Haematology Flashcards
What is the inheritance of Von Willebrand Disease?
Autosomal Dominant
What are the lab findings in Von Willebrand Disease?
- APTT increased
- Bleeding time increased
- Factor VIII reduced
What is Von Willebrand Disease?
A reduction, absence of or defective Von Willebrand Factor - which is released from the endothelium and is needed for platelet activation. Circulates in the plasma bound to factor VIII
What is the deficiency in haemophilia A?
Deficiency in clotting factor VIII (8)
What is the deficiency in haemophilia B?
Deficiency in clotting factor IX
Blood film: Howell Jolly bodies. What condition is this associated with?
This is seen post splenectomy or hyposplenism (such as autosplenectomy/splenic infarction which occurs in sickle cell anaemia)
Blood film: Spherocytes. What condition is this associated with?
Hereditary spherocytosis and
Autoimmune haemolytic anaemia (AIHA)
How to distinguish between hereditary spherocytosis and AIHA?
Hereditary - Coombs -ve
AIHA - Coombs positive
Blood film: smudge cells. What condition is this associated with?
CLL chronic lymphocytic leukaemia
Blood film: Heinz bodies. What condition is this associated with?
G6PD (glucose 6 phosphate deficiency)
Blood film: Schistocytes
A sign of microangiopathic haemolytic anaemia. Seen in DIC, TTP, HELLP syndrome, also macroangiopathic haemolytic anaemias - prosthetic heart valve and aortic stenosis.
Schistocytes (eg, “helmet cells”) are seen on peripheral blood smear due to mechanical destruction (schisto = to split) of RBCs.
Blood film shows elliptocytes. What condition is this suggestive of?
Hereditary elliptocytosis - autosomal dominant disorder
What type of anaemia do you get in G6PD deficiency?
Normocytic anameia
Acute haemolytic anaemia - both intravascular and extravascular but mostly intravascular
Blood film: Heinz bodies and bite cells
What are the features of TTP?
- Fever
- Thrombocytopenia
- microangiopathic hemolytic anemia
- CNS sympoms
- Renal failure
What are the blood film findings in DIC?
Schistocytes (fragmented RBCs)
What is the cause of TTP?
Deficiency in ADAMTS13 ( von willebrand factor cleaving enzyme)
Which is the first antibody made in response to infection?
IgM
What class of antibody is Rheumatoid Factor?
IgM
Which antibody is found in tears/saliva/sweat
IgA (protects mucous membranes)
Anaphylaxis is mediated by which antibody?
IgE
Which is the only antibody that crosses the blood brain barrier?
IgG
Allergic contact dermatitis is what type of hypersensitivity reaction?
Type IV
What is hereditary spherocytosis?
Autosomal dominant disorder affecting the RBC membrane making it more fragile and destroyed more quickly by the spleen.
Causes a normocytic anaemia
What is the structure of a normal haemoglobin molecule?
2x alpha global chains, and 2x beta global chains
What is thalassaemia?
An inherited disorder affecting either the alpha or beta units of haemoglobin
Results in a microcytic anaemia
What is the structure of fetal haemoglobin?
2x alpha and 2x gamma china s (declines in the first year of life)
Hypersegmented neutrophils (polymorphs) on a blood film is indicative of?
B12/folate deficiency
Reed Sternberg cells on biopsy are indicative of what disease?
Hodgkin’s lymphoma
Heinz bodies (bite cells) on a blood film are indicative of what condition?
Glucose 6 phosphate dehydrogenase deficiency
Basophilic stippling on a blood film is suggestive of what?
lead poisoning
Howell Jolly bodies on a blood film are suggestive of?
They are RBC remnants
They indicate impaired or absent splenic function
Blood film: Aur rods. This is indicative of what condition?
Acute Promyelocytic Leukemia (APL) a subtype of AML
Splenectomy increases the risk of infection by which organisms?
encapsulated bacteria such as:
- Streptococcus pneumoniae
- Haemophilus influenzae
- Neisseria meningitidis
- Salmonella
“SHiNS”).
What is selective IgA deficiency?
Most common immunoglobulin deficiency
Usually asymptomatic
But can associated with increased respiratory, gastrointestinal, and genitourinary infections.
Associated with risk for anaphylaxis with blood product transfusions.
JAK2 mutation is associated with which conditions?
- Essential thrombocytosis (high platelets)
- Polycythemia rubra vera (high RBCs)
What is pernicious anaemia?
Autoimmune condition - anti-intrinsic factor antibodies and antiparietal cell antibodies - affecting gastric parietal cells –> atrophic gastritis –> low intrinsic factor.
