Deep Vein Thrombosis

General Information

Classification: Cardiovascular

What is it?

Figure 1 DVT presenting with edema and cyanosis in left leg (Source: OpenI, NLM)

A thromboembolic disorder characterized by clot formation, typically in the deep calf vein or mesenteric/cerebral veins

Risk Factors: ischemia, genetics (anticoagulation proteins C and S, antithrombin III, factor V Leiden), obesity, pregnancy, age (>60 yrs), Virchow triad

Evaluation

  • Symptoms (patients often asymptomatic): edema, tenderness, cyanosis with venous gangrene, hypertension
  • Lab biomarkers:
    • Cholesterol, HDL-C, ApoA1: higher levels could be associated with decreased risk
    • D-dimer test, coagulation profile

Types

  • Provoked (secondary to prior conditions) vs unprovoked (idiopathic/endogenous reasons)
  • Proximal (above knee) vs distal (below)

Pathophysiology

  1. Fibrinolytic response (see below) to post-injury coagulation/thrombosis formation
  2. Thrombosis, if lodged, or emboli, if dislodged, leads to ischemia, particularly in the lower extremities (*below the knee, at calves)

Physiological Blurb: Hemostatic Response & Coagulation Cascade

Normal prevention: endothelial cells secrete nitric oxide and PGI-2

  • Prostacyclin: inhibits platelets from binding to endothelial lining
  • Heparin sulfate: binds to antithrombin 3 (degrades coagulation factors/CFs 2, 9, 11)
  • Thrombomodulin: binds to thrombin (F2), which activates Pc (degrades factors 5, 8)

1. Vascular spasm

Smooth muscles contract to reduce blood loss

Damaged endothelial cells secrete endothelin, which further stimulates contraction

2. Platelet plug formation

Platelets bind to von Willebrand factor (produced by endothelial cells) via glycoprotein1-b

  • Binding stimulates secretion of ADP, thromboxane A2, serotonin
    • ADP and thromboxane stimulate platelet aggregation (bind to each other via glycoprotein2-b/3-a
      • Platelets linked by fibrinogen
    • Thromboxane and serotonin induce smooth muscle contraction

3. Coagulation cascade

1. Intrinsic pathway OR

Phosphatidylserine groups surround platelets in negative charge, activating F8, 9, 10, 11, 12

Extrinsic pathway

Damaged cells release TF (F3), activate proconvertin (F7), and F9/10

2. Common pathway

  1. Prothrombin is activated to thrombin
  2. Thrombin induces polymerization of fibrinogen to fibrin (reduces blood flow and loss)
  3. Thrombin also activates F13 (crosslinks fibrin to stabilize the platelet plug)

4. Clot retraction

Platelets secrete platelet-derived growth factor/PDGF (induces proliferation of smooth muscle lining and repairs connective tissue) and vascular endothelial growth factor/VEGF (regenerates endothelial lining)

5. Fibronolysis

Tissue plasminogen activator

  • Converts plasminogen to plasmin, degrading fibrin mesh → releases fibrinogen, d-dimer

Treatment

Provoked DVT (typically acute/transient risk factors)

  • Low molecular weight heparin (if secondary to cancer or liver disease)
  • Vitamin K antagonists/VKAs (kidney disease)
  • Thrombolytic therapy
  • Endovascular interventions (stenting, thrombectomy)

Unprovoked/chronic DVT

  • Long-term anticoagulation therapy

Comments!

Leave a comment

More posts