SAS 3
Hematologic Disorders
1. Patient Case Presentation
Chief complaint
“I’ve been feeling really tired for the last couple of months and I’ve
noticed my hands and feet feel like they are buzzing, tingly, and numb.”
History of present
illness
Ann Minor is a 71-year-old woman who presents to the Veterans Affairs
Medical Center (VAMC) emergency department accompanied by her
daughter. On questioning,
● She states that she has been experiencing fatigue, lethargy, and
generalized weakness for 2–3 months.
● She also has been experiencing tingling and numbness in her
feet and hands, especially while knitting or manipulating small
objects.
● Patient denies weight loss, fever, night sweats, or vision
changes.
Past
history
medical
Medications
admission
on
Allergies
Family/social
history
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Allergic rhinitis
HTN
Hyperlipidemia
Type 2 DM
Insomnia
Menopause
History of DVT (November 1971)
PTSD (Military related; 1965)
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Docusate sodium 100 mg po BID
Aspirin 81 mg po daily
Chlorpheniramine maleate 8 mg po BID
Omeprazole 20 mg po once daily before breakfast
Multivitamin 1 tab po daily
Metformin 500 mg po BID
Pravastatin 20 mg po at bedtime
Lisinopril 10 mg po daily
Amitriptyline 50 mg po daily
No known drug allergies
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Physical
exam
and review of
systems
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Father deceased at age 64 of MI
Mother deceased at age 86; had Alzheimer’s disease
Widowed × 4 years, lives alone approximately 45 miles from
VAMC; family lives on the same farm 1 /4 mile away
(+) tobacco
1 ppd since age 19
(+) alcohol, 1 glass of wine occasionally
She lives on limited income and social security benefits.
(+) fatigue, paresthesias, tongue soreness;
(–) SOB, headache, chest pain, joint pain, hot flashes, polyuria,
or polydipsia
Gen: Elderly, thin Caucasian woman in NAD, with normal affect and
speech, who is pleasant and cooperative and appears tired
VS: BP 146/88, P 89, RR 18, T 36.9°C; Wt 50.9 kg, Ht 5'6'', BMI 18.1
Skin: Pale, turgor normal
HEENT: PERRLA; EOMI; fundi showed no cotton-wool exudates; (–)
photophobia; (+) glossitis; poor dentition
Neck: Supple without LAD; normal carotid upstrokes; no masses; no
lymphadenopathy or thyromegaly
Lungs: Bilateral breath sounds; no rales, rhonchi, or wheezes
CV: RRR by auscultation; no murmurs or gallops
Abd: Soft, nontender; no organomegaly; no masses; normal bowel
sounds present; no abdominal bruits
Ext: No lower extremity erythema, pain, or edema; normal pulses; (+)
paresthesias
Rect: Good sphincter tone; guaiac (–) stool
Neuro: A & O × 3; CN: visual field intact, hearing intact; sensory:
proprioception intact bilaterally; coordination intact; decreased pinprick
on both UE and LE; decreased vibratory sensation LE; (–) ataxia
Labs (All fasting)
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Peripheral Blood Smear Morphology Anisocytosis +1
Basophilic stippling
Poikilocytosis
Hypersegmented neutrophils
Large platelets 2+
Macrocytic red blood cells with megaloblastic changes
Problem list
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Macrocytic anemia consistent with vitamin B12 deficiency
Peripheral sensory neuropathy possibly associated with vitamin
B12 deficiency
Paresthesia suggests abnormality affecting the sensory nervous
system; this could indicate peripheral neuropathy.
Tingling and numbness in the feet and hands, especially while
knitting or manipulating small objects could be indicative of
Peripheral sensory neuropathy.
Due to the cells having an irregular shape (Poikilocytosis),
Anisocytosis is also present and it is most commonly a result of
anemia.
Basophilic stippling is a frequent manifestation of hematologic
disease in the peripheral blood, and it is also observable in bone
marrow aspirates.
