Methotrexate Induced Pancytopenia: A case report
Christine Rajathi1, Cecily Ruba2, Mahalakshmi3
1IMCU, Kauvery Hospital, Cantonment.
2Nurse Educator, Kauvery Hospital, Cantonment,
3Nursing Superintendent, Kauvery hospital, Cantonment
Abstract
The well reported Methotrexate (MTX) toxicities are based on the duration and cumulative losing of drug. The typical toxicities can be predicted by the timing of drug administration. Oral ulcers and Pancytopenia are well-known toxicities that occur late. Low dose MTX ttherapy can become problematic, in particular with the middle aged, who are at a greater risk for significant myelo suppression. We present a case of 58 years’ young female with pancytopenia, with severe neutropenia.
Background
Methotrexate is a widely used drug most commonly used in the treatment of varicose malignancies and autoimmune disorders, including rheumatoid arthritis and elective abortions. It is an inhibitor of cellular proliferation. As such cells with the highest turnover or reduced half-life are more susceptible to its effects. As a consequence, when a patient’s oral epithelial cells are affected mucositis develops, Pancytopenia leads to increased bleeding and easily bruising, macrocytic erythrocytes and an increased risk of infection.
Case Presentation
A 58 years’ young Indian female, with a past medical history of type 2 DM on treatment since 2 years, and Rheumatoid Arthritis, presented to the emergency room with oral ulcers, fever, loose stools and abdominal pain. She also experienced increasingly bruising for the last couple of weeks. These bruises progressed to open ulcers provoked by minimal trauma.
The patient had no prior haematological or oncological pathologies. Her home medications included Tab.Metformin 500mg Folic acid and Methotraxate. Her Rheumatologist had recently changed her dosage of Methotexate from 40mg weekly once, approximately 2 weeks prior due to worsening of her Rheumatoid arthritis symptoms.
Apparently the patient did not have a proper outpatient monitoring of CBC, Creatinine or liver functions tests after MTX dose was increased.
Social History
She did not have history of cigarette smoking or alcohol addiction
No known medicine or environmental allergies.
Past Medical History
She is a known case of Type 2 DM and Rheumatoid Arthritis and on treatment.
Past Surgical history
No known surgical history.
Physical Examinations
Vital signs
| Pulse | 140/ bpm |
|---|---|
| Respiratory rate | 28mins |
| Blood pressure | 140/80 mmhg |
| Temperature | 98.8°F |
| Skin | Multiple Petechiae scattered in the upper body pallor |
| Mouth | Oral Ulcers |
| Upper body | Petechiae Scattered in the upper body. |
| Foot | Pedal Edema |
Initial evaluation
Bone marrow done: Report was markedly hypo cellular and showed trilineage reduction consistent with drug induced cytopenia.
Consideration of Methotrexate Dosage
MTX may be administered orally in low doses (5-10 mg/mz) or parenteral in high dose (725 mg/mz). The starting dose is usually 5 to 10mg given as a single weekly dose. Frequent administration is associated with a significantly increased risk of liver toxicity. If the oral dose of MTX exceeds 15 mg, consideration should be given to splitting the dose with each halt given to 12 hours apart for improved bio availability.
Investigations
Patient became pancytopenia
| WBC | 300cells/cumm, |
| Basophil | 0.0%, |
| Lymphocytes | 1.4% |
| Packed cells volume | 25.8% |
| Hb | 6.2 |
| MCV | 92.1 |
| Platelet | 4000cells/cumm, |
Her last CBC 1 Week prior was WBC (5600 cells/cu mm),
After 2 days her
| Hb | 8.6 |
| Platelet | 27000 |
| Creatinine | 3.6 |
| Sodium | 116 |
| Potassium | 3.1, |
| Dengue IgG IgM | negative |
ANA was (2+) and DNA Negative
Bone Marrow study: markedly hypo cellular and showed tri-lineage reduction consistent with drug induced cytopenia.
Ultra sonogram abdomen: Revealed renal parenchymal changes. Suggestive of chronic Kidney disease
Treatment during hospitalization
The patient was transfused 10units of platelets and 2 units of packed cells during her ward stay and given broad spectrum antibiotics and antifungals. Next day fever settled, serum creatinine showed a decreasing trend and leucopenia improved on administration oPEGylated G–CSF.
