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Massive blood transfusion
References
Author: John R Hess, MD, MPH
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Section Editor: Arthur J Silvergleid, MD
Contributor
Disclosures
Deputy Editor: Jennifer S Tirnauer, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2022. | This topic last updated: Sep 09, 2021.
INTRODUCTION
Massive transfusion, historically defined as the replacement by transfusion of 10 units of red cells in 24 hours, is a treatment for massive and uncontrolled hemorrhage. It
identifies groups of patients across multiple medical specialties with significant failure of vascular integrity and is also a situation in the transfusion service where the
administrative constraints around issuing blood can delay patient care.
It is an arbitrary definition in that patients who use 9 units are not fundamentally different from those who use 10, whereas those who use 10 units over half an hour are very
different from those who use the same volume spaced over the course of a day. With more rapid and effective therapy, alternative definitions for catastrophic bleeding such as
three units of red blood cells over one hour or any four blood components in 30 minutes are more sensitive in identifying patients needing rapid issue of blood products for
the treatment of shock and prevention of death [1,2]. Such high volume and rapid transfusion episodes are associated with a number of hemostatic and metabolic
complications [3]. Effective massive transfusion involves the selection of the appropriate amounts and types of blood components to be administered and requires
consideration of a number of issues including volume status, tissue oxygenation, management of bleeding and coagulation abnormalities, as well as changes in ionized
calcium, potassium, and acid-base balance.
An overview of the Advanced Trauma Life Support approach to massive transfusion with crystalloid fluids and packed red cells is presented here [4,5], as is the "damage
control" approach using red cells and plasma in a 1:1 ratio [6]. Other issues related to the use of blood products are discussed separately. (See "Use of blood products in the
critically ill" and "Indications and hemoglobin thresholds for red blood cell transfusion in the adult" and "Practical aspects of red blood cell transfusion in adults: Storage,
processing, modifications, and infusion" and "Initial management of NON-hemorrhagic shock in adult trauma".)
EPIDEMIOLOGY
In a review of all 97,000 episodes of transfusion of 10 or more red blood cell (RBC) units in consecutive 2-day periods over a 25-year period in two countries (Sweden,
population 10 million, and Denmark, population 5 million), the most common clinical situation leading to massive transfusion was cardiac surgery [7]. Other situations leading
to massive transfusion, such as gastrointestinal hemorrhage, ruptured abdominal aortic aneurism, liver transplant, trauma, and obstetric catastrophes, were less frequent.
In a second study involving 1300 episodes of transfusion of 20 units of RBCs in consecutive two-day periods in four countries, bleeding occurred for similar reasons [8].
Bleeding rates appeared to be increased, as might be expected in tertiary care centers.
Trauma is the most studied example from among indications for massive transfusion.
●
In a review of experience in a major trauma center during the year 2000, 8 percent of all admitted patients received RBC transfusions, 3 percent received more than 10
units of RBCs during their admission, and 1.7 percent received 10 units in the first 24 hours [9].
●
A subsequent National Institutes of Health (NIH)-sponsored collaboration of trauma centers studying the cytokine response to injury reported that the fraction of all
patients receiving RBC transfusions who receive 10 or more units of RBCs has decreased by 40 percent, coinciding with the practice of earlier transfusion of plasma and
platelet units [10].
Taken together, these data suggest that most injured patients never need massive transfusion and can be treated based on physical assessment and laboratory tests; however,
approximately 3 percent of the most severely injured individuals will require more prompt treatment of bleeding, with attention to coagulopathy; this in turn reduces total
blood use in some of them.
Appropriate care requires knowing both "classic" and "hemorrhage-control" forms of resuscitation and when to use them. (See "Initial management of NON-hemorrhagic
shock in adult trauma".)
BLOOD AND VOLUME REPLACEMENT
The management of the patient who is being rapidly and massively transfused requires careful and ongoing consideration of a number of complex physiological relationships.
The primary concerns are maintaining cardiac output, oxygen carrying capacity, and hemostatic potential. This requires an understanding of both the progression of needs in
successively more "blood deficient" patients and of the composition of blood components.
