exercise tolerance and quality of life with use of intravenous ferric carboxymaltose (in addition to standard therapies) in iron-deficient patients with CHF. (Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009; 361: 2436-2448) Iron deficiency should be looked for and treated in patients with CHF to reduce symptoms and improve exercise tolerance and quality of life (Grade B recommendation).

Chronic Heart Failure

Cancer

RBC transfusions are resource-intensive and have been associated with short and long-term morbidity, cancer recurrence and mortality.

ESA therapy reduces transfusion incidence and volume in patients with cancer and chemotherapy-induced anaemia and may improve functional or performance status.

ESA therapy is associated with complications in some patients, particularly where baseline Hb is near normal. - Both the effectiveness and the risks vary in different

diagnostic subgroups Iron therapy may be used as primary therapy or to

augment the response to ESAs

Cancer

Chronic Kidney Disease

ESAs can be used to reduce RBC txn in dialyzed and non dialysis-dependent CKD patients

There is a significantly lower cardiovascular mortality (but not overall mortality) in CKD patients treated with ESAs

ESAs can improve quality of life in dialyzed and non dialysis-dependent CKD patients with diabetes - However, caution should be used in this population

because of the increased risk of MI, stroke and thromboembolic events seen in some patients, particularly with higher Hb targets

In anaemic CKD patients receiving ESAs, IV iron may reduce the need for anaemia intervention and improve functional or performance status.

Chronic Kidney Disease

Gastrointestinal

At the time the Medical Module was developed there was limited good quality evidence to guide transfusion practice in acute upper GI blood loss, resulting in 2 Practice Points

RCT (N = 921) compared Restrictive Strategy (Hb <70 g/L [n=461]) vs Liberal Strategy (Hb <90 g/L [n = 461]) in Upper GI bleeding

51% Restrictive Strategy vs. 15% Liberal Strategy, did not receive transfusions (P<0.001)

Outcome Restrictive Strategy N=(444)

Liberal Strategy (N=445)

Hazard Ratio with Restrictive Strategy (95% CI)

P Value

Probability of survival at 6 weeks

95% 91% 0.55 (0.33 to 0.92) [HR for death]

0.02

Further bleeding 10% 16% 0.62 (0.43 to 0.91) 0.01

Hospital LOS (days) 6.9±8.7 11.5±12.8 0.01

Adverse events 40% 48% 0.73 (0.56 to 0.95) 0.02

Restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding

Survival according to Transfusion Strategy

N Engl J Med. 2013

Gastrointestinal

Although anaemia in inflammatory bowel disease (IBD) is multifactorial, iron deficiency and anaemia of chronic disease are common etiological factors.

IV iron therapy is frequently used in IBD patients because oral iron has drawbacks (e.g. intolerance, lack of compliance, poor absorption and worsening of inflammation).

Chemotherapy and haematopoietic stem cell transplantation

In this patient population clinical guidance for RBC transfusion is contained in PPs 1,2, and 3 of the Medical Module: RBC transfusion should not be dictated by Hb alone Transfusion of a single unit of RBCs followed by

clinical assessment to determine further need.

Retrospective single-center analysis from July 2007 to December 2009 comparing two cohorts of patients receiving either double- or single-unit RBC transfusions (139 pts who received 272 therapy cycles)

Restricted analysis to patients with hematologic malignancies receiving intensive chemotherapy or HSCT

RBC transfusion trigger was a morning hemoglobin level of 60 g/L or the presence of symptoms of anemia such as fatigue, resting dyspnea, and dizziness

Single-unit transfusion led to a 25% reduction of RBC usage per therapy cycle and 24% per aplasia day, but was not associated with a higher outpatient txn frequency.

Multivariate analysis, single-unit transfusion resulted in a reduction of 2.7 RBC units per treatment cycle (P=0.001).

Pre-transfusion Hb levels were lower during the single-unit period (median 61 g/L versus 64 g/L)

More txns were administered to patients with Hb values of 60 gl/L or less (47% versus 26%).

No evidence of more severe bleeding or more platelet transfusions during the single-unit period and the overall survival was similar in both cohorts.

Chemotherapy and haematopoietic stem cell transplantation

The prophylactic use of platelets in chemotherapy and HSCT accounts for most of the platelet concentrates use in Australia

The Medical Module provides clinical guidance on platelet transfusion based on evidence available at the time of the systematic review

Prophylactic use of Platelets

No evidence that a prophylactic platelet transfusion policy prevents bleeding

There is no evidence to suggest a change from the current practice of using a platelet count of 10 x 10(9)/L

Platelet dose does not affect the number of patients with significant bleeding

There is no evidence that platelet dose affects the incidence of WHO grade 4 bleeding

Multicentre (n=14) randomized open-label noninferiority trial comparing prophylactic (n=299) vs non-prophylactic (n=301) platelet txns in patients receiving chemotherapy or undergoing stem cell transplantation and whose morning plt counts were less than 10x109

Primary outcome: Bleeding events of WHO grade 2,3 or 4 up to 30 days after randomization

Secondary outcomes: Number of days with bleeding events, time to first bleeding event, number of plt and RBC txns, time until recovery from thrombocytopenia, hospital LOS, adverse txn events

Myelodysplastic syndrome and Thalassaemia

Patients receiving chronic RBC transfusions account for a significant proportion of blood usage

Appropriate use of RBC transfusion is of great important – both for patient welfare and management of a scare and costly resource

With ESA therapy there is a favourable impact on mortality in patients with refractory anaemia with ringed sideroblasts (RARS), but not other MDS subgroups 1

Combining ESAs with granulocyte/macrophage colony-stimulating factor (GM-CSF) results in fewer RBC transfusions in patients with MDS with no significant difference in thromboembolic incidence or stroke 2

Patients with an erythroid response with ESA therapy show improvement in physical, emotional and functional well-being and overall quality of life 1

1. Greenberg PL et al. Blood. 2009 2. Thompson JA et al Blood. 2000

Myelodysplastic syndrome

Relevant Practice Points for RBC transfusion in MDS

Thalassaemia

There is no high-level evidence to guide practice in this patient population

In patients with thalassaemia the effect of the pretransfusion Hb threshold on mortality is uncertain

A pretransfusion Hb concentration of 90 – 100 g/L may reduce transfusion volume compared with 100 – 120 g/L 1,2,3

1. Masera G, et al. British J Haematol 1982 2. Torcharus K, et al Southeast Asian J Trop Med and Pub Health 1993 3. Cazzola M, et al. Transfusion 1997

Coagulopathy

Coagulopathy

Coagulopathy

5.2 Delivering patient blood management “The traditional laissez-faire attitude to blood administration results in risk to patients, expense to society and the waste of a gift given to save a life.”

6 Implementing, evaluating and maintaining the guidelines “Patient blood management requires effective coordination of care… The NBA together with the Jurisdictional Blood Committee and key stakeholders is developing a program to facilitate uptake of the guidelines…. The program will include the development of a comprehensive toolkit to support the introduction of patient blood management practices in the clinical setting.