46. Disorders of hemostasis (thrombotic diateses). DIC – syndrome.

Disorders of hemostasis (thrombotic diathesis). DIC - syndrome

• ⭐ Hemostasis - the stoppage of blood flow
• Disorders of hemostasis fall into two main categories:

1. Inappropriate formation of clots within the vascular system
2. Failure of blood to clot in response to appropriate stimulus

Thrombotic diathesis

1) Endothelial dysfunction

• No structural damage but alterations in function of factors produced:

1. a) Prostaglandin I2 + Nitric oxide

• Vasodilators and inhibit platelet formation

1. b) Thrombomodulin

• Inhibits factor 5 and 8

1. c) Tissue plasmin activator (TPA)

• Promotes fibrinolysis

2) Impaired blood flow

• Normal blood flow is laminar while pathologic is turbulent
• Turbulent blood flow is caused by an obstruction (e.g. atherosclerotic plaque) causing the blood cells to swirl and hit the endothelium activating clot formation
• Endothelial damage caused by plaque promotes platelet adherence → adhere and release growth factors that cause proliferation of smooth muscle → further development of the atherosclerotic plaque
• Stasis of blood flow (e.g. after prolonged sitting) causes the accumulation of activated clotting factors and platelets and prevents their interaction with inhibitors
• The thrombocytes sediment and change form releasing their contents → 𝝰 granules (clotting factors), 𝝱 granules (constrictors)

3) Hypercoagulability

• Can be due to congenital or acquired factors:

1. a) Congenital

• Mutation that changes shape of factor 5 (“factor 5 Leiden”) → can’t be bound to by its inhibitor protein C → hyperactivity of factor 5
• Impaired production of protein C (inactivates factors 5a and 8a) and protein S (cofactor for protein C)
• Congenital antithrombin III deficiency → antithrombin inhibits thrombin → deficiency leads to blood clotting more than normal

1. b) Acquired

• Trauma, burn, sepsis
• tissue factor release activating extrinsic pathway of DIC
• Paraneoplastic syndrome
• Pregnancy
• components of blood
• Elevated levels of estrogen → induces liver enzymes in production of pro-coagulation factors
• Visceral obesity
• production of plasminogen factors
• antithrombotic properties of vessels

Antiphospholipid antibody syndrome (Hughes syndrome)

• Autoimmune syndrome commonly seen in young women that increases venous and arterial clotting
• Characterised by the production of abnormal proteins called antiphospholipid antibodies
• Forms:

1. a) Primary disorder - exhibits only the manifestations of the hypercoagulable state
2. b) Secondary disorder - seen in persons with well-defined autoimmune disorders, such as systemic lupus erythematosus

• Thrombosis may be precipitated by trauma, surgical conditions, use of drugs such as oral contraceptives, or abrupt withdrawal of anticoagulant drugs
• Antiphospholipid syndrome is also a cause of renal microangiopathy, resulting in renal failure caused by multiple capillary and arterial thrombosis