Correction of a deficit in blood volume with crystalloid volume expanders works well for most mildly and moderately ill or injured patients. Volumes up to 30 liters of crystalloid
fluid can be life lifesaving in adults, but correction of the fluid deficit with crystalloid solutions occurs at the expense of increasingly severe tissue swelling, with stiff lungs and
abdominal compartment syndrome ultimately being limiting. Along the way, blood dilution becomes an increasing problem and requires treatment with RBCs (oxygen
carrying), plasma (osmotic and clotting proteins), and platelets. Attempts to treat dilutional coagulopathy once it is established run into the problem that, other than RBCs,
blood components themselves are already dilute or do not deliver high concentrations of blood cells and plasma proteins efficiently.
Packed RBCs (pRBCs) in additive solution typically have a hematocrit of approximately 60 percent, with the remainder of the volume consisting of 10 percent plasma and 30
percent saline-based anticoagulant and nutrient additive solutions. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and
infusion", section on 'Anticoagulant-preservative (A-P) solutions'.)
Therefore, the fluid portion of pRBCs is 25 percent plasma, with the concentration of all of the plasma coagulation factors at 25 percent of normal (0.25 units/mL). The
prothrombin time (PT) International Normalized Ratio (INR) of a unit of RBCs is typically 2.5 but may be unmeasurable because the fibrinogen content can be at concentrations
too low for accurate testing. pRBCs typically contain citrate anticoagulant (1 millimole) and have a supernatant potassium concentration of 1 mEq/L on the day of manufacture,
which increases by 1 mEq for each day of storage due to potassium leakage from the RBCs. The 160 to 220 mL of RBC in a typical unit of RBCs raise the recipient hematocrit by
approximately 3 percent and the hemoglobin concentration by approximately 1 g/dL.
Fresh Frozen Plasma (FFP) and other forms of plasma derived from whole blood or apheresis are typically 80 percent plasma and 20 percent anticoagulant. The typical 250 mL
unit delivers 200 units of each coagulation factor and 600 mg of fibrinogen at an INR of 1.1. It contains 7 mEq of citrate and has a potassium concentration of 4 mEq/L.
Whole blood-derived platelet concentrates (a pool of six being a standard adult dose) have been largely replaced by apheresis platelets, which are stored in plasma, or in onethird plasma and two-thirds platelet additive solution (saline based). Apheresis platelets typically have a volume of approximately 300 mL and contain >300 billion platelets with
a volume <3 mL. The remainder of the volume of the platelet unit is 80 percent plasma and 20 percent anticoagulant or it may be 26 percent plasma and 74 percent salinebased anticoagulant and additive solution. Apheresis platelet units contain six or two mEq of citrate and 4 or 2 mEq/L of potassium.
Cryoprecipitate is a concentrate of the cold-insoluble proteins of plasma, including fibrinogen, factor VIII, von Willebrand factor, and factor XIII, in a small volume (10 to 20 mL
per unit of Cryoprecipitate, obtained from one unit of plasma). A pool of five units of Cryoprecipitate contains approximately 1.5 g fibrinogen in a volume of 50 to 100 mL,
which consists of 80 percent plasma and 20 percent anticoagulant.
Whole blood, which is available in limited amounts in certain facilities, contains 160 to 240 mL of RBCs and approximately 100 billion platelets in approximately 270 to 350 mL
of 80 percent plasma and 20 percent anticoagulant, with 9 mEq of citrate. The extracellular potassium will increase during storage similarly to packed RBCs.
With knowledge of the contents and concentrations of the available blood products, it is possible to calculate and plot concentrations in administered combinations of such
products [11]. With the additional recognition that one-third of administered platelets end up in the spleen and that 30 percent of stored platelets do not circulate, one can
calculate the effects of the administration of blood products on in vivo circulating blood components.
