Disorders of blood coagulation

Question 1

primary haemostasis

Answer 1

• endothelium releases von-Willebrand factors, which circulates in the blood
• when collagen is exposed to blood because of damage, von Willebrand factors bind to it
• platelets express receptors for both collagen and von Willebrand factors and becomes activated when these proteins bind to them
• activated platelets express functional fibrinogen receptors

Question 2

what stores von Willebrand factors

Answer 2

weibel palade bodies

Question 3

secondary haemostasis

Answer 3

-Tissue factor (TF), expressed by nearly all sub endothelial cells activates the coagulation cascade to initiate a minor burst of thrombin.
-Factor FVlla binds to Tissue Factor, which ultimately leads to conversion of prothrombin to thrombin
-Thrombin activates receptors on platelets as well as the endothelium, amplifying platelet aggregation and initiating release of stored von Willebrand Factor from endothelial cells.
-Thrombin activates two cofactors, Factor Vllla
and Factor Va which subsequently form calcium ion-dependent complexes on the surface of platelets with Factor IXa (tenase complex) and Factor Xa (the prothrombinase complex).
-These
complexes greatly accelerate production of Factor Xa and thrombin, respectively. This is the amplification stage of the coagulation cascade
-The greatly increased production of thrombin via tenase and prothrombinase contributes considerably
more to the process. Thrombin will convert fibrinogen to the fibrin mesh

Question 4

Fibrinolysis

Answer 4

• Plasminogen is activated to plasmin by tissue plasminogen activator, t-PA.
• Plasmin degrades the fibrin mesh to fibrin degradation products which can be cleared.

Question 5

what can be used as a marker to check for ongoing fibrinolysis

Answer 5

d-dimer

Question 6

Natural anticoagulant (antithrombin)

Answer 6

-Antithrombin (AT) is a serpin (serine protease inhibitor)
-Activity greatly enhanced by
binding to heparan binding sites on
endothelial cells
-Major checkpoint to inhibit
coagulation (thrombin, IXa, Xa)

Question 7

Natural anticoagulant (Protein c and s)

Answer 7

-Protein C and protein S are natural anticoagulant plasma proteins
-Protein C is activated by thrombin bound to thrombomodulin (TM) on
endothelial cells to form activated protein C (APC)
-Protein S is an APC cofactor which
helps binding to cell surfaces
-APC degrades cofactors FVa and
FVllla

Question 8

what is haemophilia

Answer 8

• failure to clot leading to haemorrhage
• caused by a mutations in coagulation factor( haemophilia A and B)
• causes by platelet disorder(von Willebrand disease)
• caused by collagen abnormalities ( fragile blood vessels and bruising)

Question 9

what is thrombophilia

Answer 9

excessive clotting leading to thrombosis

Question 10

what is disseminated intravascular coagulation (DIC)

Answer 10

whole body clots

Question 11

2 types of haemophilia and which factor is mutated in each

Answer 11

• Haemophilia A - Mutated FVlll

- Haemophilia B - mutated FIX

Question 12

what is von Willebrand disease

Answer 12

inherited defect/ deficiency in vWF

Question 13

what are the 3 bleeding disorders

Answer 13

Haemophilia A
haemophilia B
von willebrand disease

Question 14

what is factor V Leiden mutation

Answer 14

resistance to activated protein C (APC) which means FVa is not inactivated which increases risk of DVT

Question 15

what is antithrombin difiecency

Answer 15

thrombin,IXa and FXa are not inactivated which increases risk of DVT

Question 16

what are the 4 excessive clotting disease

Answer 16

• factor v leiden mutation
• antithrombin deficency
• protein C deficiency
• protein S deficiency

Question 17

development of a venous thrombus depends are what 3 things

Answer 17

• alteration in the constituents of the blood
• changes in normal blood flow
• damage to the endothelial layer

Question 18

some symptoms of DVT (7pts)

Answer 18

• swelling
• skin changes
• pain and tenderness of veins
• limb swelling
• superficial venous distention
• increased skin temperature
• skin decolourisation

Question 19

what are some of the anti-coagulant

Answer 19

warfarin, heparin, direct oral anticoagulant (DOACs)

Question 20

what are some of the thrombolytics/fibrinolysis

Answer 20

plasminogen activators (tpa) and streptokinase

Question 21

what are some pre treatment investigation

Answer 21

clotting screen:
---prothrombin time
---partial thromboplastin time
---thrombin time
FBC
Renal screen
Liver function test

Question 22

Treatment for DVT

Answer 22

anticoagulants

Question 23

treatment for Pulmonary embolism

Answer 23

Alteplase (tissue plasminogen activator )
streptokinase
followed by anticoagulant to prevent recurrence