A 54-year-old woman with pancytopenia
A 54-year-old woman with a 1-month history of progressive weakness was transported to the emergency department of a local hospital when a family member found her unresponsive. Before this event, the patient had said she had been feeling tired and cold and looking pale for several weeks.
In the emergency department, her temperature was low. Cableomputed tomography (CT) of the head showed a 1.4-cm hyperdense extraaxial mass. Imaging of the chest showed focal consolidations within the anterior segment of the right upper lobe and the left and right lower lobes.
A urine toxicology screen was positive for acetaminophen (Tylenol), opiates, and benzodiazepines. She was given three doses of naloxone (Narcan), which raised her level of arousal; however, she later became obtunded again and was intubated and transferred to Cleveland Clinic.
A new CT scan of the head confirmed a small left temporal, extradural, calcified lesion with no mass effect or overt bleeding; it appeared most compatible with a solitary calcified meningioma—a likely benign finding.
Her medical history includes hypertension, type 2 diabetes (controlled with diet), and osteoarthritis of the spine. In 1999, she had undergone a hysterectomy that necessitated a blood transfusion. She has never smoked tobacco and does not consume alcohol or use illicit drugs. In the past she worked as a nurse’s aid in a nursing home. However, for the past several years she has stayed at home. Her only avocation of note is gardening.
Initial physical examination
The patient is intubated and sedated. Her temperature is 35.3°C (95.5°F), blood pressure 122/81 mm Hg, heart rate 83 beats per minute, and respiratory rate 14 on assist-controlled ventilator settings with an Fio2 of 100% and a positive end-expiratory pressure of 5 cm H2O.
Her pupils are round, equal, and reactive to light. Her face is symmetric and notable for hirsutism over the chin. Her neck is supple and without lymphadenopathy or thyromegaly.
Rhonchi can be heard at both lung bases. She has normal bowel sounds, and her abdomen is soft and nondistended, with no masses or palpable hepatosplenomegaly. She has no pedal edema on either side, and no clubbing or cyanosis. Her skin is intact, without rashes, lesions, or tattoos. She is able to withdraw from painful stimuli in all four extremities.
INITIAL TESTS PROVIDE A CLUE
1. Which of the following is the likely cause of this patient’s pancytopenia?
- Folate deficiency
- Gastrointestinal bleeding secondary to colon cancer
- Paroxysmal nocturnal hemoglobinuria
- Myelophthisis
- Other
Causes of pancytopenia are listed in Table 2.
Folate deficiency
Folate is necessary for thymidylate synthesis, a rate-limiting step in DNA synthesis. The minimum daily requirement for dietary folate intake is 50 μg.
Severe deficiency of folate has been reported to cause pancytopenia in alcoholics.1 Abuse of alcohol leads to an abrupt decrease in serum folate (within 2 to 4 days of ceasing intake of proper amounts of folate, as in an alcoholic binge) by inhibiting its absorption in the proximal jejunum as well as its metabolism in the liver.2 The resulting folate deficiency, if sustained, can develop into megaloblastosis in 5 to 10 weeks.
The duration of weakness and pallor reported by this patient would raise suspicion of folate deficiency if she had a history of malnutrition or of alcohol abuse, but she has neither. Further, her mean corpuscular volume is 82.5 fL, red blood cell folate 391 ng/mL (reference range 257–800 ng/mL), and serum vitamin B12 1,886 pg/mL (22–700 pg/mL), and she has no macro-ovalocytes or hypersegmented neutrophils on a peripheral blood smear. This makes folate or vitamin B12 deficiency less likely.
Gastrointestinal bleeding due to colon cancer
Iron-deficiency anemia, hematochezia, melena, a change in bowel habits, and abdominal pain may be manifestations of colon cancer. Cancers of the colon originate from adenomatous polyps arising from the colonic mucosa.
The quantity of occult blood loss depends on the site of the tumor. Patients with tumors in the cecum or ascending colon lose an average of 9 mL/day, whereas those with tumors in the transverse, descending, or sigmoid colon or rectum lose less than 2 mL/day.3
Pertinent laboratory findings in iron-deficiency anemia are a low iron concentration, a low transferrin saturation, a depleted serum ferritin, and a normal to high total iron-binding capacity. An initial microcytic normochromic anemia eventually progresses to a microcytic hypochromic anemia that has a tendency to increasingly demonstrate anisocytosis and poikilocytosis.
Our patient’s symptoms, signs, and laboratory values (with normocytic normochromic anemia) are inconsistent with symptomatic colon cancer leading to iron-deficiency anemia.
