Haem Flashcards
Contents of cryoprecipitate
Factor 8 Factor 13 Fibrinogen Fibronectin Von wilebrand factor
Haemochromatosis mutations
H63D
C282Y
Both mutations in the HFE gene (human haemochromatosis gene), gene product is HH protein which regulates hepcidin production.
Homozygous c282y most common clinical haemochromatosis
Heterozygous compound c282y/h63d mild, homozygous H63D
Heterosexual h63d rarely clinically seen
Most sensitive test for diagnosing haemochromatosis
Transferrin saturation- more than 50% in women and 60% in men
How do you tell the difference between haemophilia a and b on lab testing
You cannot- lab wise indistinguishable
Clinically haemophilia B (factor 9 def) can present in adulthood, not really for haem A. Mixing study will correct prolonged ATPP in congenital but only partially in acquired factor 8 deficiency
Factor 5 def get long PT and APTT
Factor twelve def gives long APTT but normal PT as well but no actual bleeding manifestations
Causes of isolated long APTT
Low 8,9,12, 11
Acquired clotting factor inhibitors against factor 8
Lupus anticoagulant
Plus minus also prolonged PT- UFH, anti phospholipid Ab
Inherited thrombophilias
More potent: protein c, protein s, anti thrombin deficiencies
Less potent more common: prothrombin G20210A gene mutation, factor v Leiden
Percentage of JAK 2 in PRV, IMF, ET
95% for PRV
50-60% for others
Name of effect where taking spleen out attenuated the disease process
Abscopal effect
Hyper viscosity clinical triad
Visual changes, mucosal bleeding, mental state changes
To diagnose waldenstroms macroglobulinaemia need 2 things…
Greater than ten percent lymphoplasmocytic bone marrow cellularity and IgM M protein
What is the use of serum transferrin receptor
Derived from BM erythroid precursors, hence increase with increasing erythropoesis. Inversely proportional to iron levels eg low iron gives high level
Not as specific as low ferritin
What is free transferrin receptor/log ferritin ratio use?
Better than serum free transferrin receptor at differentiating ACD from iron def anaemia.
Less than one - ACD
more than two - iron def
More than 2 could also mean both
Causes of B12 def
Pernicious anaemia, bariatric surgery, gastritis, autoimmune metaplastic strophic gastritis
Malabsorption syndrome, Crohn’s disease, blind intestinal loops, ileal resection or bypass, fish tapeworm infection
Pancreatic insuff
Strict vegan or pregnant plus veg
Agents that block absorption - biguanides, h2 receptor antag, ppis, N2o anaesthesia, neomycin
Inherited transcobalmin II def
Role of methylmalonic acid and homocysteine levels in suspected B12 and folate def
Folate def–> sensitive high levels homocysteine
B12 def–> sensitive high levels both MMA and homocysteine
These are metabolites waiting around to be processed but no B12 or folate to help
Useful when borderline levels of tests
Ab testing in pernicious ansemia
Intrinsic factor Ab not sensitive (50-70%) but specificity approaching 100%
Anti parietal cell ab more sensitive but less specific
Increase in serum gastrin, decreased pepsinogen 1 and decreased pepsinogen 1:2 highly sensitive but not specific
Cold agglutinin causes
Cold IgM ab AIHA lymphoproliferative disorders Mycoplasma Mononucleosis EBV HIV Drugs Idiopathic
Immune DAT + causes
Post transfusion Drugs SLE CLL idiopathic
Lenalidomide associated Thrombosis
Increased risk arterial and venous thrombosis in patients on lenalidomide- increased risk if newly diagnosed, high dose Dex, hyperviscosity, recent surgery, cvc, anthracyclines
Causes of pancytopaenia
Central (BM failure): drugs B12/folate Aplastic anaemia MDS haem malignancy myelofibrosis non haem infiltration- solid tumour or storage disorder haemophagocytic syndrome
Peripheral:
hypersplenism
sepsis
dilutional in pregnancy
What congenital malformations are seen in Fanconi anaemia 60-70% of the time?
Cafe-au-lait spots and hypopigmentation abnormal thumbs short stature microcephaly short stature hypogonadism and delayed development
What is WHIM? (AKA Lazy leukocyte syndrome)
warts, hypogammaglobulinaemia, infections, myelokathexis (cells cannot migrate out of bone marrow)
CXCR4 mutation
hypercellular bone marrow- cells cannot migrate
rarely fatal
Cyclic neutropaenia- what does it look like and what is the clinical significance?
cyclic neutropaenia 3 weekly
autosomal dominant
ELANE mutation (neutrophil elastase)
usually mild but can be severe and cause death
give regular G-CSF to reduce nadir and infection
Chediak -Higashi syndrome- what does it look like and what are the causes? Cause of neutropaenia
Occulocutaneous albinism
Severe neutropaenia and life threatening pyogenic infections where most die by 7 years
Mild coagulopathy
Progressive neurological deterioration with peripheral neuropathy if do not die of infection
Accelerated phase- lymphohistiocytosis usually fatal
Autosomal recessive
see giant GRANULES in leuks and plateelts
Disorder of lysosome trafficking regulatory proteins
HSCT best treatment but only a cure for haem not neuro degeneration
Discuss picture and cause of Schwannmann diamond blackfan syndrome (cause of neutopaenia)
Present in infancy with severe persistent or intermittent neutropaenia Get infections May have other cell lines affected /AA Pancreatic insufficiency in most Bony abnormalities, short stature Dental defects INCREASED RISK AML Aut recessive HSCT result of ribosomal dysgenesis
Felty’s syndrome- what is it?
