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Severe Hyponatremia with Normokalemia in Pembrolizumab-Lenvatinib Combination Therapy for Metastatic Renal Cell Carcinoma: A Case of Suspected Secondary Adrenal Insufficiency and Clinical Differentials Devina Ravelia Tiffany Subroto; Steven Jonathan; I Putu Bayu Triguna
Open Access Indonesian Journal of Medical Reviews Vol. 6 No. 1 (2026): Open Access Indonesian Journal of Medical Reviews
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/oaijmr.v6i1.826

The combination of Pembrolizumab and Lenvatinib has become the standard first-line treatment for advanced renal cell carcinoma (RCC). However, the overlapping toxicity profiles of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) create significant diagnostic challenges, particularly regarding electrolyte disturbances. Differentiating ICI-induced secondary adrenal insufficiency from TKI-induced toxicity or syndrome of inappropriate antidiuretic hormone (SIADH) is critical, especially in resource-limited settings where rapid hormonal assays are unavailable. A 67-year-old male with metastatic clear cell RCC presented with confusion, fatigue, and nausea 14 days after initiating palliative Pembrolizumab and Lenvatinib. He had a history of partial nephrectomy and was on Candesartan. Evaluation revealed severe hypotonic hyponatremia (113 mmol/L), acute kidney injury (Creatinine 2.2 mg/dL), and a hypertensive crisis (BP 229/138 mmHg). Notably, despite renal impairment and angiotensin receptor blocker therapy, potassium levels were normal (4.2 mmol/L). The hyponatremia was refractory to 3% hypertonic saline. Suspecting secondary adrenal insufficiency, empiric high-dose corticosteroids were administered, resulting in rapid normalization of serum sodium and resolution of symptoms. In conclusion, in patients receiving ICI-TKI therapy, the specific profile of severe hyponatremia with normokalemia—particularly in the context of renal insufficiency and RAAS blockade—serves as a high-value clinical indicator of preserved mineralocorticoid function. This points toward secondary adrenal insufficiency rather than primary adrenal injury or TKI-induced renal tubular acidosis. This case underscores the utility of deductive physiology in oncology practice.

Severe Erythema Nodosum Leprosum Complicated by Warm Autoimmune Hemolytic Anemia: Navigating the Immunosuppressive Paradox Devina Ravelia Tiffany Subroto; Kadek Cahya Adwitya; I Putu Bayu Triguna
Open Access Indonesian Journal of Medical Reviews Vol. 6 No. 1 (2026): Open Access Indonesian Journal of Medical Reviews
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/oaijmr.v6i1.834

Erythema nodosum leprosum (ENL) is a severe, systemic immune-complex mediated complication of multibacillary Hansen’s disease. While anemia of chronic disease is frequently observed in leprosy, the concurrent development of Warm Autoimmune Hemolytic Anemia (wAIHA) is an exceptionally rare and precarious clinical entity. This comorbidity creates a therapeutic paradox wherein the high-dose corticosteroids required to halt hemolysis may exacerbate the risk of sepsis in patients with necrotic skin lesions and compromised barrier function. We report the case of a 42-year-old male with multibacillary Hansen’s disease on multidrug therapy who presented with high-grade fever, progressive fatigue, and necrotic cutaneous lesions. Laboratory evaluation revealed life-threatening normocytic normochromic anemia (Hemoglobin 3.5 g/dL) and a leukemoid reaction (WBC 42,540/µL). Hemolysis was confirmed by elevated lactate dehydrogenase (564 U/L), indirect hyperbilirubinemia, and a strongly positive direct Coombs test (IgG). A diagnosis of wAIHA secondary to severe necrotic ENL was established. Standard high-dose pulse steroid therapy was deemed high-risk due to the patient’s extreme neutrophilia (NLR 80.25) and open necrotic ulcers. Consequently, a tailored regimen of intermediate-dose intravenous methylprednisolone (62.5 mg twice daily) combined with broad-spectrum antibiotics was initiated. This strategy successfully suppressed hemolysis and resolved the ENL reaction without precipitating secondary opportunistic infections. In conclusion, the coexistence of wAIHA and ENL suggests a shared mechanism of dysregulated T-cell immunity and molecular mimicry. This case demonstrates that in scenarios involving high infectious risk, an individualized, intermediate-dose corticosteroid protocol can achieve remission while mitigating the dangers of profound immunosuppression.

Precipitation of Occult Lymphomatous Hemorrhage by Early Initiation of Factor Xa Inhibitors: A Pharmacovigilance Case Study and Critical Reappraisal of DOAC Safety Kadek Cahya Adwitya; I Putu Bayu Triguna
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 2 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i2.1511

