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INTRODUCTION�

Transfusion of red blood cells (RBCs) is the primary management of anemia, which affects 90% of critically ill patients.

Definition of anemia – haemoglobin (Hgb) <12g/dL in females and <13g/dL in males.

Anemia in the setting of older age, critical illness, trauma and surgery has been associated with poor prognosis, as indicated in several studies.

Patients in the setting of critical illness have multiple causes of anemia, including active hemorrhage, blunted erythropoietin production, inflammatory cytokine production, increased hepcidin, iron deficiency and underlying disease (e.g., renal failure).

RBC transfusion in anemia can increase oxygen delivery, increase cell mass and potentially resolve anemic symptoms. However, transfusion can contribute to fluid overload, fever, reaction, immunomodulation, multiple organ dysfunction, hypothermia & coagulopathy.

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DISCUSSIONS

Types of Products

Restrictive vs. Liberal Transfusion Threshold

Transfusion Guidelines

Transfusion Reactions and Infections

Trauma

Sepsis/Critically III

Physiologic Effects of RBC Transfusion

Acute Myocardial Ischemia

Gastrointestinal Bleeding

Effect of Product Age

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Physiologic Effects of RBC Transfusion�

Oxygenation is dependent on Hgb concentration, Hgb saturation, oxygen supply, cardiac output & pulmonary extraction & perfusion.

In a healthy adult, the normal daily production of RBCs is 0.25/kg, with an average lifespan of 120 days – transfused blood cells have a lifespan of 60 days.

One unit of RBCs increases Hgb by 1g/dL & hematocrit (Hct) by 3%.

RBCs can be stored to a max of 42 days, and the process of storing RBCs changes cell wall deformability, increases proinflammatory cytokines, and decreases the ability of RBCs to release oxygen to peripheral tissues.

Product transfusion can increase intrinsic blood viscosity and decrease cardiac output- diminish the ability of RBCs to improve oxygenation in critically ill patients. Whether product storage age affects patient morbidity and mortality is controversial, which will be discussed later.

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Types of Products

Leukoreduced

Prevention of febrile nonhemolytic reaction
Reduction in the risk of cytomegalovirus (CMV) infection
Reduction in the risk of transplant rejection & intrauterine transfusions.

Washed

Prevent allergic reactions - in patients with immunoglobulin A deficiency, and in patients with recurrent severe transfusion reactions

Irradiated

Prevent transfusion-associated graft vs. host disease (TAGVHD) through the gamma irradiation

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Transfusion Reactions �and Infections

Transfusion of RBCs functions as an allogeneic tissue transplantation, which associated with risk.

Transfusing RBCs introduces foreign antigens into the patient, and the host response varies with modifications to intrinsic T cells, lymphocytes response, natural killer cell function, cytokine production, and phagocyte function-known as transfusion-related immunomodulation (TRIM)

Each unit transfused also has other associated risks, such as infection (HIV, Hep C and Hep B) and transfusion reactions (Table 1)

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Effect of Product Age

Regulations allow the storage products ≤ 42 days, though the majority of transfusions include products stored 16 – 21 days, and physiologically it would seem RBCs stored for greater lengths of time would be associated with poorer outcomes.

Proposed mechanisms include increased inflammatory activity, increased adhesion of the cell membrane to vasculature, decreased 2,3-disphosphoglycerate (2,3-DPG), and increased deformation of stored RBCs.

However, debate exists on the effects of product age and morbidity and mortality in critically ill patients.

A 2008 study in the New England Journal of Medicine found that products stored for a longer time period (20 days) vs. a shorter period (11 days) were associated with mortality, intubation beyond 72 hours, renal failure, and sepsis or septicemia.

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The primary population included patients obtaining some form of cardiac surgery, and the authors claim RBC units stored ≥2 weeks have higher risks associated with transfusion.

A systematic review with 18 observational studies and 409,966 patients found a 16% increase in mortality. In fact, 1 study found that patients receiving older RBCs (stored for 14–42 days) had higher rates of sepsis, intubation > 72 hours, renal failure, and in-hospital mortality.

However, this literature conflicts with other studies noting no effect of product age with patient outcomes— mortality in particular.

A 2015 New England Journal of Medicine article in a similar group undergoing cardiovascular surgery compared transfusion with products 21 days old. Mortality was not statistically significant between the groups.

Currently, insufficient evidence exists that true harm is present with older products. Studies are retrospective in design, observational, and have small sample sizes. Several randomized trials are currently underway evaluating the effect of transfusion age.

