Venous Disorders and DVT Quiz

Venous Pathophysiology

• Venous pathophysiology is the study of the mechanisms involved in the arrest of blood from a damaged blood vessel.
• One of the key processes in hemostasis is vasoconstriction.
• Vasoconstriction occurs when a blood vessel is injured and smooth muscle cells in the traumatized vessel contract, reducing blood flow.

Hemostasis

• Hemostasis is the mechanism involved in the arrest of blood from damaged blood vessels.

Vasoconstriction

• When a blood vessel is injured, smooth muscle cells in the vessel contract.
• This reduces blood flow through the vessel.
• The nerve reflex, myogenic spasm, local humoral factors (like thromboxane A2 and serotonin), initiate these responses.

Formation of Platelet Plug

• A platelet plug is formed by normal platelets.
• Platelets are cell fragments derived from megakaryoblasts, formed in bone marrow.
• Their surface membranes contain glycoproteins making them slippery.
• Their cytoplasm contains granules playing a role in the clotting process.

Platelet Reaction

• When platelets contact damaged endothelium or collagen fibers, they undergo viscous metamorphosis, swelling and forming irregular shapes.
• Platelets become sticky and adhere to rough surfaces and fibers.
• They release chemicals, like ADP and thromboxane A2.

Aggregation

• ADP and thromboxane A2 activate nearby platelets to undergo adhesion reaction.
• Platelets adhere to each other and the original platelets, creating a platelet plug that blocks the wound.
• Platelets release factors that are involved in clotting reactions.

Coagulation

• Coagulation involves the activation or conversion of soluble factors present in the blood into an insoluble network of fibrin strands that close the wound.
• Prothrombin activator (PTA) begins the coagulation process.
• PTA forms from the intrinsic or extrinsic pathway, reacting to tissue or endothelial damage.

Coagulation continued

• PTA catalyzes the formation of thrombin from prothrombin.
• Thrombin catalyzes the conversion of soluble fibrinogen to solid fibrin polymer threads.
• Fibrin threads form a mesh, allowing plasma, blood cells, and platelets to aggregate and form the clot.

Clotting Factors

• Many substances in the blood play a crucial role in clotting.
• These substances are mainly synthesized in the liver.
• The factors are present in the blood as inactive agents.

Intrinsic Pathway

• The intrinsic pathway is initiated by trauma to blood (platelets).
• It's activated when blood contacts damaged endothelial cells or collagen fibers.
• Steps involve the activation of factors XII, XI, and IX, leading to the formation of active Factor X.

Intrinsic pathway continued

• A complex, including active Factor X, Factor V, platelet factors, and calcium ions, forms the prothrombin activator.
• Prothrombin activator converts prothrombin (inactive Factor II) to thrombin.

Extrinsic Pathway

• The extrinsic pathway is initiated by trauma to the vessel or external tissues.
• Thromboplastin (Factor III) is released from tissues when they're damaged.
• Thromboplastin activates and combines with Factor VII, which activates Factor X, leading to the formation of prothrombin activator.

Formation of the Clot

• The conversion of soluble fibrinogen into an insoluble fibrin meshwork forms the clot.
• Fibrinogen is converted to fibrin monomers by thrombin.
• Fibrin monomers polymerize into long fibrin molecules, which are cross-linked to form a mesh.
• Fibrin strands stretch across the opening, trapping blood cells to produce a barrier preventing blood loss.

Formation of the Clot continued

• The fibrin strands eventually contract, forming an impermeable barrier.

Prevention of Blood Clotting

• Endothelial surface factors, such as smoothness, glycocalyx, and thrombomodulin, prevent clotting.
• Antithrombin agents (like fibrin and antithrombin III) inhibit thrombin.

Heparin

• Heparin, secreted by mast cells, increases the effectiveness of antithrombin.
• It decreases Factor XII, XI, IX, and X effectiveness.
• Alpha-2 macroglobulin combines with coagulation factors and inactivates them.

Fibrinolysis

• Plasminogen is a normal constituent of plasma, but it's inactive.
• Plasminogen is trapped in the fibrin clot.
• Tissue plasminogen activator (released from damaged tissues) converts plasminogen to plasmin.
• Plasmin digests fibrin strands, and other clotting factors. This ultimately dissolves the clot.

DVT Annual Estimates

• 1-10 million cases of DVT annually.
• 600,000 cases of pulmonary embolism (PE) annually
• 200,000 deaths from PE annually.

DVT Incidence

• Certain medical procedures increase DVT risk.
  • Major GYN surgery (30%)
  • Average surgical patients (20-30%)
  • Older surgical patients (40-59%)
  • Hip fracture (40-50%)
  • Hip or knee replacement (50%)
  • Myocardial infarction (20-50%)
  • Stroke (30-60%)

Definitions (related to DVT)

• Thrombus: A blood clot in a blood vessel.
• Thrombophlebitis: A blood clot followed by an inflammatory reaction to the vessel wall and surrounding tissue.
• Deep Vein Thrombosis (DVT): Thrombus formation within deep peripheral veins.
• Superficial Venous Thrombosis/Superficial Thrombophlebitis: Thrombus formation in superficial veins.

