Hematological Malignancy Associated Emergency Blood 2012- Tumor Lysis Syndrome (TLS)
- Primary TLS: Before Chemo
- Secondary TLS : After Chemo
- Laboratory TLS: 2 or more abnormal
laboratory values of uric acid, potassium, phosphorus, or calcium at
presentation or a 25% change in values from the pretreatment
measurements (relatively a loose definition)
- Clinical TLS: defined as the presence of laboratory TLS plus renal dysfunction, seizures, cardiac arrhythmia, or
sudden death
- Assessing Risk of TLS :
- High Risk for TLS
- Intermediate Risk for TLS
- Low Risk for TLS
- Prevention and Treatment
- Aggressive Hydration (more so prior to the start of the induction therapy)
- Maintain u/o of 80-100 cc / hr at least
- More aggressive in young patients without co-morbidities
- Loop diuretics may be added for low urine output
- Dietary phosphate restriction may be needed
- Calcium supplementation in a symptomatic patients only to avoid calcium phosphate renal crystallization
- Allopurinol (blocks Xanthine and Hypoxanthine to Uric Acid formation) Xanthine Oxidase Inhibitor
- Rasburicase (Recombinant Urate Oxidase)
- 0.15 mg/kg one time single dose
- G6PDH Deficiency is a contraindication as hydrogen
peroxide, a byproduct of rasburicase, cannot be broken down in
G6PD-deficient patients and can lead to hemolysis or
methemoglobinemia
- Usually used in established TLS, particularly with elevated
creatinine, uric acid greater than 9 mg/dL, or in patients not
responding to allopurinol
- Urine alkalinization (NOT recommended)
- Increases uric acid solubility, but will cause xanthine precipitation (more in patients treated with allopurinol), and calcium phosphate in renal tubules
- Dialysis (in few patients)
- Hyperleucocytosis causing leukostaisis
- Definition of Hyperleucocytosis: > 100 K in AML (arbitrary definition); usually can only be diagnosed in autopsy, and in pathology
- Diagnosis: Clinical after ruling out alternate diagnosis in consideration
- Fundoscopic Examination is very important: Papilledema, Blurred disc margin, dilated blood vessels, retinal hemorrhages all point towards leucostasis
- C/F: Following are the most common sites involved
- CNS including Eyes
- Lungs
- Other organs involved are
- Monocytic variants often tend to cause leucostasis
- Leucocyte Larceny
- Pseudohyperkalemia: To avoid this, measure plasma K
- Treatment:
- No RCT to study the benefit of leucopharesis
- Ususally 2 procedures 12-24 hr apart
- If leucopharesis is unavailable, then judicious phlebotomies with BT may help in emergency
- Be careful of blood transfusion, as it may actually increase viscosity
- Dexamethasone inhibits up regulation of adhesion molecule in leukemia and endothelial cells. But has not been proven to be of benefit
- Hydroxyurea started at diagnosis
- Induction therapy once < 50 K
- Blood Potassium measured in heparinized vial to monitor for hypokalemia
- Note: APML, even in hyperleucocytosis, leucopharesis is typically not done
- Cytarabine Induced cerebellar toxicity
- HiDAC is commonly used as postremission therapy for AML due to its ability to penetrate
the BBB
- Neurologic toxicity related to HiDAC
includes gait ataxia, nystagmus, dysmetria, and dysarthria. Seizures and cerebral dysfunction occur, and peripheral neuropathy
is rarely described.
- Signs of cerebellar dysfunction usually emerge
between the third and eighth day from start of treatment. In most
patients, the symptoms resolve in 3 to 10 days, but in others
symptoms persist and can be debilitating or even fatal.
- The pathophysiology of HiDAC-induced neurotoxicity is poorly
understood and the main goal is prevention because there is no
effective treatment. Patient with AKI / CKD, or Liver Damage may be at risk of neurological damange.
- pyridoxine hydrochloride
as prophylaxis has no protective effect.
- removal of cerebrospinal fluid by lumbar puncture as well as methylprednisolone as treatment for symptomatic patients may help.
- Always examine for horizontal nystagmus, a subtle early sign of the syndrome, as
part of a daily comprehensive cerebellar examination. Imaging study are intititally usually normal.
- Thrombohemorrhegic syndrome in APL
- localized thrombosis, widespread bleeding, or both can occur hence is termed thrombohemorrhagic syndrome.
- In large studies,
the frequency of symptomatic thrombosis is 5.2%, and of
hemorrhage 7%.
- Coagulopathy manifestation:
- DIC
- primary and secondary fibrinolysis as well as
- fibrinogenolysis.
