Blood and Transfusion
Michael W. Cripps
Mitchell J. Cohen
Robert C. Mackersie
I. Introduction
The transfusion of blood and blood products is a key component in reversal of hemorrhagic shock. Blood product transfusions expand volume, improve oxygen carrying capacity, and restore coagulation homeostasis. While it is clear that blood product transfusion saves lives and reduces morbidity, they have associated risks. This chapter will focus on the transfusion management of severely injured trauma patients.
II. Epidemiology
Approximately 30 million units of blood are transfused every year in the United States, with 10% to 15% of all RBC units used to treat injured patients. Twenty five percent of trauma patients admitted receive at least a unit of packed red blood cells (pRBCs) and of those, 25% receive a massive transfusion (defined below); this latter group is the most severely injured (and therefore largest potentially preventable mortality) with a death rate of 40% to 70%.
Hemorrhage remains a leading cause of preventable death in trauma patients, with approximately 16% of preventable deaths attributed to truncal hemorrhage. Hemorrhage as the cause of death usually occurs within the first 6 hours of admission.
It is the failure to control hemorrhage that underlies the cause of many of these possibly preventable deaths. This failure is typically related to either an inability to rapidly control “surgical” hemorrhage (bleeding requiring suture/staple/ligation), or persistent “non-surgical” hemorrhage (bleeding normally expected to stop spontaneously), and an inability to reestablish relatively normal coagulation.
While exsanguination from massive (non-surgically repairable) injury is responsible for a large number of deaths, many patients with preventable mortality suffer from coagulopathy and bleeding. Up to one-third of all trauma patients who present to the hospital already have a coagulopathy.
Trauma patients are vulnerable to development of the so-called “bloody vicious cycle” or “Triad of Death,” which is comprised of coagulopathy, hypothermia, and acidosis. Each of these variables worsens the other and if not reversed, will lead to death.
Historically, the coagulopathy seen in trauma was thought to be solely the result of dilution and loss of coagulation factors following large volume resuscitation with crystalloids or unbalanced blood component transfusions (dilutional coagulopathy). More recently, a coagulopathy that develops in severe injury through an impairment of hemostasis and activation of fibrinolysis that occurs independent of the development of acidosis, hypothermia, or hemodilution has been described. It has been referred to by many terms including the “Early Trauma Induced Coagulopathy,” “Trauma Associated Coagulopathy,” and as the “Acute Traumatic Coagulopathy.” For the purposes of this chapter, we will refer to this coagulopathy as the acute traumatic coagulopathy (ATC).
Observations from recent armed conflicts refined the concept of hemostatic resuscitation (see later). This includes limiting the early administration of crystalloid fluids, advocating the use of tourniquets and hemostatic agents for direct bleeding control, and resuscitation goals directed toward the preservation
of physiologic and coagulation homeostasis rather than restoring normal or supranormal vital signs.
Conventional resuscitation involves the use of large volumes of isotonic crystalloid solutions to restore normal blood pressure, followed by pRBCs to increase oxygen carrying capacity with fresh frozen plasma (FFP) and platelets administered later to counteract the effects of hemodilution.
Hemostatic resuscitation aims to maintain intravascular volume, oxygen carrying capacity, and normal coagulation through the preemptive administration of blood and blood products that approximates ongoing losses. While the optimal ratios of pRBCs, FFP, and platelets are uncertain, a strategy of administering a ratio 1 unit of pRBCs to 1 unit of FFP to 1 unit of platelets (1:1:1 ratios) is common now when treating the severely injured.
III. Pathophysiology
Normal coagulation.
Normal coagulation following tissue injury involves subendothelial tissue factor exposure resulting in a series of protease activations (the coagulation cascade), thrombin production, thrombin burst, and the conversion of fibrinogen to fibrin which is crosslinked and combines with platelets to form a plug. These procoagulant actions are balanced by natural anticoagulants (activated protein C, TFPI, and antithrombin) and fibrinolysis which serve to break down clot when no longer needed and prevent an overly thrombogenic milieu. Hence normal coagulation is a balance between hemostatic and fibrinolytic processes, thereby allowing for tissue-specific clot formation in an injured area without resultant systemic thrombosis.