RED BLOOD CELLS
At rest, oxygen delivery is normally four times oxygen consumption, indicating the presence of an enormous reserve. Thus, if intravascular volume is maintained during
bleeding and cardiovascular status is not impaired, oxygen delivery will theoretically be adequate until the hematocrit (packed cell volume) falls to 10 to 12 percent. This is
because adequate cardiac output plus increased oxygen extraction can compensate for the decrease in arterial oxygen content. However, increasing cardiac work to increase
output requires more oxygen, so the "critical point" where oxygen consumption becomes delivery dependent is generally higher.
The American Society of Anesthesiologists recommends that hemoglobin below 6 g/dL be avoided in healthy individuals, and notes that higher values are necessary in those
with active cardiovascular disease. In healthy medical student volunteers acutely cytapheresed to hemoglobin concentrations of 5.3 g/dL, equivalent to a hematocrit of 16
percent, correct answers to digit-symbol reversal questions and the strength of retinal-evoked potentials were reduced but promptly improved with return of their own fresh or
stored RBCs [12,13]. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Rationale for transfusion'.)
Oxygen release by transfused stored red blood cells (RBCs) is stated to be diminished compared with control RBCs that have not been processed and stored. Storage reduces
2,3-bisphosphoglycerate (2,3-BPG) levels, leading to a leftward shift of the lower end of the oxyhemoglobin dissociation curve (2,3-BPG binds to deoxyhemoglobin). This
abnormality, however, has not been shown to be clinically important, as the transfused RBCs regenerate 2,3-BPG to normal levels within 6 to 24 hours after transfusion, and
most oxygen delivery occurs from the unaffected upper end of the oxygen binding curve. In a trial in children with severe malarial anemia, stored RBCs corrected acidosis to
the same degree as freshly collected RBCs [14]. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on
'Changes during in vitro storage'.)
The above considerations, however, represent the optimal clinical response to massive RBC loss with adequate volume replacement. An approach to the use of plasma and RBC
transfusions in adults with hemorrhagic shock is presented below and separately. (See 'Trauma' below and "Initial management of moderate to severe hemorrhage in the adult
trauma patient".)
ALTERATIONS IN HEMOSTASIS
A patient being massively transfused may have coagulopathy because of activation and consumption of coagulation factors secondary to tissue trauma, such as massive head
injury or muscle damage, or they may have reduced activity of coagulation factors secondary to prolonged shock, hypoxia-induced acidosis, hypothermia, or failure to clear
activation peptides that act as competitive inhibitors [15]. Such trauma-associated coagulopathy can be diagnosed as acute disseminated intravascular coagulation (acute DIC)
when there is microvascular oozing, prolongation of the prothrombin time (PT) and activated thromboplastin time (aPTT) in excess of that expected by dilution, significant
thrombocytopenia, low fibrinogen levels, and increased levels of D-dimer. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section
on 'Acute DIC'.)
Even if coagulopathy diagnostic of acute DIC does not exist and coagulation parameters are normal before blood is replaced, coagulation abnormalities may be induced by the
dilutional effects of blood replacement on coagulation proteins and the platelet count [16-18]. This occurs because packed red blood cell (pRBC) transfusions are essentially
devoid of plasma and platelets, which are removed after collection in the blood component manufacturing process. (See 'Blood and volume replacement' above.)
Many patients with massive trauma present to a trauma center with a coagulopathy of trauma that does not meet the diagnostic criteria for acute DIC or dilutional
coagulopathy. This coagulopathy is caused by widespread tissue injury/trauma, shock, and the associated physiologic changes (acidosis, hypothermia, consumption of
coagulant proteins, and fibrinolysis), combined with extensive blood loss and the dilutional effects of physiologic vascular refill and fluid replacement therapy [19].
Effects of acidosis and hypothermia — Both acidosis and hypothermia interfere with the normal functioning of the coagulation system. As examples:
●
Acidosis (excess protons) specifically interferes with the assembly of coagulation factor complexes involving calcium and negatively charged phospholipids (clustered as
"rafts" on the surfaces of platelets, cells expressing tissue factor, and damaged endothelial cells). As a result, the activity of the factor Xa/Va prothrombinase complex at a
pH of 7.2, 7.0, and 6.8 is reduced by 50, 70, and 80 percent, respectively [20]. The resulting delayed production and reduced concentrations of generated thrombin lead to
delayed fibrin production, altered fibrin structure, and increased susceptibility to fibrinolysis [21]. The interaction of acidosis with coagulopathy to increased trauma
mortality has been widely recognized. (See "Coagulopathy in trauma patients", section on 'Acidosis'.)
