What is the cause of elevated liver enzymes, leukocytosis, and thrombocytopenia in a patient with metastatic ovarian cancer, atrial fibrillation, and multiple comorbidities?

Differential Diagnosis of Elevated Transaminases, Leukocytosis, and Thrombocytopenia in This Complex Patient

The most likely causes in this patient are chemotherapy-induced hepatotoxicity with bone marrow suppression causing thrombocytopenia, acute infection from rhinovirus bronchiolitis driving leukocytosis, and possible liver metastases from ovarian cancer contributing to transaminase elevation. 1, 2

Primary Contributors to Each Abnormality

Elevated Transaminases (ALT 223 U/L = 4.7× ULN)

Chemotherapy-induced hepatotoxicity is the leading cause, as ovarian cancer chemotherapy regimens (typically platinum-based with taxanes) commonly elevate transaminases. 1

• Liver metastases from ovarian cancer are highly prevalent and cause transaminase elevation in 31% of patients with hepatic involvement, though ALT ≥3× ULN occurs in <5% of these cases. 1
• Baseline ALT >ULN occurs in 16% of cancer patients without liver metastases and 31% with liver metastases, making this elevation significant but not unexpected in metastatic ovarian cancer. 1
• Amiodarone hepatotoxicity is possible but typically causes a mixed or cholestatic pattern rather than isolated transaminase elevation, and usually develops after months of therapy. 1
• The 4.7× ULN elevation exceeds the ≥3× ULN threshold that signals potential drug-induced liver injury and warrants close monitoring. 3

Leukocytosis

Acute rhinovirus bronchiolitis with hypoxic respiratory failure is the primary driver of leukocytosis through systemic inflammatory response. 1

• Cancer itself, particularly ovarian cancer, can cause paraneoplastic leukocytosis through cytokine production. 1
• Corticosteroid use (if given for respiratory failure) would exacerbate leukocytosis. 1
• CLL (chronic lymphocytic leukemia) typically causes lymphocytosis rather than general leukocytosis, but disease progression should be considered. 1

Thrombocytopenia

Chemotherapy-induced bone marrow suppression is the most common cause in cancer patients, particularly with platinum-based regimens used for ovarian cancer. 2, 4

• Drug-induced immune thrombocytopenia (DITP) from chemotherapy agents must be considered, especially if the platelet drop is sudden and isolated. Platinum agents (cisplatin, carboplatin) and bevacizumab (commonly used in ovarian cancer) can cause immune-mediated platelet destruction. 5, 6
• Eliquis (apixaban) does NOT cause thrombocytopenia - anticoagulants affect clotting factors, not platelet production or destruction. 1
• Bone marrow infiltration by ovarian cancer metastases or CLL progression could contribute. 2
• Sepsis or DIC from severe infection could cause consumptive thrombocytopenia, though this would typically present with other coagulation abnormalities. 2

Critical Diagnostic Algorithm

Immediate Actions (Within 2-3 Days)

1. Repeat comprehensive liver panel including ALT, AST, alkaline phosphatase, total and direct bilirubin, albumin, and INR to assess for Hy's Law criteria (ALT ≥3× ULN + bilirubin ≥2× ULN), which signals severe drug-induced liver injury. 1, 7

2. Check creatine kinase to exclude muscle injury as source of transaminase elevation, particularly given hypoxic respiratory failure and potential immobility. 7

3. Obtain complete blood count with differential to characterize the leukocytosis pattern (neutrophilic vs lymphocytic) and quantify thrombocytopenia severity. 8

4. Peripheral blood smear to evaluate for schistocytes (suggesting TTP/HUS/DIC), platelet clumping (pseudothrombocytopenia), or abnormal lymphocytes (CLL progression). 2

5. Coagulation studies (PT/INR, PTT, fibrinogen, D-dimer) to exclude DIC or consumptive coagulopathy from sepsis. 2

If Platelets <50,000/μL

• Antiplatelet antibody testing (anti-GPIIb/IIIa) to detect drug-induced immune thrombocytopenia, particularly if platelet drop was sudden. 5, 6
• Consider holding anticoagulation if platelets <50,000/μL, as bleeding risk increases significantly and the 30-day ATE risk in cancer patients with AF and severe thrombocytopenia is only 2%, while major bleeding risk is 7.8%. 9
• Resume anticoagulation when platelets recover >50,000/μL. 1, 9

Liver-Specific Evaluation

• Right upper quadrant ultrasound to assess for new or progressive liver metastases, biliary obstruction, or hepatic vein thrombosis. 7
• Viral hepatitis serologies (HBsAg, anti-HCV) if not previously documented, as reactivation can occur with chemotherapy. 7
• Review all medications for hepatotoxic agents beyond chemotherapy and amiodarone. 7

Infection Workup

• Blood cultures if febrile or hemodynamically unstable. 1
• Procalcitonin to distinguish bacterial superinfection from viral bronchiolitis. 1
• Chest imaging to assess pneumonia extent and pleural effusion status (given PleurX catheter). 1

Management Strategy Based on Severity

For Transaminase Elevation (4.7× ULN)

Hold or reduce chemotherapy dose until transaminases trend downward, as ALT >3× ULN typically requires dose modification. 1

• Monitor liver enzymes 2-3 times weekly initially, then weekly once stabilizing. 7
• If bilirubin also elevated ≥2× ULN, immediately discontinue suspected hepatotoxic agents and consider hepatology consultation for potential drug-induced liver injury. 1, 7
• Amiodarone can be continued unless cholestatic pattern emerges or synthetic function deteriorates (elevated INR, low albumin). 1

For Thrombocytopenia

If platelets 25,000-50,000/μL:

• Hold anticoagulation temporarily. 1, 9
• Reduce chemotherapy dose intensity or delay next cycle. 4
• Platelet transfusion threshold is typically <10,000/μL for prophylaxis or <50,000/μL if bleeding or invasive procedure planned. 4

If platelets <25,000/μL:

• Platelet transfusion indicated as bleeding risk increases significantly. 4
• Consider thrombopoietin receptor agonists (romiplostim, eltrombopag) if chemotherapy-induced and persistent, though this requires oncology consultation. 4
• If immune-mediated thrombocytopenia confirmed, treat with corticosteroids and discontinue offending agent. 6

For Leukocytosis with Acute Respiratory Failure

• Treat underlying rhinovirus bronchiolitis with supportive care, CPAP optimization, and antibiotics only if bacterial superinfection confirmed. 1
• Monitor for tumor lysis syndrome if leukocytosis is from CLL progression (check LDH, uric acid, phosphate, calcium). 8

Common Pitfalls to Avoid

1. Don't attribute thrombocytopenia to anticoagulation - Eliquis does not cause low platelets; this is either chemotherapy-induced or immune-mediated. 1

2. Don't continue full-dose anticoagulation with platelets <50,000/μL - bleeding risk outweighs stroke risk in this timeframe. 9

3. Don't assume transaminase elevation is solely from liver metastases - chemotherapy hepatotoxicity is more common and requires different management. 1

4. Don't delay repeat testing - with ALT 4.7× ULN, repeat within 2-3 days is mandatory to assess trajectory and exclude Hy's Law criteria. 7, 3

5. Don't overlook drug-drug interactions - amiodarone inhibits P-glycoprotein and may increase Eliquis levels, though dose adjustment is not routinely required. 1

6. Don't forget bone marrow evaluation if thrombocytopenia persists despite adequate megakaryocytes on smear, as marrow infiltration by ovarian cancer or CLL progression may be present. 5, 2