FRCPath Haematology Part 2: Morphology Thalassaemias and Haemoglobinopathies Haemoglobin SC Disease

Haemoglobin SC disease is a sickling disorder which results from the co-inheritance of two abnormal ß globin genes, haemoglobin S and haemoglobin C (ßsßc). It is characterised by the presence of SC poikilocytes, abnormally contracted cells which resemble sickle cells but which have straight edges or are branched. The appearance of SC poikilocytes can be quite variable. The phenotypic severity of haemoglobin SC disease is variable; patients often have a higher steady-state haemoglobin that patients with ßsßs or ß0ßs.

Haemoglobin S arises from a point mutation in the ß globin gene. Sickle cell mutations are more common in individuals of African descent. They are also found in Central and South America, the Middle East and parts of India.

Haemoglobin C also arises from a point mutation in the the ß globin gene. The mutation is more common in West Africa, but can also be found in the Mediterranean and Caribbean regions.

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Blood film features:

  • Mild-moderate microcytic, hypochromic anaemia
  • SC poikilocytes – cells which have a variable appearance but are usually dense and may resemble sickle cells. They often have single or multiple angulated branches; some which resemble sickle cells may instead have straight edges. Classical SC poikilocytes may be quite rare, so they must be actively sought.
  • Haemoglobin SC crystals – dense, irregularly-shaped crystals of haemoglobin in cells that appear to be otherwise devoid of haemoglobin. The crystals in haemoglobin C are more rhomboidal and regular in shape.
  • Numerous boat cells – these often have an appearance of a boat viewed from the top, and are seen in many sickling disorders.
  • Polychromasia
  • Occasional sickle cells
  • Occasional target cells
  • Occasional nRBCs (not usually a prominent feature)
  • May have features of hyposplenism
  • Look for features of hydroxyurea therapy also

Cells seen in Haemoglobin SC Disease:

Peripheral blood film from a patient with haemoglobin SC disease showing an SC poikilocyte. These cells which have a variable appearance but are usually dense and may resemble sickle cells. They often have single or multiple angulated branches; some which resemble sickle cells may instead have straight edges. Classical SC poikilocytes may be quite rare, so they must be actively sought.
Peripheral blood film from a patient with haemoglobin SC disease showing an SC poikilocyte. These cells which have a variable appearance but are usually dense and may resemble sickle cells. They often have single or multiple angulated branches; some which resemble sickle cells may instead have straight edges. Classical SC poikilocytes may be quite rare, so they must be actively sought.
Peripheral blood film from a patient with haemoglobin SC disease showing an SC poikilocyte. These cells which have a variable appearance but are usually dense and may resemble sickle cells. They often have single or multiple angulated branches; some which resemble sickle cells may instead have straight edges. Classical SC poikilocytes may be quite rare, so they must be actively sought.
Peripheral blood film from a patient with haemoglobin SC disease showing an SC poikilocyte. These cells which have a variable appearance but are usually dense and may resemble sickle cells. They often have single or multiple angulated branches; some which resemble sickle cells may instead have straight edges. Classical SC poikilocytes may be quite rare, so they must be actively sought.
Peripheral blood film from a patient with haemoglobin SC disease showing an SC poikilocyte. These cells which have a variable appearance but are usually dense and may resemble sickle cells. They often have single or multiple angulated branches; some which resemble sickle cells may instead have straight edges. Classical SC poikilocytes may be quite rare, so they must be actively sought.
These are eccentric, dense, irregularly-shaped crystals of haemoglobin in cells that appear to be otherwise devoid of haemoglobin.
These are eccentric, dense, irregularly-shaped crystals of haemoglobin in cells that appear to be otherwise devoid of haemoglobin.
These are eccentric, dense, irregularly-shaped crystals of haemoglobin in cells that appear to be otherwise devoid of haemoglobin.
Boat cell seen in a patient with haemoglobin SC disease. These often have an appearance of a boat viewed from the top, and are seen in many sickling disorders.
Boat cell seen in a patient with haemoglobin SC disease. These often have an appearance of a boat viewed from the top, and are seen in many sickling disorders.
Boat cell seen in a patient with haemoglobin SC disease. These often have an appearance of a boat viewed from the top, and are seen in many sickling disorders.
Peripheral blood film from a patient with haemoglobin SC disease showing a sickle cell.
Peripheral blood film from a patient with haemoglobin SC disease showing a target cell.
This is a feature of hyposplenism which is often seen in patients with sickling disorders. It results from splenic infarction; patients usually have functional asplenia by late childhood. In SC disease however, this is variable and patients may have splenomegaly.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.
Peripheral blood film from a patient with haemoglobin SC disease. The blood film shows typical features of SC disease, including polychromasia, SC poikilocytes, SC crystals, target cells and occasional sickle cells. There are also features of splenectomy - the patient has Howell-Jolly bodies, occasional acanthocytes and a mild platelet anisocytosis.

Differential diagnosis:

  • Sickle cell anaemia (no SC poikilocytes, typically more sickle cells, no SC crystals or haemoglobin C crystals).
  • Haemoglobin C disease (no SC poikilocytes, usually milder anaemia, haemoglobin C crystals with many target cells).
  • Haemoglobin S / ß thalassaemia compound heterozygote (features of dyserythropoiesis suck as basophillic stippling and anisopoikilocytosis are more prominent, more target cells and nRBCs, no SC poikilocytes, no SC crystals).
  • ß thalassaemia intermedia / major (no SC poikilocytes, SC crystals, sickle cells or boat-shaped cells. Features of dyserythropoiesis more prominent). The sickle test in ß thalassaemia intermedia / major is negative.

Other investigations:

  • Sickle test: positive in Hb SC disease
  • Haemoglobin electrophoresis
  • HPLC

Haemoglobin electrophoresis:

Alkaline gel electrophoresis from a patient with haemoglobin SC disease. There are two variant haemoglobins, one with the mobility of haemoglobin S (red arrow) and the other with the mobility of haemoglobin C (blue arrow). The differentials for a band with the mobility of haemoglobin S are haemoglobins G, D and Lepore. The differentials for a band with the mobility of haemoglobin C are haemoglobins E, O-Arab and A2.

Acid gel electrophoresis from a patient with haemoglobin SC disease. There are two variant haemoglobins , one with the mobility of haemoglobin S (red arrow) and the other with the mobility of haemoglobin C (blue arrow). There is no normal haemoglobin A. This excludes haemoglobins G, D and Lepore as causes for the band at Hb S on the alkaline gel, as they have the mobility of Hb A on acid gel. Similarly, haemoglobins E and A2 have the mobility of haemoglobin A on acid gel and are hence excluded. Haemoglobin O-Arab has the mobility of haemoglobin S on acid gel.

HPLC:

HPLC from a patient with haemoglobin SC disease. There is no normal haemoglobin A. There are two variant haemoglobins with the retention times of haemoglobins S (red arrow) and C (blue arrow). This confirms the diagnosis of haemoglobin SC disease.

Other resources:

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