Lab Haematology Flashcards
utility of haemltocrit (non USA)
use for target for polycythaemia venesection
utility of MCHC?
Goes down if dehydrated - heridatry spherocytosis.
Otherwise pretty much constant and kind of useless
utility of basophil count?
increased in CML (until further results come back)
otherwise not very useful
Portion of T vs B cells in blood
70-80% T cells
Microcytic anaemia causes
- Thalassaemia
- Anaemia of of chronic disease (of inflammation - changing its name, not CKD)
- Iron deficiency
- Lead poisoning (rare)
- Rare: congenital sideroblastic anaemia
- Hyperthyroidism (rare)
Hepcidin release process
endotoxin
-> stimulates Kupffer cell
-> IL-6 release
-> hepcidin release from liver
characteristic RBC feature of lead poisoning?
basophilic stippling
Classic appearance of RBCs in thalassaemia
Target cell
Main types of Hb in adults
HbA
HbA2 < 3.5%
HbF < 1%
Naming of alpha thalasaemia by number of genes
One gene deletion
– (silent carrier)
- Two gene deletion
– alpha trait - Three gene deletion
– (HbH disease) - Four gene deletion
– (Barts hydrops fetalis)
Characteristic RBC appearance in alpha thalasaemia
golf ball appearance
testing for alpha thalassaemia
do a RAT test type thing these days - pretty good
naming of 2 gene alpha deletion
Either α-/α- or - - /αα
(α+/α+ or α0 /α)
Reason for maternal complications hydros faetalis
complications due to large placenta (toxaemia, post-partum haemorrhage)
nomenclature for beta thalasaemia genes
– reduced expression (β+ )
– absent expression (β0 )
most reliable test for beta thalassaemia
Increased HbA 2(α2δ2)
nomenclature for beta thalasaemia disease
how much central pallor should you have in a RBCs
1/3 at most
Definition of beta thalassaemia major
dependent on transfusions
Test for hydros faetalis?
test parents genetics
chorionic villous sampling
Clinical phenotype HbE + betal thal
variable but more severe than beta that
- since few or no normal β chains
- 30-50% require regular transfusion
- 20-50% require splenectomy
Clinical phenotype HbS + betal thal
worsens sickle trait – closer to sickle disease
Main causes for macrocytosis
Etoh (smoking more rare)
MDS (myeloma more rarely)
Liver disease - cholestatic in particular (mech unknown)
B12 (folate more rare)
Meds
Retics
Haemachromatosis (fertilising Fe)
Less common
- aplastica anaemia (pancytopaenic normally)
- anorexia
- COPD
- hypothyroid
- familial
- preggers - ?folate ?Fe supplements
Major meds causing macrocytosis
Anti-biotic (trimethoprim)
Anti-virals
Anti-Epileptic (phenytoin)
Anti-Cancer (cytotoxics)
Normocytic anaemia causes
Decreased production – decreased reticulocytes
* Lack of erythropoietin (CKD) (normocytic)
* Infiltration of bone marrow (normocytic)
* Chemotherapy
* Inflammatory process (tends toward microcytic)
* Lack of nutrients (can be macro, microcytic)
* Marrow disease such as MDS (often macrocytic)
Increased loss or destruction – increased reticulocytes
* Acute bleeding
* Haemolysis (sometimes macrocytic)
Where does extra-vascular haemolytic occur
mostly the spleen
Is intra or extra-vascular haemolysis more common
extra
Tests for AIHA
Anaemia
Reticulocytes
Blood film - Spherocytes
Bilirubin (unconjugated)
Haptoglobin - low
Direct antiglobulin test (DAT; aka Coombs)
Post-splenectomy blood cell changes
Howell Jolly bodies (nuclear remnant),
target cells,
spherocytes,
odd cells
Things that can mutate to cause spherocytosis
Ankyrin, Band 3, Spectrin, and Protein 4.2
AD disease
Causes for acquired hyposplenism
- Infarction
– Sickle cell, Essential thrombocythaemia, Polycythaemia vera - Atrophy/Hypofunction
– Coeliac, dermatitis herpetiformis, IBD, Autoimmune (SLE, RA, GN, PBC, Sjogren’s, MCTD, thyroiditis), irradiation
– Bone marrow transplantation & GVHD
– HIV/AIDS - Infiltration
– Amyloid, sarcoidosis, leukaemia, myeloproliferative, etc
Test for spherocytosis
DAT
of look at FHX
+/- genetic studies
Hereditary spherocytosis consequences
- Anaemia
- Pigment gallstones
- Splenectomy may be needed for cases with symptomatic anaemia - kids not growing
Inheritance of G6PD def
X-linked recessive
Cells in G6PD deficiency (and why)
bite cells / keratocytes
Due to Heiz bodies (precipitant DNA)
Drugs that cause drug induced oxidate haemolysis
- Sulphonamides
- Dapsone - see commonly even though not used much
- Antimalarials
- Co-trimoxazole
- Naphthalene
- etc
Causes for rouleux bodies
High globulins / fibrinogen
- Chronic infection or inflammation
- Monoclonal proteins
Causes of reactive lymphocytes
- EBV
- CMV
- Toxoplasmosis
- Other viruses occasionally - don’t cause so much lymphocytosis
Causes for cold agglutination
- EBV
- Mycoplasma
- Lymphoma
Test for lymphoma
– Morphology
* usually of a lymph node but sometimes blood, spleen, marrow, skin
– Immunophenotyping
* Immunohistochemistry and/or
* Flow cytometry
– FISH/cytogenetics occasionally
smudge/ smear cells in?