Background: The concurrent management of cancer-associated thrombosis (CAT) and active malignancy represents a precarious clinical equilibrium, particularly when the neoplasm involves occult extranodal gastrointestinal (GI) sites. While direct oral anticoagulants (DOACs) have largely supplanted low-molecular-weight heparin (LMWH) as the standard of care for CAT, emerging pharmacovigilance data suggest a specific vulnerability in patients with luminal GI malignancies. Case presentation: We report the case of a 76-year-old frail female presenting with extensive left iliofemoral deep vein thrombosis (DVT). Diagnostic evaluation identified a perfect storm of pathology: Stage IV diffuse large B-cell lymphoma (DLBCL) with bulky retroperitoneal lymphadenopathy encasing the inferior vena cava (IVC) and a suspicious infiltrative mass in the proximal jejunum. Following standard guidelines, the patient was initiated on rivaroxaban. However, this intervention precipitated a catastrophic upper GI hemorrhage (hemoglobin drop to 6.5 g/dL) within 96 hours. A retrospective pharmacokinetic audit revealed critical predisposing factors: severe hypoalbuminemia (1.6 g/dL) increasing the free drug fraction, and an estimated glomerular filtration rate (eGFR) <30 mL/min, suggesting the patient was effectively overdosed relative to her physiological clearance. Conclusion: The empiric use of rivaroxaban in elderly patients with uncharacterized abdominal masses, renal impairment, and cachexia carries unacceptable hemorrhagic risks. We advocate for a systematic bleed-risk stratification protocol, prioritizing LMWH or Apixaban, and the judicious use of IVC filters as bridging therapies in high-risk phenotypes.

A Hematological Triad: Dissecting Synergistic Oxidative and Immune Hemolysis in Dapsone-Treated G6PD Deficiency Devina Ravelia Tiffany Subroto; I Putu Bayu Triguna
Open Access Indonesian Journal of Medical Reviews Vol. 5 No. 6 (2025): Open Access Indonesian Journal of Medical Reviews
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/oaijmr.v5i6.817

Dapsone, a key component of leprosy multidrug therapy (MDT), is a well-known precipitant of oxidative hemolytic anemia in individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. Conversely, Dapsone-induced immune hemolytic anemia (DIIHA) is exceedingly rare. The concurrent presentation of both severe oxidative hemolysis and a positive Direct Antiglobulin Test (DAT) in a patient also receiving Rifampicin creates a profound diagnostic and mechanistic challenge. We present the case of a 42-year-old female with multibacillary leprosy who developed life-threatening, multifactorial hemolytic anemia (Hemoglobin 5.3 g/dL) three months after initiating MDT (Dapsone, Rifampicin, Clofazimine). A comprehensive diagnostic workup was performed, including detailed hematopathology and quantitative G6PD assay. The immunohematological evaluation was positive (DAT and IAT), but critical sub-testing, including monospecific DATs, was unavailable. The workup confirmed severe oxidative hemolysis (Heinz bodies, degmacytes) in the setting of G6PD deficiency (6.0 U/g Hb measured during 12.5% reticulocytosis). Concurrently, the polyspecific DAT and IAT were strongly positive with a pan-reactive antibody, confirming a simultaneous immune-mediated process. Due to polypharmacy (Dapsone, Rifampicin) and incomplete immunohematological data, the precise trigger for the DIIHA component—whether a rare Dapsone-induced autoantibody, a Rifampicin-induced immune-complex, or an oxidative-trigger mechanism—could not be definitively isolated. In conclusion, this case unmasks a complex, synergistic pathophysiology of concurrent oxidative and immune hemolysis. The inability to attribute the autoimmune component definitively to either Dapsone or Rifampicin highlights a critical diagnostic gap. This report underscores the necessity of a complete immunohematological workup (including monospecific DATs) in such cases and demonstrates that management must be multifaceted—addressing both the oxidative insult (drug cessation) and the severe immune-mediated destruction (immunosuppression), even in the face of etiological uncertainty.

Precipitation of Occult Lymphomatous Hemorrhage by Early Initiation of Factor Xa Inhibitors: A Pharmacovigilance Case Study and Critical Reappraisal of DOAC Safety Kadek Cahya Adwitya; I Putu Bayu Triguna
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 2 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i2.1511

Background: The concurrent management of cancer-associated thrombosis (CAT) and active malignancy represents a precarious clinical equilibrium, particularly when the neoplasm involves occult extranodal gastrointestinal (GI) sites. While direct oral anticoagulants (DOACs) have largely supplanted low-molecular-weight heparin (LMWH) as the standard of care for CAT, emerging pharmacovigilance data suggest a specific vulnerability in patients with luminal GI malignancies. Case presentation: We report the case of a 76-year-old frail female presenting with extensive left iliofemoral deep vein thrombosis (DVT). Diagnostic evaluation identified a perfect storm of pathology: Stage IV diffuse large B-cell lymphoma (DLBCL) with bulky retroperitoneal lymphadenopathy encasing the inferior vena cava (IVC) and a suspicious infiltrative mass in the proximal jejunum. Following standard guidelines, the patient was initiated on rivaroxaban. However, this intervention precipitated a catastrophic upper GI hemorrhage (hemoglobin drop to 6.5 g/dL) within 96 hours. A retrospective pharmacokinetic audit revealed critical predisposing factors: severe hypoalbuminemia (1.6 g/dL) increasing the free drug fraction, and an estimated glomerular filtration rate (eGFR) <30 mL/min, suggesting the patient was effectively overdosed relative to her physiological clearance. Conclusion: The empiric use of rivaroxaban in elderly patients with uncharacterized abdominal masses, renal impairment, and cachexia carries unacceptable hemorrhagic risks. We advocate for a systematic bleed-risk stratification protocol, prioritizing LMWH or Apixaban, and the judicious use of IVC filters as bridging therapies in high-risk phenotypes.

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