Macrocytic red blood cells also indicated possible megaloblastic
anemia.
Hypersegmented neutrophils are also associated with
megaloblastic anemia and are said to be pathognomonic of the
disease.
Excessive smoking is known to cause macrocytosis mainly by
altering the levels of Vitamin B12 and folic acid.
Elevated A1c level indicates Diabetes
Elevated BP (146/88) indicates Hypertension.
Elevated Chlorine levels (Hyperchloremia ) can be associated
with other conditions like diabetes or dehydration, which can
affect the ability of your kidneys to maintain chloride balance.
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2. Overview and discussion of disease state
A. Epidemiology of the disease
Peripheral Sensory Neuropathy
Sensory neuropathy has a prevalence of 1 to 3% in the general population, with an
increase of up to 7% in the elderly, according to studies. It has also been demonstrated
that developing countries have a lower prevalence, which may be due in part to
variations in life expectancy. Globally, Western countries are the most commonly
affected, with a slight preference for females. Diabetes mellitus is the leading cause of
peripheral neuropathy worldwide, according to public health experts. Up to 50% of older
patients with diabetes mellitus will develop distal peripheral neuropathy, which impairs
pain perception and temperature discrimination.
Macrocytic Anemia
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Macrocytosis affects 2% to 4% of the population, 60% of whom have anemia.
Alcohol use accounts for the majority, followed by deficiencies in folate and vitamin
B12 and medications.
Autoimmune causes are more common in middle-aged women. Hypothyroidism and
primary bone marrow disease account for more cases of macrocytic anemia in older
patients.
The prevalence of vitamin B12 deficiency increases in patients older than 60 years.
References:
[1] Sensory Neuropathy - StatPearls - NCBI Bookshelf (nih.gov)
[2] Moore, C. A., & Adil, A. (2022, July 11). Macrocytic Anemia - StatPearls - NCBI Bookshelf.
Macrocytic
Anemia
StatPearls
NCBI
Bookshelf.
https://www.ncbi.nlm.nih.gov/books/NBK459295/#:~:text=Epidemiology%20Macrocytosis%20aff
ects%202%25%20to%204%25%20of%20the,deficiencies%20in%20folate%20and%20vitamin%
20B12%20and%20medications. (Moore & Adil, 2022)
B. Etiology of the disease
Peripheral Sensory Neuropathy
Diabetes mellitus, nerve compression or injury, alcohol use, toxin exposure, genetic
illnesses, and nutritional deficiencies are among the often recognized causes of sensory
neuropathy
Macrocytic Anemia
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Megaloblastic anemia occurs from deficiencies in folic acid and vitamin B12. Folate
deficiency is due to diminished intake (alcohol abuse or malnutrition), increased
consumption (hemolysis or pregnancy), malabsorption (familial, gastric bypass, or
medications like cholestyramine or metformin).
Vitamin B12 deficiency appears in diminished intake (malnutrition), malabsorptive states
(atrophic gastritis either autoimmune or non-autoimmune from Helicobacter pylori or
Zollinger-Ellison syndrome, Diphyllobothrium tapeworm infection, gastric bypass, ileal
resection), or the presence of antagonists (nitrous oxide). Drugs that impair DNA
synthesis are folic acid analogs (ex. methotrexate, trimethoprim-sulfamethoxazole),
nucleic acid analogs (5-fluorouracil, zidovudine), and others (hydroxyurea, pentamidine,
phenytoin, pyrimethamine, sulfasalazine, triamterene).
Non-megaloblastic anemia, the absence of hypersegmented neutrophils, occurs in a
variety of settings. Benign conditions are alcohol consumption (RBC toxicity), hereditary
spherocytosis (impaired volume regulation increases red cell size), hypothyroidism and
liver disease (due to lipid deposition in the cell membrane), and marked reticulocytosis
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from states of excess RBC consumption such as hemolysis or turnover in pregnancy or
primary bone marrow disease (reticulocytes are larger than the average RBCs).
