Glucose-6-phosphate dehydrogenase deficiency

Pyruvate Kinase deficiency

This is where decreased pyruvate kinase gives ATP depletion meaning RBCs are unable to survive.

– Majority of patients are detected at birth whilst some only present with symptoms during stress

Symptoms:

Gives neonatal jaundice, followed by later haemolysis with splenomegaly

Diagnosis:

Enzyme assay

Management:

Often not required, but blood transfusions if severe.

Hereditary Spherocytosis

This is an autosomal dominant defect of RBC cytoskeleton, giving inflexible spherical RBCs

– They are unable to move through spleen sinusoids so get consumed by macrophages

– MCHC (mean corpuscular hemoglobin concentration) is raised

Symptoms:

Failure to thrive + Anaemia with splenomegaly + Jaundice

– Can get an aplastic crisis with a parvovirus infection

Sickle Cell Anaemia

This is an autosomal recessive mutation in the b-chain where a glutamate is replaced with valine.

– This leads to production of HbS rather than HbA, but HbA2 and HbF are still produced

– Homozygotes have HBSS (sickle cell anaemia) whereas heterozygotes have HbAS (sickle-cell trait)

i) Sickle-cell trait

This is generally asymptomatic with no anaemia and protects against P. Falciparum

– RBCs do not sickle except in kidney in hypoxia e.g. altitude or anaesthesia, which can lead to microscopic haematuria and kidney injury

– Therefore, those of African descent given a pre-operation (anaesthesia) sickle-cell test 

ii) Sickle Cell Anaemia

HbS polymerizes in low oxygen, causing RBCs to sickle and get stuck

– HbF at birth is protective for few months and hydroxyurea treatment increases HbF levels.

-However, later you get increase extravascular haemolysis + intravascular haemolysis

Symptoms:

It is characterized by periods of good health with intervening crises:

Sequestration crisis:

– Blood becomes trapped in the spleen and liver (giving organomegaly),

– Leads to severe anaemia and shock, requiring urgent transfusion

Aplastic crisis:

– Parvovirus infection leading to sudden fall in Haemoglobin

Acute chest syndrome:

– Occlusion of pulmonary microcirculation gives chest pain, SOB, bleeding.

– Most common cause of death in adult patients.

Thrombotic (Vaso-occlusive) crises:

– RBCs occlude in blood vessels leading to infarction of organs

– Gives Hand-foot syndrome –> swollen hands/feet due to occlusion, common in infants

– Autosplenectomy –> infarction gives shrunken, fibrotic spleen increasing infection risk

– Pain –> ischaemia of bone marrow gives unbearable pain

Management:

– Refer to haematology

– In infant, hydroxyurea increases levels of HbF

– Prophylactic antibiotics in splenic infarction, but control Hb with transfusions

Underproduction Conditions

These conditions are marked by decreased RBC production, characterised by a low reticulocyte count.

– In acute setting due to blood loss + onset of iron deficiency and anaemia of chronic disease

– In chronic due to 2 main conditions: Renal failure (decreased production of EPO) + Aplastic anaemia

Aplastic anaemia

This is a stem cell disorder in which the bone marrow stops making cells, leading to pancytopenia

Causes:

– Idiopathic + radiation + cytotoxic drugs + viruses (parvovirus)

– (Congenital) Fanconi anaemia –> autosomal recessive aplastic anaemia + short + microcephaly

Symptoms:

– Bone marrow failure –> Anaemia + susceptibility to infections + bleeding

– A minority of patients develop paroxysmal nocturnal hemoglobinuria or myelodysplasia

Tests:

Bone marrow biopsy is diagnostic –> Reveals an empty, fatty marrow

Management:

– Stop causative drugs + supportive care (transfusion and marrow stimulating factors)

– In young, treatment of choice is bone marrow transplant

– Immunosuppression with ciclosporin as some cases might be due to autoimmunity

Parvovirus B19

This is a respiratory DNA virus which usually affects children and has several different presentations

– Symptoms start 6 days after exposure and last about week

– Most common presentation is erythema infectiosum (fifth disease / “slapped-cheek syndrome”)

Symptoms:

– By the time you develop symptoms, you are no longer contagious (so do not avoid school)

– Very mild fever, malaise and a mild arthritis

– Rose red rash that makes cheeks appear bright red (like “slapped cheeks”) – does not involve hands/feet

N.B. This virus also infects progenitor red cells and temporary stops erythropoiesis for about a week

– Usually asymptomatic, but can lead to a significant anaemia if the patient has a preexisting disease (e.g. sickle cell anaemia or hereditary spherocytosis)

– If reticulocytes are very low (or not raised) suspect an aplastic crisis (shows bone marrow is not capable of compensatory reticulocytosis)

Management:

Supportive as infection is self-limiting