CME INDIA Case Presentation by Dr Ashutosh Chandan Dubey (Dr Strange), DNB, Med, Hindalco Hospital, Renukut, UP.
CME INDIA Case Study:
Ferritin is more than 1k/ Any Spot Diagnosis?
- Case was referred for splenomegaly on routine USG Abdomen, No symptoms
- Later complained of weakness, pain in left hypochondrium.
- CBC showing low Hb
- PBS showing microcytic hypochromic anaemia.
- Past H/O Blood transfusion.
- Mildly raised Total Bilirubin with normal LFT.
- Normal Reticulocyte count.
- No Hepatomegaly on palpation.
- H/O Anaemia in past for which patient is taking oral Iron since 2009.
Report of Hb Electrophoresis
Hb electrophoresis is suggestive of HbD disease – Punjab variant with minor thalassemia.
Need opinion for:
- Splenectomy, is it required?
- Use of Oral Iron chelators to reduce iron over load-needed or not?
- Is it HbD disease (Punjab) with Minor B Thalassemia with secondary Iron overload?
CME INDIA Discussion
Dr Sanjeev Yadav, Asso. Prof of haematology, SGPGI, Lucknow:
- Hb D Panjab are usually asymptomatic
- No need for splenectomy unless transfusion requirements are too high
- Iron chelation only if Serum Ferritin more than 800
- I think diagnosis should be Hb D Panjab homozygous
- Why thal minor A2 is less than 3.5
- To confirm please do parents HPLC.That can only give you the answer otherwise sequencing
Dr Dibyendu Dey, Onco-heamatologist, Balco Medical Centre,Naya Raipur, Chattisgarh
- Its hbD homozygous, which behaves like mild haemolytic anaemia.
- Splenomegaly usually mild, and does not need splenectomy.
- Only occasional transfusion.
- Other cause of splenomegaly must be ruled out also, especially liver disease
CME INDIA Learning Points
- Hemoglobin D (Hb-D) hemoglobinopathy occurs mainly in the northwest India (Punjab), Pakistan, and Iran. Hb-D was first discovered in the early 1950s in a mixed British and American family of Indian origin from the Los Angeles area and hence the original Hb-D was called Hb-D Los Angeles, but it was later found to be identical to the Hb-D Punjab found in India and Pakistan.
- It is interesting to note that hemoglobin D-Punjab is also known as hemoglobin D-Los Angeles. In Brazil, for hemoglobin D-Punjab is the third most common hemoglobin variant.
- It is one of the most common hemoglobin variants worldwide. It is derived from a point mutation in the beta-globin gene (HBB: c.364G>C; rs33946267) prevalent in the Punjab region, North-western Indian
- Hemoglobin D-Punjab can be inherited in heterozygosis with hemoglobin A causing no clinical or hematological alterations, or in homozygosis.
- It is the rarest form of inheritance, a condition that is commonly not related to clinical symptomatology.
- It can exist in association with other hemoglobinopathies, such as thalassemias; the most noticeable clinical alterations occur when hemoglobin D-Punjab is associated to hemoglobin S.
- Heterozygous Hb D disease is a benign condition with no apparent illness
- Hb D is when associated with Hb S or β-thalassemia, clinical conditions such as sickling disease and moderate hemolytic anemia may be observed.
- Heterozygous Hb D is rare and usually presents with mild hemolytic anemia and mild to moderate splenomegaly
- High performance liquid chromatography (HPLC) methods have been developed for hemoglobin fractionation with high sensitivity and specificity.
- Reverse-phase HPLC (RP-HPLC) of human globin chains has been reported as an important tool for detecting hemoglobinopathies.
- Although all these tests aim to diagnose Hb D-Punjab, they are not considered conclusive because of the large number of hemoglobin variants that are similar to each other.
- It is always recommended to perform molecular analysis for genotype confirmation with PCR-RFLP as an alternative esolution problems.
- When the Hb D variant is not identified by the abovementioned methodologies, sequencing of beta-globin gene or other techniques that discriminate amino acid changes are recommended.
- Compound heterozygosity for Hb D-Punjab [β121(GH4) Glu→Gln, GAA>CAA] /β-thalassemia (β-thal) must be carefully differentiated from homozygous Hb D-Punjab in premarital screening. This is essential when the partner is a carrier of β-thal trait.
- Hb-D Punjab arises from the substitution of glutamine for glutamic acid in the 121st position of the β chain. Hb-D disease can occur in four different forms, including heterozygous Hb-D trait, Hb-D thalassemia, Hb-SD disease, and very rarely homozygous Hb-D disease.
CME INDIA Tail Piece
- Until the early 1950s, only four types of hemoglobin had been described including adult hemoglobin (Hb A) and two variants (Hb S and Hb C). The fourth identified hemoglobin was Hb D which was first described by Itano in 1951.
- When Itano was analyzing a multiethnic family from the Los-Angeles region with British, American and Indian features, and found a molecule with characteristics different to the other known hemoglobins.
- It is prevalent in Punjab region, Northwest Indian, with an estimated frequency of 2.0%. In western India, more specifically in the Gujarat region, its frequency drops by one half.
- Hb D-Punjab is also common in countries such as Italy, Belgium, Austria and Turkey.
- Hb D-Punjab is the second most common hemoglobin alteration in Turkey; it occurs in 0.2% of the population of Denizli province in south-eastern Turkey, where it is the most common variant.
- Hydroxyurea (HU) administration is a potential therapeutic strategy for sickle cell anemia (Hb SS), showing efficacy in increasing Hb F levels and consequently reducing the number of painful crises, acute chest syndrome, transfusions, and hospitalizations. However, HU therapy for Hb S/D-Punjab has not been established.
- Patel et al. treated Hb S/D-Punjab patients using low doses (10 mg/kg/day) of HU noticed an effective reduction in the incidence of vaso-occlusion and the frequency of blood transfusions. These results suggest that HU is a promising therapy for clinical symptomatology in Hb S/D-Punjab individuals.
- Although not always associated with relevant clinical history, Hb D-Punjab is a relatively common hemoglobin worldwide; it is the third most common hemoglobin variant in Brazil.
- Greater attention is given when the association of Hb D-Punjab with another abnormal hemoglobin or thalassemia leads to clinical symptoms.
- Torres Lde S, Okumura JV, Silva DG, Bonini-Domingos CR. Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis. Rev Bras Hematol Hemoter. 2015;37(2):120-126. doi:10.1016/j.bjhh.2015.02.007
- Patel S., Purohit P., Ranjeet S.M., Dehury S., Meher S., Sahoo S. The effect of hydroxyurea on compound heterozygotes for sickle cell-hemoglobin D-Punjab—a single centre experience in eastern India. Pediatr Blood Cancer. 2014;61(8):1341–1346.
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Below is the details of my medical problem :
Thalassemia Minor with Hb D Punjab ( facing following problems due to this )
Because of this hemoglobin disorder it causes jaundice and my indirect bilirubin goes high around 10.22 and direct is 0.94
Also because of RBC breakdown it creates gallstones and increasing my spleen 17.6 mm
My haemoglobin is always between 9 to 10.30.
causes paleness in my eyes and body.
it further creates other problems in my body like other deficiencies such as VITAMIN B12 AND VITAMIN D3, spleen enlarge, gallstones etc.