a) complete blood cell count with red cell indices
b) hemoglobin electrophoresis
c) red cell osmotic fragility test
d) restriction-fragment length polymorphism (RFLP) analysis of her ß-globin gene
e) reticulocyte count

View Answer A: complete blood count with red cell indicees

Erythrocytes of the beta-thalassemia heterozygote have an MCV of 55 to 80 fl and a corresponding reduction in MCH. The RDW is normal in contrast to iron deficiency anemia, in which it is high. People who are silent carriers can have a normal MCV value. The red cell count is often elevated and the blood film commonly shows target cells and basophilic stippling (Plate III-4, M). Reticulocyte counts may be elevated (2% to 3%), but this is an inconsistent finding. Detection of most heterozygotes is simplified by the presence of an elevated HbA2 level (4% to 6%), which is most accurately measured by column chromatography. HbF level may be slightly increased (1% to 3%). In delta-beta-thalassemia carriers, the HbA2 level is normal or reduced, and the HbF concentration is increased (5% to 20%).

Homozygotes are severely anemic with hemoglobin levels of less than 5 g/dl in the absence of transfusion. MCV and MCH are reduced, and the reticulocyte count strikingly elevated. The blood film findings are characterized by nucleated red cells, Pappenheimer and Howell-Jolly bodies, marked anisocytosis, poikilocytosis, and polychromatophilia. The bone marrow is hypercellular with marked erythroid hyperplasia and increased iron stores. Heinz bodies can be demonstrated by special staining methods (Plate III-4, P). Fetal hemoglobin is the major hemoglobin component, with absent or very reduced levels of HbA. The HbA2 level shows considerable variation. Other indicators of chronic hemolysis are present, such as unconjugated hyperbilirubinemia, elevated LDH level, and decreased haptoglobin. Radiography of the skull may show the "hair on end" appearance of an enlarged diploic space, and other bones may appear osteoporotic.

Differential diagnosis

The heterozygous beta thalassemias may be confused with iron deficiency and other microcytic anemias. There are few disorders that may be confused with the severe homozygous beta thalassemias. Improperly managed patients with serious growth retardation, impaired nutrition, and marked hepatosplenomegaly superficially resemble individuals with advanced cirrhosis of the liver or malignancy.

Treatment

Heterozygous beta thalassemias require only recognition, so that iron is not injudiciously administered, and carriers can be offered counseling. Screening programs, based on the detection of microcytosis and presence of elevated HbA2 levels, are practical in groups with a high disease prevalence. When a family is at risk for having homozygous offspring, prenatal diagnosis is possible. In parts of Greece, Italy, and Cyprus, screening, counseling, and prenatal diagnosis have led to a nearly 100% reduction in the numbers of homozygotes born.

Intensive transfusion therapy and chelation of excessive iron have improved the management of severe disease. When transfusion is started very early in life and the hemoglobin levels are kept at 9 to 10 g/dl, erythropoiesis is suppressed, marrow expansion does not occur, severe hemolysis is not present, and growth and development are near normal. Besides the usual complications of transfusion, such as alloimmunization and transmission of retroviral infection, the iron burden, deposited in tissues as a result of the destruction of transfused blood, must be removed by chelation to prevent the development of transfusion-induced hemochromatosis. Desferrioxamine (Desferal), a chelating agent, is given by prolonged subcutaneous or intravenous infusion, 8 to 12 hours nightly, 5 to 6 days weekly, at doses of 2 to 6 g/day, using a portable infusion pump. The regimen must be tailored to each individual as the amount of iron excreted varies. Although optimum chelation therapy can induce negative iron balance, the ultimate effects of this treatment are not yet known. When treatment is started after significant iron accumulates, the cardiomyopathy may not always be reversible and is a leading cause of death, although intense chelation may reduce the prevalence of arrhythmias and congestive failure. Ideally, chelation should be started in young children before the acquisition of excessive iron stores. Low doses of vitamin C may increase the excretion of iron by desferrioxamine and can be used in vitamin C depleted individuals while they are receiving chelation treatment. An effective oral chelating agent that provides relief from the arduous regimen of subcutaneous infusion may soon be available.

Splenectomy may be performed when the red cell survival shortens. This reduces the excessive red cell destruction and cytopenias of hypersplenism and lengthens the interval between transfusions. Severe postsplenectomy infection is a risk that must be weighed and argues for delaying surgery as long as possible. Polyvalent pneumococcal, Haemophilus influenzae and Neisseria meningitidis vaccine should be given before surgery and prophylactic penicillin afterward.

Bone marrow transplantation has been employed in severe beta thalassemia and considerable experience has been gained in Italian centers. It is the sole way to eradicate the disease. However, the best candidates are the youngest children, as older, more heavily transfused patients are less likely to become engrafted and have higher morbidity and mortality. Because transfusion and chelation can allow normal development and a decent quality of life for many years, and because bone marrow transplantation still has appreciable short-term mortality, the decision to recommend this therapy has been very difficult. However, in children who have little or no liver disease as a result of efficient chelation, transplantation using haploidentical donors results in a disease-free survival rate of 95%. If these results are replicable, then early transplantation may be the most efficacious and cost-effective method of treatment and free the patient from the lifelong burden of parenteral chelation therapy. If the promise of an effective oral chelating drug is realized, the arguments regarding early transplantation may have to be reconsidered.

