Crit Bit Corner

Case Study

59 y.o. male with a history of:

• AML dx in 2025
• NSTEMI s/p PCI
• Ischemic cardiomyopathy EF 25%

Presented to ER with SOB, vomiting, and diarrhea.

Patient was admitted with Acute Myeloid Leukemia (AML)—a disease defined by rapid, uncontrolled proliferation of immature white blood cells. From the start, the patient carried a high tumor burden, meaning there were already massive numbers of abnormal cells circulating and occupying the bone marrow. On admission, the patient was relatively stable. Labs were abnormal, but consistent with the diagnosis. Pt developed an AKI requiring iHD. The plan was straightforward: initiate therapy, monitor closely, and manage expected complications. Treatment began with a combination of medications designed to aggressively target the leukemia:

• Hydroxyurea

• Cytarabine

• Fludarabine

• Gilteritinib

Each of these therapies had a different mechanism, but they all shared the same goal: kill leukemic cells quickly and effectively.

And they did... Within the first 24–48 hours, the patient’s course began to change.

• Urine output started to decline.
• Potassium began to rise.
• Phosphate and uric acid followed.
• Calcium started to fall.

At the bedside, the patient described vague but concerning symptoms:

• Increasing fatigue
• Nausea
• Generalized weakness
• A sense that something “wasn’t right”

Telemetry began to show subtle changes—more ectopy, less stability. Then the shift accelerated.

• Potassium continued climbing.
• The QRS began to widen.
• Hemodynamics became unstable.

Despite escalating interventions, the patient ultimately arrested.

This progression felt sudden. But it wasn’t.

It was the predictable physiologic consequence of Tumor Lysis Syndrome (TLS) unfolding in real time.

How the Medications Work

Understanding these medications is key to understanding why TLS develops so quickly.

Hydroxyurea: Rapid Cytoreduction

Hydroxyurea works by inhibiting ribonucleotide reductase, an enzyme required to convert ribonucleotides into deoxyribonucleotides—the building blocks of DNA.

Without these building blocks:

• Cells cannot synthesize DNA
• Rapidly dividing cells (like leukemic blasts) are particularly affected

Clinical effect:

• Rapid reduction in circulating white blood cells

TLS implication:

• Causes early, rapid cell death, releasing intracellular contents into circulation almost immediately

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Cytarabine: Disrupting DNA Replication

Cytarabine is a pyrimidine analog that becomes incorporated into DNA during replication.

Once incorporated:

• It inhibits DNA polymerase
• Terminates DNA chain elongation
• Triggers apoptosis (programmed cell death)

Clinical effect:

• Highly effective at killing rapidly dividing leukemic cells

TLS implication:

• Leads to massive intracellular breakdown as large numbers of cells undergo apoptosis simultaneously

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Fludarabine: Blocking DNA Synthesis and Repair

Fludarabine is a purine analog that interferes with multiple aspects of DNA metabolism:

• Inhibits DNA polymerase
• Inhibits DNA primase
• Disrupts DNA repair mechanisms

This leads to:

• Accumulation of DNA damage
• Cell death, even in cells not actively dividing

Clinical effect:

• Potent cytotoxicity against leukemic cells

TLS implication:

• Expands the number of cells undergoing death—not just rapidly dividing ones

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Gilteritinib: Targeted Cellular Shutdown

Gilteritinib is a FLT3 inhibitor.

FLT3 is a receptor tyrosine kinase that, when mutated in AML, drives:

• Uncontrolled proliferation
• Survival signaling in leukemic cells

By inhibiting FLT3:

• The survival pathways of the cancer cells are shut down
• Cells undergo apoptosis

Clinical effect:

• Targeted killing of AML cells with FLT3 mutations

TLS implication:

• Even though it is “targeted,” it can still lead to rapid and effective tumor cell death, contributing to TLS

The Cellular Breakdown

To understand TLS, you have to think at the level of the cell. Every tumor cell contains:

• High concentrations of potassium
• Phosphate stored in nucleic acids and ATP
• DNA and RNA, which are rich in purines

When these cells rupture:

Potassium floods the bloodstream

Potassium is primarily intracellular. When cells lyse, potassium rapidly shifts into the extracellular space, overwhelming the body’s ability to redistribute or excrete it. This leads to acute hyperkalemia, often the earliest and most dangerous abnormality.

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Phosphate rises dramatically Tumor cells contain large amounts of phosphate. When released, phosphate levels increase quickly and bind circulating calcium. This leads to:

• Hyperphosphatemia
• Secondary hypocalcemia

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Nucleic acids become uric acid

DNA and RNA are broken down into purines, which are metabolized into uric acid. Uric acid is poorly soluble—especially in acidic urine—and begins to:

• Form crystals
• Deposit in renal tubules
• Obstruct flow

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Calcium drops

As phosphate binds calcium, serum calcium levels fall. This contributes to:

• Neuromuscular irritability
• Seizures

Early Warning Signs

Before collapse, TLS gives clues. Subtle clinical changes:

• Nausea and vomiting
• Fatigue or weakness
• Muscle cramping
• Decreasing urine output

Lab trends:

• Rising potassium
• Rising phosphate
• Rising uric acid
• Falling calcium

The key is recognizing the pattern, not just isolated abnormalities.

Hyperkalemia Treatment

Calcium: Protects the Heart, Does Not Fix the Problem

Calcium works by:

• Increasing the threshold potential of cardiac cells
• Restoring the gap between resting and threshold potentials

This stabilizes the cardiac membrane and reduces the risk of arrhythmia. But it does nothing to remove potassium from the body. Calcium buys time. It does not solve hyperkalemia. This is why a patient can transiently improve on the monitor but still arrest if potassium is not corrected.

Shifting Potassium: Temporary Measures

• Insulin + glucose drives potassium into cells
• Beta-agonists stimulate intracellular uptake
• Bicarbonate helps in acidotic states

These are temporary redistributions—not removal.

Removing Potassium: The Only Definitive Fix

• Renal excretion (if kidneys are functioning)
• Potassium binders
• Dialysis (most effective and rapid in severe TLS)

Case Study Cont.

What happened to this patient followed a clear physiologic sequence:

Treatment triggered rapid tumor cell death. ↓ Intracellular contents flooded the bloodstream. ↓ The kidneys became overwhelmed and began to fail. ↓ Potassium rose to levels that disrupted cardiac conduction. ↓ Electrical instability progressed to cardiac arrest.

This process unfolded over hours—not seconds.

Why This Case Matters

TLS is one of the clearest examples of why trends matter more than isolated values. The opportunity to intervene is not when potassium is critically high—it is when it is rising. It is when:

• Urine output begins to fall
• Phosphate and uric acid begin to climb
• The overall pattern starts to emerge

By the time the monitor changes, the process is already advanced.