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HbH

Stanford University School of Medicine

View larger version (149K): [in this window] [in a new window]   1A Figure 1A. Low power view of the peripheral smear 100X.

View larger version (136K): [in this window] [in a new window]   1B Figure 1B. Peripheral smear 500X. Note the hypochromicm microcytic RBC and the target cells.

View larger version (136K): [in this window] [in a new window]   1C Figure 1C. Peripheral smear 500X. Note the hypochromicm microcytic RBC and the target cells.

View larger version (60K): [in this window] [in a new window]   Figure 2. Hemoglobin Electrophoresis. The patient has HbA and a faster running hemoglobin HbH.

View larger version (141K): [in this window] [in a new window]   Figure 3. Brilliant Cresyl Blue Staining of RBC. The blue stained inclusions I the RBC are oxidatively denatured precipitates of HbH.

View larger version (131K): [in this window] [in a new window]   Figure 4. Alpha Globin gene cluster on chromosome 16 indicating the 2 major alpha globin genes, alpha-2 and alpha-1.

View larger version (83K): [in this window] [in a new window]   Figure 5. Alpha Thalassemia Syndromes. In the more common deletional forms of alpha thalassemia the severity of the anemia is directly relationed to the number of alpha genes which have been deleted. This in turn is reflected in the alpha:beta globin synthesis ratio.

	Clinical Summary

TOP Clinical Summary Diagnosis Discussion Differential Diagnosis

History of present illness: She was recently married and wants to have a family, but went to her PCP because she felt that she had less energy than her friends. She has no history of melena or bright red blood per rectum (BRBPR), and her menstrual history seemed normal. She thinks that her mother and 2 maternal aunts have anemia.

Physical examination: She is a pale but otherwise alert, healthy young woman. No scleral icterus is present and her chest and heart exam are normal. A soft spleen tip is palpable in the left upper quadrant (LUQ). No edema is present.

Labs: White blood cells (WBC) 4600, normal differential, platelets 421,000/ul, hematocrit (Hct) 27, hemoglobin (Hgb) 8.1gm/dl, red blood cells (RBC) 4.58M/ul, mean corpuscular volume (MCV) 59, mean corpuscular hemoglobin (MCH) 17, mean corpuscular hemoglobin concentration (MCHC) 30. Retic 3.1% Absolute retics 142,000/ul, ferritin 482 ng/ml, serum iron 149, transferrin 193, % sat 77%. Peripheral smear (Figure 1A, Figure 1B and Figure 1C).

Sex
Female

Age
21

	Diagnosis

TOP Clinical Summary Diagnosis Discussion Differential Diagnosis

 
The hemoglobin electophoressis reveals HbA2 is 1%, HbF is 0.5%, and HbH is 16%.  The BCB test shows the typical inclusions of denatured HbH precipitated by the mild oxidative attack by the dye BCB.

	Discussion

TOP Clinical Summary Diagnosis Discussion Differential Diagnosis

 
Pathophysiology: Normally alpha and beta globin chains are synthesized in a tightly coordinated manner so that the alpha/beta synthesis ratio is 1.00+/-.05. HbH disease is a moderately severe form of alpha thalassemia. There are 2 alpha genes on each chromosome 16 (alpha-2 and alpha-1) giving total of 4 (Figure 4). In HbH disease 3 alpha genes are usually deleted, (Figure 5)  --/alpha -. This produces an imbalance such that beta globin chains accumulate and form beta-4 tetramers= HbH. HbH functions poorly as a hemoglobin, susceptible to denaturation and incapable of releasing oxygen to tissues normally.

Management: The patient needs to be told that she probably has a stable condition and that she might need a RBC transfusion if she has an intercurrent illness, such as parvovirus infection that reduces erythropoeisis.  Her husband should be screened because if he is a heterozygote for the alpha zero (Figure 5) genotype ( --/ ), one quarter of their fetuses could have HbH and another  one quarter  of her fetuses could have no alpha chains and thus alpha thal-hydrops fetalis (Figure 4).

	Differential Diagnosis

TOP Clinical Summary Diagnosis Discussion Differential Diagnosis

 
The peripheral smear and the indices indicate that the patient has a significant hypochromic, microcytic anemia, with only a modest reticulocyte response and no morphologic abnormalities of  WBC or platelets. Iron deficiency is unlikely given her medical history, ferritin, and SI/transferrin/%saturation values. The history does not contain evidence for a disorder that can cause anemia of chronic disease (ACD) and in any case the MCV is probably too low for ACD. Furthermore there is no evidence for either lead toxicity or sideroblastic anemia/ myelodysplastic syndrome (MDS).  The likely diagnosis is then either alpha or beta thalassemia and accordingly a hemoglobin electrophoresis (Figure 2) and BCB (brilliant cresyl blue) test (Figure 3) are ordered.

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Related ASH-SAP Chapter:

Chapter 6: Hemolytic anemias

This Article Figures Only Services Similar articles in this journal Alert me to new content in the Image Bank Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schrier, S. Search for Related Content PubMed Articles by Schrier, S. Related Collections Hemolytic Disorders Related ASH-SAP Chapter Social Bookmarking                   What's this?