Page 1263 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

870 PART 7: Hematologic and Oncologic Disorders

plasminogen activator (t-PA), which increases ongoing fibrinolysis TABLE 92-5 Platelet Transfusion Parameters for Patients with Acute Leukemia 10
further propagating DIC. In addition to careful examination of the
39
peripheral smear and bone marrow aspirate for APL cells, diagnostic Clinical Scenario Platelet Transfusion Target
studies should include polymerase chain reaction (PCR), fluorescent in Routine platelet transfusion for prophylaxis against bleeding >10,000 platelets/µL
situ hybridization (FISH), and cytogenetic analysis to identify the pres-
ence of the PML/RAR fusion gene and t(15;17) translocation. 46 “Minor” invasive procedure or active DIC >50,000 platelets/µL
Even before verification of clinically suspected APL by molecular Suspected CNS bleed >100,000 platelets/µL
studies, treatment of APL with ATRA should begin. The bleeding and Data from Carlson KS, DeSancho MT. Hematological issues in critically ill patients with cancer. Crit Care
clotting complications of APL are a result of undifferentiated circulating Clin. January 2010;26(1):107-132.
APL cells, and differentiation and resolution of the coagulopathy can
start with ATRA therapy (45 mg/m daily in two divided doses). There is
2
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little downside to the initiation of ATRA, and if the diagnosis of APL performed and every effort made to obtain human leukocyte antigen
is not verified with molecular studies, ATRA therapy can be discontinued. antibody (HLA)–matched platelets for the patient.
In addition to ATRA, fibrinogen, PT and aPTT levels should be deter- The transfusion goal for packed red blood cell transfusion has histori-
mined as frequently as every 6 hours, and cryoprecipitate and fresh cally been a hemoglobin concentration above 8 g/dL or a hematocrit of
frozen plasma (FFP) should be aggressively administered to normalize greater than 30%. This is higher than the range suggested for nonleu-
clotting parameters. This is a critical part of the initial management of kemia patients; however, individuals with leukemia are at higher risk
APL, and failure to adequately treat DIC with resulting hemorrhage is of thrombocytopenia-associated bleeding, and the additional reserve is
the cause of early mortality in what is considered an otherwise curable felt to be helpful in this scenario. This is also a group of patients who
form of leukemia. are often profoundly hypoalbuminemic, and there is therapeutic benefit
Differentiation of APL cells is an important step in management of from improved oncotic pressure with higher red cell volumes. The one
APL, but carries with it the risk of differentiation syndrome. The hall- caveat is with patients at risk for hyperleukocytosis in which addition of
marks of this differentiation syndrome include capillary leak pathophysi- further cell mass within the bloodstream could tip the balance toward
ology and the presence of dyspnea, fever, peripheral edema, hypotension, hyperviscosity and leukostasis. In these cases, red cell transfusion should
acute renal failure, and congestive heart failure. Pulmonary infiltrates be minimized or avoided until pharmacologic or mechanical cytoreduc-
and pericardial and pleural effusions may be seen radiographically. tion has started and risk of leukostasis resolved.
15
If differentiation syndrome or ATRA-syndrome is suspected, steroids There are now thrombopoietic agents such as romiplostim and eltrom-
should be administered immediately (10 mg intravenous dexametha- bopag that are approved for treatment of steroid-refractory thrombocyto-
sone twice daily until resolution of symptoms followed by a taper). penia, but these are not indicated in the acute leukemia population at this
ATRA therapy also carries the risk of triggering hyperleukocytosis as time. They increase platelet counts over the course of days to weeks, and are
undifferentiated APL cells within the bone marrow are rapidly released not appropriate in an acute setting. Furthermore, the effect of these agents
into circulation. WBC counts >10,000/m should prompt consideration in a leukemic bone marrow is unknown. Similarly, erythroid-stimulating
3
of addition of anthracycline (idarubicin is traditionally used) if not agents are not indicated as the erythropoietin receptor is expressed in some