●
Hypothermia reduces the enzymatic activity of plasma coagulation proteins, but it has a greater effect by preventing the activation of platelets via traction on the
glycoprotein Ib/IX/V complex by von Willebrand factor [22]. In tests of shear-dependent platelet activation, this pathway stops functioning at 30°C in half of individuals
and is markedly diminished in most of the rest. This profound effect on platelet-mediated primary hemostasis means that massive bleeding in conjunction with a core
temperature of <30°C was rarely survived in the past [23]. The onset of this effect is seen at core temperatures of 34°C and below.
Coagulation proteins — The replacement of blood loss with pRBCs and a crystalloid volume expander will result in gradual dilution of plasma clotting proteins, leading to
prolongation of the PT and aPTT. In an adult, there will be an approximate 10 percent decrease in the concentration of clotting proteins for each 500 mL of blood loss that is
replaced. Additional bleeding based solely on dilution can occur when the level of individual coagulation proteins falls to 25 percent of normal. This usually requires 6 to 10
units of red cells in an adult.
Thus, the PT, aPTT, and fibrinogen or a viscoelastic test of coagulation (also called point of care testing) (
table 1) should be monitored in patients receiving massive blood
transfusions of this magnitude. (See "Clinical use of coagulation tests", section on 'Evaluation of abnormal results' and "Clinical use of coagulation tests", section on 'Point-ofcare testing'.)
Two to eight units of fresh frozen plasma (FFP) should be given if the values exceed 1.5 times control. Each unit of FFP might be expected to increase the clotting protein levels
by 6 percent in an adult, but because of losses in product preparation, storage, and of transfused factors to the interstitial space, typical increments are of the order of 2.5
percent [24]. Cryoprecipitate or, when available, virus-inactivated fibrinogen concentrate, may be used when fibrinogen levels are critically low (ie, <100 mg/dL) [4]. (See
"Clinical use of plasma components" and "Disorders of fibrinogen", section on 'Cryoprecipitate and Fresh Frozen Plasma (FFP): Dosing and monitoring' and "Disorders of
fibrinogen", section on 'Fibrinogen concentrate: Dosing and monitoring'.)
Platelet count — A similar dilutional effect on the platelet concentration can be seen with massive transfusion [25]. In an adult, each 10 to 12 units of transfused RBCs are
associated with a 50 percent fall in the platelet count; thus, significant thrombocytopenia can be seen after 10 to 20 units of blood, with platelet counts below 50,000/microL.
For replacement therapy in this setting, six units of whole blood derived platelets or one apheresis concentrate should be given to an adult; each unit should increase the
platelet count by 5000/microL or 30,000/microL for a full six unit adult dose. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Massive blood
loss'.)
MONITORING RECOMMENDATIONS
In the massively transfused patient, assumptions about possible dilutional effects of RBC transfusion should be confirmed by measurement of the PT, aPTT, and platelet count
or a viscoelastic test after the administration of every five to seven units of red cells. Replacement therapy should be based on these parameters rather than on any formula
(eg, one unit of fresh frozen plasma (FFP) for every four units of red cells), except in patients with severe trauma and possibly obstetric hemorrhage. (See 'Obstetric
hemorrhage' below.)
PATIENT POPULATIONS
Trauma — While replacement therapy with plasma, platelets, and red blood cells should not generally be based upon any set formula, results from a number of observational
studies suggest that in patients with severe trauma and coagulopathy requiring massive blood replacement, survival is improved when the ratio of transfused Fresh Frozen
Plasma (FFP; in units) to platelets (in units) to red blood cells (RBCs; in units) approaches 1:1:1 (ie, the "damage control" approach) [26-33]. (See "Platelet transfusion:
Indications, ordering, and associated risks", section on 'Massive blood loss' and "Initial management of moderate to severe hemorrhage in the adult trauma patient".)
