Page 2593 - Hematology_ Basic Principles and Practice ( PDFDrive )

2310 Part XIII Consultative Hematology

“surgical” and “coagulopathic” causes of bleeding. Failure to surgically Over the last several years, there has been an increased emphasis
control bleeding vessels at the operative site is the most frequent cause on more aggressive blood component therapy, driven by data from
of postoperative bleeding and is suggested by evidence of hemorrhage both military and civilian trauma populations. 124-127 These studies
restricted to the operative site and manifesting as an expanding have demonstrated that higher ratios (approaching 1 : 1) of plasma
hematoma, excessive blood in surgical drains, or saturated wound and platelets to red blood cells are associated with improved outcomes
dressings. Conversely, coagulopathic bleeding is suggested by slower in massively transfused patients. Patients receiving less than massive
“oozing” at the operative site in addition to evidence of bleeding transfusion may also benefit from higher plasma-to-red blood cell
128
outside the operative field that may be seen as petechiae, purpura, or ratios. Furthermore, maintaining an adequate fibrinogen level is
121
bleeding at sites of venipuncture, urinary or vascular catheters, or essential for successful management of dilutional coagulopathy.
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nasogastric and endotracheal tubes. In addition to careful physical Appropriate and timely management for these patients needs to be
examination, laboratory tests, including PT/INR, aPTT, and platelet facilitated in order to avoid prolonged hypotension, acidosis, and
count, are an essential part of the evaluation. Other useful tests may tissue-level ischemia, all of which can predispose to the development
include a fibrinogen level, and a test for fibrin degradation products of DIC (Chapter 139).
or D-dimer and thromboelastography to search for evidence of DIC
or increased fibrinolysis. The peripheral blood smear should also be
reviewed to examine platelet morphology and number, and to identify Cardiopulmonary Bypass
possible red blood cell fragmentation that may occur in DIC. The
possibility of a preexisting hemostatic abnormality that may have Cardiopulmonary bypass is associated with unique hemostatic
been missed before surgery should also be considered. changes. Perfusion through the extracorporeal membrane oxygenator
When evaluating coagulation test results in surgical patients, has profound effects on platelets and clotting factors: platelet count,
changes that normally occur in response to surgery must be consid- hematocrit, and levels of coagulation and fibrinolytic factors are
ered. These vary depending on the extent of tissue dissection and the reduced to approximately 50% of baseline after starting bypass and
duration of the procedure. Consumption and hemodilution from remain reduced throughout the procedure, with the exception of
crystalloid and blood product infusion can lead to acute reductions factor V, which may be further reduced to less than 20%. 129-131 These
of coagulation factors and platelets during surgery and in the initial changes may be caused in part by exposure to artificial surfaces and
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postoperative period. This is typically followed by changes resulting also by a tissue factor–dependent pathway related to surgical trauma.
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from the acute-phase response, including increases in fibrinogen and Cardiopulmonary bypass results in significant platelet dysfunction
factor VIII levels, and the platelet count during the first postoperative reflected by release of α-granule contents, the generation of platelet
week. 114 microparticles, abnormal ex vivo platelet aggregation test results, and
Alterations in coagulation factor levels that occur during surgery a transient prolongation of the bleeding time. 130,131,133,134 In addition
and in the initial postoperative period can limit the reliability of the to quantitative and qualitative platelet function defects, cardiopulmo-
PT/INR and aPTT in evaluating the bleeding surgical patient. Clini- nary bypass also results in platelet activation, which may trigger
134
cal practice guidelines have consistently recommended transfusion of thrombotic and inflammatory complications. Patients with acute
fresh-frozen plasma if the PT/INR and aPTT results are prolonged coronary syndrome (who may be candidates for urgent cardiac
more than 1.5-fold compared with the mean reference range. 115-117 surgery) are sometimes given GPIIb/IIIa inhibitors, which may
However, there are differing opinions on the utility of coagulation further impair platelet function. If surgery cannot be delayed, con-
135
studies to guide transfusion practices, 118,119 and prospective studies sideration of prophylactic platelet transfusions may be required.
are needed. Inadequate neutralization of heparin with protamine sulfate after
cardiopulmonary bypass may result in a prolonged aPTT and throm-
Coagulopathy Associated With Massive Blood bin time with a normal reptilase time, and is an indication for
administration of additional protamine sulfate. The use of DDAVP,
Loss/Transfusion antifibrinolytic drugs, and rFVIIa to reduce the hemorrhagic compli-
cations of cardiac surgery was discussed earlier. Fibrinogen concentrate
Massive bleeding (loss of one or more blood volumes in a 24-h has also been shown to reduce blood loss and transfusion require-
period) may occur in the setting of severe trauma or major surgery ments during cardiac surgery. 136
and requires aggressive fluid resuscitation and transfusion of blood
products. The mechanisms involved in the coagulopathy that accom-
panies massive transfusion have not yet been fully elucidated but are Orthotopic Liver Transplantation
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multifactorial in nature. Similar to chronic liver disease, procoagu-
lant, anticoagulant, profibrinolytic, and antifibrinolytic factors are all In addition to the complex coagulopathy of end-stage liver disease,
affected, resulting in a complex coagulopathy. Impaired thrombin orthotopic liver transplantation is accompanied by major alterations
generation is compensated in part by reduction in the activity of in hemostasis. The surgical procedure itself can be divided into three
137
antithrombin and other protease inhibitors. Fibrinogen levels can fall stages, each with its own profile of coagulation abnormalities.
rapidly and are proportional to the degree of hemodilution. Antifi- Bleeding during the preanhepatic stage, while the host liver is surgi-
brinolytic protein levels are decreased, rendering clots more susceptible cally isolated, is due primarily to the patient’s preexisting coagulopathy
121
to lysis. In addition to a dilutional coagulopathy, other complica- and is determined by the severity of the underlying liver disease.
tions, including consumptive coagulopathy, hypothermia, electrolyte Excessive fibrinolysis may be encountered during this stage in
abnormalities (because of citrate intoxication), and acid-base distur- 10%–20% of those with cirrhosis. The anhepatic stage begins with
bances, may also develop. 121 surgical removal of the liver. Bleeding during this stage is primarily
138
In patients without a preexisting coagulopathy, replacement of hemostatic because of DIC and excessive fibrinolysis. As the donor
approximately 1.5 blood volumes is the threshold for the develop- liver is reperfused, the postanhepatic stage begins, and serious bleed-
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ment of dilutional coagulopathy. At that point, PT/INR, aPTT, ing is often encountered as a result of a combination of hyperfibri-
fibrinogen level, and platelet count should be determined. If the PT/ nolysis, metabolic acidosis, hypothermia, electrolyte abnormalities,
INR or aPTT is prolonged greater than 1.5-times control, the and sometimes impaired cardiac function. 138,139
fibrinogen level is below 100 mg/dL, or the platelet count is reduced The multifactorial nature of the coagulopathy associated with
to 50,000–70,000/µL, clinical coagulopathy is suspected and appro- orthotopic liver transplantation requires a combination of therapeutic
priate blood product administration is indicated, particularly if interventions. In addition to transfusion of blood products, other
additional blood loss is expected. The same coagulation parameters hemostatic agents such as DDAVP and antifibrinolytics may be useful
should be measured again with the replacement of each additional and were discussed earlier. There has also been much interest in the use
half-blood volume (i.e., 5–6 units of red blood cells). 123 of rFVIIa, and some randomized, placebo-controlled trials have been