- The pathogenesis includes
- overexpression of annexin II, which increases plasmin generation by
tissue plasminogen activator approximately 60-fold, and elastases
from promyelocytes, which cleave fibrinogen and degrade fibrinolytic inhibitors.
- In addition, secondary fibrinolysis generates thrombin by aberrant tissue factor expression, resulting in tissue plasminogen activator release from the endothelium.
- In APML, occurs mostly during induction and is almost exclusively intracranial (65%) and
pulmonary (32%).
- Bleeding Risk in APL:
- transfuse platelets to maintain the level at or more than
50 000/uL for the first several days.
- transfuse cryoprecipitate,
even several times a day, until the fibrinogen is maintained at least
150mg/dL.
- Early death, usually because of hemorrhage, has
emerged as the major cause for treatment failure in APL.
- Intracranial hemorrhage (ICH) may occur in any thrombocyto-
penic patient with acute leukemia but is most common in APL,
monocytic leukemia, and ALL.
- 4 factors were identified predicting the outcome of
ICH: low albumin, elevated LDH, age more than 60 years, and
relapsed disease.
- The most common presenting symptom is
mental status change; and at the first such clinical sign, patients
need to be monitored closely by repeat radiologic imaging (CT/
MRI). We maintain the platelet count more than 50 000/uL.
- Early
neurosurgical consultation is advised; and if ICH is firmly diagnosed, the platelets should be kept above 100 000/uL, if possible,
and emergent neurosurgical intervention should be considered.
- APL differentiation syndrome
- L-Asparaginase–associated thrombosis
- Leukemic meningitis
- In AML, incidence at diagnosis
or relapse is low (3%-7%).
- In contrast to ALL, where CNS prophylaxis is mandatory, it is unknown whether prophylaxis in AML can prevent CNS relapse.
- Among AML, high-risk APL are at higher risk of CNS infiltration.
- The pathogenesis of
leukemic infiltration in CNS is unknown but involves interruption
of tight junctions of the blood-brain barrier through adhesion
molecules on leukemic blasts or increased permeability from
vascular endothelial growth factor.
- An increased risk of CNS
involvement in AML occurs with a high WBC, high circulating
blast count, high LDH, and younger age. It is more commonly
associated with inv(16)(p13q22), chromosome 11 abnormality, or
trisomy 8.
- Monocytic lineage leukemias are also associated with
a 5.7-fold increased risk of CNS disease.
- CSF study and MRI with contrast may be needed. MRI alone is
neither sensitive nor specific enough to establish the diagnosis of
CNS leukemia.
- Neutropenic fever Blood 2012
- Definition:
- Fever is defined as a single oral temperature measurement of
>38.3°C (101°F) or a temperature of >38.0°C (100.4°F) sus-
tained over a 1-h period. 2010 Update by IDSA
- Neutropenia is defined as an ANC of ,500 cells/mm3 or an
ANC that is expected to decrease to ,500 cells/mm3 during the
next 48 h. 2010 Update by IDSA
- ‘‘profound’’ is sometimes used to describe neutropenia in which the ANC is ,100 cells/mm3 2010 Update by IDSA
- ‘‘functional neutropenia’’
- Frequencies of gram-positive, gram-negative, and
polymicrobial bacteremia were approximately 57%, 34%, and
9%, respectively.
- Although isolation of gram-positive organisms
was more common than isolation of gram-negative organisms,
gram-negative bacteremias were associated with greater mor-
tality (5% vs 18%).
- Fluroquinolones reduce all-cause mortality and infection-
related mortality and have been recommended in high-risk patients.
- Initial antibiotics
are directed at covering Pseudomonas aeruginosa and other
Gram-negative bacteria because of higher morbidity associated
with these infections
- Vancomycin is added initially only in cases of
soft tissue infection, suspected catheter-related infections, in a
hemodynamically unstable patient, or in a patient who is previous
colonized with Gram-positive bacteria.
- Coagulase-negative staphylococci, which are
the most commonly identified cause of bacteremia in neutropenic patients, are weak pathogens that rarely cause rapid
clinical deterioration, so there is usually no urgent need to
treat such infections with vancomycin at the time of fever
- A single blood culture positive or coagulase-negative
staphylococci should generally be dismissed as attributable to
a contaminant, assuming that a second set of blood specimens
have been drawn that have negative culture results.
