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Tumor lysis syndrome (TLS)

  • Pathophysiology: When initiating treatment for a malignancy with a large tumor burden or high cell turnover rate, rapid cell lysis can occur, releasing intracellular contents (potassium, phosphorus, and nucleic acids that break down into uric acid) into the systemic circulation. This can lead to kidney injury (uric acid is a renal vasoconstrictor and deposits in the tubules) and electrolyte abnormalities.

  • Symptoms: Nausea, vomiting, symptoms of hyperkalemia (arrhythmias), hypocalcemia (seizures), renal failure

  • Diagnosis: ↑uric acid, ↑phos, ↑K+, ↓Ca2+ (due to calcium-binding by phosphorus)

  • Prophylaxis/treatment:

    • - Hydration: Aggressive IVF to maintain urine output 80–100 cc/hr to improve excretion of uric acid and phosphorus

    • - Uric Acid: For high risk cases, give rasburicase before treatment, then start allopurinol. For intermediate risk cases, start allopurinol before treatment. Add rasburicase before or during treatment if uric acid ≥ 8 mg/dL (consult heme/onc before starting). Allopurinol decreases the efficacy of rasburicase, so wait to give allopurinol until after rasburicase normalizes the uric acid level if possible.

    • - Electrolyte management: Treat hyperkalemia, give phosphate binders. Do not replete calcium unless necessary for symptoms, particularly if phosphate is high as it can worsen renal damage.

Disseminated intravascular coagulation (DIC)

  • Diagnosis: ↓fibrinogen, ↑D-dimer, ↓platelets, ↑aPTT/PT, schistocytes on smear

  • Treatment: Supportive care, transfuse blood products as needed, treat underlying cause

Hyperviscosity syndrome/leukostasis

  • Pathophysiology: Increased viscosity of blood due to increased protein or increased cellularity

    • - Hyperproteinemia from monoclonal gammopathies (most common Waldenström; IgM is large and sticky)

    • - High WBC from leukemia/lymphoma can cause leukostasis, which has a seven day mortality of 20–40%. The disease type and “stickiness” of the WBCs determine the level at which the WBC count becomes dangerous:

      • AML (>50–100K/μl)

      • ALL (>100–150K/μl)

      • CML (>200–250K/μl)

      • CLL (>400–500K/μl)

  • Clinical features: Fever, chest pain, shortness of breath, blurry vision, headache, AMS, priapism

  • Diagnosis: WBC, SPEP, light chains, BMP, LFTs, TLS/DIC labs

  • Treatment: Aggressive hydration. Call hematology.

    • - Hyperproteinemia → Plasmapheresis

    • - Hyperleukocytosis → Leukapheresis +/– cytoreduction (hydroxyurea). Avoid RBC and platelet transfusions. Start chemotherapy ASAP.

Neutropenic fever

  • Definition: Single oral temperature ≥38.3°C (101°F) or ≥38°C (100.4°F) for ≥1hr + absolute neutrophil count (ANC) <500/μl or predicted nadir <500/μl within 48 hrs based on trend (IDSA Guidelines)

  • Source of infection:

    • - Most often from gut translocation due to breakdown of GI barrier after receiving chemotherapy. However, a pathogen is isolated in only 20–30% of cases (Freifeld et. al. Clinical Infectious Diseases 2011).

    • - Most common pathogens: GNRs, GPCs (line infections and mucositis), fungal (more common if prolonged neutropenia, TPN, or prolonged broad-spectrum antibiotics)

  • Diagnosis:

    • - Examine mouth to evaluate for mucositis, lines for signs of infection, skin to evaluate for infection, abdominal exam (do not perform a digital rectal exam in neutropenic patients)

    • - Labs: CBC with differential, CMP, blood cultures ...

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