However, she had a worsening respiratory failure and requirements of NIV during ICU stay. Cardiologist review was obtained and no obvious cardiac pathology was evident.
Methotrozeate induced probable lung toxicity was considered and she was started on steroids. In View of worsening metabolic and respiratory acidosis family was advised intubation. CT chest could not be done. She was intubated. as per family request she was discharged against medical advice.
Family opted to continue furthers therapy at government hospital hence, she was advised to be shifted in a ventilated ambulance urgently as soon as possible for further critical care management. Risk of life threatening, infections and bleeding have been explained to family.
Further follow up could not be done since we could not contact them thereafter.
Crucial treatment plan with calcium folinate for Methotrexate toxicity.
High dose IV calcium folinate (leucovorin) rescue is commonly used for elevated plasma methotrexate levels, However, it is less effective at high methotrexate concentrations. Tere have also been reports of treatment failure as a result of competitive cellular uptake and reduced methotrexate efficacy. It is also important to remember that calcium folinate does not reduce serum methotrexate levels, but rather replenishes the intra cellular pool of tetrahydrofolate to mitigate methotrexate toxicity.
Calcium folinate rescue should be started within 24 to 36 hours of the start of the Methotrexate infusion and the prescribed dose administered every six hours until plasma Methotrexate levels are less than 0.1 micromol /L (or 0.05 micromol/L where measurable)
Methotrexate levels are generally recommended to be measured at 24,48 and 72 hours post-completion of the infusion.
Glucarpridase
Glucarpridase (also known as carboxypeptidase G2 or CPG2) is a recombinant bacterial enzyme that rapidly lowers plasma methotrexate levels by converting it to inactive metabolites,
Glucarpidase is recommended for patients with a toxic plasma methotrexate level who have been treated with all standard rescue and supportive measures.
Skilled nursing care
Key nursing care interventions for a patient with methotrexate-induced pancytopenia:
- Monitor CBC Regularly: Track white blood cell (WBC), hemoglobin, and platelet counts frequently to assess the severity of pancytopenia and guide treatment decisions.
- Implement Neutropenic Precautions: Enforce strict hand hygiene, mask usage, and limit exposure to crowds to minimize the risk of infection due to neutropenia.
- Observe for Signs of Infection: Monitor for fever, chills, sore throat, or other infection symptoms. Early detection of infection is critical as the patient is immunocompromised.
- Assess for Bleeding: Check for signs of thrombocytopenia, such as bruising, petechiae, or unexplained bleeding (e.g., nosebleeds, gums). Implement bleeding precautions if necessary.
- Administer Blood Products as Needed: If hemoglobin or platelet levels drop significantly, administer blood transfusions (e.g., packed red blood cells, platelets) as ordered by the healthcare provider.
- Support with Pain and Comfort Measures: Provide comfort measures for symptoms like fatigue, pain, and mucositis (e.g., soft foods, warm saline mouth rinses).
- Monitor for Gastrointestinal Symptoms: Methotrexate can cause nausea, vomiting, and mucositis. Administer antiemetics and ensure hydration as needed.
- Provide Patient Education: Educate the patient about signs of infection, bleeding, and when to seek help, as well as the importance of following the prescribed methotrexate regimen.
- Encourage Rest and Energy Conservation: Fatigue is common with anemia, so encourage frequent rest and energy conservation techniques to help manage symptoms.
- Promote Emotional Support: Offer emotional support and counseling to help the patient cope with the stress and anxiety related to the diagnosis of pancytopenia and the need for prolonged treatment.
These interventions focus on prevention, early detection, and supportive care to manage the risks associated with methotrexate-induced pancytopenia.
Conclusion
Thus Methotrexate-induced pancytopenia is a serious complication that requires careful monitoring and management to prevent life-threatening consequences such as infection, bleeding, and anemia. Early detection through regular blood count assessments is essential to guide treatment decisions, including potential dose adjustments or discontinuation of Methotrexate. Supportive care, including blood transfusions and infection control measures, plays a critical role in managing the patient’s condition. Despite these interventions, the prognosis can be poor, particularly in patients with underlying comorbidities or severe bone marrow suppression. A comprehensive, multidisciplinary approach, including patient education and emotional support, is vital to improving outcomes and quality of life for patients affected by this complication.
Ms. Christine Rajathi
OT-Incharge
Ms. Cecily Ruba
Nurse Educator
B. Mahalakshmi
Nursing Superintendent
