Q2 LONG ANSWER 10M ★ High-yield

Define thrombosis. Describe Virchow triad and the morphology and fate of a thrombus.

Pathology · 2nd Professional — Para-Clinical

Definition

Thrombosis is the formation of a solid or semi-solid mass from the constituents of blood within the vascular system during life.

Haemostasis is the physiological version of the same process; thrombosis is haemostasis occurring in the wrong place or to excess

Virchow’s Triad — the Pathogenesis

Component	Mechanism	Examples
1. Endothelial injury	Exposes subendothelial collagen and tissue factor; loses the normal antithrombotic surface. The dominant factor in arterial and cardiac thrombosis	Atherosclerotic plaque rupture, myocardial infarction, vasculitis, hypertension, smoking, hyperhomocysteinaemia, indwelling catheters
2. Abnormal blood flow	Stasis or turbulence — disrupts laminar flow, brings platelets into contact with endothelium, prevents dilution of clotting factors, and activates endothelium. The dominant factor in venous thrombosis	Immobility, long flights, cardiac failure, atrial fibrillation, aneurysm, varicose veins, hyperviscosity (polycythaemia, myeloma)
3. Hypercoagulability	An altered balance of pro- and anticoagulant factors	Primary — factor V Leiden, prothrombin gene mutation, antithrombin III, protein C or S deficiency. Secondary — pregnancy and the puerperium, oral contraceptives, malignancy, nephrotic syndrome, surgery, trauma, burns, antiphospholipid syndrome

CLINICAL PEARL

Which limb of the triad dominates tells you what the thrombus looks like. Arterial thrombi form on damaged endothelium under fast flow, so they are pale, platelet-rich and firmly attached. Venous thrombi form in stasis, so they are red, red-cell-rich and loosely attached — which is precisely why they embolise so readily.

Morphology

Feature	Arterial (pale, white)	Venous (red, stasis)
Site	Coronary, cerebral, femoral arteries; heart chambers	Deep veins of the leg (90%), pelvic veins
Composition	Platelets and fibrin predominate	Red cells enmeshed in fibrin
Attachment	Firm	Loose — embolises readily
Lines of ZAHN	Present — alternating pale platelet/fibrin and dark red cell layers	Poorly formed or absent
Growth	Retrograde, against the flow	Propagates in the direction of flow, toward the heart

Thrombus compared with post-mortem clot

Feature	Thrombus	Post-mortem clot
Formed	During life	After death
Attachment to wall	Attached	Not attached; lifts out easily
Surface	Dry, granular, friable	Smooth, shiny, gelatinous — "chicken fat and redcurrant jelly"
Lines of Zahn	Present	Absent
Shape	Conforms to the vessel but not a perfect cast	A perfect cast of the vessel

Fate of a Thrombus

1. Propagation — the thrombus enlarges and may occlude the vessel → 2.
Embolisation — it detaches and travels to a distant site → 3.
Dissolution (lysis) — fibrinolysis removes it
effective only in a recent thrombus, which is why thrombolysis must be given early → 4.
Organisation — ingrowth of granulation tissue converts it to a fibrous plug → 5.
Recanalisation — new channels form through the organised thrombus, partly restoring flow

Clinical Effects

Arterial thrombosis causes ischaemia and infarction — myocardial infarction, stroke, gangrene of a limb, mesenteric infarction
Venous thrombosis causes congestion and oedema distal to it, and carries the risk of pulmonary embolism
Deep vein thrombosis — calf pain, swelling, warmth; but over half are clinically silent, which is why the first sign may be a fatal pulmonary embolism
Cardiac mural thrombus after infarction or in atrial fibrillation embolises to the brain, kidney, spleen and limbs

Sites and Special Forms of Thrombosis

Site	Setting	Consequence
Deep veins of the leg	Immobility, surgery, pregnancy, malignancy	Pulmonary embolism; post-thrombotic syndrome
Cardiac mural thrombus	After myocardial infarction; atrial fibrillation; dilated cardiomyopathy	Systemic embolism to brain, kidney, spleen, limbs
Valvular (vegetations)	Infective endocarditis; non-bacterial thrombotic endocarditis of malignancy; Libman–Sacks in lupus	Septic emboli; mycotic aneurysm
Arterial, on a plaque	Atherosclerosis of coronary, cerebral or femoral arteries	Myocardial infarction, stroke, gangrene
Portal and hepatic veins	Cirrhosis, polycythaemia, malignancy	Portal hypertension; BUDD–CHIARI syndrome
Cerebral venous sinus	Dehydration, pregnancy and puerperium, oral contraceptives, sepsis	Raised intracranial pressure, seizures, venous infarction
Superficial veins	Varicose veins	Painful and troublesome but rarely embolises

Cerebral venous sinus thrombosis is disproportionately common in Indian obstetric practice, from dehydration and the puerperal state, and must be considered in any young woman with headache and seizures after delivery

Applied Aspects

Prophylaxis is the whole point — early mobilisation, graduated compression stockings, and low molecular weight heparin for surgical and immobile patients. Every one addresses a limb of Virchow triad
D-dimer is useful for its negative predictive value — a normal value largely excludes thrombosis, but a raised one is non-specific
Doppler ultrasound is the investigation of choice for deep vein thrombosis
Antiphospholipid syndrome causes both arterial and venous thrombosis and recurrent fetal loss, and paradoxically prolongs the aPTT in vitro while causing thrombosis in vivo
Thrombophlebitis migrans (Trousseau sign) — migratory superficial thrombophlebitis suggesting an occult malignancy, classically of the pancreas
Post-thrombotic syndrome follows valve destruction after a deep vein thrombosis, giving chronic swelling, pigmentation and venous ulceration
Warfarin needs heparin cover for the first few days, because protein C has a shorter half-life than the clotting factors and falls first — producing a transient PROcoagulant state and, rarely, warfarin-induced skin necrosis
Arterial and venous thrombosis are prevented by different drugs — antiplatelet agents for arterial (where platelets dominate) and anticoagulants for venous (where fibrin dominates). This follows directly from the composition of each thrombus
Recanalisation restores some flow but the vessel is never normal again, and the valves are permanently destroyed
A thrombus in an artery causes pain, pallor, pulselessness, paraesthesia, paralysis and perishing cold — the six Ps of acute limb ischaemia, an emergency measured in hours
Homans sign is unreliable and potentially dangerous, and has been abandoned in favour of imaging
Superficial thrombophlebitis of the long saphenous vein near the saphenofemoral junction may propagate into the deep system and warrants anticoagulation, unlike thrombophlebitis elsewhere
Anticoagulation does not dissolve an existing thrombus — it prevents propagation and allows the body’s own fibrinolysis to work, which is why improvement is gradual
Duration of anticoagulation depends on whether the thrombosis was provoked: three months for a provoked event, longer or indefinite for an unprovoked or recurrent one
Thrombosis in an unusual site — cerebral sinus, mesenteric or hepatic vein — should prompt a search for a myeloproliferative disorder or paroxysmal nocturnal haemoglobinuria

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