already included in the induction regimen to acutely bring down the subtypes of acute leukemia and in vitro studies have suggested that eryth-
24,29,51
peripheral leukocyte count to prevent this complication. ropoietin stimulation can provide growth advantage to leukemia cells.
ATRA can also cause pseudotumor cerebri. This complication is most
common in younger patients receiving ATRA therapy, and should be DISSEMINATED INTRAVASCULAR COAGULATION
managed by a combination of lumbar puncture, acetazolamide, cortico- A complication of acute leukemia and its treatment is acute disseminated
steroids, and narcotic analgesia. 36,46 intravascular coagulation (DIC). All forms of acute leukemia predispose
to DIC, but it is especially pronounced and significant in APL. DIC is
ANEMIA AND THROMBOCYTOPENIA the pathologic activation of the coagulation cascade and fibrinolysis and
results in inappropriate consumption of platelets, clotting factors,
Patients with acute leukemia frequently present with concurrent anemia and endogenous anticoagulants. The presence of DIC places patients at
and thrombocytopenia, and systemic complications from both can be risk for venous thromboembolism (VTE) and bleeding and should be
severe. Transfusion of platelets and red blood cells is indicated, but aggressively managed with supportive measures. End-organ damage can
cutoffs for these depend on the clinical situation, and consideration also result from microthrombi deposition, which is common in the renal
for infectious complications from CMV-contaminated blood products glomeruli and predisposes to concurrent acute renal failure. Laboratory
should be considered in their selection. evidence of DIC includes prolonged aPTT, PT, and thrombin time as
Prophylactic platelet transfusion is indicated for patients with acute well as hypofibrinogenemia and thrombocytopenia. D-dimer and fibrin
leukemia when the platelet count is less than 10,000/m in order to degradation products are also markedly elevated. As with all patients
3
decrease the risk of bleeding or at higher platelet numbers if there is with DIC, treatment of the underlying pathology is critical for resolution
active bleeding (ie, epistaxis, significant gingival bleeding, GI bleeding). of the consumptive coagulopathy. Acute DIC will resolve as the degree of
For patients undergoing major surgery or procedures such as central leukemic burden diminishes, but patients will often persist with chronic
venous catheter placement, bronchoscopy, lumbar puncture, thoracen- low-level DIC for an extended period following induction therapy.
tesis, or abdominal paracentesis, platelets should transfused to a target of The management of DIC in patients with leukemia is twofold: treat-
50,000/m . If a CNS bleed is suspected, the transfusion parameter is ment of the leukemia and supportive management of the consumptive
3 10,50
increased to greater than 100,000/m 3 10,23 (Table 92-5). There is evidence coagulopathy. During acute DIC, platelet count should be maintained
that in most cases, single and random pooled donor platelets are equally with transfusions to a higher limit of 50,000/m . A 10 mg dose of vitamin
3
effective at improving posttransfusion platelet counts and result in K should be given in patients with a prolonged PT. With normal liver
similar hemostatic benefits. Failure of platelet transfusion to improve synthetic function, this will help rapidly increase the amount of vitamin
50
platelet count as predicted should trigger investigation for causes K–dependent factors (II, VII, IX, X, and proteins C and S) available for
of platelet consumption/bleeding, alloimmunization, or hypersplenism. coagulation. Clotting factors should also be repleted with transfusion of
Especially in the acute leukemia patient, DIC and sepsis in the setting of FFP and cryoprecipitate. Isolated clotting factor concentrates are typically
poor marrow production of platelets are frequent contributing causes. not used to correct the global coagulopathy in DIC. Instead, FFP should
10
If alloimmunization is suspected (ie, platelet count fails to increase be given at an initial dose of 15 mL/kg of body weight, although 30 mL/kg
by 1 hour following transfusion), platelet antibody testing should be may give more complete correction if there is evidence of either PT or

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