Platelets and Plasma

Question 1

Platelets

Answer 1

• Determine bleeding time: PT (prothrombin time)

• Small cytoplasmic anucleate cells that block up holes in blood vessels

• Made in bone marrow from cells called megakaryocytes which undergo endomitosis (DNA doubles but cell doesn’t divide)
Cell surface membrane will then bleb- lose fragments which are the platelets

Inactive platelets are smooth and discoid
Active platelets are increased in SA and will become pseudopoid
When activated they release two types of granules- electron dense granules and alpha dense granules

Electron granules will be released for energy to produce a platelet plug. Mediators of electron granules will be: ADP, Ca2+, ATP, Serotonin, Thromborane. This will provide energy for active process of platelet plug formation

Alpha dense granules will help mediate the formation of scaffolding of platelet plug structure
Factors include
Platelet dense growth factor, VWF, Heperinatagonist and fibrinogen

• Spherical, enucleate - cannot repair itself

• Lifespan: 7-10 days

• Normal number: 140-400 x 109/l

Hormonal factor is thrombopoetin

Question 2

Reduced numbers: thrombocytopenia

Answer 2

main risk is cerebral bleeding) > 80 = increased bleeding, > 20 = spontaneous bleeding

Cuts can cause bleeding out

Question 3

High numbers: thrombocytosis,

Answer 3

can lead to arterial & venous thrombosis, leading to an increased risk of heart attack + stroke

Clot risk

Question 4

Proteins in the blood

Answer 4

Coagulation protiens

Plasma proteins

Albumin

Carrier proteins

Immunoglobins

Question 5

Coagulation proteins (enzymes)

Answer 5

Produced in liver

Key enzyme is thrombin (makes platelet plug)

Vitamin K is essential for correct synthesis of a=coagulation factors (2, 7, 9, 10)- remember as 1972

They circulate in inactive form, function is to make blood clot, converts soluble fibrinogen into insoluble fibrin polymer
Overactivity = thrombosis
Failure= bleeding

Question 6

Plasma protiens

Answer 6

Soluble and in plasma component

Question 7

Albumin

Answer 7

most numerous protein in plasma, produced in liver, maintain oncotic pressure, lack of albumin results in oedema, carries; fatty acids, steroids & thyroid hormones

Question 8

Carrier proteins

Answer 8

for nutrients, hormones

Question 9

Immunoglobins

Answer 9

antibodies produced by plasma cells (differentiate B lymphocytes), several classes; IgG (most important), IgM (all start of as this), IgA, IgE, produced in response to non-self protein antigens

Question 10

Haemostasis

Answer 10

the arrest of bleeding, involving the physiological processes of blood coagulation and the contraction of damaged blood vessels

Question 11

Why is blood usually fluid inside blood vessels?

Answer 11

• The proteins of the coagulation cascade and the platelets circulate in an inactive state

• Proteins and platelets are only activated by tissue factor, which is present on every single cell APART from endothelial cells thus when endothelium is punctured etc. blood comes into contact with tissue factor and thus starts clotting

Question 12

Thrombosis

Answer 12

If blood clots inside vessel

Question 13

Bleeding disorder

Answer 13

if blood fails to clot outside vessels

Question 14

Bleeding

Answer 14

Results in the beginning of the coagulation cascade - series of proteolytic enzymes that circulate in an inactive state being activated (usually by exposure to tissue factor) in a cascade or waterfall sequence

• in order to generate the key enzyme THROMBIN which cleaves fibrinogen creating fibrin polymerisation i.e a blood clot

Question 15

Coagulation cascade

Answer 15

Very complex, multiple steps allow for biological amplification & allows for regulation

• its is NOT a all or nothing response thus it can be graduated in response to severity of challenge

Question 16

Platelets (organised anucleate particles)

Answer 16

responsible for primary haemostasis = bleeding time, they adhere to damaged endothelium and aggregate to form platelet plug that blocks hole in vessel

Question 17

Bleeding disorders- Haemophilia

Answer 17

(Recessive X linked)