Some cases of macrocytosis are normal variants associated with a genetic
predisposition or found in infants, patients with Down syndrome, and pregnant women.
Others are spurious findings include hyperglycemia concentrates the blood, and when
diluted, the RBCs swell with volume, leukocytosis and paraproteinemia increase sample
turbidity for overestimates of RBC size, or operator error from occlusion of microscope
aperture or sample left out at room temperature too long.
References:
[3] Peripheral Neuropathy: Evaluation and Differential Diagnosis - PubMed (nih.gov)
[4] Moore, C. A., & Adil, A. (2022, July 11). Macrocytic Anemia - StatPearls - NCBI Bookshelf.
Macrocytic
Anemia
StatPearls
NCBI
Bookshelf.
https://www.ncbi.nlm.nih.gov/books/NBK459295/#:~:text=Epidemiology%20Macrocytosis%20aff
ects%202%25%20to%204%25%20of%20the,deficiencies%20in%20folate%20and%20vitamin%
20B12%20and%20medications. (Moore & Adil, 2022)
C. Pathophysiology of the disease
Peripheral Sensory Neuropathy
Positive sensory symptoms are also typical when small- and medium-sized fibers are
affected. This manifestation is primarily caused by the disruption of the afferent neurons,
which transmit impulses from the body's extremities. If these symptoms progress, the
patient will experience "writhing" movements in their hands and feet when they close
their eyes. Pins and needles and "electricity" complaints in the affected extremities,
which have a stocking-glove pattern, are examples of classic clinical findings.
Numbness is a negative neuropathic symptom that frequently affects the foot and is
multifocal and non-length dependent.
Macrocytic Anemia
The equation for mean corpuscular volume [MCV (fL) = Hct (%) X 10 / RBC
(106/microgram)] explains how macrocytic anemia represents large red blood cells
(RBCs) in comparison to total amount. Folate and vitamin B12 are necessary for RBC
nucleic acid synthesis. Without DNA or RNA, erythropoiesis is ineffective with
nuclear/cytoplasmic asynchrony, resulting in larger erythrogenic precursors with
abnormal nuclei (ex. hypersegmentation) but normal cytoplasms. Anemia occurring in
the presence of macrocytosis and hypersegmented neutrophils is known as
megaloblastic anemia. The absence of hypersegmented neutrophils characterizes nonmegaloblastic anemia. This occurs from mechanisms discussed earlier: abnormalities
involving the RBC membrane, excess erythrocytic precursors, increased cell volume, or
RBC toxicity.
Daily folate needs are 100 to 200 micrograms, and the body can absorb 400
micrograms/day. Healthy patients have stores for 4 months. Folate is largely absorbed in
the small bowel. In comparison, daily vitamin B12 requirements are one microgram, and
the body can absorb 2 to 3 micrograms/day. Most patients have several years of B12
stores. Vitamin B12 is absorbed in the ileum when bound by an intrinsic factor (IF), a
protein produced by the gastric parietal cells. Abnormalities in these cascades cause
deficiencies in folate or vitamin B12, respectively.
References:
[5] Sensory Neuropathy - StatPearls - NCBI Bookshelf (nih.gov)
[6] Moore, C. A., & Adil, A. (2022, July 11). Macrocytic Anemia - StatPearls - NCBI Bookshelf.
Macrocytic
Anemia
StatPearls
NCBI
Bookshelf.
https://www.ncbi.nlm.nih.gov/books/NBK459295/#:~:text=Epidemiology%20Macrocytosis%20aff
ects%202%25%20to%204%25%20of%20the,deficiencies%20in%20folate%20and%20vitamin%
20B12%20and%20medications. (Moore & Adil, 2022)
D. Clinical presentation
Peripheral Sensory Neuropathy
Early peripheral neuropathy may manifest as sensory changes that frequently progress,
such as sensory loss, numbness, pain, or burning sensations in the extremities that are
distributed "stocking and glove" style. Proximal numbness, distal weakness, or atrophy
may appear in later stages.
