Haematology Flashcards
What causes alpha thalassemia and how is it inherited?
Defective alpha glob in chain of haemaglobin
AR inheritence
- silent carrier (heterozygous)
- Alpha thal minor (2 defective genes)
- HbH (3 defective genes)
- Hb Barts Hydrops Fetalis (all 4 defective genes) 4 gamma chains as no alpha chains
What will alpha thalassemia blood tests show?
Low Hb, Low MCV and MCH
Blood film: hypochromic microcytic RBC, +/- target and golf cells
haemoglobin electrophoresis: HbH may be present
gene testing can confirm
treatment for alpha and beta thalassemia
mild: nil
severe : tranfusions
if beta thalassemia major may also need iron chelating agents or spleenomegaly
What causes beta thalassemia and how is it inherited?
AR inherited - most commonly seen in Mediterranean, African and South East Asian populations
Usually due to a point mutation messing up beta thalassemia production
Can be minor, intermedia or major
What are the symptoms of Beta- thalassemia major and when do they start
SOB, pallor, fatigue
Hepatospleenomegaly
Hypoxia from haemolysis
Jaundice from excessive bilirubin
secondary haemachromatosis due to excessive heme/iron
chipmunk facies / crew cut skull
start in the first 3-6 months of life
What will beta thalassemia blood tests show?
Low Hb, Low MCV and MCH
Blood film: hypochromic microcytic RBC, +/- target cells
High ferritin, serum iron and transferinand bilirubin may be present
gene testing can confirm
Signs and blood findings of folate deficiency
Signs of anaemia
Glossitis
IHD sx: CP, atherosclerosis
Neural tube defects in newborns
Pancytopenia: anaemia, WBC and RBC precursers affected
What is myelofibrosis ?
Where the bone marrow gets fibrosed /replaced with connective tissue
Primary: JAK-stat pathway overactivated and fill the bone with abnormal cells (platlets and fibroblasts) that make too much connective tissue
Secondary: Essential thrombocythemia, or PCV
Bloods for haemachromatosis will show
High iron/ferritin
High transferrin sat % (as lots of transferrin binding sites occupied by iron)
Low TIBC (as less binding sites available to carry iron)
Treatment of haematchormatosis
regular venesections
+/- iron chelating agents
What causes Auto immune haemolytic anaemia
- Idiopathic
- trigger: vira linfections, SLE, lymphoma/leukemia, penicillin,cephalosporin
Col dcan also be triggered by mycoplasma, EBV/galndular fever
How does autoimmune haemolytic anaemia happen
Body creates antibodies against our own RBCs
Broken down in the liver/spleen
Warm AI haemolytic anaemia vs cold
Warm: due to IgG antibodies at warm >37degrees bind to RBCs and induce haemolysis
Cold (rare): IgM antibodies at 0-10 degrees
Bloods for autoimmuen haemolytic anaemi
Low Hb
Normal MCV (as bone marrow pumps out lots of reticulocytes which are the same size as RBCs)
High reticulocytes
high LDH, bilirubin and iron (due to RBC break down)
direct coombs or antigen test
Treatment of autoimmune haemolytic anaemia
- RBC transfusion
- Steroids or immunosuppresives
- plasmophoresis for severe cases
CML vs CLL
which cells are affected
CML: issue with neu, basophils, eosinophils
CLL: lymphocytes (B cells and T cells)
CML is caused by
Switch between chromosome 9 and 22 causing philidelphia chromosome t(9:22) which causes inappropriate myeloid cell division
ofted builds up in the spleen and liver (hepatospleenomegaly)
CLL ic caused by
excessive B and T cells
Builds up in lympnodes first, (lyphadenopathy) causing small lymphomas
Treatment of CML vs CLL
CML : Biological therapy to target protein from t(9:22)
As there isn’t a specific CLL target the therapy involves chemo, stem cell transplants or bone marrow transplants
Symptoms of myelofibrosis
- bone pain
- fatigue
- itching
- weightloss
- can cause hepatospleenomegaly and pulm HTN, excessive clotting and VTE
What would you see with a patient with myelofibrosis
- on their bloods
- on a blood smear
- in their bone marrow
Bloods: initially excessive platlets, then a pancytopenia
Smear: tear drop RBCs (as they get squeezed throguh fibrotic tissue)
Marrow: increase in haematopoetic cells and early myelofirbrosis
Treatment of myelofibrosis
Ruxolitinib- to inhibit the JAKstat mechanism
Stem cell transfusions
transfusions for pancytopenia
EPO for anaemia
What are some atypical signs of IDA
- kolionychia
- Pica
- hair loss
- itch
What do IDA bloods show
Low HB
Low MCV
Low ferritin, serum iron and transferrin (amount of iron bound to transferrin)
High TIBC
High RDW (lots od differently sized RBCs)
What causes Anaemia of chronic disease
chronic inflammation states mess up RBC production
ie: infections, malignancy, diabetes, autoimmune conditions
usually a mild anaemia
difference between hogkins and non hodgkins lymphoma
Hodgkins
- x1 site of LNs
- Reed steenberg cells
- Rarer
- better prognosis
Non-Hodgkins
- Multiple sites
- Extranodal: skin, gut
- no reed stenberg cells (usually)
- 90% cases, small amount assoc w EBV
Both have B sx (night sweats, WL, fevers)s, pruitis, fatigue, lymphadenopathy
What types of cells do you get in hodgkins lymphoma
Crippled B cells that dont make antibodies as they should
Hodgkins cells: Large mononuclear B cells OR
Reed Stenberg cells: 2x hogkins cells stuck together
Symptoms of non hogkins lymphoma
The release of cytokines causes symptoms like fever, drenching night sweats, and weight loss.
