Untitled Quiz

Thrombosis

• Thrombosis is the formation of a thrombus (blood clot) in the arterial or venous circulation, composed of platelets, fibrin, red blood cells, and white blood cells.
• If part of a venous thrombus breaks off and travels to the pulmonary artery, it can cause a pulmonary embolism (PE).
• Emboli in the left-sided circulation can cause peripheral arterial occlusion, potentially in the lower limbs or cerebral circulation, leading to a thromboembolic stroke.

Venous Thromboembolism (VTE) - Etiology

• VTE is primarily caused by a combination of blood flow stagnation and hypercoagulability.
• Vascular injury can also contribute to VTE, although it is not always necessary for its development.
• The structure of a VTE thrombus differs from that of an arterial thrombus. Platelets in venous thrombi are more uniformly distributed.

VTE - Risk Factors

• Reduced blood flow (bed rest, surgery, heart failure) increases risk.
• Hypercoagulability factors (surgery, pregnancy, estrogen administration, malignancy, myocardial infarction, acquired/inherited coagulation disorders) increase risk.

Oestrogens

• Oestrogens increase the concentration of clotting factors (I, II, VII, VIII, IX, X) and decrease fibrinolytic activity.
• They also reduce antithrombin III, increasing thrombosis risk.
• Higher dose estrogen-containing contraceptives are associated with a higher risk of venous thrombosis.
• Hormonal replacement therapy, pregnancy, and the puerperium (up to 6 weeks after delivery) are recognised VTE risk factors.

Surgery (VTE Risk Factor)

• Venous blood stagnation in the calves during surgery, along with tissue trauma, contributes to VTE risk.
• Prolonged immobility or travel (greater than 3 hours, approximately 4 weeks before or after surgery) also increases risk.

Other VTE Risk Factors

• Age over 60
• Critical care admission
• Dehydration
• Significant medical conditions (heart disease, metabolic/endocrine/respiratory pathologies, acute infections, inflammatory conditions)

Coagulation Cascade

• The coagulation cascade is a complex series of enzymatic reactions that lead to fibrin formation and clot development.
• Key players include activators (tissue factor, von Willebrand factor, collagen), pathways (intrinsic, common, extrinsic), and inhibitors (antithrombin, protein C, protein S, tissue factor pathway inhibitor). (Diagram showing these reactions)

Diagnostic Algorithms for VTE

• D-dimer test (for ruling out/suspected DVT or PE)
• Wells score (for assessing DVT or PE likelihood)
• Compression ultrasound (CUS) (for diagnosing DVT)
• Imaging techniques (CTPA or V/Q scans) (for diagnosing suspected PE)

Pulomnary Embolism (PE) Diagnostic Algorithm

• D-dimer test
• Wells score
• Imaging (CTPA or V/Q scans)

VTE Treatment

• Treatment aims to restore normal circulation and prevent valve damage. Recurrent VTE/PE also need prevention during the risk period.

Objectives Confirmed VTE Treatment

• Thrombolytic therapy (sometimes followed by anticoagulation)
• IVC filter placement (for high VTE risk patients)
• Outpatient treatment (using Rivaroxaban, Apixaban, LMWH/fondaparinux overlap with Warfarin, INR ≥ 2.0)

Antiplatelet and Anticoagulant Drugs

• Oral anticoagulants (e.g., Warfarin) work by inhibiting vitamin K dependent clotting factors.
• Heparin (unfractionated or low-molecular-weight heparins - LMWHs) have different mechanisms. Heparin enhances the action of antithrombin III blocking clotting factors.
• Dabigatran, a direct thrombin inhibitor, rapidly reduces thrombus formation.
• Rivaroxaban, a factor Xa inhibitor, prevents activation of clotting factors.
• Clopidogrel is an oral antiplatelet pro-drug that prevents platelet aggregation.
• Prasugrel is a platelet P2Y12 receptor inhibitor.

Fibrinolytic Drugs

• Thrombolytics (e.g., Streptokinase, Alteplase, Reteplase, Tenecteplase, Urokinase) are used for life-threatening acute massive PE, particularly when venous damage is likely.
• They dissolve existing thrombi.
• There may be significant potential safety issues in use of fibrinolytics (e.g. haemorrhage.)

Treatments for Arterial Thromboembolism

• Aspirin
• Clopidogrel
• Glycoprotein IIb/IIIa inhibitors
  • Abciximab
  • Eptifibatide
  • Tirofiban

VTE and PE, Etiology and Treatment Summary:

• Underlying diseases/problems (e.g. heart conditions, vascular problems) increase risk. Certain medical procedures (surgery) increase risk.
• Treatment often involves a combination of anticoagulants/antiplatelet drugs.