Haemostasis

Question 1

What is haemostasis for?

Answer 1

To prevent bleeding and to prevent unnecessary coagulation, allow blood to flow

Question 2

Principles of haemostasis

Answer 2

Make a clot

Control clotting

Break it down

Question 3

What is essential for haemostasis?

Answer 3

Keep blood moving - heart, venous valves, calf pump

Blood vessels

Platelets

Coagulation factors

Anticoagulant factors

Question 4

What are platelets?

Answer 4

Megakaryocytes produce platelets in the bone marrow

Platelets ‘bud’ from cytoplasm

Normal platelet count is 150-400 109/L

Normal lifespan 7-10day

Question 5

Platelet adhesion?

Answer 5

Damage to vessel wall

Exposure of underlying tissues

Platelets adhere to collagen via vWF / receptor

Question 6

Platelet activation…

Answer 6

Secrete ADP, thromboxane and other substaces to become activated and activated other platelets

Involved in activation of the clotting cascade

Provide some coagulation factors by secretion from internal stores

Question 7

Platelet aggregation

Answer 7

Cross linking of platelets to form a platelet plug

Question 8

What does the clotting cascade mean?

Answer 8

Amplification system activation of precursor proteins to generate thrombin (IIa)

Thrombin converts voluble fibrinogen to insoluble fibrin.

Enmeshes initial platelet plug to make stable clot

…Controlled

Natural anticoagulants to inhibit activation

Cot destroying proteins which are activated by thr clotting cascade (carefully balanced).

Question 9

Where are coagulation factors made?

Answer 9

They are made in the liver

Question 10

What is the clotting cascade?

Answer 10

PT - extrinsic pathway. VII

APTT - Intrinsic. VIII IX XI XII

Commo pathway - V, X, Prothrombin, Fibrinogen

Question 11

Lab tests?

Answer 11

PT - measures extrinsic and common pathway. INR is derived from this and it used to measure warfrin.

APTT measured intrinsic and common pathway

Fibrinogen count measues the amount of fibrinogen

Question 12

VonWillebrand Factor?

Answer 12

Involved in platelet adhesion to the vessel wall, platelet aggregation. And also carries factor VIII

Question 13

Vessel Wall?

Answer 13

Vasoconstriction

Production of Von Willebrands Factor (vWF)

• -Essential for plt adhesion
• -Carrier and ‘protector’ of Factor 8 (clotting protein).

Exposure of Collagen and Tissue factor which initiates activation of clotting factors (proteins).

Question 14

Natural anticoagulants?

Answer 14

Stop further coagulation

• Protein C
• Protein S
• Anti-Thrombin

Question 15

Fibrinolysis?

Answer 15

Plasminogen to Plasmin which break down clots. This is activated by plasminogen activator.

Question 16

D Dimers?

Answer 16

D-dimer is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.

Question 17

Clinical relevance of haemostasis

Answer 17

Bleeding disorders

Arterial rhomboid disorders

Venous thrombotic disorders

Abnormal blood test results

Drug therapy for pro- or anti- thrombotic purposes

Question 18

Coagulation Factor disorders?

Answer 18

Congenital : haemophilia A (F8) Haemophilia B (F9)

Acquired: Liver disease, Vitamin K (F2,7,9,10) Anticoagulants including Warfrin (inhibits Vit K - reduction in 2,7,9,10)

Question 19

Clinical symptoms of coagulation factor disorders?

Answer 19

Clinical severity correlates with extent of deficiency

Muscle haematomas

Recurrent haemarthroses

Joint pain and deformity

Prolonged bleeding post dental extraction

Life threatening post op and post traumatic bleeding

Intracerebral haemorrhage

Question 20

Haemophilia A?

Answer 20

X-linked recessive

Congenital lack of factor VIII

Mild/moderate/severe depending on amount of factor VIII present

Diagnosed pre-nasally or soon after birth if family history, to usually in infancy if new spontaneous mutations

Bleeding into muscles/and joints and post-operatively

Treated with recombinant factor VIII or DDAVP

Question 21

See in blood results?

Answer 21

Prolonged APTT as less factor 8

Question 22

Haemophilia B?

Answer 22

Similar presentation to haemophilia A

Congenital reduction in factor IX

Question 23

Von Willebrands Disease?

Answer 23

Relatively common

• Usually autosomal dominant, affects makes and females
• vWF carried Factor VIII and mediates platelet adhesion tot he endothelium

Abnormal platelet adhesion to vessle wall

Reduced FVIII amount / activity (FVIII can be low in addition to low VWF levels)

Several genetic defects cause this condition

Main type due to a reduction in vWF production ie not enough

(others where activity reduced)

Question 24

Symptoms of vWD?

Answer 24

Skin and mucous membrane bleeding

• Epistaxis
• Gum bleeding
• Bruising

Prolonged bleeding

• Heavy periods
• Post surgery
• Post dental extraction

Question 25

Vessel wall abnormalities?

Answer 25

Easy bruising Spontaneous bleeding from small vessels Skin mainly Can be mucous membranes

Question 26

Problems with Vessles?

Answer 26

Congenital * -Hereditary Haemorrhagc Telangiectasia (HHT) * -Autosomal Dominant * -Dilated microvascular swellings increase with time * -GI haemorrhage can lead to iron deficiency anaemia * Connective tissue disorders - Ehlers Danlos Acquired * Senile purpura * Steroids * Infection * Scurvy

Question 27

Disseminated Intravascuar Coagulopathy?

Answer 27

Type of microangiopathic haemolytic anaemia Pathological activation of coagulation Numerous microthrombi are formed in the circulation This leads to consumption of clotting factors and platelets and a haemolytic anaemia Clotting tests are affected - usually raised PT / INR, low fibrinogen and raised D dimers / fibrin degradation products

Question 28

Triggers of disseminated intravascular coagulopathy?

Answer 28

Malignancy Massive tissue injury eg burns Infections - usually gran negative sepsis Massive haemorrhage and transfusion ABO transfusion reaction Obstetric causes - placental abruptly, pre-eclampsia, amniotic fluid embolism. **Only way to treat it is to treat underlying cause**

Question 29

Thrombophilias?

Answer 29

These are acquired or congenital defects of haemostasis which can increase a patient’s risk of thrombosis Congenital causes include deficiency on natural anticoagulants (Protein C, Protein S and antithrombin) and an abnormal factor V (factor V Leiden - relatively common) Acquired causes include antiphospholipid syndrome These are relatively rare conditions and many patients with them do not develop clots unless they have additional risk factors.