Haemostasis and Thrombosis

• Haemostasis encompasses the mechanisms and disorders of both bleeding and thrombosis
• Normal Haemostasis involves vasoconstriction, platelet plug formation, and blood coagulation
• Vasoconstriction occurs due to endothelial damage leading to thromboxane release and systemic vasoconstriction
• Platelet plug formation involves platelets adhering to exposed collagen, secreting granule contents, and aggregating
• Blood coagulation occurs when Thrombin is generated, proteolysing Fibrinogen to form insoluble Fibrin monomers
• The Coagulation Cascade involves initiation, amplification, and feedback inhibition processes
• Initiation involves TF + Factor VII leading to activation of Factors IX and X, generating Thrombin
• Amplification includes Thrombin back-activating FV, FVIII, FXI, and further reactions leading to clot formation
• Feedback Inhibition mechanisms involve TF-FVIIa inhibition by TFPI, Antithrombin forming active complexes with IX, X, XI, and thrombin, and the activation of the Protein C pathway by thrombin
• Fibrinolysis removes insoluble fibrin through the generation of plasmin, which breaks down fibrin into Fibrin Degradation Products (FDPs)
• Von Willebrand Factor promotes platelet adhesion to subendothelium at the site of vascular injury and is a carrier protein of FVIII
• Bleeding Disorders can be Inherited (e.g., Von Willebrand Disease, Haemophilia A/B) or Acquired (e.g., Medication-related, Immune, Liver Disease, DIC)
• Haemophilia A is characterized by Factor VIII deficiency, while Haemophilia B is characterized by Factor IX deficiency
• Von Willebrand Disease is an autosomal dominant disorder that causes secondary Factor VIII decrease and impairs platelet function
• Acquired Bleeding Disorders can be caused by medication, immune-mediated factors, mechanical stress, liver disease, or DIC
• Thrombosis can be Venous (e.g., DVT, PE) or Arterial (e.g., MI, Stroke) and can occur in various locations in the body
• Venous Thrombosis includes DVT, PE, and thrombosis in unusual sites like CVST and splanchnic veins
• Arterial Thrombosis includes MI, Stroke, and ischemic limb conditions
• Venous Thrombosis includes DVT, PE, and thrombosis in unusual sites like CVST and splanchnic veins
• Unusual Site Thrombosis:

  • Splanchnic Veins
  • Portal Vein
  • Splenic Vein
  • Hepatic Vein
  • Mesenteric Veins
  • Cerebral Vein & Sinus Thrombosis (CVST)
  • Retinal Veins
  • Arterial
  • Myocardial Infarction
  • Ischaemic Stroke
  • Peripheral Artery Occlusion
  • Cardiac Thrombus
  • Renal Artery Infarction
  • Splenic Infarction
  • Mesenteric Artery Infarction
  • Retinal Artery Occlusion
• Less Common Sites of VTE:

  • Upper Limbs
  • Cerebral Veins
  • Splanchnic Veins (Mesenteric Veins, Hepatic Veins, Portal Vein)
• VTE Risk Factors & Virchow’s Triad:

  • Abnormal blood flow
  • Hypercoagulability
  • Endothelial damage
  • Immobility
  • Increasing age
  • Surgery
  • Travel
  • Pregnancy and Puerperium
  • Trauma
  • Prior VTE
  • OCP and HRT
  • Cancer
  • Antiphospholipid Antibody Syndrome
  • Myeloproliferative Disease
  • Inherited Thrombophilia
• Inherited Thrombophilia:

  • Rarely tested
  • Most frequent indication is for otherwise-unprovoked venous thrombosis with a strong family history, particularly in 1st degree relatives
• Acquired Risk Factors for VTE:

  • Hospitalisation
  • Cancer
  • Hormone-Associated (Pregnancy, OCP, HRT)
  • Antiphospholipid Antibody Syndrome
  • Surgery
  • Travel
  • Myeloproliferative disorders
• VTE Diagnosis:

  • Clinical Suspicion DVT or PE?
  • Consider D-Dimer test in combination with a clinical risk prediction model
  • Ultrasound of lower limb veins
  • CT Pulmonary Angiogram (CT-PA) or Ventilation Perfusion (V/Q) scan
• Management of VTE:

  • Anticoagulation is mainstay of treatment
  • DOACs are now first line anticoagulant in most cases
  • Warfarin is first line in some situations
  • Duration of anticoagulation should be minimum 3-6 months
  • Consider indefinite duration if deemed unprovoked, particularly in men, or in the presence of a persistent major provoking factor
• Post-Thrombotic Syndrome (PTS):

  • Persistent swollen, painful leg post DVT
  • No evidence that routine wearing compression stockings after DVT reduces rate of PTS
  • Recent study of catheter-direct thrombolysis in above knee DVT also failed to show a significant reduction in PTS
• Disseminated Intravascular Coagulation (DIC):

  • Inappropriate, excessive activation of haemostatic system
  • Presentation can be acute hemorrhagic disorder or indolent, subacute thrombotic disorder
  • Underlying Disorder leads to systemic activation of coagulation, widespread intravascular fibrin deposition, consumption of platelets and clotting factors, thrombosis, and bleeding
  • Pathogenesis is due to dysregulation of several homeostatic mechanisms
  • Management involves treating the underlying cause and may require blood products if active bleeding or invasive procedure is required