IF is needed for B12 absorption - thus you get B12 deficiency
What is sideroblastic anaemia?
Causes microcytic anaemia
Can be hereditary (rare) or acquired
Unable to utilise iron for haem synthesis
Iron levels may be normal or high.
Iron replacement does not help.
Acquired causes - lead poisoning, chronic alcoholism, pyridoxine (B6) deficiency
What is an important drug cause of sideroblastic anaemia?
Isoniazid
INH binds to pyridoxine (b6), making it unavailable for absorption by the body - b6 deficiency is one of the causes of sideroblastic anaemia
what is the most common cause of sideroblastic anaemia?
chronic alcoholism
The finding of the Philadelphia chromosome is indicative of which condition?
CML
The Philadelphia chromosome is formed by which gene translocation?
BCR-ABL gene
t(9:22)
What gene translocation do you find in Burkitt’s lymphoma
C-myc
t(8:14)
What infection is associated with Burkitt’s lymphoma?
EBV
What chromosomal translocation do you find in Acute promyelocytic leukaemia
t(15;17)
What drug is commonly used to treat CML?
Imatinib (tyrosine kinase inhibitor)
What type of anaemia do you typically find in sickle cell anaemia
Normocytic anaemia
High reticulocytes
What is an aplastic crisis
Infection with parvovirus B19 in someone with sickle cell anaemia - affects RBC precursor cells - RBC production is halted- causing severe acute anaemia
What is haptoglobin?
A protein released from the liver that binds to free Hb molecules that have been released from RBCs that have been haemolysed in the circulation - essentially mopping up the Hb. The Haptoglobin-Hb complex is removed by the liver, thus- lower levels of Haptoglobin are a marker of intravascular haemolysis
Haptoglobin is normal in extravascular haemolytic
What is a marker of extravascular haemolysis?
Elevated unconjugated bilirubin
What are the key features of paroxysmal nocturnal haemoglobinuria?
- haemolytic anaemia –> haemoglobinuria - presenting as red urine first thing in the morning
- Pancytopenia
- venous thromboses
- Coombs negative
RBCs become more susceptible to complement mediated haemolysis.
Intravascular haemolysis so haptoglobin is low.
What is the treatment for paroxysmal nocturnal haemoglobinuria?
eculizumab (monoclonal antibody that works as acomplement inhibitor)
What is myeloma?
Malignant proliferation of plasma cells
What are the features of myeloma?
CRAB
C- hypercalcaemia
R- renal involvement
A- anaemia
B - bone lytic lesions
How do you classify leukaemia?
Myeloid vs lymphoid cells
Bone marrow is affected
Tumour cells found in peripheral blood
acute vs chronic
acute - acute myeloid leukeamia, acute lymphoblastic leukeamia
chronic myloid leukeamia
chronic lymphoid leukeamia
What are the classic age ranges for the different leukaemia’s?
ALL - birth to 14yo
AML - 15yo to 39
CML 40-60
CLL >60yo
What cells are affected in ALL?
They can be B or T cell
85% are precuser B cells affected
15% are precursor T cells affected - T cell ALL usually presents as a mediastinal mass
The malignant pre-B and pre-T lymphoblasts seen on peripheral smear are morphologically indistinguishable, so the subclassification of ALL is dependent on immunophenotyping.
What is AML
Myeloid precurser cells give rise to a variety of blood cells - so there are many subtypes
You get malignant proliferation of myeloid precurser cells in the bone barrow. Accumulation of these immature, neoplastic blast cells in the marrow surpasses the remaining normal progenitor cells by physical replacement - BM failure - causing anaemia, neutropenia, thrombocytopenia. in AML
you get myeloblasts on blood film which is not usual to see.
What are the key features to tell apart ALL and AML?
ALL -lymphadenopathy
AML - lymphadenopathy is rare, myeloblast cells on peripheral smear
Aur rods in cells in APML
What is the treatment for APL?
Trans-retinoic acid
What is the hallmark finding in CML?
BCR-ABL fusion gene (philadelphia chromosome) - translocation of genes 9:22
How do you classify lymphoma?
Hodgkin’s vs non-hodgkins
Can also be classified by high grade and low grade
What are two classic features of Hodgkin’s lymphoma
- presence of reed-stern berg cells on lymph node biopsy
- B symptoms - night sweats, weight loss
- Lymph nodes are painful after drinking alcohol
What are the key features of acute haemolytic transfusion reaction?