However, if possible, products < 21 days should be given, with studies suggesting harm with older products (i.e., those stored for > 21 days).

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Transfusion Guidelines

The most commonly referenced includes the American Association of Blood Banks (AABB)

AABB recommendations include the following :

Adhere to a restrictive transfusion strategy (7-8g/dL) in hospitalized, stable patients.

Adhere to a restrictive strategy in hospitalized patients with pre-existing cardiovascular disease and considering transfusion for patients with symptoms or a Hgb level of ≤ 8g/dL.

No recommendation for a against liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with ACS.

Transfusion decisions be influenced by symptoms and Hgb concentration.

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Restrictive vs. Liberal Transfusion Threshold

The AABB recommendations have their origins in several large clinical trials evaluating thresholds, specifically restrictive vs liberal.

Restrictive strategies typically have a threshold of 7g/dL.

Studies incorporating a restrictive threshold have been evaluated in various populations, including patients with sepsis, critically ill patients admitted in ICU, cardiac surgery, orthopedic surgery and trauma patients with primary hypotheses that restrictive transfusion strategies were as safe as, or more safe than, liberal thresholds.

Adverse effects of RBC transfusion were also evaluated, including infection, transfusion reaction and immunomodulation. These adverse effects could impact patient morbidity and mortality.

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Sepsis/�Critically III

The care of the patient with sepsis underwent a revolution with early goal-directed therapy (EGDT) in 2001, in which blood transfusion was a central component of the protocol.

The Surviving Sepsis Guidelines advised transfusion to Hgb of 10 g/dL or Hct of 30% during the first 6 hours if hypoperfusion persisted despite fluids and vasopressor support.

However, this threshold and ready transfusion in sepsis bundles was questioned because of the weak observational evidence.

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Study case :

The Transfusion Requirements in Septic Shock (TRISS) trial enrolled approximately 1000 patients with septic shock and Hgb ≤9 g/dL who underwent randomization to 2 groups: 1 with a threshold 7g/dL and 1 with 9g/dL. If patients met the threshold, 1 unit leucoreduced RBCs was transfused.

Result : The primary outcome of death by 90 days did not differ between 2 groups and neither did the use of life support, mechanical ventilation, vasopressor support, or renal replacement therapy.

Conclusion : Avoiding unnecessary transfusions reduced the need for an expensive resource and reduced the risk of worsening infection or immune reaction.

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Gastrointestinal �Bleeding

The studies evaluating transfusion threshold in patients with GI bleeding provide important information, because investigations were performed in patients with active hemorrhage.

Study case 1:

The pre-eminent study by Villanueva et al. was a trial of adults with hematemesis or melena randomized to restrictive strategy (7g/dL vs. 9g/dL). This trial excluded patients with minor bleeding or massive bleeding and patients with concern for acute coronary syndrome (ACS). All patients underwent endoscopy ≤6 hours after presentation.

Result : Patients in the restrictive group had lover mortality rates compared to the liberal group. The rate of bleeding was also lower in the restrictive group and fewer products transfused.

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Study case 2:

This study was conducted in the UK enrolled patients ≥18 years of age who had upper GI bleeding, randomizing patients to restrictive (8g/dL) and liberal (10g/dL) thresholds, with no difference in clinical outcomes. These findings in randomized trial are supported by a meta-analysis evaluating studies with restrictive vs. liberal transfusions for upper GI bleeding.

Result : The meta-analysis found restrictive transfusion groups had decreased death, shorter hospitalization and a significantly smaller amount of blood transfused.

Why do transfusion potentially worsen outcomes in GI bleeding?

It is hypothesized that transfusions counteract the splanchnic vasoconstriction caused in hypovolemia, increasing pressure in the splanchnic circulation and impairing clot formation. Transfusion may also alter coagulation properties.

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The concept of hemostatic resuscitation is paramount in these patients, with a restrictive transfusion strategy decreasing the number of transfusions and perhaps lowering mortality.

Restrictive transfusion in the setting of GI bleeding is recommended, with a transfusion threshold of 7g/dL. Higher mortality, rebleeding, the need for intervention, and more frequent cardiac and pulmonary adverse effects are suggested by a meta-analysis in 2013.

Of note, these investigations of patients with GI bleeding are some of the only studies conducted in active bleeding, suggesting a transfusion threshold of 7 g/dL in active hemorrhage in patients with no symptoms of anemia with hemodynamic stability.