The physiology supporting the 1:1:1 (FFP:platelets:RBCs) approach derives from the existence of the acute coagulopathy of trauma and the dilute nature of conventional blood
products. Patients who present with uncontrolled hemorrhage and shock have typically lost 30 to 40 percent of their blood volume. Conventional resuscitation with crystalloid
will rapidly lead to greater than 50 percent dilution of coagulation factors and a diminution of thrombin generation. Resuscitation with FFP, platelets, and RBCs at 1:1:1 unit
ratios means that the actual blood being given has a coagulation factor concentration of 65 percent of normal, a platelet count of 88 x 109/L, and a hematocrit of 29 percent.
Because 30 percent of the platelets and 10 percent of the RBC administered will not circulate, the effective concentrations are a plasma coagulation factor concentration of 65
percent, platelet count of 55 x 109/L, and a hematocrit of 26 percent. Thus, giving blood products, and nothing but blood products, barely keeps levels above conventional
transfusion triggers. More of any one product merely dilutes the other two, such that giving two units of RBC for every unit of plasma and platelets (1:1:2) leads to a plasma
coagulation factor concentration of 52 percent, platelet count of 55 x 109/L, and hematocrit of 40 percent; and, after storage related losses, a plasma coagulation factor
concentration of 52 percent, platelet count of 37 x 109/L, and hematocrit of 36 percent [34]. Any crystalloid solution administered will further dilute all three blood components.
Clinical studies that have shown a benefit for the 1:1:1 approach in massively injured and rapidly bleeding patients include:
●
A trial that randomly assigned 680 patients with major bleeding from severe trauma to receive transfusion of 1 versus 2 units of RBC for every unit of FFP and platelets (ie,
FFP to platelets to RBC of 1:1:1 versus 1:1:2) found slightly better outcomes with the 1:1:1 approach [35]. Patients assigned to 1:1:1 were more likely to have adequate
hemostasis (86 versus 78 percent) and had fewer exsanguination deaths at 24 hours (9 versus 15 percent). Overall mortality at 1 and 30 days were not different between
the groups, although there was a trend favoring 1:1:1 at both time points. Adverse events were also similar between the groups.
●
A retrospective study of 246 patients who presented to an Army combat support hospital in Iraq has produced some data to evaluate the merits of this regimen [26].
When patients who received massive transfusion were stratified by transfusion therapy regimen, patients who received a high ratio of FFP to RBCs (median of 1:1.4) had a
survival rate of 81 percent, compared with 66 percent for those with an intermediate ratio (median 1:2.5) and 35 percent for those who received a low ratio of FFP to RBCs
(median of 1:8).
●
In a retrospective study of 467 massively transfused trauma patients, 30-day survival was increased in patients transfused at a high FFP:RBC ratio (ie, ≥1:2) as well as in
those transfused at a high platelet:RBC ratio (ie, ≥1:2) [27]. The combination of high FFP and high platelet to RBC ratios was associated with decreased truncal
hemorrhage and increased six-hour, 24-hour, and 30-day survivals, with no change in deaths due to multiple organ failure.
●
In a retrospective study of 694 massively transfused trauma patients who did not receive fresh whole blood, those receiving a high ratio of apheresis platelets (equivalent
to six units of pooled platelets) per stored RBC unit (ie, ratio ≥1:8) had a higher 24-hour survival (95 percent) compared with those receiving a medium (ie, ratio 1:16 to 1:8,
87 percent) or a low ratio (ie, <1:16, 64 percent) [32]. On multivariate analysis, higher FFP:RBC ratios and higher apheresis platelets:RBC ratios were both independently
associated with improved survival at both 24 hours and 30 days.
Such observations have led these and other authors to recommend that patients who have sustained severe traumatic injuries and/or who are likely to require massive
transfusion receive a 1:1:1 ratio of FFP to platelets to RBCs at the outset of their resuscitation and transfusion therapy [26-33]. Additional aspects of transfusion and other
interventions for trauma management are discussed in detail separately. (See "Initial management of moderate to severe hemorrhage in the adult trauma patient".)
