Correspondence Address:
Ujjawal Khurana
Department of Pathology, Govt. Medical College, Sector-32-A, Chandigarh - 160 047
India

Full Text

Sir,

We are reporting a case of Hb H disease, which is not an uncommon, but is an under diagnosed entity in Indian setup.

A 22-year-old male presented with history of generalized weakness for one month and high-grade fever for eight days. The patient was a laborer, a resident of Bengal, working in Simla for the past 2 months. He gave past history of intermittent jaundice for the last two years, the last episode being 6 months back. None of the siblings had similar history and parents did not give history of consanguineous marriage. On general physical examination, he was pale, had mild hemolytic facies with submandibular and right axillary lymphadenopathy 0.5 cm each. Spleen was palpable 6 cm below the left costal margin with no accompanying hepatomegaly. On admission, his hemoglobin was 5.6 gm%, TLC 8700/ ml, Platelet count 70,000/ml, 26 nucleated RBCs/100WBCs, a corrected TLC of 6904 /ml, MCV 76.8 fl, MCH 21.0pg and MCHC 27.3%. His ESR was 47mm at 1st hour. Biochemical investigations revealed: Total serum bilirubin 1.5mg%, conjugated fraction being 0.8, AST 221 IU/L, ALT 117 IU/L and alkaline phosphatase 360 IU/L. Ultrasonography of abdomen revealed an enlarged spleen spanning 18.9cm. As the patient hailed from Bengal and presented with high-grade fever and splenomegaly, a possibility of kala azar was kept clinically.

After initial evaluation, he was given a blood transfusion. On the day of bone marrow examination (after 6 days of admission), his TLC had dropped from 8700 to 3800/ml. Hemoglobin was now 7.9gm%, platelet count 82,000/ml, MCV 82 fl, MCH 21pg, MCHC 26% with a differential leucocyte count of polymorphs 66,lymphocytes 29, monocytes 3 and eosinophils 2 while there was only one nucleated RBC per 100 WBC count. The peripheral blood film showed presence of microcytes, macrocytes, elliptocytes, teardrop cells, fragmented cells and polychromatophils. Basophilic stippling and Cabot rings were also seen. Neutrophils showed nuclear hypersegmentation. The reticulocyte preparation showed 10% reticulocytes and an occasional golf-ball like inclusion in the RBCs. On incubation of the preparation for one hour at 37�C, frank HbH inclusions were seen in about 70% of the RBCs [Figure 1]. Fine needle aspirate of left cervical lymph node showed reactive lymphoid hyperplasia and afterwards patient underwent bone marrow procedure. Bone marrow aspirate was hypercellular and showed erythroid hyperplasia, moderate megaloblastosis along with dyserythropoiesis and with an iron of grade 2+ on Perls'stain. No L.D bodies were seen. Both blood and bone marrow culture were sterile. Cellulose agar gel electrophoresis on peripheral blood at pH 8.6 showed a fast moving band in the region of Hb H along with a band in HbA region [Figure 2]. The patient was given antibiotics, vitamin B12 and folic acid and was advised splenectomy. The patient refused splenectomy and was lost to follow up.

HbH disease is seen most commonly in Asian population (South East Asia, Meditarranean and parts of Middle East). [1] Hemoglobin H has extremely high affinity for oxygen and therefore is not useful for oxygen exchange, leading to tissue hypoxia disproportionate to level of Hb. [2] It is prone to oxidation, leading to formation of intracellular inclusions. The instability of HbH is a major cause of anemia, as precipitates of oxidized HbH form in older red cells, which are then removed by splenic macrophages leading to hemolysis. [1] To some extent precipitation occur in early erythroid precursors causing ineffective erythropoiesis. HbH disease shows considerable variability in clinical and hematologic severity. [3] The most relevant features are microcytic hypochromic anemia, hepatosplenomegaly and mild hemolytic facies. [1],[4] The hemoglobin concentration ranges from 7 to 10gm% and MCV ranges from 60-70 fl whereas MCH is approximately 18 pg. [1] All of these features were present in our case besides Hb 5.6gm%, MCV 76fl and presence of hemolytic facies. Reticulocytes range between 1.5 - 10% and a to β globin chain synthesis ratio is markedly reduced in order of 0.2 to 0.7. [3] Hb electrophoresis at alkaline pH shows a fast moving band (HbH) ranging from 1 - 40% in addition to bands in HbA, HbF and HbA2 region.[1],[4] Reticulocytes in our case were 10% and the diagnosis was confirmed by electrophoresis. One of the most sensitive methods for detection of HbH consists of incubation of peripheral blood cells for 1 - 3 hours at 37�C in presence of supravital dye, which induces precipitation of HbH as inclusion bodies. [5] As a rule, at least 10% of the cells develop inclusions and in many cases, the percentage is considerably greater as was seen in our case.

Patients with HbH disease should undergo splenectomy if excessive anemia or transfusion requirement develops. Oxidative drugs should be avoided. Iron overload leading to death can occur in more severely affected patients; however in our case the iron content was in the normal range.

Thus to conclude, anemia, mild hemolytic facies, splenomegaly, HbH inclusions on supravital dyes are general indicators of HbH disease and Hb electrophoresis at alkaline pH helps to confirm the diagnosis. Also a to β globin chain synthesis ratio can be further confirmatory while determination of a globin genotype may be useful for prognosis of HbH disease, non deletional forms being more severe than deletional forms. [3]

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