Haematology

Front 1

What is the viscosity of blood?

Back 1

1.1-1.2 Centipoise

Front 2

What are the factors that influence blood viscosity

Back 2

RBC and protein conc.

increased cells increase viscosity

smaller vessels increase viscosity

Front 3

What is the average volume of blood in a person?

Back 3

70mL/kg for adults

children may have slightly higher. ~10mL/kg

Front 4

What is aperture impedance?

Back 4

Based on the detection of electrical resistance as cells pass through a small aperture.

Voltage pulses determine number of cells

Height of pulses determine cell volume

Front 5

how does light scatter and fluorescence measure cells

Back 5

degree of scatter:

0= size

7= complexity

90= lobularity

90 (d)= granularity

Front 6

What is RDW

Back 6

Red cell distribution width.

can measure anisocytosis

Front 7

What is the lifespan of cells in the blood?

Back 7

RBCs 120 days

Platlets 10 days

Granulocytes hours

Front 8

Name the Haematopoietic tissue

Back 8

Fetus 0-2 months = yolk sac

2-7 months = liver/spleen

5-9 months = bone marrow

infants = bone marrow (all bones)

Adults = vertebrae, ribs, sternum, skull, sacrum and pelvis, proximal end of femurs

Front 9

Haemopoiettic Stem cells

Back 9

~1% of bone marrow

CD34 expressed

Pluripotent

Can self renew

Front 10

Describe the haemopoietic cell % in bone marrow

Back 10

Erythropoietic cells ~20%

Granulopoetic cells ~60%

Lymphocytes ~15%

Megakaryocytes <0.1%

Other: Plasma and macrophages

Front 11

WBC diff %s

Back 11

Neutrophils 40-75%

Eosinophils 1-5%

Basophils <1%

Monocytes 2-8%

Lymphocytes 20-45%

Front 12

Platlet range

Back 12

150-400 x10^9/L

Front 13

Reticulocyte description

Back 13

Anuclear

Spherical shape

mRNA remains (bluish colour) polychromataphilia

Can be found in blood

Front 14

Haemoglobin structure

Back 14

A A2B2 (A from C16, B from C11)

A2 A2D2 (D from C11)

F A2G2 (G from C11)

Front 15

Hb prevelence

Back 15

Hb A 95% in adult

HbF small % after birth

HbA2 small levels are normal in adults

Front 16

Unloading vs Loading of 02

Back 16

Basic and low 2,3 DPG favors loading

Acidic and high 2,3 DPG favors unloading

Front 17

RBC membrane composistion

Back 17

Lipid Bi layer

Spectrin, actin, arkyrin and Band 3

Front 18

RBC metabolism

Back 18

Glycolysis, (anaerobic production of ATP)

Hexose monophosphate shunt keeps GSH in a reduced state via NADP->NADPH

methaemoglobin pathway keeps Fe in a 2+ state

Front 19

Folate and B12

Back 19

Required for DNA production

daily requirments is:

1ug for b12

100ug for folate

Front 20

Reference range

Back 20

WBC 4-10 x10^9/L

Hb 115-160 g/L

Plt 150-400 x10^9/L

RBC 3.9-5.6 x10^12/L

Hct .38-.45

MCV 800-100fL

RDW 9-15

MCH 27-32pg

MCHC 320-360 g/L

Front 21

Causes of Iron deficiency

Back 21

Chronic blood loss

Malabsorbtion

Poor diet

Phlebotomy

Front 22

Iron deficient anaemia symptoms

Back 22

Shortness of breath

tiredness

headaches

pallor of the mucous membranes

tachycardia

Front 23

Causes of macrocytosis

Back 23

Alchol, liver disease, pregnancy, hyperthyroidism, reticulocytosis, aplastic anaemia, red cell aplasia, folate and b12 def,myeloidsplasia and paraproteinaemia

