Page 1974 - Hematology_ Basic Principles and Practice ( PDFDrive )

1748 Part XI Transfusion Medicine

TPE is not indicated in the treatment of individuals with diarrhea Dosage
associated hemolytic uremic syndrome (HUS) (also termed throm-
botic microangiopathy, Shiga toxin mediated) unless there are severe One unit of plasma derived from a unit of whole blood contains 200
neurological symptoms. Seven randomized control trials were per- to 280 mL. When plasma is collected by apheresis, as much as
formed evaluating the efficacy of TPE for typical cases of HUS. These 800 mL can be obtained from one individual (“jumbo” plasma
trials found that the use of plasma was not superior to supportive units), but the majority of units clinically used have a volume around
therapies alone. TPE with plasma replacement fluid, however, is 250 mL. On average, there is 0.7 to 1 unit/mL of activity of each
currently indicated in diarrhea-negative (atypical) HUS (aHUS), coagulation factor per milliliter of plasma and 1 to 2 mg/mL of
which is caused by a number of inherited and sporadic conditions fibrinogen. The appropriate dose of plasma may be estimated from
that lead to the uncontrolled activation of the alternative complement the plasma volume, the desired increment of factor activity, and the
system (i.e., deficiency or autoantibody to complement factor H). A expected half-life of the factor being replaced (i.e., factor VII has a
complete discussion of aHUS is beyond the scope of this chapter. half-life of only 4–6 hours, and thus plasma doses should be repeated
Typically, all patients diagnosed with aHUS are empirically treated every few hours if replacing factor VII in a patient with factor VII
with TPE or plasma transfusions until underlying disease or mutation deficiency). Alternatively, the plasma dosage may be estimated as 10
is further defined, which then determines treatment. TPE has been to 15 mL/kg, and ideally should be ordered as the number of milli-
theoretically proposed to effectively remove the potentially causative liters to be infused. The frequency of administration depends on the
autoantibody or mutated circulating complement regulator, while clinical response to the infusion and correction of laboratory param-
replacing absent or defective complement regulators. The reported eters. Moreover, plasma infusions should be given as close to the time
clinical response varies depending on the underlying cause, however. as it is needed to allow for its maximum hemostatic effect if given
For some causes of aHUS, plasma infusion can be initiated. Recently, preprocedure. A recent one-year evaluation of 10 U.S. hospitals
Eculizumab, a humanized monoclonal antibody against C5, has been revealed that the current median dose of plasma was 2.0 units with
shown to be an effective alternative treatment for some causes of 15.2% receiving only 1 unit. The median weight-adjusted plasma
aHUS (see Chapter 134). dose was only 7.3 mL/kg with only 29% of doses being at least
TPE with plasma replacement may also be indicated in other 10 mL/kg and 15.5% being 15 mL/kg. Based on these findings, a
thrombotic microangiopathies. Some medications cause thrombotic large proportion of patients in the United States are likely being
microangiopathies that require plasma exchange. Current examples underdosed.
include ticlopidine and clopidogrel, and potentially cyclosporine or
tacrolimus. Lastly, TPE with plasma may also be used in the treat-
ment of thrombotic microangiopathy associated with stem cell Compatibility
transplantation.
Plasma as replacement fluid, either partially or completely, for Plasma is screened for unexpected RBC antibodies during product
TPE is used in other diseases with risk of hemorrhage caused by the testing and should be ABO-type compatible for transfusion (see
resulting coagulopathy, such as diffuse alveolar hemorrhage, liver later). Notably, group AB plasma is universally compatible with all
failure, and perioperatively. patients and group O plasma is only compatible with patients with
group O RBCs.
Prophylactic Use of Plasma

Studies have shown that prophylactic administration of plasma to
nonbleeding recipients with abnormal coagulation studies (i.e., PT, Plasma Product ABO Type
aPTT, INR) is unlikely to produce a clinical benefit and unnecessarily
exposes the patient to the risks of plasma transfusion. Moreover, Patient ABO type O A B AB
systematic reviews of whether a prolonged PT or aPTT even predicts O Yes Yes Yes Yes
bleeding found no significant difference in the risk of bleeding A No Yes No Yes
between patients with a prolonged PT or aPTT and those with B No No Yes Yes
normal clotting parameters in the setting of bronchoscopy, central AB No No No Yes
vein cannulation, angiography, or liver biopsy. Despite this ambigu-
ity, a number of randomized control trials and metaanalyses have Yes = compatible blood types
evaluated the efficacy of the prophylactic use of plasma products to No = incompatible blood types
reduce the risk of bleeding. One trial, the Northern Neonatal Nursing
Initiative Group Trial, randomized 776 neonates, and evaluated
whether plasma transfusion prophylaxis could prevent intraventricu- Adverse Events
lar hemorrhage in comparison with volume expanders (gelofusine or
dextrose-saline). In a second large randomized clinical trial, 275 Plasma transfusion is associated with a number of infectious and
patients were randomized to see whether plasma transfusions could noninfectious adverse events. Transfusion transmitted diseases tradi-
prophylactically prevent bleeding in acute pancreatitis patients. tionally include HIV, hepatitis B, and hepatitis C (Chapter 120),
Neither large study showed clinical benefit of prophylactic plasma which are currently rare. Noninfectious risks include allergic reac-
use. In one systematic review, 55 other randomized clinical trials were tions, TRALI, transfusion-associated circulatory overload (TACO),
reviewed and evaluated. Only 17 of these 55 involved a control group and hemolytic reactions (Chapter 119).
that did not receive plasma. Overall, like the two largest studies, the
results of these randomized control trials failed to show evidence for
the efficacy of prophylactic plasma use across multiple clinical and Transfusion-Related Acute Lung Injury
laboratory outcomes. Similarly, a second metaanalysis evaluated 25
independent studies of minor surgical procedures and found that TRALI is noncardiogenic pulmonary edema associated with the
there was no significant difference in bleeding risk between those who transfusion of blood products. TRALI is usually caused by neutrophil
did and did not have a coagulopathy. Despite this evidence, current and pulmonary endothelial activation, usually caused by transfused
recommendations still indicate that a pretransfusion INR of ≥1.5 to donor white cell antibodies, including human leukocyte antigen
1.7 be used as a transfusion trigger, as the prophylactic use of plasma (HLA) antibodies and human neutrophil antigen (HNA) antibodies.
is theoretically justified when the clinical risk of bleeding is greater These donor antibodies react with the recipient’s white cells in the
than potential harms of using plasma. pulmonary vasculature causing leukoagglutination, activation of the