Severe bleeding disorder, bleeding disorder; bleeding into muscles and joints, not enough clotting factors in blood = slow clotting time or long PTT (prothrombin time). ONLY AFFECTS MALES SINCE ITS X-LINKED INHERITANCE. Gene responsible is on x chromosome thus only affects males, FEMALES ARE CARRIERS

Question 18

Types of Haemophilia

Answer 18

Haemophilia A: bleeding into muscles and joints
Deficiency in clotting factor 8
Treat with factor 8

Haemophilia B: bleeding into muscles and joints
Deficiency in clotting factor 9
Treat with factor 11
Less common since gene is smaller

Question 19

Bleeding disorders- Von Willebrands disease

Answer 19

• Autosomal dominant inheritance (can get MALE-MALE TRANSMISSION) - affects ALL generations, males and females alike
• Lack of Von Willebrands Factor (VWF)
• VWF is required for platelets to bind to damaged blood vessels, so lack of VWF = platelet dysfunction, hence muco-cutaneous bleeding
• Usually a mild bleeding disorder

Question 20

Muco-cutaneous bleeding

Answer 20

bleeding in skin & mucous membranes e.g. easy bruising, prolonged bleeding from cuts, nose bleeds (epistaxis), spontaneous gum bleeding/GI loss etc.

Often unrecognised and undetected

Question 21

Acquired bleeding disorders

Answer 21

• Recent onset, not lifelong and no family history
• May be generalised or localised bleeding
• Most common cause: anti-platelet or anti-coagulation medication

Question 22

Other causes of acquired bleeding disorders

Answer 22

Liver disease

Vitamin K deficiency

Drugs

Disseminated intravascular coagulation (DIC):

Question 23

Liver disease

Answer 23

• SITE OF SYNTHESIS OF COAGULATION FACTORS & FIBRINOGEN - Liver disease is often associated with bleeding and prolonged prothrombin time (PTT)
• Most common cause of liver disease in alcohol

Question 24

Vitamin K deficiency

Answer 24

VITAMIN K IS NEEDED FOR THE CORRECT SYNTHESIS OF COAGULATION FACTORS II, VII, XI & X (2, 7, 9 & 10) - 1972

• Vitamin K is a fat soluble vitamin
• Deficiency is caused by malabsorption - especially in obstructive jaundice - Manifests as prolonged PTT
• Treat with IV Vit K
• With deficiency coagulation factors are still produced but they do not work - Newborns are vitamin K deficient, given it at birth

Question 25

Drugs

Answer 25

• Aspirin affects platelet function
• Heparin and warfarin (most widely used oral anticoagulant - works by inhibiting vitamin K) affect coagulation cascade
• Steroid make tissues thin and cause bruising and bleeding

Question 26

Disseminated intravascular coagulation (DIC)

Answer 26

• Breakdown of haemostatic balance
• Simultaneous bleeding & microvascular thrombosis
• Life threatening condition
• Causes: 1) sepsis 2) obstetric (anything that goes wrong with pregnancies e.g. dead foetus + pre-eclampsia 3) malignancy

Question 27

Not very common DIC

Answer 27

• Activation of the coagulation cascade inside blood vessels, thrombin is produced, causing fibrinogen > fibrin, form microvascular thrombosis’(platelet plugs) everywhere e.g. in organs etc
• Results in the deficiency of clotting factors & platelets since they’ve been used up in the formation of the micro-vascular thrombosis’ - doctors think its a blood condition causing deficiency but its because of the micro-vascular thrombosis
• Treatment of DIC, treat underlying cause and stop generations of intravascular thrombin then transfuse new platelets etc.

Question 28

Platelet plug and Coagulation Cascade

Answer 28

When a blood vessel is damaged, its first response is to constrict (due to neural control + release of endothelin-1 (released by endothelia cells)

This temporarily slows the flow of blood in the affected area.
Furthermore, this construction presses opposed endothelial surfaces of the vessel together and this contact induces a stickiness capable of keeping them ‘glued’ together

• Permanent closure of the vessel by constriction & contact stickiness only occur in the very smaller vessels of the microcirculation
• The stopping of bleeding depends on two interdependent processes that occur in rapid succession: 1) formation of a platelet plug 2) blood coagulation - platelets are involved in both processes