Haematology/Oncology Flashcards
Which condition is associated with Warfarin induced skin necrosis?
Protein C deficiency.
Protein C deficiency is an autosomal codominant condition which causes an increased risk of thrombosis.
Protein C is a vitamin K-dependent anticoagulant protein, which acts by inactivating factors Va and VIIIa, thus preventing the formation of thrombin. In patients with Protein C deficiency, starting warfarin therapy can lead to an imbalance between procoagulant and anticoagulant factors, predisposing them to thrombotic events and causing skin necrosis.
What are the features of acute intermittent prophyria (AIP)?
AIP is a rare autosomal dominant condition caused by a defect in Porphobilinogen Deaminase, an enzyme involved in the biosynthesis of haem. The results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen.
The classical presentation is a combination of abdominal, neurological and psychiatric symptoms:
- Abdominal: abdominal pain, vomiting
- Neurological: motor neuropathy
- Psychiatric: e.g. depression
- Hypertension and tachycardia common
Causes of Thrombocytosis? (abnormal high platelet count)
- Reactive: platelets are an acute phase reactant - platelet count can increase in response to stress s
- Malignancy
- Essential thrombocytosis or as part of another myeloproliferative disorder such as chronic myeloid leukaemia or polycythaemia rubra vera
- Hyposplenism
Mutation seen in essential thrombocytosis?
Myeloproliferative disroder. Megakaryocyte proliferation results in an overproduction of platelets.
Features:
- platelet count > 600 * 109/l
- both thrombosis (venous or arterial) and haemorrhage can be seen
- characteristic symptom is a burning sensation in the hands
- a JAK2 mutation is found in around 50% of patients
CALR (calreticulin) is also a more commonly found gene mutation in ET in around 20% of JAK-2 negative patients
Management for immune thrombocytopenia (ITP)?
- First-line treatment for ITP is oral prednisolone.
- Pooled normal human immunoglobulin (IVIG) may also be used. Raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required.
Emergency treatment, life-threatening or organ threatening bleeding: Platelet transfusion, IV methylprednisolone and intravenous immunoglobulin.
- Platelet count >30*109/L: Observation
- Platelet count <30*109/L: Oral Prednisolone
Investigation for hereditary spherocytosis?
Autosomal dominant defect of red blood cell cytoskeleton. Normal biconcave disc shape is replaced by a sphere-shaped RBC. RBC survival reduced as destroyed by the spleen.
Eosin-5′-maleimide (EMA) binding test.
Drugs that can trigger haemolysis in G6PD deficiency?
A person with G6PD has alot of CASH:
- Ciprofloxacin
- Antimalarial: Primaquine
- Suplha groups: Sulfamethoxazole (Co-Trim), sulphasalazine, sulfonylureas
- Heinz bodies
Mode of inheritance of G6PD deficiency?
Male (X-linked recessive).
It is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans.
“Heinz Bodies and its precipitated by beans”
Features of Polycythaemia Vera?
- Pruritus, typically after a hot bath.
- Splenomegaly
- Hypertension
- Hyperviscosity
- Arterial thrombosis and venous thrombosis
- Haemorrhage (secondary to abnormal platelet function)
- Low ESR
Investigation for Polycythaemia Vera?
JAK-2 Mutation screen.
If the JAK2 mutation is negative can do Red cell mass testing.
Investigation for hereditary angioedema?
Hereditary angioedema is an autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH, C1 esterase inhibitor) protein.
Serum C4 is the most reliable and widely used screening tool.
Mx for Chronic Lymphocytic Leukemia?
Fludarabine, Cyclophosphamide and Rituximab (FCR) has now emerged as the initial treatment of choice for the majority of patients.
Adverse effect of Cyclophosphamide?
- Haemorrhagic cystitis
- Myelosuppression
- Transitional cell carcinoma
Adverse effect of Bleomycin?
Lung fibrosis.
Mx for pregnant patient with antiphospholipid syndrome?
- Low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing.
- LMWH once a fetal heart is seen on ultrasound. This is usually discontinued at 34 weeks gestation
Features of Vitamin B12 deficiency?
- Macrocytic anaemia
- Sore tongue and mouth
- Neurological symptoms: the dorsal column is usually affected first (joint position, vibration) prior to distal paraesthesia
- Neuropsychiatric symptoms: e.g. mood disturbances
Causes of Vitamin B12 deficiency?
- Pernicious anaemia: most common cause
- post gastrectomy
- vegan diet or a poor diet
- disorders/surgery of terminal ileum (site of absorption)
Crohn’s: either diease activity or following ileocaecal resection - Metformin (rare)
Mx of Vitamin B12 deficiency?
If no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months.
If a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord.
Mx for Von Willebrand disease?
Von Willebrand’s disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion.
(epistaxis, menorrhagia)
- Tranexamic acid for mild bleeding
- Desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
- Factor VIII concentrate
Blood film features seen in hyposplenism?
(post splenectomy, Coeliac disease)
- Target cells
- Howell-Jolly bodies
- Pappenheimer bodies
- Siderocytes
- Acanthocytes
Blood film in megaloblastic anaemia?
Hypersegmented neutrophils
