haematology, blood transfusion and haemostasis

3 substances in blood

• Erythrocytes

• Leukocytes

• Thrombocytes

what is Haematopoiesis

Formation of blood cells

sites of haematopoiesis in fetus

• 0-2 months - yolk sack

• 2-7 months - liver & spleen

• 7-9 months - Bone marrow

sites of haematopoiesis in Infants

Bone marrow

Sites of haematopoiesis in adults

• vertebrae,

• ribs

• sternum

• skull

• sacrum

• proximal ends of femur

• liver

role of stem cells in haematopoietic system

to self renew

and differentiate into progenitors

role of progenitor cells in haematopoietic system

they differentiate into mature, short lived cells

Erythrocytes days in circulation

120

erythrocytes sequestered in?

spleen

erythrocytes shape

biconcave discoid shape

• flexibility and allows for gas exchange

Hemoglobin in fetus

2a and 2y -& HbF

haemaglobin in adults

2a and 2b -& HbA

Erythropoiesis negative feedback

1. stimulus: low blood volume, decreased O2 carried

2. sensor: specialised kidney cells

3. response: erythropoietin released into blood (EPO)

4. Effect: EPO> red bone marrow, preventing cell death, increasing production

neutrophil

60% of wbcs

lobed nucleus

fine granules

6-10hours

non-specific defence against bacterial and fungal infection

pink stain

eosinophils

• 1% of wbcs

• large granules

• bilobed nucleus

• 4-5hours

• parasitic infection defense

• allergies

basophils

• <1% of wbcs

• large granules

• anaphylactic hypersensitivity, inflammatory response

• methylene blue

Monocytes

• 5% of wbcs

• very large

• 10 hours

• matures to phagocytic tissue macrophages

• removes aged rbcs, debris

lymphocytes

• 33% of wbcs

• large round nucleus

• recognition of foreign substances

phagocytosis

1. pseudopodia forms during attachment

2. phagosome forms, bacterium ingested

3. phagosome forms w/ lysosome

4. lysosomal enzyme digests

T-lymphocytes

• developed in thymus after bone marrow

• 40-805 of blood lymphocytes

• cell-mediated immunity

• 2 sub types: T-helper & T-cytotoxic cells

B-lymphocytes

• bone marrow derived

• 10-30% of lymphocytes

• produce antibodies

NK-Lymphocytes

• Natural killer cells

• 5-15% of lymphocytes

• innate immunity

• non specific defense

• targets cancer cells

Thrombocytes

• platelets

• discord, anucleate cells

• granular cytoplasm

• 10-12 days

• atherosclerosis

Plasma

• 60% of total blood volume

• pale, yellow, aqueous, electrolytes and proteins

• 
  

plasma extracellular ions?

Cations - Na²⁺ , (K⁺, Ca²⁺, Fe²⁺, Mg²⁺)

anions - Cl^- , (HCO₃^- , SO4 2-, HPO4 2-)

blood group O antigens

L- fructose added- H antigen

blood group A antigen

N-acetylgalactosamine, H antigen

Blood group B antigen

D-galactose, H antigen

Blood group AB antigen

N-acetylgalactosamine H antigen & D-galactose, H antigen

Blood gp. A plasma antigens

anti B, will agglutinate with anti A and anti AB

Blood gp. B plasma antigens

Anti A, will agglutinate with anti B and anti AB

Blood gp. AB plasma antigens

contains anti A and anti B, will agglutinate with anti A and anti B and anti AB

Blood gp. O plasma antigens

Contains nether, will not agglutinate

IgM

• 10% or Ig serum

• Heavy u chains

• primary IR

• naturally occuring

IgG

• 75% of serum Ig

• heavy y chains

• secondary IR

• needs stimulatory event to occur

Haemolytic Disease of the Foetus & Newborn

1. Mother Rh specific Bcells detect foestus’ different RhD group in its RBCs

2. Rh specific Bcell forms plasma cells and memory cellls

3. Plasma cells form Anti Rh IgM

4. Memory cells release IgG

5. IgG can cross placenta, attcking foetal RBCs

Preventing HDFN?

Rhogam prevents B cell activation and memory cell formation

How to determine blood group?

• plasma w/ known antibodies mixed w/ patient’s rbcs

• > this tells you the antigens present on rbcs

• rbcs w/ known antigens mixed w/ patients plasma

• > confirms antibodies present

Symptoms of wrong transfusions?

fever

pain

circulatory collapse

hemorrhage

death?