For the subset of patients who present with widespread tissue trauma (as in combat injuries) and who present with coagulopathy or the high likelihood of coagulopathy, an
approach using plasma as the primary resuscitation fluid has been advocated by the United States military. The treatment of such patients is discussed in depth separately.
Early administration of plasma during helicopter transport is associated with a 10 percent improvement in survival [36]. (See "Coagulopathy in trauma patients", section on
'Treatment'.)
Cardiac surgery — Cardiac surgery is the most common cause of massive transfusion. In a subset analysis of a large randomized controlled trial of complex cardiac surgeries
requiring repeat midline sternotomy, patients receiving transfusion of more than 5 units of RBCs had a threefold excess mortality if they did not also receive 5 units of plasma
[37].
Obstetric hemorrhage — Gravid and parturient women are hypercoagulable with compensatory hyperfibrinolysis. When vascular disruption leads to massive bleeding, those
with low fibrinogen are at increased risk for bleeding [38]. Additional management recommendations related to these changes are presented separately. (See "Disseminated
intravascular coagulation (DIC) during pregnancy: Clinical findings, etiology, and diagnosis" and "Placental abruption: Management and long-term prognosis".)
Liver disease — Liver disease not only leads to the reduced production of normal coagulation factors, but to the production of abnormal factors such as dysfunctional vitamin
K-dependent factors and dysfunctional fibrinogens and the failure to clear activation fragments of coagulation factors, which can act as competitive inhibitors of coagulation
enzymes by occupying binding sites [39]. The presence of such inhibitors of coagulation can reduce the effectiveness of conventional treatment. (See "Hemostatic
abnormalities in patients with liver disease".)
COMPLICATIONS OF MASSIVE TRANSFUSION
Citrate infusion — Large amounts of citrate are given with massive blood transfusion, since blood is anticoagulated with sodium citrate and citric acid [40]. Metabolic alkalosis
and a decline in the plasma free calcium concentration are the two potential complications of citrate infusion and accumulation.
Metabolic alkalosis — The pH of a unit of blood at the time of collection is 7.10 when measured at 37°C due to citric acid and phosphate present in the
anticoagulant/preservative in the collection bag. The pH then falls 0.1 pH unit/week due to the production of lactic and pyruvic acids by the red cells. Acidosis does not develop
in a massively bleeding patient even if "acidic" blood is infused as long as tissue perfusion is restored and maintained. In this setting, the metabolism of each mmol of citrate
generates 3 mEq of bicarbonate (for a total of 23 mEq of bicarbonate in each unit of blood). As a result, metabolic alkalosis can occur if the renal ischemia or underlying renal
disease prevents the excess bicarbonate from being excreted in the urine. This may be accompanied by hypokalemia as potassium moves into cells in exchange for hydrogen
ions that move out of the cells to minimize the degree of extracellular alkalosis [41,42]. (See "Potassium balance in acid-base disorders".)
Low ionized calcium level — Citrate binding of ionized calcium can lead to a clinically significant fall in the plasma free calcium (ionized calcium) concentration. (See "Relation
between total and ionized serum calcium concentrations".) This change can lead to paresthesias and/or cardiac arrhythmias in some patients [43]. (See "Clinical manifestations
of hypocalcemia", section on 'Acute manifestations'.)