Macrocytic Anemia
❖ Patients with Vitamin B12 deficiency complain of mood disturbances and neurologic
symptoms like loss of balance, memory loss, paresthesias,peripheral neuropathy.
❖ The symptoms of macrocytosis are attributable either to the anemia itself or to the
underlying condition causing the anemia. They may include the following:
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References:
Dyspnea – This is a consequence of anemia; in acute or severe anemia, the
volume of hemoglobin in the blood is inadequate to provide appropriate
oxygenation of the tissues
Headache – This is a symptom of anemia due to decreased oxygenation of the
tissues
Fatigue – This may be attributed to underlying disease, if present, or to inadequate
blood volume
Sore tongue – This may reflect glossitis or atrophy of the tongue, which are
common findings in folate and vitamin B12 deficiencies
Diarrhea or other gastrointestinal (GI) symptoms – These may be present in
patients with tropical or celiac sprue; sprue may cause folate or vitamin B12
deficiencies
Paresthesia or gait disturbances – These suggest vitamin B12 deficiency
[7] Peripheral Neuropathy: Evaluation and Differential Diagnosis - PubMed (nih.gov)
[8](Macrocytosis Clinical Presentation: History, Physical Examination, 2022)
https://emedicine.medscape.com/article/203858-clinical
E. Diagnosis
Peripheral Sensory Neuropathy
● Peripheral neuropathy has many potential causes. Besides a physical exam, which may
include blood tests, diagnosis usually requires;
❖ Neurological examination- check your tendon reflexes, your muscle strength and
tone, your ability to feel certain sensations, and your posture and coordination.
❖ A full medical history- review your medical history, including your symptoms,
lifestyle, exposure to toxins, drinking habits and a family history of nervous
system (neurological) diseases.
Macrocytic Anemia
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Complete blood count (CBC): Healthcare providers use this test to evaluate your red
blood cell count and function.
Peripheral blood smear (PBS): This test is a technique healthcare providers use to
examine your blood cells. Unlike some blood tests that are analyzed by a machine,
healthcare providers analyze your blood cells by looking at them under a microscope.
Reticulocyte count: A reticulocyte count measures the number of immature red blood
cells (reticulocytes) in your bone marrow. Healthcare providers measure reticulocytes to
determine if your bone marrow is producing enough healthy red blood cells.
References:
[9]Peripheral neuropathy - Diagnosis and treatment - Mayo Clinic
[10]C. (n.d.). Macrocytic Anemia: Causes, Symptoms, Types & Treatment. Cleveland Clinic.
https://my.clevelandclinic.org/health/diseases/23017-macrocytic-anemia (n.d.)
F. Treatment guidelines and alternatives
Peripheral Sensory Neuropathy
Pain relievers- such as nonsteroidal anti-inflammatory drugs, can relieve mild
symptoms.
Anti-seizure medications- developed to treat epilepsy, may relieve nerve pain
Topical treatments- can cause modest improvements in peripheral neuropathy
symptoms
Antidepressants- have been found to help relieve pain by interfering with chemical
processes in your brain and spinal cord that cause you to feel pain.
Therapy:
- Transcutaneous electrical nerve stimulation (TENS)
- Plasma exchange and intravenous immune globulin
- Physical Therapy
- Surgery
Macrocytic Anemia
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Patients deficient in vitamin B12 or folate should receive replacement therapy.
Folate 1 mg/day may be prescribed in patients with folate deficiency.
Intramuscular vitamin B12 injections (100-1000 mcg/mo), continued indefinitely, may be
prescribed.
References:
[11]Peripheral neuropathy - Diagnosis and treatment - Mayo Clinic
[12](Macrocytosis Treatment & Management: Approach Considerations, Diet, 2022)
https://emedicine.medscape.com/article/203858-treatment#showall
G. Discussion of treatment options, including drugs of choice, alternatives, monitoring,
and side effects
Peripheral Sensory Neuropathy
Pain relievers containing opioids, such as tramadol (Conzip, Ultram, and others), or
oxycodone (Oxycontin, Roxicodone, and others, can lead to dependence and addiction,
so these drugs are generally not prescribed unless all other treatments have failed.
