Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome causes primary immunodeficiency due to a combined B-
and T-cell dysfunction. It is inherited in a X-linked recessive fashion and is thought to
be caused by mutation in the WASP gene.
Features
● recurrent bacterial infections (e.g. Chest)
● eczema
● thrombocytopaenia
● low IgM levels
●
Sideroblastic anaemia
Sideroblastic anaemia is a condition where red cells fail to completely form haem,
whose biosynthesis takes place partly in the mitochondrion. This leads to deposits
of iron in the mitochondria that form a ring around the nucleus called a ring
sideroblast. It may be congenital or acquired.
Congenital cause: delta-aminolevulinate synthase-2 deficiency
Acquired causes
● myelodysplasia
● alcohol
● lead
● anti-TB medications
Investigations
● full blood count
○ hypochromic microcytic anaemia (more so in congenital)
● iron studies
○ high ferritin
○ high iron
○ high transferrin saturation
● blood film
○ basophilic stippling of red blood cells
● bone marrow
○ Prussian blue staining will show ringed sideroblasts
Management
, ● supportive
● treat any underlying cause
● pyridoxine may help
Superior vena cava obstruction
Superior vena cava (SVC) obstruction is an oncological emergency caused by
compression of the SVC. It is most commonly associated with lung cancer.
Features
● dyspnoea is the most common symptom
● swelling of the face, neck and arms - conjunctival and periorbital oedema may
be seen
● headache: often worse in the mornings
● visual disturbance
● pulseless jugular venous distension
Causes
● common malignancies: small cell lung cancer, lymphoma
● other malignancies: metastatic seminoma, Kaposi's sarcoma, breast cancer
● aortic aneurysm
● mediastinal fibrosis
, ● goitre
● SVC thrombosis
Management is dependant on the individual patient and malignancy and advice
should be taken from the oncology team. Options include:
● endovascular stenting is often the treatment of choice to provide symptom
relief
● certain malignancies such as lymphoma, small cell lung cancer may benefit
from radical chemotherapy or chemo-radiotherapy rather than stenting
● the evidence base supporting the use of glucocorticoids is weak but they are
often given.
Thrombotic thrombocytopenic purpura
Pathogenesis of thrombotic thrombocytopenic purpura (TTP)
● abnormally large and sticky multimers of von Willebrand's factor cause
platelets to clump within vessels
● in TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which
breakdowns ('cleaves') large multimers of von Willebrand's factor
● overlaps with haemolytic uraemic syndrome (HUS)
Features
● rare, typically adult females
● fever
● fluctuating neuro signs (microemboli)
● microangiopathic haemolytic anaemia
● thrombocytopenia
● renal failure
Causes
● post-infection e.g. urinary, gastrointestinal
● pregnancy
● drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
● tumours
, ● SLE
● HIV
●
Thrombocytosis
Thrombocytosis is an abnormally high platelet count, usually > 400 * 109/l.
Causes of thrombocytosis
● reactive: platelets are an acute phase reactant - platelet count can increase in
response to stress such as a severe infection, surgery. Iron deficiency
anaemia can also cause a reactive thrombocytosis
● malignancy
● essential thrombocytosis (see below), or as part of another myeloproliferative
disorder such as chronic myeloid leukaemia or polycythaemia rubra vera
● hyposplenism
Essential thrombocytosis
Essential thrombocytosis is one of the myeloproliferative disorders which overlaps
with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis.
Megakaryocyte proliferation results in an overproduction of platelets.
Features
● platelet count > 600 * 109/l
● both thrombosis (venous or arterial) and haemorrhage can be seen
● a characteristic symptom is a burning sensation in the hands
● a JAK2 mutation is found in around 50% of patients
Management
Wiskott-Aldrich syndrome causes primary immunodeficiency due to a combined B-
and T-cell dysfunction. It is inherited in a X-linked recessive fashion and is thought to
be caused by mutation in the WASP gene.
Features
● recurrent bacterial infections (e.g. Chest)
● eczema
● thrombocytopaenia
● low IgM levels
●
Sideroblastic anaemia
Sideroblastic anaemia is a condition where red cells fail to completely form haem,
whose biosynthesis takes place partly in the mitochondrion. This leads to deposits
of iron in the mitochondria that form a ring around the nucleus called a ring
sideroblast. It may be congenital or acquired.
Congenital cause: delta-aminolevulinate synthase-2 deficiency
Acquired causes
● myelodysplasia
● alcohol
● lead
● anti-TB medications
Investigations
● full blood count
○ hypochromic microcytic anaemia (more so in congenital)
● iron studies
○ high ferritin
○ high iron
○ high transferrin saturation
● blood film
○ basophilic stippling of red blood cells
● bone marrow
○ Prussian blue staining will show ringed sideroblasts
Management
, ● supportive
● treat any underlying cause
● pyridoxine may help
Superior vena cava obstruction
Superior vena cava (SVC) obstruction is an oncological emergency caused by
compression of the SVC. It is most commonly associated with lung cancer.
Features
● dyspnoea is the most common symptom
● swelling of the face, neck and arms - conjunctival and periorbital oedema may
be seen
● headache: often worse in the mornings
● visual disturbance
● pulseless jugular venous distension
Causes
● common malignancies: small cell lung cancer, lymphoma
● other malignancies: metastatic seminoma, Kaposi's sarcoma, breast cancer
● aortic aneurysm
● mediastinal fibrosis
, ● goitre
● SVC thrombosis
Management is dependant on the individual patient and malignancy and advice
should be taken from the oncology team. Options include:
● endovascular stenting is often the treatment of choice to provide symptom
relief
● certain malignancies such as lymphoma, small cell lung cancer may benefit
from radical chemotherapy or chemo-radiotherapy rather than stenting
● the evidence base supporting the use of glucocorticoids is weak but they are
often given.
Thrombotic thrombocytopenic purpura
Pathogenesis of thrombotic thrombocytopenic purpura (TTP)
● abnormally large and sticky multimers of von Willebrand's factor cause
platelets to clump within vessels
● in TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which
breakdowns ('cleaves') large multimers of von Willebrand's factor
● overlaps with haemolytic uraemic syndrome (HUS)
Features
● rare, typically adult females
● fever
● fluctuating neuro signs (microemboli)
● microangiopathic haemolytic anaemia
● thrombocytopenia
● renal failure
Causes
● post-infection e.g. urinary, gastrointestinal
● pregnancy
● drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
● tumours
, ● SLE
● HIV
●
Thrombocytosis
Thrombocytosis is an abnormally high platelet count, usually > 400 * 109/l.
Causes of thrombocytosis
● reactive: platelets are an acute phase reactant - platelet count can increase in
response to stress such as a severe infection, surgery. Iron deficiency
anaemia can also cause a reactive thrombocytosis
● malignancy
● essential thrombocytosis (see below), or as part of another myeloproliferative
disorder such as chronic myeloid leukaemia or polycythaemia rubra vera
● hyposplenism
Essential thrombocytosis
Essential thrombocytosis is one of the myeloproliferative disorders which overlaps
with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis.
Megakaryocyte proliferation results in an overproduction of platelets.
Features
● platelet count > 600 * 109/l
● both thrombosis (venous or arterial) and haemorrhage can be seen
● a characteristic symptom is a burning sensation in the hands
● a JAK2 mutation is found in around 50% of patients
Management
