Page 2591 - Hematology_ Basic Principles and Practice ( PDFDrive )

2308 Part XIII Consultative Hematology

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blood loss with a single intraoperative dose of rFVIIa, rFVIIa
A 56-year-old man has undergone aortic arch replacement for an resulted in little or no reduction in blood loss in a patients without
aortic dissection. During the procedure he underwent circulatory arrest cirrhosis undergoing partial hepatectomy. 81,82 Overall therefore, the
for 35 min, with a lowest recorded temperature of 18°C. His total
bypass time was 225 min. After rewarming, there was considerable published experience of rFVIIa in noncardiac surgery is still too
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bleeding and he received 10 units of packed red blood cells, 8 units limited and subject to bias to draw meaningful conclusions.
of fresh frozen plasma, 4 pooled units of platelets, and 20 units of Neurosurgical patients are distinct from other groups in that
cryoprecipitate. He was transferred from the operating room to the rather than treating massive hemorrhage, the goal is to treat relatively
intensive care unit in stable condition. small bleeds within a closed space where even mild or modest benefit
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A consultation is made to the hematologist 1 hour later because of may result in significantly better outcomes. A randomized, placebo-
excessive drainage (>500 mL) from his chest tubes. controlled study of 399 patients with intracerebral hemorrhage sug-
Important information to consider: gested that treatment with rFVIIa within 4 hours after the onset of
• likelihood of surgical bleeding versus coagulopathy symptoms limited growth of the hematoma, reduced mortality, and
• current temperature
• evidence of clotting within the chest tubes improved functional outcomes at 90 days, albeit with a small increase
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• current coagulation studies (if available) in the frequency of thromboembolic events. In a subsequent larger
• hemodynamic status trial in patients with intracerebral hemorrhage, rFVIIa failed to
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Upon discussion with the surgeon and intensive care unit team, it improve mortality and disability at 90 days. Therefore rFVIIa
is noted that the temperature is 35.5°C, there is little clot in the chest should not be used for this indication.
tubes, and he requires hemodynamic support with epinephrine and The primary safety concern with the off-label use of rFVIIa is
norepinephrine. His recent coagulation studies reveal an INR of 1.8, an thrombosis. In hemophilia, the risk for thrombosis is estimated to be
aPTT of 48 s, a thrombin time of 59 s, and a fibrinogen level of 2.5 g/L. less than 1%. 86,87 In contrast, the risk is much higher with off-label
Possible treatments: use. Both arterial and venous thromboembolic events have been
1. warming blanket
2. protamine sulfate 50 mg by slow intravenous infusion: for heparin reported, and thromboembolic events were the probable cause of
rebound death in the majority of the reported fatalities. Half of the thrombo-
3. calcium gluconate 1–2 g intravenous bolus: for excessive citrate embolic events occurred within 24 hours of the last dose of rFVIIa,
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(from blood products) and many occurred within 2 hours. Therefore off-label use of
4. blood products (using a warming line) rFVIIa should be restricted to cases where there are no alternatives.
5. consider rFVIIa: 40–80 mcg/kg
Interpretation: The likelihood is that despite the extensive transfu-
sion, the combination of a prolonged time on bypass and cooling to MANAGEMENT OF PATIENTS WITH
18°C has resulted in a coagulopathy. This is further evidenced by HEMOSTATIC ABNORMALITIES
the prolongation of the coagulation tests and the lack of visible clots
within the chest tubes. Although items 1–3 are important as adjunctive
therapies, they are unlikely to be sufficient on their own. The utility Patients with known hemostatic abnormalities are often referred
of further blood products in this situation cannot be understated, before surgery for assessment of bleeding risk and recommendations
because in order for rFVIIa to work effectively, it relies on the presence regarding perioperative management. The approach to these patients
of underlying substrate, which is effected by judicious use of blood should be according to the following considerations: (1) evaluation
products. Although the use of rFVIIa in this scenario is off-label, its use of the risk for bleeding associated with the specific surgery or proce-
is justified when the surgeon feels that the likelihood that bleeding is dure (see Table 159.1); (2) careful consideration of the need for
too diffuse to be stopped by surgical intervention and is likely caused surgery and its urgency; greater risks are warranted for correction of
by coagulopathy.
life-threatening conditions than for elective procedures; (3) recogni-
tion of the nature and severity of the patient’s hemostatic abnormality
and the ability to correct it; and (4) consideration of the duration of
of rFVIIa in trauma patients, questions regarding optimal dosing and replacement that will be required, with appreciation of potential
timing of administration remained. In an attempt to address these bleeding that may be associated with events in the postoperative
issues, the Western Trauma Association Multi-Center Trials Group period such as removal of sutures and deep drains, and the need for
conducted a case registry of 380 adult trauma patients who received postoperative rehabilitation. The following sections discuss periopera-
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adjunctive rFVIIa for hemorrhage control. This registry was unable tive management of some common coagulation abnormalities; the
to define a precise role for rFVIIa in traumatic bleeding. However, a management of congenital factor deficiencies and von Willebrand
pH of less than 7.2, platelet count of less than 100,000/µL, and blood disease are discussed elsewhere in this text (see Chapters 135, 137,
pressure less than or equal to 90 mmHg were each found to be and 138).
predictors of poor response to rFVIIa, suggesting that correction of
shock, acidosis, and thrombocytopenia should precede the use of
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rFVIIa in bleeding trauma patients. The CONTROL trial, which Thrombocytopenia
randomized 560 actively bleeding trauma patients to rFVIIa or
placebo, found no differences in overall mortality, organ system Thrombocytopenia is one of the most common acquired hemostatic
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failure, or adverse events in either group. Thus although initial abnormalities, and the availability of platelet transfusion makes con-
reports were encouraging, there is currently insufficient evidence to sideration of both emergency and elective surgery reasonable even in
support a role for the routine use of rFVIIa in the setting of trauma. severely thrombocytopenic patients. The best index of bleeding risk
The use of rFVIIa in cardiac surgery is controversial. Because in thrombocytopenic patients is the platelet count. In nonsurgical
perioperative bleeding is a major cause of morbidity and mortality, patients a threshold platelet count of 10,000/µL is widely used for
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there is off-label use of rFVIIa in this patient population. A number prophylactic transfusions, yet there is inadequate scientific evidence
of case reports and uncontrolled case series in both adult and pediatric to determine the platelet count below which the risk for surgical
populations have suggested that rFVIIa is effective in decreasing bleeding is increased. 89,90 The American Society of Anesthesiologists
blood loss and transfusion requirements in patients with intractable Task Force on Blood Component Therapy concluded that prophylac-
bleeding after cardiopulmonary bypass. However, in the absence of tic platelet transfusion in surgical patients is usually indicated when
data from well-designed clinical trials demonstrating efficacy and the count is below 50,000/µL and is rarely indicated when the count
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with the current widespread use of tranexamic acid in such patients, is above 100,000/µL. Clinical trials addressing this issue are still
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rFVIIa is rarely used in this setting. lacking. For low-risk surgery, a single transfusion to increase the
rFVIIa has been used in a variety of other surgical settings with platelet count to more than 50,000/µL followed by close observation
divergent results. Although a trial in patients undergoing retropubic may suffice, whereas transfusion to maintain the platelet count at
prostatectomy demonstrated a greater than 50% reduction in surgical greater than 50,000/µL for moderate-risk surgery and greater than