Haematology Clinical Flashcards
What is methaemoglobinaemia?
Haemaglobin which has been oxidised from Fe2+ to Fe3+. There is usually small amounds but methaemoglobinaema is when too much forms, When this happens oxygen cannot bind and it leads to tissue hypoxia. This happens when there is a lack of the enzymes that convert metheomoglobin to normal haemagolin.
What causes methaemoglobinaemia?
Congenital - problem with the synthesis of cytochromone B5 reductase. There are two types.
Acquired - exposure to substances such an benzocain, dapsone and nitrates. These medicines act as oxidants which creates more methaemoglibin
What are the symptoms of acquired methaemoglobinaemia?
Presents acutely - cyanosis (when methhaemoglobin 15%)
Headaches
Seizures, breathlessess, Palpitations, MI
Levels over 70% are usually fatal
How is methaemoglobinaemia diagnosed?
Blood is a brown colour
Low sats with Normal partial pressure of O2
Multiple wavelengh co oximeter
How to do treat acquired methaemoglobinaemia
Oxygen and IV methylene blue
What are the two types of congenital methaemoglobinaemia?
Type 1: Cytochrome B5 reductase in absent in only in red cells (methaemoglobinaemia are between 10 - 15%)
Type 2: Cytochrome B5 reductase in absent in all cells (methaemoglobinaemia levels are over 35%)
What is acute intermittent porphyria?
A rare autosomal dominant condition caused by a defect in porphobillinogen deaminase - an enzyme involved in the biosynthesis of haem. This results in toxic accumulation of delta aminolaevulinic acid and porphobillinogen. It presents eith abdominal and neuropsyhciatric symptoms in 20 - 40 year olds.
How do you diagnose acute intermittent porphyria?
- Urine turns red on standing
- Raised urinary porphobilinogen (higher during attacks)
- Porphibilinogen deaminase raised on a red cell assay.
- Riased serum levels of delta aminolaevulinic acid and porphobilinogen
What are the types of sickle cell crisis?
Thrombotic ‘painful crisis’
Sequestrian - sicling within organs such as the spleen on lungs causes pooling of blood with worsening of anaemia
Acute chest syndrome
Aplastic - caused by parvovirus infection
Haemolytic
Where is the mutation in seen in polycythaemia rubra vera?
JAK 2 gene mutation - causes this gene to be always activated and cause unchecked red blood cell production. After a period of time scarring occurs (spent phase) and the bone marrow is not able to produce blood cells - this is called myelofibrosis
What is the treatment for polycythaemia rubra vera
- Venesection
- Hydroyurea
- Ruxolitinib (JAK 2 Inhibitor)
- Aspirin
What can polycyethaemia vera progress to?
Myelofibrosis and AML (5 - 15%)
What does the BCR ABL gene code for?
A fusion protein which has excess tyrosine kinase activity
What is the most common gene mutation see in CML?
Philidelphia chromosone (translocation between chromosone 9 and 22)
What is the first line treatment for CML?
Imatinib - inhibits the tyrosine kinase acssociated with the BCR ABL defect
What is the most common cause of inherited thrombophilia in the UK?
Factor V Leiden (activated protein C resistance)
What is factor V Leiden disease?
A mutation in the factor V Leiden protein. It means that activated factor V (clotting factor) is inactivated 10 times more slowly by activated protein C than normal. Hetrozygotes have a 4 -5 x increase risk of VTE. Homozygtes have a 10 x increase
Are auer rods seen in the blood film of AML or ALL?
AML
What is the treatment for acute promyelocytic leukemia?
All trans retinoic acid (ATRA) vitamin A derivitive
What is the most important prognostic factor in AML?
Cytogenetics - deletion of chromosome 5 or 7 have a poor prognosis
Being over 60 and having more than 20% blasts after the first course of chemo are also poor prognostic factors
What translocation is associated with acute promyelocytic leukemia
t(15;17)
What is the treatment for qcute chest syndrome in sickle cell patients?
Oxygen
IV fluids
Pain relief
Incentive spirometry if rib or chest pain
Antibiotics
Transfusion to be considered in the hypoxic patient.
What is thrombotic thromocytopenic purpura?
A condition associated with pregnancy where there are abnormally large and sticky multimers of von willebrands factor which causes platelets to clump within vessels. This causes a low platelet count, low haemaglobin and kidney, heart and brain dysfunction.
What is the treatment for Thrombotic thrombocytopenic purpura?
Plasma exchange
Steroids
Immunosuppressants
Vincristine