Virchow's Triad

• Virchow's triad describes three main factors that contribute to DVT formation.
• The three factors are: Stasis, Endothelial injury, Hypercoagulability.

Vessel Damage

• Direct trauma.
• Previous thrombosis.
• Inflammation.
• Infection.
• These can cause activation of clotting factors.
• These can inhibit natural fibrinolysis..
• These can expose blood to collagen fibers

Stasis of Blood Flow

• Bed rest
• Immobility
• Spinal cord injury
• Venous obstruction − Pregnancy are all causes of decreased blood flow, leading to a greater risk of DVT.
• Calf muscle inactivity allows clotting factors to accumulate locally.

Hypercoagulability

• Pregnancy.
• Neoplastic disease/cancer.
• Oral contraceptives/estrogen replacement.
• Excessive clotting factors.
• Absence of normal fibrinolytic factors.

Formation of Venous Thrombus (Location)

• 90% of DVTs occur in the legs.
• Acute DVT usually begins with platelet and fibrin deposits accumulating behind venous valve cusps.
• Usual site in muscular veins of the calf.

Formation of Venous Thrombus (Propagation)

• Thrombus grows and may form a free-flowing clot loosely attached to the venous wall.
• It may fill the vein and occlude it, partially or completely obstructing venous return.
• A thrombus may spontaneously dissolve or lyse.

Formation of Venous Thrombus (Fate)

• Thrombus organization.
• Clot contraction pulls vein walls together.
• New channels are formed in the vessel lumen
• Vein valves may be destroyed.

Symptoms (clinical manifestations) (clinical diagnosis)

• Silent DVT: no symptoms initially or pain/swelling and tenderness.
• Increased venous resistance, pressure, edema, extravasation of blood.
• Symptoms include persistent leg pain with acute onset, persistent leg swelling, calf pain/tenderness, leg discoloration.
• DVTs are often clinically asymptomatic or have vague symptoms.

Complications

• Embolization
• Phlegmasia cerulea dolens: severe DVT with pain, swelling, cyanosis
• Unnecessary treatment
• Post-phlebitic syndrome
• Chronic venous insufficiency
• Venous stasis ulcer

Venous vs. Arterial Symptoms

• Venous symptoms tend to be acute onset, with swelling, calf/thigh pain, and local tenderness, but pallor is different.
• Arterial symptoms are more progressive, with intermittent pain when walking, coolness of the foot/limb, pallor, and eventual gangrene.

Deep Vein Thrombosis (Obstructive vs. Non-Obstructive)

• Acute DVT is characterized by distended veins, a new propagating clot that isn't tightly attached to the vein wall, and high risk of embolization; larger lumen with thrombus.
• Chronic DVT is characterized by a smaller vein lumen with a consolidated clot, tight attachment to the vein wall, and low risk of embolization.
• Non-obstructive chronic DVT presents with a thrombus that's eccentric, may have a free-floating tail, normal flow around the clot, and adheres to the vein wall.

Deep Vein Thrombosis (Fate of thrombus)

• Lysis of thrombus: rate of lysis depends on its size and the flow in the channels of the vein.
• Neointimal thickening: thrombus adheres to, and fibroelastic tissue incorporates into the vein wall.
• Restoration of flow: partial reopening of native or formation of collateral channels.
• Post-thrombotic syndrome (PTS)/Post-phlebitic syndrome: Chronic deep vein obstruction, chronic deep valve incompetence, and symptoms like progressive leg pain and swelling.

Varicose Veins

• Primary varicose veins: dilated, elongated, and tortuous superficial veins, especially in the legs, due to incompetent valves in superficial veins.
• Secondary varicose veins: valve damage from DVT causes retrograde flow in perforators and deep veins, resulting in increased venous pressure and complete flow disruption

Pregnancy and Varicose Veins

• Pregnancy may exacerbate varicose veins.
• Enlarged uterus compresses the inferior vena cava (IVC) and iliac veins.
• Hormonal changes make veins more compliant.
• Reduced venous flow velocity may increase venous distention making it more likely.

Risk Factors

• Family history
• Increasing age
• Female gender
• Pregnancy
• Obesity
• Standing occupations
• History of previous DVT is common

Clinical Manifestations (Varicose Veins)

• Cosmetic disturbance, pain, soreness, aching, burning, throbbing, and cramping are common complaints.
• Other symptoms include muscle fatigue, restless legs, swelling, discoloration, inflammatory dermatitis, recurrent/chronic cellulitis, cutaneous infarction, or ulcerations, malignant degeneration.

Venous Stasis Ulcers

• Increased venous pressure causes capillary distention and increased capillary pressure, opening junctions between endothelial cells, and causing proteins and fluid to seep into the tissues.
• Reduced oxygen transfer leads to ischemia and ulceration.

Superficial Thrombophlebitis

• Thrombosis of superficial veins.
• Not as serious as DVT.
• Risk factors can be IV infusions and IV drug abuse..
• Symptoms include erythema, inflammation, local tenderness, and a palpable cord or mass. Superficial thrombophlebitis generally causes more pain than DVT.