GI tract involvement > bowel obstruction.
Bone marrow > fatigue, easy bruising, or recurrent infections.
spinal cord involvement > LL weakness/numbness
Is burkitts lymphoma more aggressive
More aggressive B cell lyphoma - starry sky on film
mantle cell also very aggressive
What is sickle cell anaemia
AR inherited condition
RBC in the shape of a sickle/cresent which damages the cell membrane increases the rate of their destruction
This is due to a mutation causing a defect in the beta - globin chain
Is it dangerous to be a sickle cell carrier (heterzogyous gene carrier)
No, not unless you are in extreme conditions (high altitude etc)
It can actually be protective against malaria
What is HbS
sickle haemaglobin (normal alpha, mutated beta chains)
Carries oxygen normally, but when deoxygenated can stick together into long chains (sickle-ing) causing the RBC to be crescent shaped
- this happens in small vessels or in acidosis
Signs/symptoms of sickle cell anaemia
Anamia, sickle cells and howell jolly cells on film
Bone formation else where as bone marrow is in overdrive
- hair on end skull xray
- enlarged cheeks
Hepatomegaly
Blood can clog up in the
- hands (dactylisis)
- Spleen (splenic infarcts/sequestration).»_space;> high infection risk to encapsulated bacteria
- Bone (AVN of bone)
What is antiphopholipid syndrome?
Autoimmune disease with antiphospholipid antibodies which attack phospholipids in the cell membrane
leads to a hypercoagulable state, increasing VTE risk, endocarditis, kidney failure, livedo reticularis, pregnancy complications, headaches/seziures
What are the pregnancy related complications of antiphospholipid syndrome?
- Placental infarctions causing miscarriage
How to diagnose antiphospholipid syndrome
clinical hx + presence of antibodies
Treatment of antiphospholipid syndrome
- aspirin
- avoid smoking and COCP
- Pregnancy: LMWH and aspirin
What causes PCV
JAK2 mutations which causes over production of RBCs
later leads to myelofibrosis
positive JAk2 and low EPO
WCC and PLT may also be high
tx: aspirin and hydroxyurea
Symptoms of PCV
fatigue, dizziness, increased sweating, redness in the face, blurred vision, and itchy skin especially after a hot shower.
Itchiness develops due to the increased number of basophils and mast cells which contain histamine that causes itching when released.
Splenomegaly or spleen enlargement is also common because the excess red blood cells buildup in the spleen, which usually helps with removing excess cells.
Haemophilia A is a deficiency in?
Factor 8 (VIII) - X linked reccessive
this is by far the most common haemophilia
Part of the INTRINSIC Pathway
Linked with Von willibrands, liver disease, DIC, vit K deficiency
Haemophilia B is a deficiency in?
Factor 9 - X linked recessive
Part of the INTRINSIC pathway
How to test for haemophilia
prolonged APTT (tests intrinsic and common pathways)
Normal PT, platlets
What cells are abnormal in Multiple myeloma
Abnormal plasma cells (from B cells), that uncontrollably divide and crowd out the bone marrow
How does multiple myeloma cause issues in all the other parts of the body
plasma cells produce excessive amounts of monoclonal antibodies that deposit in the tissues
Kidney > renal failure
bloodstream > viscous blood (blurred vision, headache)
Pathologic fractures (bone pain)
Tests for MM
FBC: anaemia, pancytopenia
UEs: High Creatinine, high calcium
Blood smear: roleux formation
Excess kappa or lamba light chains causing a abnormal FLC kapp:lambda ratio
Excess M protein/paraprotein (abnormal immunoglobulin)
Bone marrow: excess plama cells
What is MGUS
A patient with abnormal m protein/paraprotein immunoglobulins but doesn’t meet MM criteria
ITP
isolated low plt
often brusing and mucosal bleeding
Bloods: smear, retic, coags, LFTs, ANA, viral screening (HIV, hepatitis)
Tx: prednisone1mg/kg or 40mg for a week
refer if severe
can be presentation for lupus
issue w PPIs in the setting of IDA
reduces acid levels and can reduce iron absorption
link between iron and platelets
low iron can cause high PLT count
What stages of life do you commonly have low B12
pregnancy (haemodilution)
elderly (dietary w tea/toast diet and terminal ileitis)
best tests for pernicious anaemia
intrinsic factor AB - best
parietal cell ABs - not as specific