An acquired cause of neutropaenia
Mild-moderate, chronic neutropaenia
Triad of seropositive RA, splenomegaly, neutropaenia
1% all RA patients
Probably autoimmune
Often also have LGL syndrome- large granular lymphocyte syndrome (neutropaenia with increase in circulating NK cells, often total lymphocytes normal, not malignant)
What is chronic idiopathic neutropaenia/benign chronic neutropaenia
neutrophil equivalent of ITP!
may see with SLE or other autoimmune
Ab testing positive in only 30-40%
mostly mild , never need tx
What are the causes of transient acquired neutopaenia? (7)
- Drug idiosyncratic neutropaenia
- Virus- usually in prodrome, rarely important, may be longer in hep B, HIV
- Sepsis- bad prognostic indicator
- Neonatal isoimmune- Ab from mother
- Nutritional- B 12, folate, COPPER deficient (eg short gut, TPN, malabs)
- Hypersplenism - mild usually
- Haemodialysis- severe neutropaenia on blood taken during dialysis- C’ activation on dialysis membrane causes neuts to latch onto lung endothelium. An artifact only
Drug idiosyncratic neutropaenia (8)
NSAIDS Carbimazole, propylthiouracil Antiepileptics Sulfonamides Dapsone Rituximab CAPTOPRIL!!
sulfonamides? list
sulfamethoxazole, sulfonylureas, sotalol, cox2 inhibitirs, diuretics, protease inhibitors
How bad does neutropaenia have to be to confer a septic risk?
Low risk until around 0.5 then rises sharply
Risk greater if falling counts, empty bone marrow, prolonged length neutropaenia
If abscess formation- implies good reserve of functioning neuts
If gingivitis, mucositis, raised CRP, febrile, suggests poor reserve and high septic risk
What is better for immunosupression in aplastic anaemia? Horse or rabit ATG?
Horse significantly better.
Drug causes of Aplastic anaemia?
Chloramphenicol Gold (especially doses over 200mg) NSAIDS sulfonamides antiepileptics arsenics
and then obviously- chemotherapy, adverse interaction eg aza+ allopurinol, methotrexate in renal impairment
Other causes of acquired aplastic anaemia (other than drugs)
80% idiopathic Irradiation Viral (parvoB19 though usually PRCA), hep, HIV, EBV Chemical- benzene (rubber), glue vapours Immune- eosinophilic fasciitis, SLE, GVHD PNH (1/3 get it) Pregnancy- usually resolve with delivery Thymoma/thymic Ca
What is dyskeratosis congenita? Cause of marrow failure
Marrow failure with increased risk malignancy
Somatic abnormalities not seen at birth but develop with time- nail dystophy(nails disappear with time) + leukoplakia + upper trunk hyperpigmentation
Also premature greying, pulmonary fibrosis, cirrhosis, short stature
Related to shortening telomere length
BM failure in three quarters, median age 10
malignancy age 30+ esp SCC and AML
Allogeneic BMT only cure but will not cure somatic complaints
Fanconi anaemia as a cause of bone marrow failure- what does it look like?
Most diagnosed as kids but may be missed until even early 20s
AR or X linked
Congenital malformations in 60-70% - cafe-au-lait, hypopigmentation, abnormal thumbs, short stature, microcephaly, delayed development, hypogonadism
Defects related to DNA repair and stabilisation
BM - shows hypocellular and dysplastic cells
Specific test is for chromosomal fragility in lymphocytes when exposed to mitomycin C or DEB
Siblings should all be tested even if physically nothing wrong with them
By age 40 complete BM failure in 90%
one third leukaemia or MDS
a third solid CA- head neck skin vulva
80% mortality age 40
Side effects of Hodgkin Lymphoma treatment
Adriamycin–>
Bleomycin–>
Radiation–>
Cardiac
Respiratory
Breast
When can you NOT rely on HbA1c
iron def anaemia Haemolysis Haemoglobinaemia Kids Gestational diabetes HIV CKD
What are the 4 sickle cell crises?
1 Thrombotic- painful/vaso-occlusive. Precipitated by infection, dehydration, deoxygenation. eg hip AVN, hand foot syndrome in kids
2 Sequestration (sickling and sequestration within organs like spleen or lungs–>worse anaemia). Example is the acute chest syndrome- dyspnoea, pain, pulm infiltrates, low sats, DEATH
3 Aplastic parvovirus–>sudden drop Hb
4 Haemolytic- rare. worse anaemia from extra haemolysis
What gives you a falsely reassuring G6PD assay?
reticulocytes! They have higher levels
What does G6PD do?
Two things-
makes NADPH to protect against oxidative stress
oxidises glucose 6 phosphate
What is TPO and how do romiplostim and eltrombopag work?
Romiplostim TPO receptor agonist
Eltrombopag TPO mimetic
thrombopoetin
In beta thal, does iron chelation provide symptomatic benefit?
Yes, desferrioxamine does provide MORTALITY benefit, but local reaction, deafness, retinal toxicity, infection, growth retardation
Hyposplenic blood picture
Howell Jolly bodies
Target cells
nucleated red cell
acanthocyte