- ABO incomptability causing acute intravascular haemolysis of donor RBCs
- fever, chills
- dark urine (haemoglobinuria)
What are the symptoms of TACO (transfusion associated circulatory overload)
Acute pulmonary oedema - hypervolaemia
- SOB
- Crackles in the chest
- Hypertension
What are the symptoms of TRALI Transfusion Related Acute Lung Injury?
- Acute pulmonary oedema
- SOB
- Crackles
- HYPOTENSION
What is the direct Coombs test?
Detects presence of antibodies against RBCs
Distinguishes between immune haemolytic vs non-immune (G6PD deficiency)
Coombs test positive if immune/antibodies detected
Coombs test negatibe if no antibodies
What is henoch-schonlein purpura?
- small vessel vasculitis caused by IgA immune complex deposition in capillaries - particularly in the skin and kidneys - leading to inflammation
- affects mostly children and is the most common vasculitis in children
- typically occurs in children after a viral URTI
- Remember, IgA is found in mucous membrane linings of the body
What are the key features of henoch-schonlein purpura?
- palpable purpura on legs and buttocks
- arthritis
- abdominal pain
- Intusseseption which can cause bloody stools
- AKI/IgA nephropathy (Berger disease)
Management: conservative
What is idiopathic (immune) thrombocytopenic purpura?
- autoimmune (IgG mediated) destruction of platelets
- autoantibodies against Gp2/3 receptors on platelets that lead to increased destruction by the spleen
- Type 2 hypersensitivity reaction
- Presents as acutely low platelets in a child following a viral URTI
- In children usually resolves within few weeks or months
- In adults, typically chronic
What is thrombotic thrombocytopenic purpura? TTP
Mutation in ADAMTS13 gene
leads to increased platelet activation and aggregation
this leads to multiple micro thrombi around the body
How does TTP present?
medical emergency
1. fever
2. thrombocytopenia because platelets are used up in formation of microthrombi around the body
3. microangiopathic hemolytic anemia
4. renal dysfunction (occlusion of renal arteries by microthrombi)
5. neurologic dysfunction.
What are some causes of microangiopathic haemolytic anaemias?
A type of non immune haemolysis
increased coagulation, leading to the narrowing of small blood vessels –> RBC membrane damage –> increased hameolysis of RBCs
- DIC
- TTP
- haemolytic uraemia syndrome
What are some examples of haemolytic anaemia with positive and negative Coombs test?
Positive
- Haemolytic disease of the newborn (rhesus incompatibility)
- acute haemolytic transfusion reaction
- Autoimmune haemolytic anaemia (AIHA)
Coombs negative
- Paroxysmal nocturnal haemoglobinuria
- G6PD deficiency
- hereditary spherocytosis
How do you treat high INR in a patient who was taking warfarin who has major bleeding (eg intracranial bleeding)
IV Vitamin K and prothrombin complex concentrate
PCC contains plasma derived concentrate of vitamin K coagulation factors II, VII, IX, X protein C and S
Reverses warfarin Anticoagulation within 10 mins
What are the lab findings in tumour lysis syndrome?
- AKI - raised urea and creatinine
- hyperkalaemia
- high phosphate
- high uric acid
- hypocalcaemia
calcium and phosphate deposition in the kidneys causes kidney failure
Methotrexate causes what sort of anaemia?
macrocytic - because methotrexate can cause folate deficiency - this leads to megaloblastic anaemia
(The most common type of anaemia in RA overall is anaemic of chronic disease)
What are the lab findings of DIC?
- low platelets
- increased PT and aPTT due to depletion of clotting factors
- low fibrinogen
- d-dimer raised
- microangiopathic haemolytic anaemia - peripheral blood film will show schistocytes
What is the microangiopathic and macroamgiopathic haemolytic anaemia?
Anaemia caused by mechanical or shear stress destroying RBC membrane leading to haemolysis.
Blood film shows schistocytes which are fragment pieces of RBCs.
What is polycythemia rubra Vera?
- High RBCs
- JAK2 mutation
- Usually presents age >60
- Hyperviscosity of blood
- Splenomegaly
Increased risk of thrombotic events such as stroke, MI and DVT and splenic infarcts
Pruritis after a warm bath due to abnormal release of histamine from mast cells.
Ruddy complexion
EPO is low (negative feedback)
What is the mechanism of action of Apixaban and Rivaroxaban?
Direct factor Xa inhibitors.
Function of Vitamin K?
Needed as a cofactor for the synthesis of clotting factors II, VII, IX and X and proteins C and S.
