Haemostasis and haemolytic diseases introduction

vascular system, platelets, coagulation system, fibrinolytic system, common diseases

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