Coagulopathy
The inability to control major hemorrhage can be due to “non-surgical bleeding,” defined as bleeding that continues despite the surgical control of identifiable bleeding sources. This often manifests clinically as diffuse microvascular hemorrhage. The principal causes are hemodilution resulting from excessive crystalloid administration relative to the administration of blood and blood products (FFP, platelets), and a non-dilutional ATC.
Dilutional coagulopathy
Dilutional coagulopathy occurs with hemodilution resulting from the transfusion of large volumes of intravenous crystalloid and/or from an imbalance in blood component resuscitation. The dilutional loss of clotting factors and platelets limits the extent of the fibrin/platelet plug that can be formed at the site of injury. Transfusion solely with pRBCs, containing no platelets or clotting factors, further exacerbates the coagulopathy.
Acute traumatic coagulopathy (ATC)
Up to 33% of major trauma patients present initially with a coagulopathy that is neither disseminated intravascular coagulation (DIC) nor dilutional and is associated with major tissue injury and hypoperfusion (shock). Abnormal coagulation that occurs in this setting is often referred to as the ATC.
ATC is characterized by both impaired clot formation and enhanced fibrinolysis. Recent work suggests that activation of the protein C system is a primary cause of ATC.
Other causes of coagulopathy
The combination of hypothermia, acidosis, and coagulopathy left untreated is lethal. Each of these problems worsens the other.
Acidosis. Metabolic acidosis is usually related to inadequate tissue perfusion (shock) leading to an accumulation of lactate. This acidosis can be further exacerbated by administration of large volumes of normal saline which, as a consequence of the high chloride concentration in normal saline (154 mEq/L), can lead to a hyperchloremic acidosis. Acidosis inhibits thrombin and factors VIIa, Xa, and Va. Coagulation factor complex activity necessary for normal coagulation is disrupted by acidosis.
Hypothermia. Nearly two-thirds of trauma patients have a temperature of 36°C or below on presentation; 9% have a temperature ≤33°C. Acidosis and
hypothermia produce a synergistic effect with greater mortality. Hypothermia can be graded as mild (36 to 34°C), moderate (34 to 32°C), and severe (<32°C). The hypothermia of the injured patient is covered in Chapter 42.
Hypothermia directly affects the coagulation cascade by inhibiting tissue factor activity, platelet aggregation, platelet adhesion, and increasing the time it takes for thrombin formation. Enzymatic inhibition of the coagulation cascade generally begins at temperatures less than 33°C.
Measures to prevent hypothermia include the administration of warm fluids (crystalloid and blood products), use of blankets, warming devices, and increasing the ambient temperature.
The contribution of hypothermia alone to overall coagulation disorders is relatively small compared to ATC and dilutional coagulopathy.
Hypocalcemia. Calcium is a coagulation cofactor (Factor IV), required at several points in the coagulation cascade. pRBCs are preserved in citrate which binds calcium. While there are no definitive studies that show improved outcomes with reversal of hypocalcemia, intravenous calcium is often used in patients receiving massive transfusions.
DIC. DIC is a systemic process of consumptive coagulopathy in concert with diffuse microvascular thrombosis. In trauma patients, there are several mechanisms that can lead to DIC:
Tissue factor exposure is induced at the site of tissue injury which leads to activation of the coagulation cascade that in turn, leads to diffuse intravascular thrombin generation.
Systemic embolism of tissue-specific thromboplastins from sites of injury (including bone marrow lipid material, amniotic fluid, and brain phospholipids) can also lead to widespread generation of thrombin.
DIC is characterized by simultaneous systemic thrombosis and hemorrhage, and typically occurs in the setting of large amounts of tissue factor exposure in the blood in a short period of time. There may be some clinical overlap between DIC and ATC, but the latter occurs in the absence of the low platelet and fibrinogen levels typically seen in DIC.