CLL
clefted and cerebriform cells in?
Sezary syndrome / peripheral T cell lymphoma
granular lymphocytes in?
arge granular lymphocyte leukaemia (associated with neutropenia and RA - Felty’s)
starry sky cells in?
Burkitt lymphoma
owl eye looking cells in?
Hodgkin’s
Cell surface markers B cells
- CD19
- CD20
- Kappa
- Lambda
Cell surface markers for T cells
- CD3
- CD4
- CD8
- CD5
Increased VWF in?
Thrombotic microangiopathies
- Multimers not cleaved (TTP)
- Too much VWF secreted from toxin-stimulated kidney endothelium (HUS)
Decreased VWF in?
Genetic: von Willebrand disease
Acquired: von Willebrand syndrome
* Aortic stenosis and LV assist devices
* Essential thrombocythaemia – VWF depleted by very high platelet numbers
* Immune mediated, malignancy, hypothyroidism
no ADAMTS 13 =
TTP
Clinical features TTP
All patients have:
- thrombocytopenia
- microangiopathic haemolytic anaemia.
Most common symptoms are nonspecific:
- abdominal pain, nausea, vomiting, and weakness (microvascular thrombi in many organs).
Neurological signs occur in about half.
Renal failure can occur.
Fever uncommon
TTP treatment
- plasma exchange to replace the ADAMTS13 and to remove antibodies
(Reduces mortality from ~90% to ~20%)
Main cause of HUS?
- ~ 90% of cases caused by Shiga-toxin producing E. coli
- Strep pneumoniae HUS (SP-HUS) ~ 5%
- Atypical HUS (aHUS) ~ 5% (Genetic)
Type of VW disease
- Type 1 – reduced level of VWF protein
- Type 2 – reduced function
- activity < 70% of expected for protein level
- different subtypes depending on the position of the mutation
- Type 3 – very low levels (both alleles affected)
Tests for T2 VWD
- VWF activity assay
OR - Ristocetin co-factor activity (VWF:RCo)
- ristocetin alters conformation (mimicking shear forces) induces platelet binding
- Collagen binding assay (VWF:CB)
- Factor VIII levels
What is Heyde’s syndrome?
acquired VW syndrome d/t valvular disease
acquired VW syndrome causes
In certain conditions, large VWF multimers are broken/proteolysed leading to loss of HWM forms = Acquired type 2a VWD.
- Valvular disease (Heyde syndrome), ventricular assist devices, congenital heart disease: shear-stress-induced proteolysis
- Essential thrombocythaemia, polycythaemia vera: excessive binding to abnormal platelets + proteolysis
Autoantibody-mediated loss of function in myeloma/lymphoma and SLE
Diagnostic criteria APLS
Clinical features APLS
Haematologic
* Thrombocytopenia
* Haemolytic anaemia
Dermatologic
* Livedo reticularis or racemosa Livedoid vasculopathy (recurrent, painful skin ulcerations)
Neurologic
* Cognitive dysfunction (in the absence of stroke)
* Subcortical white-matter changes
Renal
* Acute thrombotic microangiopathy
* Chronic vaso-occlusive lesions
Cardiac
* Valve vegetations or thickening