Preliminary studies have suggested that hydroxyurea may increase the level of HbF and raise the hemoglobin level in some individuals with severe beta thalassemia. This therapy may be enhanced by the administration of erythropoietin. These are exciting experimental observations but await further study before their use can be recommended. Further over the horizon are other HbF-inducing agents, such as butyrate analogs, and means of altering the genetic defects of thalassemia by gene therapy.

12. An 84 year old woman is brought to the office by her daughter, who is your patient. The mother has just moved in whith the family because she can no longer take care for herself due to progressive, long-standing dementia. The daughter hopes you will help take care of her mother. On physical examination the mother has no evidence of any other chronic disease. She does not respond to your words or to the physical examination. You notice that she smells of urine. On examination of the pelvis there is a diffuse erythematous rash extending over the prineum to the medial thighs bilaterally. You suspect the rash relates to urinary incontinence. The daughter is present at the mother's examination. The best opening remark to the daughter is:

a) "You should take better care of your mother"
b) "How long have you left your mother in this condition?"
c) "Your mother needs to wear diapers"
d) "This rash should respond to cleansing with mild soap and drying with a clean towel three times a day"
e) "This is a rash caused by urine. My nurse wll insert a Foley catheter"

View Answer D: "This rash should respond to cleansing..."

a) hypokalemia
b) hypomagnesemia
c) hyponatremia
d) metabolic acidosis
e) noninsulin-dependent (tyype II) diabetes mellitus

View Answer A: Hypokalemia

For an explanation of this answer you can go to http://www.studynow.com and visit the section on search drugs (search for chlorthalidone).

Explanation by Chris:

67 y/o female has received 6 weeks of CHLORTHALIDONE (at the appropriate dose of 50mg QD) for her Hypertension, presents with acute/sudden onset ?? of muscle weakness, cramps, and polyuria.
- we are not given the actual period of the onset of symptoms, but the introduction implies that this is a recent occurence.
- chronic use of diuretics certainly causes hypokalemia, but symptoms such as the muscle weakness and cramps experienced by our patients appear at levels less than 2.5mEq.
* Hyponatremia also figures into the list of possible causes, but many patients are asymptomatic even with levels of 130mEq, and when do they do develop the forementioned symptoms it is often accompanied by an altered mental status, this patient seems to be fully alert and oriented relegating this possibility after HypoK+ on the differ dx list.
* Hypomagnasemia is not likely to occur ithis patient (ie. NO hyperalimentation) and she does not present with the typical manifestations of the associated hypocalcemia: fasciculations, Chvostek, and Trousseau. Therefore this lyte disturbance is also not very likely.
* diabetes is a rather remote possibility as this pt seems to have been closely followed as the history suggests with no documentation of any associated findings. A presentation this late in life is highly unusual. We have Not enough evidence to incriminate diabetes.
* metabolic acidosis is also unlikely, as there is no identifiable cause for this complication.
- the polyuria "may" be expected, as some patients admit to "increasing their diuresis" after receiving this class of meds.
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Hypokalemia is the most probable offender (A).

a) aspirate the mass under ultrasonic guidance
b) obtain a carcinoembryonic antigen (CEA) tumor marker
c) reexamine her in 3 months
d) schedule diagnostic laparoscopy
e) schedule exploratory laparotomy

View Answer E: Exploratory laparotomy

From Chris:

71 y/o pt on her annual health exam; asymptmatic. P.E. significant for a
10 cm right adnexal mass, with both cystic-solid components.
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Post-menopausal pt with a large adnexal mass. This ominous finding
demands of us to R/O an ovarian neoplasm as our first and foremost
priority. Nonetheless other causes exist:
- Uterine Leiomyomas (affectionately known as "myomas")
- Colon CA
- Retroperitneal Tumor
- "Full bladder"
- "Feces in colon

Myomas in this pt are ruled out by virtue of (-) U/S findings. The pt is
described as being in "good health," and we can assume in this case that
no weight loss has occured.. therefore if a retroperitonal neo
(Pancreatic CA) that size would most certainly have caused this woman to
be cachetic and symptomatic (ie. jaundice), she's not. Colon Ca, not
likely since again there is no history of weight loss, pain or anemia
(expected of an advanced Right-sided Colon CA). Thus our dx is R/O
Ovarian (malignant) neoplasm.
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There is a general consensus among Gynecologists to remove ALL masses
in postmenopausal women due to a rather relatively "high" frequency of
malignancy. An indication for removal of a suspected ovarian mass is
"persistence of several months" and ">8cm diameter." The answer is (E)
exploratory lap.
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The cystic-solid (loculated) nature of the mass in question points to
the following ovarian tumors as suspects:

Benign and more frequent: mucinous cystadenoma, serous cystadenoma >>
cystic teratoma (aka "dermoid cyst")
Malignant & less frequent: mucinous cystadenoCA, serous adenoCA
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Clinical Pearl:
- prepubertal female with pelvic mass: R/O germ-cell tumor (50%
malignant), therefore malignant until proven otherwise.
- reproductive age " " ": observe mass for >1 menstrual cycle (ie.
functional follicular cyst vs..)
- postmenopausal " " ": remove all masses.

+ 80% of all Ovarian CAs are benign.

a) aggressiveness to compensate for a poor self-image cause by short stature
b) attention-deficit/hyperactivity disorder due to inherited factors
c) a reaction to his father's drinking
d) reduction in his mother's attention because of his new sibling
e) a toxic reaction to organic fumes from his father's clothes and work materials

View Answer D: reduction in his mother's attention because of his new sibling

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