Front 24

macrocytic anaemia

Back 24

Tear drop cells

ovalmacrocytes

hypersegmented neutrophils

Front 25

Microcytic anaemia

Back 25

Tear drop cells

target cells

pencil cells

Front 26

α-Thalassaemia types

Back 26

αα/α- silent/thalassaemia trait

αα/-- or α-/α- thalassaemia trait

α-/-- Hb H disease

--/-- Hb Barts/ Hyrops fetalis

Front 27

Hb barts / Hardrops fetalis

Back 27

Almost all Hb is Hb H

total failure of the α-globin gene

most die during pregnancy or die after birth

Front 28

Hb H disease

Back 28

Greatly reduced α-globin synthesis

results in hypochromatic microcytic anaemia

Excess ß-globin results in Hb H (ß4)

Hb H can precipitate anc cause RBC lyses

Front 29

Clinical Features of Hb H

Back 29

May be mild

Hb ussually 70-100g/l

MCV 50-65

MCH 15-20

Spleenomegaly

Could have jaundice

Front 30

α-thalassaemia trait

Back 30

Asymptomatic

Microcytosis W/ or W/out anaemia

Partner testing if patient is αα/--

Front 31

ß-thalassaemia

Back 31

Results from reduced rate of ß-globin

most common are point mutations in ß-globin locus

>200 types reported

Front 32

Categories of ß-thalassaemia

Back 32

ß naught- No globin expression from the gene

ß+ - Reduced production of ß-globin

Front 33

clinical types of ß-thalassaemia

Back 33

ß- major

ß- intermedia

ß- Trait

Front 34

ß-thalassaemia trait

Back 34

Heterozygosity for ß thalassaemia

usually asymptomatic

may become symptomatic when under stress

Front 35

ß-thalassaemia trait

clinical indicies

Back 35

↓MCV/MCH

↑RCC

Hb studies: ↑Hb A2

+/- ↑Hb F

Front 36

ß-thalassaemia major

Back 36

Homozygous or compound heterozygous for ߺ thalassaemia

excess α-globin precipitates and causes damage to developing RBCs

↓RBC life

Transfusion dependent anaemia

Not present inu tero or at birth

Presents after 1st year of life

Front 37

Symptoms of ß-thalassaemia major

Back 37

Bony deformaties

hepatosplenomegaly

transfusion dependent after 1st year of life

growth of sexual organs can be delayed

survival and quality of life is transfusion dependent

BM transplant is curative but there is sig mortality

Front 38

ß-thalassaemia clinical indices

Back 38

↓↓MCV/MCH

Hb Studies: Hbf and Hb A2; minimal to no Hb A

Front 39

ß-thalassaemia intermedia

Back 39

Anaemia hb 70-100g/l

may have spleenomegaly and bony deformities

Not usually transfusion dependant

Types

ߺ ß+

ß+ ß+

ßn ߺ(dormant)

ßn ߺ +excess α chains (ααα)

Front 40

Delta Beta thalassaemia

Back 40

Deletions of ß locus which removes both ß, δ genes

similar clinical features as ߺ thalassaemia

hypochromatic microcytic ±anaemia

↑HbF

Hb A2 is low or normal

Front 41

Hb Lepore

Back 41

Fusion between ß and δ genes

similar to ß trait

Partner testing should be offered

Front 42

Hb E

Back 42

Substitution mutation

Hb E trait asymptomatic, 50% will have abnormal indices

HB E disease usually asymptomatic

mild anaemia with microcytosis

Front 43

HbE/ß thalassaemia

Back 43

variable severity (trait, major, intermedia)

not easy to predict phenotype

~50% will be transfussion dependant

~50 will require splenectomy

Front 44

Hb C

Back 44

ß-globin varient

common in africa

Heterozygous Hb C is asympotmatic

Homo Hb C: Spleenomegaly and gallstones may be present

Significant when co-inherited with Hb S

Front 45

Hb S

Back 45

Glu>Val replacement

deoxy Hb S undergoes polymerisation

When there is enough Hb S polymer there will be Sickling will cause sickle cell disease

Front 46

Sickle cell disease types

Back 46

Homo Hb SS

Hetero: Hb S/C,

Hb S/ß thalassaemia,

Hb S/D punjab,

Hb S/C harlem

Hb S/O arab

Front 47

Describe iron overload

Back 47

Raised serum iron and transferrin (>45%)

