19. Coagulation disorders

31/12/2025

Name 2 inherited platelet disorders

• Glanzmann’s Thrombasthenia

• Bernard-Soulier syndrome

Name 3 acquired platelet disorders

• Immune thrombocytopenia (ITP)

• Thrombotic thrombocytopenic purpura (TTP)

• Disseminated intravascular coagulation (DIC)

Aetiology of glanzmann’s thrombasthenia

• Autosomal recessive

• Caused by mutations in ITGA2B, ITGB3

• Causing reduced function of the fibrinogen receptor

  • So platelets fail to bind to each other and the platelet plug cannot be stabilised by fibrinogen

Glanzmann’s thrombasthenia platelet count

Normal

Glanzmann’s thrombasthenia Lumi aggregometry test result

No visible platelet aggregation

Glanzmann’s thrombasthenia flow cytometry test result

Absence of the fibrinogen receptor

Glanzmann’s thrombasthenia genetic test result

Mutations in these genes:

• ITGA2B

• ITGB3

Treatment for Glanzmann’s thrombasthenia

• Platelet transfusion

• Novoseven- synthetic factor VII which reduces bleeding

• For women- brith control to stop period and iron to support blood loss

Aetiology of Bernard-Soulier syndrome

• Autosomal recessive disease

• Caused by mutations in GPIBA, GPIBB and GP9

• Severe reduction/ reduced function of vWF and thrombin receptor

  • Leads to thrombocytopenia and giant platelets

Mutations in which genes are associated with Bernard-Soulier syndrome?

• GPIBA

• GPIBB

• GP9

What are the arrows pointing at in this image?

Bernard-Soulier platelets

Bernard-Soulier syndrome Platelet count

Low

Bernard-Soulier Lumi aggregometry test result

• Low response to ristocetin

• Sometimes a low response to thrombin

Bernard-Soulier syndrome flow cytometry test result

Decreased levels of receptors in the vWF and thrombin receptor complex

Bernard-soulier syndrome genetic test result

Mutations in these genes:

• GPIBA

• GPIBB

• GP9

Treatment fot Bernard-Soulier syndrome

Platelet transfusion

Aetiology of Immune thrombocytopenia

• Platelets are destroyed by the body’s immune system

  • Primary: atuo-immune anti-platelet antibodies

  • Secondary: other auto-immune disease/ infection by bacteria or virus

• Low platelet count resulting in bleeding

Symptoms of immune thrombocytopenia

Petechiae

Platelet count for immune thrombocytopenia

Low

Treatment for immune thrombocytopenia

• Steroids: to reduce antibody production which slows down platelet destruction

• Intravenous gamma globulin: Antibodies that neutralise the antibodies destroying platelets

Aetiology of thrombotic thrombocytopenia purpura

• Haemolytic condition

• Platelets clump together in small vessels leading to a low platelet count

• Low levels/ decreased function of ADAMTS13:because antibodies have formed against ADAMTS13

What does ADAMTS13 do?

Cleaves multimeric vWF into monomeric fragments to inactivate vWF

Symptoms of thrombotic thrombocytopenic purpura

• Petechiae

• Purpura

Treatment for thrombotic thrombocytopenia purpura

Plasma exhange: healthy plasma containing ADAMTS13 and removal of antibodies

Aetiology of disseminated intravascular coagulation

• Severe thrombotic condition leading to blood clots

• Caused by the release of tissue factor from endothelial cells, activating the extrinsic pathway

• Can occur with severe sepsis or cancer

• Platelets and coagulation factors are used up which can lead to uncontrollable bleeding

Symptoms of disseminated intravascular coagulation

• Petechiae

• Purpura

• Ecchomyosis

Treatment for disseminated intravascular coagulation- bleeding/ low platelet count

• Platelet concentrate

• Blood transfusion

Treatment for disseminated intravascular coagulation- thrombosis/risk of thrombosis

Use low molecular weigh heparin as prophylaxis

What is thrombophilia?

• An abnormal tendency to form clots

When is thrombophilia often identified?

After deep vein thrombosis

What are 3 key types of inherited thrombophilia

• Protein C deficiency

• Protein S deficiency

• Factor V leiden

How does deep vein thrombosis for?

• Enhanced coagulation

• Change in blood flow

• Damage to vessel wall starts coagulation

Aetiology of protein C deficiency

• Autosomal dominant

• Deficiency makes it difficult to prevent coagulation, so clotting is promoted

What is the role of protein C

• Natural anticoagulant

• Activated by thrombin

• Cleaves factor Va and VIIIa to prevent thrombin formation

Aetiology of protein S deficiency

• Autosomal dominant

• Deficiency leads to purpura fulminans

  • Skin bleeds and dies rapidly

Where is protein S synthesised and which vitamin is it dependent on?

• In the liver

• Vitamin K

What is protein S?

A non-enzyme co-factor for protein C

Factor V leiden aetiology

• Autosomal dominant

• Point mutation in the gene that encodes for factor V

• Mutation makes protein C inable to inactivate factor Va

What does factor V leiden increase the risk of?

• blood clots in legs and lungs

• Venous thromboembolism (VTE)