Platelets and Plasma Flashcards
Platelets
• 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
Reduced numbers: thrombocytopenia
main risk is cerebral bleeding) > 80 = increased bleeding, > 20 = spontaneous bleeding
Cuts can cause bleeding out
High numbers: thrombocytosis,
can lead to arterial & venous thrombosis, leading to an increased risk of heart attack + stroke
Clot risk
Proteins in the blood
Coagulation protiens
Plasma proteins
Albumin
Carrier proteins
Immunoglobins
Coagulation proteins (enzymes)
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
Plasma protiens
Soluble and in plasma component
Albumin
most numerous protein in plasma, produced in liver, maintain oncotic pressure, lack of albumin results in oedema, carries; fatty acids, steroids & thyroid hormones
Carrier proteins
for nutrients, hormones
Immunoglobins
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
Haemostasis
the arrest of bleeding, involving the physiological processes of blood coagulation and the contraction of damaged blood vessels
Why is blood usually fluid inside blood vessels?
• 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
Thrombosis
If blood clots inside vessel
Bleeding disorder
if blood fails to clot outside vessels
Bleeding
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
Coagulation cascade
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
Platelets (organised anucleate particles)
responsible for primary haemostasis = bleeding time, they adhere to damaged endothelium and aggregate to form platelet plug that blocks hole in vessel
Bleeding disorders- Haemophilia
(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
Types of Haemophilia
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
Bleeding disorders- Von Willebrands disease
- 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
Muco-cutaneous bleeding
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
Acquired bleeding disorders
- Recent onset, not lifelong and no family history
- May be generalised or localised bleeding
- Most common cause: anti-platelet or anti-coagulation medication
Other causes of acquired bleeding disorders
Liver disease
Vitamin K deficiency
Drugs
Disseminated intravascular coagulation (DIC):
Liver disease
- 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
Vitamin K deficiency
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
Drugs
- 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
Disseminated intravascular coagulation (DIC)
- 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
Not very common DIC
- 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.
Platelet plug and Coagulation Cascade
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