Group A can donate to…

A, AB

Group B can donate to…

B, AB

Group AB can donate to…

AB

Group O can donate to…

A, B, AB

4 main systems w/ prevention & arrest of blood loss

• vascular system

• platelets

• coagulation system

• fibrinolytic system

what is haemostatic balance between?

the procoagulant environment and the anticoagulant environment

what happens if vascular endothelium is damaged

coagulation is encouraged, collagen exposed, loss of negative coating

thrombopoiesis

formation of platelets

where and by what platelets formed

in bone marrow

by megakaryocytes

modulated by TPO

where is TPO produced and what do plts do

liver and kidney - constant level

platelets remove TPO from circulation

low plts affect of TPO

more TPO reaches bone marrow

TPO mature

they release plts

vascular lumen

vascular endothelium

internal elastic lamina

tunica intima

tunica media

external elastic lamina

tunica adventitia

TPO produced > Blood > Low plt no.s

Less TPO absorbed > more reaches bone marrow > more TPO= more plt production

TPO produced > Blood > High plt no.s

More TPO absorbed > less reaches bone marrow > less TPO= less plt production

platelet ultrastructure

• a granule

• electron dense granule

• dense tubular system

• glycolax

• mitochondria

• open canalicular system

• plasma membrane

• submembranous filaments

• glycogen

Platelet activation

1. contact w/ damaged endothelium

2. shape change

3. granule contests released

4. platelet aggregation activated

coagulation system/ cascade

• tissue damage

• enzyme cascade

• thrombin amplification loop

• stable fibrin clot

Plts roles

• 1’ haemostatic plug

• contraction of 2’ haemostatic plus - via fibrin meshwork

• release growth hormones

plts & 2’ haemostatic plug contraction

formed by coagulation cascade

func. of cytoplasmic contractile elements

reduces endothelial gal

allowing for tissue regrowth

plts release growth promotors

plt derived growth factor ( PDGF)

fibroblast mitogen

chemotactic for fibroblasts, neutrophils, smooth muscle cells

Vascular endothelium role when damaged

• exposes subendothelium (collagen)

• activates plts

• 1’ haemostatic plug forms

Vascular endothelium role when intact

• Thrombomodulin binds thrombin to vascular endothelium

• complexed thrombin doesnt clot fibrinogen

• activates protein C

• stimulation fibrinolysis

control of coagulation

many inhibitors in loop and cascade

fibrinolytic system function

break down formed fibrin within the circulation

> via rapid & localised formation of plasmin (a powerful proteolytic enzyme)

Intact vascular endothelium produces….(5)

1. t-PA (tissue plasminogen activator)

2. plasminogen

3. plasmin

4. fibrin

5. FDP

Main Haemostasis points

1. clot initiation

2. clot formation

3. fibrinolysis

1. Clot initiation

platelet aggregation

1. coagulation activation → 2.Thrombin…

2. Clot formation

1. Coagulation → 2.thrombin + fibrinogen → fibrin → fibrin polymers → retraction →3. Fibrin fragments

3. fibrinolysis

2. retraction → 3. fibrin fragments

Quantitative disorders means…

defect in altered numbers

Qualitative disorders means….

defect in altered functions

disorders may involve

• platelets

• inhibitor

• coagulation proteins

• vascular endothelium

• systematic disorders

disorders may be…

congenital

acquired

disorders may result in ….

excessive bleeding

excessive clotting

Bernard - Soulier disease

• congenital

• platelets

• glycoprotein deficiency

• haemorrhagic

Haemophilia A

• congenital

• coagulopathies

• X- linked recessive

• Factor VIII deficiency

• haemorrhagic

Haemophilia B

• congenital

• coagulopathies

• X- linked recessive

• Factor IX deficiency

• haemorrhagic

von Willebrand’s diease

• congenital

• coagulopathies

• pseudo haemophilia

• haemorrhagic

DIC (disseminated intravascular coagulation)

• Acquired

• causes: viral infection, trauma, malignancies, burns, liver failure

• decreased clotting factors

• decreased platelets

• increased fibrinolysis

• haemorrhagic

Anti thrombin deficiency & Protein C deficiency

• congenital

• alteration in homeostatic balance

• prevents clot formation

• anti-throbin, anti-coagulant deficiency

• Thrombotic

arterial & venous thrombosis

• acquired thrombophilia

• risk factors: increased age, obesity, immobility, smoking

• Thrombotic

how to get reference ranges

1. define normality parameters

2. define population

3. measure value of the parameter

Anaemia definitions

a reduction in Hb conc. in blood

( accompanied by a decrease in RBC count)

Anaemic causes: production problems

• marrow func. = apoplastic anaemia

• diet = iron deficiency, smaller rbcs, microcytic

• diet = vit. B12 / folate deficiency, larger rbcs, macrocytic

Anaemic causes: premature destruction

• Abnormal rbcs removed

• haemoglobinopathies (abnormal globin structure)

• Thalassaemias (a/b) -rate of globin synthesis

• Hereditary spherocytosis - RBC structural defects

• Haemolytic anaemia - auto immune or mechanical

Anaemic causes: blood loss

• ulcers

• menstruation

• trauma

Anaemic symptoms - general

• shortness of breath

• weakness

• lethargy

• cardiac failure

• pallor of mucous membrane

Anaemic symptoms - specific

• spoon nails w/ iron deficiency

• leg ulcers w/ sickle cell

haematological malignancies (3)

1. acute leukaemias

2. chronic leukaemias

3. non- leukaemic proliferative disorders

acute leukaemias are…

agressive

rapidly fatal

accumulation of early BM hematopoietic progenitors

chronic leukaemias are…

slow progression

difficult to cure

maturation block at later ontogenetic stage

non- leukaemic proliferative disorders

• myeloma

• lymphoma

• polycythaemia

haematological malignancies definition

clonal

they arise from a single cell in the marrow/lymphoid tissue, which underwent genetic mutation in cellular genes

malignant transformation