Nerve pain may be relieved by anti-seizure medications such as gabapentin (Gralise,
Neurontin, Horizant) and pregabalin (Lyrica), which were developed to treat epilepsy.
Drowsiness and dizziness are possible side effects. Topical treatments such as
Capsaicin cream which contains a substance found in hot peppers, can cause modest
improvements in peripheral neuropathy symptoms. You might have skin burning and
irritation where you apply the cream, but this usually lessens over time. Some people,
however, can't tolerate it. The serotonin and norepinephrine reuptake inhibitor duloxetine
(Cymbalta, Drizalma Sprinkle), as well as the antidepressants venlafaxine (Effexor XR)
and desvenlafaxine (Pristiq), may also help with the pain of diabetic peripheral
neuropathy. Antidepressants can cause dry mouth, nausea, drowsiness, dizziness,
appetite changes, weight gain, and constipation.
Macrocytic Anemia
Management of macrocytosis consists of finding and treating the underlying cause. In
the case of vitamin b12 or folate deficiency, treatment may include diet modification and
dietary supplements or injections. If the underlying cause is resulting in severe anemia,
you might need a blood transfusion.
References:
[13] Peripheral neuropathy - Diagnosis and treatment - Mayo Clinic
[14] Macrocytosis:
What
causes
it?
(2023,
January
25).
Mayo
Clinic.
https://www.mayoclinic.org/macrocytosis/expert-answers/faq-20058234
FARM NOTES
Findings
Ann Minor is a 71-year-old Caucasian woman who presents to the Veterans Affairs Medical
Center (VAMC) emergency department with her daughter because of fatigue, lethargy, and
generalized weakness for 2–3 months. She also has been experiencing tongue soreness; and
tingling and numbness in her feet and hands, especially while knitting or manipulating small
objects. The patient denies weight loss, fever, night sweats, or vision changes. The patient
also doesn’t experience SOB, headache, chest pain, joint pain, hot flashes, polyuria, or
polydipsia.
PMH includes allergic rhinitis, HTN, hyperlipidemia, type 2 DM, insomnia, menopause,
history of DVT (November 1971), and PTSD (Military related; 1965). The patient’s father died
due to MI; while her mother had Alzheimer’s disease. She lives alone, approximately 45 miles
from VAMC, and is living on limited income and social security benefits. She smokes tobacco,
1 ppd since the age 19. She also drinks 1 glass of wine occasionally.
BP 146/88, P 89, RR 18, T 36.9°C; Wt 50.9 kg, Ht 5’6’’, BMI 18.1 (underweight). Her
skin is pale. Her tongue is inflamed (glossitis) and sore. Have poor dentition. She experiences
paresthesia. She is negative in the guaiac stool test. Have decreased pinprick (UE & LE) and
vibratory sensation (LE). Lab results (fasting): high chloride, A1C, MCV, T. Bilirubin, AST, and
EPO; and low Hgb, and B12. HDL is 45 mg/dL and LDL-C is 113 mg/dL. Peripheral blood
smear morphology shows anisocytosis +1, basophilic stippling, poikilocytosis,
hypersegmented neutrophils, large platelets 2+, and macrocytic RBC with megaloblastic
changes.
