Hematology‎ > ‎

Oncological Emergencies


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
        • Usually takes 1-3 days
      • 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 
        • Kidneys, Heart, Penis
    • 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 Emergencies
How I treat hematologic emergencies in adults with acute leukemia Blood 2012
Comments