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Acute Myocardial �Ischemia

Transfusion in patients with myocardial ischemia, whether unstable angina, non-ST elevation myocardial infarction, or ST elevation myocardial infarction is a gray area, with much less investigation as compared to other conditions.

Myocardial oxygen demands are high in the setting of ischemia, and during anemic states, oxygen delivery increases through stroke volume and heart rate, potentially worsening ischemia. On the other hand, circulatory overload and increased thrombogenicity may worsen with product transfusion.

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Study Case :

The AABB currently does not identify a transfusion threshold in this population. Two small randomized trials with 155 patients compared transfusion triggers in patients with acute myocardial ischemia.

Result : One of these found increased congestive heart failure in patients transfused, but the other trial (with 110 patients) found rates of unscheduled revascularization within 30 days, death, or myocardial infarction of 10.9% in the liberal group and 25.5% in the restrictive group. The authors suggested that a liberal transfusion strategy is associated with decreased cardiac events and death.

Unfortunately, the AABB does not make recommendations for this population. The meta-analysis provides the best data, with suggestions of risk with transfusion. Additional trials are needed in this population, but a restrictive threshold of 7g/dL is likely safe if the patient is hemodynamically stable.

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Trauma

Most physicians would agree that transfusion is required in the setting of acute, life-threatening trauma with massive hemorrhage.

In fact, Hgb levels in active hemorrhage fail to accurately predict the actual RBC mass present, and anemia is often only discovered when non-RBC fluid replacement is provided.

In major trauma victims not undergoing massive transfusion, RBC transfusion has been associated with increased mortality, lung injury, infection rates, multiple organ failure, and renal injury.

One trial has evaluated restrictive transfusion strategy for trauma patients using data from the Transfusion Requirements in Critical Care (TRICC) trial. Investigators used a threshold of 7 g/dL (restrictive) and 10 g/dL (liberal). Patients included critically ill trauma patients with Hgb <9g/dL, and investigators found that mortality, multiple organ dysfunction, and duration of stay were similar between the 2 groups.

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At this time, resuscitation of the trauma patient with hemorrhage should be performed based on clinical status and not laboratory values.

If the patient is in hemorrhagic shock, with acute hemorrhage and hemodynamic instability, transfusion is warranted.

In acute trauma, a specific transfusion threshold is not warranted as a trigger for transfusion. Once the patient is hemodynamically stable, transfusion should be considered in the setting of anemic symptoms (e.g., chest pain, shortness of breath, or poor distal perfusion), with 1 unit of RBCs given at 1 time.

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Conclusion

RBC transfusions have been used for many years for the treatment of anemia. Increased morbidity and mortality has been found with anemia in the setting of critical illness, trauma, surgery, and older age. The transfusion threshold of 10 g/dL has recently been questioned, and RBC transfusion is not without risks, which include transfusion reaction, infection, and potentially increased mortality.

The AABB currently recommends a transfusion threshold of Hgb 7 g/dL. This evidence-based review evaluated the current literature of RBC transfusion impact on physiology, transfusion reactions, RBC product age, and transfusion thresholds.

Studies evaluating transfusion are, for the most part, small in sample size, retrospective, and observational in nature, affecting their applicability.

The majority of investigations have also been completed in critical care settings. Age of products transfused likely has no effect on products before 21 days of storage, but additional study is required.

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A Hgb level of 7 g/dL is safe in patients with critical illnesses, sepsis, gastrointestinal bleeding, and trauma.

However, the provider at the bedside should evaluate the patient for symptoms associated with anemia and transfuse based on the risks and benefits.

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Discussions

Statistics

Our Services

Problems We Encountered

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TOTAL NUMBER OF TEST DONE IN CTD (2022)

Requisition For	JAN	FEB	MAR	APR	MAY	JUN	JUL	AUG	SEP	OCT	NOV	DEC	TOTAL
GROUPING, SCREEN AND HOLD	4317	3533	3812	3588	3953	4196	4195	4561	4324	4543	4432	4289	49743
CROSS MATCHING CONVERT	1111	985	1012	988	1106	1205	1172	1156	1191	1233	1168	1148	13475
CROSS MATCHING EMERGENCY	158	102	124	148	170	150	162	165	163	187	170	126	1825
CROSS MATCHING RED CELL	1195	1042	1206	1268	1152	1212	1292	1264	1237	1220	1284	1352	14724
ISSUE COMPONENT	536	494	462	505	448	522	512	600	546	595	563	609	6392

TOTAL : 86159

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