Page 1973 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 115 Transfusion of Plasma and Plasma Derivatives 1747

transfusion ratio, but did find that those who were randomized to patients with severe liver disease, bleeding, and DIC, plasma infu-
receive more plasma (1 : 1:1 ratio) achieved hemostasis more fre- sions often fail to normalize the PT and PTT.
quently. Consequently, data support no advantage of 1 : 1:1 versus
1 : 1:2, and further study comparing 1 : 1:2 versus 1 : 1:3 is needed.
Questions regarding best practice still remain. One European Rapid Reversal of Warfarin Effect
group has suggested that the use of prothrombin complex concentrate
(PCC) and fibrinogen concentrates, instead of plasma, provide a Warfarin inhibits the hepatic synthesis of vitamin K-dependent clot-
safer alternative for massive transfusion patients. The increased use ting factors (factors II, VII, IX, and X) by blocking the recovery of
of whole blood, as an alternative to using the 1 : 1:1 component the form of vitamin K that is active in the carboxylation of these
ratio, is being studied and has been shown to have similar efficacy proteins. Warfarin therapy induces functional deficiencies of these
in pilot trials. Other studies are investigating the early use of cryo- factors, which correct within 48 hours after the discontinuation of
precipitate and the use of concentrated and/or lyophilized plasma. warfarin if diet and vitamin K absorption are normal.
The optimal blood type for emergency plasma transfusions is also The use of plasma in the context of warfarin anticoagulation is
under active investigation. During the initial resuscitation phase of well established, but is becoming less relevant because of the avail-
these patients, the patient’s blood type is often unknown. Emergency ability of four factor PCC. Recent randomized control trials compar-
release plasma, traditionally group AB, is used until blood typing has ing PCC with plasma have demonstrated a similar clinical efficacy
been completed, and the plasma used can be switched to the patient’s between the two products, but superior rate of INR normalization
identified ABO type. The theoretic advantage in using group AB for those who receive PCC. Plasma is generally not indicated for
plasma is its lack of anti-A and anti-B antibodies, thus theoretically warfarin reversal when the patient is not bleeding and when the
avoiding the risk of acute hemolytic transfusion reactions. However, patient has an INR <9, as vitamin K administration corrects the
since AB plasma is the least common type of plasma, there is a coagulopathy in 12 to 18 hours. In patients anticoagulated with
possibility of shortages. Studies now support the use of group A warfarin who have active bleeding, require emergency surgery, or have
plasma in massive support situations as the universal product, and serious trauma, however, the deficient clotting factors can be imme-
have so far shown no increased risk to the recipient and no substantial diately provided by PCC, or plasma transfusions Plasma use may not
effect on clinical outcomes. Some provide low titer, typically defined be optimal in all situations of warfarin-induced bleeding, though, as
as less than 1 : 100, group A plasma while other do not titer group large volumes of plasma might be required for adequate warfarin
A plasma. Since patients typically receive group O RBCs and about reversal, and lengthy infusion times, especially in those who are
80% of the population is group O or group A, the risk of hemolysis volume sensitive, might delay needed surgical intervention.
is low. Consequently, four factor PCC, which was approved for use by
In the recent past, trauma patients would be provided primar- the FDA in April 2013, should be chosen as the first-line therapy for
ily crystalloid and albumin, followed by component transfusion rapid reversal of life or limb threatening warfarin anticoagulation. For
therapy based on specific transfusion “triggers.” A hemoglobin less nonemergent or nonthreatening reversal, vitamin K can be adminis-
than 8 g/dL for RBCs, a PT greater than 1.5 times normal for tered. Studies have shown that PCC can reverse a warfarin-induced
plasma, a platelet count less than 50,000/µL for platelet transfu- coagulopathy faster with lower mortality and less volume overload
sions, and a fibrinogen less than 100 g/dL for cryoprecipitate were than plasma or vitamin K alone. Also, INR levels need to be closely
often used. These “triggers” have now been incorporated as part of followed to ensure warfarin reversal is sustained.
some massive transfusion protocols as algorithms to guide therapy.
In these protocols, component therapy is guided by rapid and regular
laboratory value correlation. To improve the speed by which one can Thrombotic Thrombocytopenic Purpura and
address coagulation abnormalities, some protocols now use throm- Other Thrombotic Microangiopathies
boelastography (TEG) or other point-of-care tests. TEG technology
provides a dynamic and global assessment of the coagulation process, In patients with TTP, plasma exchange (TPE) with plasma as the
and can provide rapid assessments of the patient’s platelet function, replacement fluid is life-saving. Plasma infusion or exchange is also
coagulation cascade, and fibrinolysis. The mechanism underlying critical in the treatment of individuals who have congenital TTP. TPE
TEG technology and the interpretation of TEG data are beyond has decreased the mortality of TTP from over 90% to less than 10%
the scope of this chapter. Currently, sufficient data are lacking to (see Chapter 134). Six randomized control trials have demonstrated
universally recommend the use of TEG in massive transfusion that TPE is most effective in patients who have an autoantibody to
protocols. ADAMTS13. This is caused by both the removal of a patient’s plasma
Massive transfusion in other conditions, such as liver, cardiac, or containing the inhibitor coupled with the addition of donor plasma
orthopedic surgery and obstetric hemorrhage, likely have a different containing the functional vWF-cleaving protease. The FDA has also
pathophysiology and thus transfusion management of these patients approved the use of cryoprecipitate-reduced plasma for refractory
may be different than trauma patients. Studies exploring the use of TTP, defined as those who are unresponsive to plasma exchange with
massive transfusion protocols in these situations are lacking, but FFP. Some authorities advocate the use of cryoprecipitate-reduced
institutions should have policies in place for rapid availability of plasma as a first-line therapy for TTP, as these products have a lower
blood products and laboratory testing. level of vWF than FFP, a comparable ADAMTS13 activity, and lower
amounts of ADAMTS13–larger vWF multimer complexes. However,
the most recent multicenter prospective randomized trial comparing
Disseminated Intravascular Coagulation exchange transfusion with plasma and cryoprecipitate reduced plasma
for the initial treatment of TTP demonstrated equal efficacy between
DIC may be secondary to sepsis, liver disease, hypotension, surgery- plasma and cryoprecipitate-reduced plasma for the initial therapy in
associated hypoperfusion, trauma, obstetric complications, leukemia TTP.
(usually promyelocytic), or underlying malignancy. Successful treat- Standard therapy involves daily TPE with plasma replacing 1.0 to
9
ment of the underlying cause is paramount. Recent guidelines suggest, 1.5 plasma volumes until the platelet count is above 150 × 10 /L,
based on low quality evidence, that plasma therapy should not be and lactate dehydrogenase is near normal for 2 to 3 consecutive days.
initiated based on abnormal laboratory results alone. Rather, patients Treatment should be initiated immediately or at least within 24 hours
with DIC and bleeding, those requiring an invasive procedure, and of diagnosis, and if TPE is not available to initiate treatment, plasma
those at risk for bleeding complications should be given plasma in infusions can be used until TPE is available. The total number of
amounts sufficient to correct or ameliorate the coagulopathy or treatments required is variable and is based on each individual’s clini-
hemorrhagic diathesis. Large volumes of plasma are often necessary cal response, but studies have shown that the median number of
to correct the coagulation defect in these patients. However, in TPEs needed to establish hematologic recovery is about 7 to 8.