Clinical Vignette:

A 36-year-old male came in to your clinic for the chief complaints of anemia and jaundice.

At the time of presentation, the patient was a recent immigrant from Iran who wished to establish care with
a local physician. He had been chronically jaundiced and anemic since childhood, with multiple episodes of
severe anemia requiring transfusion. He reported receiving more than 30 units of blood prior to age 17. Folic
acid and Iron supplements were his only medication. He has no history of tobacco or alcohol abuse.

The patient is married with 1 child and works as a university professor. His mother and 1 sister both have
persistent anemia also, although they are not as severely affected as he is. His father and 3 brothers have no
known hematologic disorders.

Physical Examination:

The patient was a well-nourished, well-developed male appearing jaundiced.

The following vital signs were recorded: blood pressure 130/75 mmHg, Heart rate 72 beats per minute,
Respiration rate 16 breaths per minute, and temperature of 36.8 Celsius.

Icteric sclera, pale conjunctiva, no anterior neck mass, no cervical lymph nodes palpated.

Adynamic precordium, distinct heart sounds, normal heart rate and regular rhythm

Equal chest expansion, Clear Breath sounds

Nontender splenomegaly was noted extending to the level of the umbilicus.

Full and equal pulses, pale nailbeds, skin appears jaundiced

No neurosensory or motor deficits.

Guide Questions for the Students:

2. What is the most likely diagnosis and what are the differential diagnoses for these findings?

Most likely diagnosis: Hb E-β0-thalassemia. The high normal RBC count with decreased Hb is most
consistent with thalassemia being the etiology for the patient’s microcytic hypochromic anemia. The MCV to
RBC count ratio of 8.8 (48.7/5.52) also favors thalassemia and not iron deficiency, as does the elevated
bilirubin and ferritin. The only α-thalassemia presenting with severe anemia and a low MVC is Hb H disease,
and this was ruled out by the HPLC and gel electrophoresis studies. The absence of Hb A by HPLC rules out
Hb E/β+-thalassemia, a condition in which Hb A usually represents approximately 30% of the total Hb.9
Homozygous Hb E without concurrent thalassemia would have a similar appearance on HPLC fractionation
and Hb electrophoresis but is inconsistent with the clinical picture, as this condition alone causes only mild, if
any, anemia and microcytosis. Although family history, severity of disease, and laboratory studies all support
the diagnosis, molecular studies are necessary as definitive proof for coinheritance of Hb E and β-
thalassemia since Hb A2 quantitation is not possible.

Differential diagnoses:

Anemias can be separated into macrocytic or microcytic based on the MCV being either increased (>100 fL)
or decreased (<80 fL), respectively. Macrocytic anemias are normochromic and are most commonly
associated with vitamin B12 and/or folate deficiency. Microcytic hypochromic anemias are caused by a
quantitative defect in Hb synthesis. The differential diagnosis includes iron deficiency anemia, anemia of
chronic disease, thalassemia, and sideroblastic anemia.

Symptoms iron deficiency anemia of chronic thalassemia sideroblastic

anemia disease anemia
Icteric sclera +
pale conjunctiva +
Blood
transfusion

Case 4:

Mr. Hank McCoy consulted at the emergency room for dyspnea. On a quick interview, Mr.

McCoy is 23 years old and has been having flu-like symptoms for 4 days (fatigue, headache, myalgia). The
sudden onset of difficulty of breathing prompted him to go immediately to the ER.

On further probing, his skin has always been slate-gray which he apparently inherited from his father. It
wasn’t noticeable at birth. During childhood, he was pale and eventually his color changed and deepened
into slate-gray during his teens. No consultation was done. He has no prior hospitalizations.

Other systems: occasional mild headaches that started during his teens

Physical Examination at the Emergency Room:

awake, unable to ambulate

BP 100/60 HR 110 RR 24

Pale palpebral conjunctiva, cyanotic lips, generalized grayish skin discoloration

Symmetrical chest expansion, clear breath sounds

Distinct heart sounds, regular heart rate, no murmurs

Soft nontender abdomen

No clubbing in the extremities

Guide to Presentation
9. Discuss your treatment and management
Treatment varies based on the kind of methemoglobinemia that you have. For example, a newborn
with the Type 2 form of the condition will need very different treatment from someone who
developed the condition because they were exposed to toxic substances or used certain
recreational drugs.
People with Type 1 methemoglobinemia or Hemoglobin M disease may not need treatment. If they
do, healthcare providers may use the following medications to reduce methemoglobin levels:

Methylene blue: The medication is a well-known antidote for methemoglobinemia.

Exchange transfusion (which replaces abnormal hemoglobin with normal

hemoglobin) may be considered for G6PD-deficient patients who are severely
symptomatic or unresponsive to methylene blue.
Patients who are on long-acting medication (eg, dapsone) may have initial
treatment success with subsequent relapse of symptoms. Gastric lavage followed
by charcoal administration may decrease this prolonged drug effect. These
patients should be monitored closely and retreated with methylene blue as
necessary.

Vitamins C and B2.

It was concluded that vitamins especially vitamin C and E can reduce oxidative effects which
induced methemoglobin formation in vitro and could be used as an alternative medication.

Treatment for acquired methemoglobinemia

Depending on circumstances, acquired methemoglobinemia may be a medical emergency that
requires immediate treatment such as intravenous hydration and oxygen. Most people with
acquired MetHb receive methylene blue.

What are treatment complications?

People with G6PD deficiency may develop hemolysis if they have repeated methylene blue
treatments. Hemolysis happens when your red blood cells fall apart earlier than usual or
inappropriately.

 
Thalassemia Iron deficiency Anemia of
  anemia chronic disease
 Age: 36 years + - -

Male + - -

Mother and daughter have persistent anemia +

but father and brothers have no disorder

Icteric sclera + + -

Pale conjunctiva + + -

Jaundiced skin + - -

Pale nail-beds + + +