-
- Bacteremia due to viridans streptococci, which may be re-sistant to b-lactams and fluoroquinolones, may result in shock
and adult respiratory distress syndrome. Gastrointestinal mucositis, ceftazidime use, and prophylaxis with ciprofloxacin or levofloxacin are important risk factors for
developing serious viridans streptococci bacteremia during
neutropenia
- ciprofloxacin monotherapy is not an adequate therapy for febrile neutropenic patients because of its weak
activity against gram-positive organisms, especially viridans
streptococci. In combination with vancomycin or clindamycin, however, it is a suitable alternative for patients who are allergic to b-lactams.
- The use of granulocyte
transfusion does not improve survival.Although
controversial, we often use daily granulocyte transfusions for
deep-seated fungal infection not responding well to initial therapy.
- Diagnositic Tests:
- How is blood culture obtained 2010 Update by IDSA
- At least 2 sets of blood cultures are recommended, with a
set collected simultaneously from each lumen of an existing
central venous catheter (CVC), if present, and from
a peripheral vein site; 2 blood culture sets from separate
venipunctures should be sent if no central catheter is present
- a ‘‘set’’ consists of 1 venipuncture or catheter access
draw of $20 mL of blood divided into 1 aerobic and 1 anaerobic
blood culture bottle
- 2 blood culture sets detect
80%–90% of bloodstream pathogens in critically ill patients,
whereas >3 sets are required to achieve .96% detection
- In the neutropenic patient with cancer, collection of
blood culture sets from all CVC lumens (if present), as well as 1
set from a peripheral vein, is advocated during the initial evaluation of fever. Some experts have suggested obtaining both sets
of blood cultures from the CVC alone, without peripheral vein
sampling. However, the Panel does not favor this approach for
initial evaluation, because a catheter-related infection cannot be
ruled out without the simultaneous peripheral culture
-
Studies have
suggested that a CVC blood culture that becomes positive at
least 120 min earlier than a simultaneously drawn peripheral
vein blood culture indicates that the catheter is likely to be the
source of infection
- If
fever persists after empirical antibiotics have been started, then 2
sets of blood cultures (via catheter or periphery) may be obtained
on each of the next 2 days.
- Tests for Fungus: See under fungal infection
-
What Environmental Precautions Should be Taken When
Managing Febrile Neutropenic Patients? MUST READ 2010 Update by IDSA

MASCC < 21 : High Risk patients MASCC score = or >21 Low Risk Patients
2010 Update by IDSA
- Neutropenic enterocolitis / necrotizing colitis / iliocecal syndrome / typhlitis (from the Greek term typhlon, meaning cecum)
- is an ill-defined syndrome characterized by fever and abdominal pain in the setting of neutropenia
- nausea (75%), vomiting (67%), abdominal distension, and watery or bloody diarrhea may be present
- abdominal distension and tenderness or a right lower abdominal mass may be seen
- Carries high mortality
- Polymicrobial Bacteremia is commonly reported
- Pseudomonas spp is most frequent
- Others are E coli, Klebsiella spp,
Staphylococcus aureus, and streptococci
- Approximately 15% of patients have fungal organisms isolated in the blood,
with Candida being the most common isolate.
- The pathogenesis of NE is linked to the damaged gastrointestinal mucosa. This is attributable to chemotherapy and neutropenia
leading to intestinal dysfunction and microbial invasion with, secondarily, edema, inflammation, ulceration, transmural necrosis,
and possible perforation.
- Diagnsosis
- Abdominal CT is often useful.
- Most authors agree that bowel thickening more than 4 mm is a mandatory criterion for establishing the diagnosis of NE.
- A more than or equal to 10-mm wall
thickening was associated with 60% mortality compared with
4.2% with less thickening.
- Ddx:
- appendicitis, diverticulitis, and
ischemic colitis.
- Treatment:
- Abx, Bowel rest, fluid resuscitation, nasogastric suction, parenteral nutrition, and early surgical consultation
- Although equally efficacious as daunorubicin,
Adriamycin is never used in AML following a classic study in
1982, which demonstrated significantly greater incidence of NE
with Adriamycin.
- Parenteral alimentation and nasogastric suction have not proven
useful and are not used in our centers.89 Antibacterial prophylaxis
with quinolones in high-risk neutropenic patients, as recommended
in recent guidelines,86 is an appealing approach, although it is not
known if the incidence is reduced.
- Keratinocyte growth factors,
such as palifermin or repifermin, have been approved (palifer-
min) for prevention of oral mucositis after intensive chemotherapy.
However, no study has demonstrated a reduction in NE with
keratinocyte growth factors, and they are not used for this purpose.
- Transfusion-associated GVHD
Oncological EmergenciesHow I treat hematologic emergencies in adults with acute leukemia Blood 2012 |