Recommendations for calcium infusion — By extrapolation from animal studies, it is possible to calculate the maximum transfusion rate that would permit a normal liver to
metabolize excess citrate, thereby avoiding hypocalcemia. The maximum citrate infusion rate should be 0.02 mmol/kg per minute (since this represents the maximum rate of
citrate metabolism) and the citrate concentration in whole blood is 15 mmol/L (0.015 mmol/mL). Thus:
Maximum citrate infusion rate (mmol/kg per min)
= (mmol citrate per mL of blood x mL of blood infused per min) ÷ wt (kg)
mL of blood infused per min = (0.02 ÷ 0.015) x wt (kg) = 1.33 x wt (kg)
For a 50 kg recipient with normal hepatic function and perfusion, the maximum rate of blood transfusion to avoid citrate toxicity is 66.5 mL/min, which is equal to 8.9 units of
whole blood per hour (450 mL per unit) and 26.7 units of red cells per hour (approximately 150 mL per unit). Thus, significant hypocalcemia should not develop in this setting
except under extreme circumstances. However, the risk is substantially greater in a patient with either preexisting liver disease or ischemia-induced hepatic dysfunction. In
such patients, the plasma ionized calcium concentration should be monitored and calcium replaced with either calcium chloride or calcium gluconate if ionized hypocalcemia
develops:
●
If 10 percent calcium gluconate is used, 10 to 20 mL should be given intravenously (into another vein) for each 500 mL of blood infused.
●
If 10 percent calcium chloride is used, only 2 to 5 mL per 500 mL of blood should be given.
Calcium chloride may be preferable to calcium gluconate in the presence of abnormal liver function, since calcium chloride does not require normal liver function to release
ionized calcium [4]. In contrast, calcium gluconate metabolism is decreased in the setting of abnormal liver function, resulting in a slower release of ionized calcium.
Care must be taken to avoid administering too much calcium and inducing hypercalcemia, ideally by monitoring the ionized calcium concentration.
PREVENTION OF HYPOTHERMIA
A high capacity commercial blood warmer should be used to warm blood components toward body temperature when more than three units are transfused.
Rapid transfusion of multiple units of chilled blood may reduce the core temperature abruptly and can lead to cardiac arrhythmias [44]. Six units of RBCs at 4°C will reduce the
body temperature of a 70 kg adult by 1°C. This heat loss can be additive with the evaporative heat loss associated with an open abdomen or other body cavity which, by itself,
can lead to a 1°C decrease in core temperature in 40 minutes. Thus, 10 units of cold blood products and an hour of surgery can lead to a 3°C drop in core temperature and
hypothermic coagulopathy.
PREVENTION OF HYPERKALEMIA
Infants and patients with renal impairment may develop hyperkalemia because of potassium leakage due to prolonged blood storage or irradiation [44]. (See "Practical aspects
of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Hyperkalemia'.)
In storage, the supernatant of RBCs increases in [K+] by 1 mEq/day, increasing from approximately 3 mEq/L at the time of donation to 45 mEq/L during 42 days of storage.
Irradiation can increase this rate to 1.5 mEq/day. Nevertheless, because the volume of suspending solution in a unit of red cells in additive solution is small (150 mL), the actual
amount of free K+ infused with a unit of RBC is only approximately 7 mEq, and this is rapidly pumped back into the transfused cells as they warm. As a result, potassium is only
a problem when long-stored red cells are infused directly into the central circulation at high concentrations, as occurs with blood-primed cardiopulmonary bypass machines,
high volume transfusion devices, or infants transfused through umbilical catheters.
In these patients, the following steps can be used to minimize the risk of hyperkalemia:
●
Select only red cells collected less than 10 days prior to transfusion.
●
Any unit of red cells can be washed immediately before infusion to remove extracellular potassium.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Transfusion
and patient blood management".)
SUMMARY AND RECOMMENDATIONS
●
The management of the patient who is being massively transfused requires careful and ongoing consideration of a number of complex physiological relationships. The
primary concerns are maintaining cardiac output, oxygen carrying capacity, and hemostatic potential. There is no clear threshold for hematocrit, platelet count, or
coagulation factor deficiency below which blood use is futile. (See 'Blood and volume replacement' above and "Initial management of moderate to severe hemorrhage in
the adult trauma patient".)
●
As volume is replaced, attention must be paid to coagulation parameters, platelet count, and metabolic status. (See 'Alterations in hemostasis' above and 'Complications
of massive transfusion' above.)