IV. Laboratory Monitoring of Transfusion and Coagulation
The goal of laboratory studies is to provide an ongoing, timely evaluation of coagulation and oxygen carrying capacity. The currently available laboratory studies for transfusion initiation and monitoring includes:
Blood type, screening and cross matching. Send this early to prepare for transfusion. Seek cross matching when transfusion is likely.
Complete blood count (CBC). The CBC is used primarily for the hemoglobin concentration (to assess oxygen carrying capacity) and the platelet count.
Coagulation panel–-prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR). These tests are used to determine coagulation status.
PT. Used to assess the extrinsic pathway of coagulation (Factors I, II, V, VII, and X).
PTT. Functional measure of the intrinsic pathway of coagulation (VIII, IX, XI, and XII).
INR. The results of the PT may vary among institutions depending on the type of analytical system used. The INR was devised to standardize the results by utilizing an international sensitivity index (ISI) that is specific to each analytical system. The INR is calculated by (PTtest/PTnormal)ISI.
However, these tests are problematic in trauma patients for multiple reasons:
The coagulopathic state in trauma patients is in constant flux as they are continuously receiving large volumes of blood, plasma, and platelets.
The standard coagulation lab examinations take time to analyze, so the result reported does not necessarily reflect the patient’s coagulation state when the results are returned.
For the PT/PTT analysis, the patient’s blood sample is warmed to 37°C and mixed with platelet-poor plasma, which may not represent the true coagulation state in a hypothermic trauma patient.
A PT greater than 1.5 times normal following severe injury is often a diagnostic criterion for ATC. While the prevalence of prolonged PT is higher, prolongation of the PTT is more specific with more robust predictive value for mortality.
Newer alternatives to traditional coagulation testing such as thromboelastography, may offer a more accurate assessment of actual in vivo coagulation. (See Section “Thromboelastography” below).
Fibrinogen and D-dimer. Fibrinogen is a soluble plasma glycoprotein that is converted by thrombin into fibrin during blood coagulation. The D-dimer is the fibrin degradation product that is found after clot dissolution.
Low levels of fibrinogen and elevated D-dimer can act as surrogate markers of clotting factor consumption and hyperfibrinolysis, respectively.
The D-dimer is elevated in almost all trauma patients, leaving its absolute clinical value in question.
Recent data indicates that there is a benefit from increased fibrinogen levels, suggesting a role for more frequent fibrinogen level measurements during resuscitation of severely injured patients.
Thromboelastography. Thromboelastography (TEG) is an assessment of the viscoelastic properties of clot formation in fresh or citrated whole blood in real time. This test synthesizes information from standardized tests (PT, PTT, thrombin time, fibrinogen level, and platelet count) into a single dynamic readout providing simultaneous information regarding time to clot initiation, clot strength, and fibrinolysis. This allows immediate analysis and goal directed therapy of the coagulation disorder.
The TEG (Fig. 7-1) is measured on a small aliquot of warmed whole blood and measures the clotting time (R value), clot formation (alpha angle), clot strength (MA, maximal amplitude), and clot lysis (LY 30).
Figure 7-1. Thromboelastography (TEG) Measurement.
Several standardized coagulation parameters can be derived from the TEG, and are calculated in real time by the TEG software:
SP (split point). The time from sample placement (or activation with an exogenous procoagulant) until the earliest detectable resistance. Depending on the nature of the activator, this roughly corresponds to the results of the standard PT/INR and PTT coagulation tests.
R (reaction time). The time from sample placement or activation until the tracing amplitude reaches 2 mm, corresponding to the initiation phase of clotting. Both SP- and R-times are prolonged in the presence of clotting factor deficiencies, anticoagulants, and hypofibrinogenemia, and may be shortened in hypercoagulable states.
K (clot formation time). Time elapsed between the R-time and the point where the tracing amplitude reaches 20 mm, a measure of the amount of time required for a standardized degree of viscoelasticity to be reached once clotting is initiated; this corresponds to the potentiation phase of clot formation during which thrombin begins to cleave soluble fibrinogen. The K-time is prolonged by depletion of clotting factors, fibrinogen, or platelets.Related posts:
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