Raised serum ferritin

increased iron in the liver and heart

abnormal liver function tests

Front 48

organ dysfunction with iron overload

Back 48

Cardiomyopathy

reduced sexual organ development

Diabetes

Hyperthyroidism

cirrhosis, haemosiderosis

Front 49

Iron overload pathogenesis

Back 49

Genetic haemochromatosis

95% homo for HFE mutation

HFE chromosone 6 (90% for c282y mutation)

Juvenile haemochromatosis (HFE2) Chromosone 1

Haemochromatosis type 3 HFE3

classic phenotype but no HFE mutation

African Iron overload

Excess iron intake

ineffective erythropoiesis

Repeated blood transfusion

Front 50

Intrinsic pathway

Back 50

Front 51

extrinsic pathway

Back 51

Front 52

common pathway

Back 52

Front 53

inhibition of clotting cascade

Back 53

Front 54

Finrinolyses

Back 54

FIIa stimulates the tPA, uPA is released from endothelial cells.

tPA and uPA activate plasminogen to plasmin

Plasmin breaks down fibrin

Front 55

Haemophilia A

Back 55

80-85% of Haemophilias

prolonged aPPT and not PT

Plasma FVIII ~1%

Treated with recom FVIII

Front 56

Haemophilia B

Back 56

Prolonged aPTT and Normal PT time

↓Factor IX

Treated with conctrated F IX

Front 57

lupus anticoagulant

Back 57

Antibodies bind to phospholipids, this reduces the amount in plasma, thus increases the aPTT, dRVVT and PT.

Adding excess phospho lipids correct it.

Mixing studies does not correct

Front 58

vWF

Back 58

Encoded on chromosome 12

Produced in endothelial cells and in MK's

mulitmers range from 1000-20000kDa

Front 59

Functions of vWF

Back 59

Binds to collagen which links platlets

stabilises fVIII

Front 60

vWF disease

Back 60

Type 1: 70% if vWD

normal functioning vWF but in redused amounts

Type 2: functional deficiency of vWF

Type 3: No detectable vWF

Front 61

coag and pregnancy

Back 61

↑fibrinogen, II, V, VII, VIII, IX, and X

↓XI, XIII, fibrinolysis and protein C and S.

Front 62

schistocytes and their causes

Back 62

Mechanical damage to the microvascular (abnormal surfaces, cardiac lesion, fibrin strands)

Can for micro spherocytes

usually reticulocytes present

sharp pointy ends

assoc with thrombocytopaenia (disseminated intravascular coag, thrombotic thrombocytopaenic purpura, Haemolytic ureamic syndrome.)

Front 63

Haemolysis from infections

Back 63

direct damage to RBC (malaria)

Toxin production (clostridium)

Oxidant stress

microangiopathic HA (meninoccaemia)

Auto antibody prod

Front 64

Enviromental

Back 64

KIdney disease: burr cells

Hepatic dysfunction: Acanthocytes

Front 65

Lab features of haemolysis

Back 65

Hb Norm or ↓

Reticulorcytes ↑

polychromasia

spherocytes, fragmented cells

↑uncojugated bilirubin

BM: erythroid hyperplasia

Front 66

Intrinsic Red cells defects

Back 66

Hereditory spherocytosis

enzyme defect g6pf

Thalassaemia

abnormal red cells

Front 67

Extrinisic red cell defects

Back 67

Severe hepatic or renal dys

red cell frag: DIC, HUS, TTP

Infections

Auto or allo-immune

Front 68

Heriditory spherocytosis

Back 68

Defect of RBC membrane proteind (Band 3, spectrin, actin) most testing targets band 3,

Fluctuating anaemia and jaundice

RBCs prematurely destroyed in spleen

spleenomegaly and gallstones

Front 69

Diagnosis of heriditory spherocytosis

Back 69

hb can be variable

blood film; spherocytes and polychromasia

flow cyt EMA shows reduced binding to band 3

direct anglobulin test

Front 70

Diagnosis of spherocytes

Back 70

heriditory spherocytosis

auto immune HA

drug induces HA

ABO HA

Front 71

Megoblastic anaemia

Back 71

Inhib of DNA but not RNA

in ↓b12 deficiency there is an inhability to use n-Methy-tetrahydrofolate

In ↓Folate deficiency there is an inhability to synthesise n-methy-tetrahydrofolate → ↓ thyamine for DNA synth