Blood Coagulation

Question 1

Describe the process of primary haemostasis

Answer 1

• When a cut occurs in a BV there is damage to subendothelial (contains collagen and tissue factor) and endothelial tissue which exposes von williebrand factor. Platelets are attracted to the VWB and bind to it via their glycoprotein receptors 1b, V and IX. This binding activates the platelets causing them to release their granular contents and causes aggregation and exposure of phospholipids on their surface. This forms a platelet plug.

Question 2

Every step in secondary haemostasis requires what?

Answer 2

• Phospholipids from the platelet surface and calcium

Question 3

Explain the extrinsic pathway of secondary haemostasis (initiation of the coagulation cascade)

Answer 3

Tissue factor binds to factor VII (7) activating it. Activated factor VII causes the activation of factor X (10). Activated factor 10 causes the activation factor V (5) which forms a complex with activated factor 10 and factor II (2 also known as prothombim) to form a prothombinase complex which causes the activation of factor 2 (prothombin to thrombin)
Factor IIa will go onto to activate fibrinogen into fibrin and factor XIII. Factor XIII then can cross link the fibrin which makes it stronger

Question 4

Explain the intrinsic pathway (propagation of the coagulation cascade)

Answer 4

The extrinsic pathway makes a small amount of thrombin which can go on to activate factor XI and factor VIII. Activated factor XI will activate factor IX. Now activated factors VIII and IX stimulate the prothombinase complex resulting in the formation of more thrombin.

Question 5

Explain the naturally occurring regulation of the coagulation cascade

Answer 5

There are different naturally occurring antithrombotics:
Antithrombin - downregulates almost all the clotting factors
Thrombomodulin - Thombin attaches itself to receptor called thrombomodulin which leads to the activation of protein C.
Protein S - The co-factor of protein C, these two together down regulate factors V and VIII.
Tissue factor pathway inhibitor (TFPI) - Activated factor X stimulates activation of TFPI which blocks activation of factor VII.

Question 6

Describe the process of fibrinolysis

Answer 6

Plasminogen is activated by tissue plasminogen activator (produced by fibrin) and urokinase into plasmin. Plasmin then breaks down cross linked fibrin into fibrin degradation products (FDPs) including D-dimer

Question 7

What can inhibit the process of fibrinolysis?

Answer 7

• Plasminogen activator inhibitors can inhibit tPA and urokinase.
• Thrombin activated fibrinolysis inhibitor can inhibit urokinase
• Alpha 2 antiplasmin can directly inhibit plasmin

Question 8

What are some methods on measuring primary and secondary haemostasis

Answer 8

Primary - historically via bleeding time. However can use FBC (platelet count) and platelet function
Secondary - Prothrombin time (PT), activated partial thromboplastin time (APTT), Thrombin clotting time (TCT) and individual coagulation factor assays

Question 9

What are the pre-analytical sample requirements

Answer 9

• Citrate sample which chelates all calcium,
• centrifugation which separates cellular components and leaves sample with platelet poor plasma

Question 10

Describe the process of prothrombin time and what it depends on

Answer 10

• Patients plasma is mixed with thromboplastin (reagent if tissue factor and phospholipids), its warmed to 37 degrees then calcium is added. Time to clot is measured.
• Depends on factors in extrinsic and common pathways so factor VII and factors X, V, II and finbringoen

Question 11

What is the international normalised ration (INR)

Answer 11

• Standardised prothrombin time. It is used to monitor oral coumarins. It should be close to 1.0

Question 12

Describe the process of activated partial thromboplastin time and how it depends on

Answer 12

• Patients plasma is mixed with a contact factor and phospholipids (partial thromboplastin). The mixture is warmed to 37 degrees then calcium is added and time to clot is measured.
• It depends on intrinsic factors ( VIII, IX, XI and XII) and common pathway factors (V, X, II and Fibrinogen

Question 13

Describe the process of thrombin clotting time and what it depends on

Answer 13

• At 37 degrees, add patients plasma, bovine thrombin. Measure time to clot
• Less dependant on phospholipids and calcium. However depends on how much fibrinogen is present in patient plasma and how well it functions. Will be prolonged by inhibitors of thrombin such as heparin, FDPs and paraproteins