●
The coagulation system should be frequently monitored with measurements of the PT, aPTT, fibrinogen concentration, and platelet count or a viscoelastic measure (also
called point of care testing) (
table 1), preferably after each five units of blood replaced. If the PT and aPTT exceed 1.5 times the control value, the patient should be
transfused with at least two units of fresh frozen plasma. If the platelet count falls below 50,000/microL, six units of random donor platelets, or one unit of apheresis
platelets, should be given. (See 'Alterations in hemostasis' above and "Clinical use of coagulation tests", section on 'Evaluation of abnormal results' and "Clinical use of
coagulation tests", section on 'Point-of-care testing'.)
●
The best approach to blood transfusion in trauma is unknown. Transfusions are given based upon the patient's injuries and response to the initial transfusions, with
attention being paid to any underlying cardiopulmonary disease. In some cases where there is insufficient time to obtain laboratory values to guide transfusion, it may be
necessary to use the “damage control” approach of transfusing red blood cells, platelets, and plasma in a set ratio. (See 'Trauma' above.)
For the subset of patients who present with widespread tissue trauma (as in combat injuries) and who present with coagulopathy or the high likelihood of coagulopathy,
an approach using plasma or whole blood as the primary resuscitation fluid has been advocated by the most experts. The treatment of such patients is discussed in depth
separately. (See "Coagulopathy in trauma patients", section on 'Treatment'.)
●
Management of massive transfusion in other special scenarios (eg, obstetric hemorrhage, liver disease) is discussed separately. (See "Hemostatic abnormalities in
patients with liver disease" and "Placental abruption: Management and long-term prognosis".)
●
A blood warmer should be used whenever more than three units are transfused. Hypothermia should be either avoided or minimized. (See 'Prevention of hypothermia'
above.)
●
Acid-base balance and the plasma ionized calcium and potassium levels should be periodically monitored, particularly in patients with coexistent liver or renal disease or
in those with massive hemorrhage and low cardiac output [42]. (See 'Complications of massive transfusion' above and 'Prevention of hyperkalemia' above.)
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Topic 7931 Version 32.0
GRAPHICS
Various types of thromboelastograms
Native TEG
Measures clot formation in the absence of a specific activator in either untreated whole blood or in citrated whole blood after recalcification.
Rapid-TEG
(rTEG)
Tissue factor is used as the activator inducing clot formation via the extrinsic pathway. Compared with native TEG, rTEG gives a readout of clot characteristics within about 10 minutes. The
corresponding RoTEM test is the EXTEM.
Kaolin-TEG
Phospholipid and kaolin are used to induce activation via the intrinsic pathway. The corresponding RoTEM test is the INTEM, which uses phospholipid and ellagic acid as activators.
Heparinase
treatment
Simultaneous measurements can be performed comparing heparinase-treated blood with untreated blood to identify the effects of endogenous heparan sulfates, exogenous heparin, and
heparinoids. The corresponding RoTEM assay is the HEPTEM.
Platelet
mapping
Platelet mapping assesses platelet function via the cyclooxygenase and ADP/P2 signaling pathways. The decrement in MA can be measured in the presence of platelet antagonists such as
acetylsalicylic acid, dipyridamole, and clopidogrel and compared with the untreated MA.
Fibrin function
testing
The RoTEM FIBTEM test activates the extrinsic pathway in the presence of cytochalasin D, which is a cytoskeletal inhibitor of platelet activity. This test qualitatively assesses fibrinogen levels since
the clot formation in this test is attributable to fibrin polymerization alone.
TEG: thromboelastogram; ADP/P2: adenosine diphosphate/P2 receptor; MA: maximal amplitude.
Graphic 55087 Version 3.0
Contributor Disclosures
John R Hess, MD, MPH Equity Ownership/Stock Options: Medcura [Hemorrhage control agent, inventor, stock holder, and options holder]. Patent Holder: US Army; University of Maryland [Four patents regarding
methods and formulations for red blood cell storage]; Medcura [Hemorrhage control agent, holder of two US patents]. Consultant/Advisory Boards: Hemerus Medical, LLC [Consultant]. All of the relevant financial
relationships listed have been mitigated. Arthur J Silvergleid, MD No relevant financial relationship(s) with ineligible companies to disclose. Jennifer S Tirnauer, MD No relevant financial relationship(s) with ineligible
companies to disclose.
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