Medications:
● Docusate sodium 100 mg po BID
● Aspirin 81 mg po daily
● Chlorpheniramine maleate 8 mg po BID
● Omeprazole 20 mg po once daily before breakfast
● Multivitamin 1 tab po daily
● Metformin 500 mg po BID
● Pravastatin 20 mg po at bedtime
● Lisinopril 10 mg po daily
● Amitriptyline 50 mg po daily
Assessment
- Macrocytic anemia consistent with vitamin B12 deficiency
- Peripheral sensory neuropathy possibly associated with vitamin B12 deficiency
- Elevated blood pressure
- Increased chloride
- Increased A1C
- Increased MCV
- Increased AST
- Increased EPO
- Decreased Hgb
Recommendation/ Resolution
Pharmacologic:
● Recommend to take vitamin B12. Although the patient is taking multivitamin, she still
has vitamin B12 deficiency. Recommended dose is 1000 micrograms oral vitamin B12
daily for 1 month followed by 125 to 250 micrograms daily or administer 1000
micrograms IM B12 every week for 4 weeks and then administer monthly to replace
vitamin B12 stores.
● Continue Multivitamin 1 tab po daily for vitamin B-complex deficiencies.
● Continue Metformin 500 mg po BID for type 2 diabetesConsider discontinuing
Docusate sodium 100 mg po BID it has no indication for the patient since she has no
constipation.
● Continue Omeprazole 20 mg
● Continue Aspirin 81 mg po daily
● Continue Chlorpheniramine maleate 8 mg po BID for allergic rhinitis
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● Continue Pravastatin 20 mg po at bedtime for hyperlipidemia
● Continue Lisinopril 10 mg po daily for hypertension.
● Consider changing Amitriptyline to Paroxetine for PTSD
Non-pharmacologic:
● Recommend smoking cessation.
● Avoid relevant allergens that may trigger allergic rhinitis.
● Recommend having a dash diet by eating more fruits, vegetables, and low-fat dairy
foods are recommended, cutting back on foods that are high in saturated fat,
cholesterol, and trans fats, eating more whole-grain foods, fish, poultry, and nuts and
limiting sodium, sweets, sugary drinks, and red meats.
Monitoring
● Counsel patient to take Aspirin 81 mg po daily
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Counsel patient to take Omeprazole 20 mg to avoid gastrointestinal bleeding. Take
this medicine only as directed by the doctor. Do not take more of it, do not take it more
often, and do not take it for a longer time than prescribed. Omeprazole tablets may be
taken with food or on an empty stomach, preferably in the morning. Swallow the
capsule and tablet forms of omeprazole whole. Do not open the capsule. Do not crush,
break, or chew the capsule or the tablet.
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Counsel patient to take chlorpheniramine maleate 8 mg orally every 12 hours.This
medication may be taken with food or milk if stomach upset occurs. It is an
antihistamine used to relieve symptoms of allergic rhinitis. Chlorpheniramine maleate
may improve sleep quality regardless of whether the inflammation is allergic.
If you are taking the extended-release capsules, swallow them whole. Do not crush or
chew extended-release capsules or tablets. Doing so can release all of the drug at
once, increasing the risk of side effects.
Do not increase the dose or take the medication more often than recommended by the
doctor or the package instructions without your doctor's approval. Take the medication
regularly in order to get the most benefit from it. To help the patient remember, take
this at the same time(s) each day.
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Counsel patient in taking vitamin B12 to restore B12 stores.
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Counsel patient to take Metformin 500 mg po twice a day with food to decrease the
potential for side effects like diarrhea, nausea, gas, and bloating.
When taking metformin, avoid eating white bread, white rice, white pasta, candy, soda,
desserts, and snacks like chips or crackers since it can spike your blood sugar and will
not necessarily make the metformin not work.
Metformin interacts with alcohol, so avoid binge drinking or regular alcohol intake
when on the medication.
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Counsel patient to take Lisinopril 10 mg po daily for hypertension and management of
DVT.
Counsel patient to take Sertraline
Counsel patient to take Rosuvastatin 20 mg po at bedtime for hyperlipidemia and the
patient has multiple risk factors of ASCVD.
References:
Sertraline: a review of its use in the management of major depressive disorder in elderly
patients
https://pubmed.ncbi.nlm.nih.gov/12093324/#:~:text=Sertraline%20is%20generally%20well%20t
olerated,of%20tricyclic%20antidepressants%20(TCAs).