Thrombosis

Normal haemostasis

Well regulated process Maintain blood in a fluid, clot free

state in normal vessels Induce rapid and localized

haemostatic plug at the site of vascular injury

Thrombosis Formation of a solid mass from the constituents of blood within the vasculature (blood

vessels / chambers of heart) During life

The pathologic opposite of haemostasis is thrombosis

An inappropriate activation of normal haemostatic process in uninjured vasculature or thrombotic occlusion of a blood vessel after relatively minor injury

Mechanism of thrombosis Platelets adhere to

endothelium forming a projecting mass

Liberation of thromboplastins from platelet aggregate leads to initiate coagulation cascade

Blood clot formation occurs

Pathogenesis

Three primary influences predispose to thrombus formation.

These are described as Virchow’s triad

Virchow’s triad

There are three main factors leading tothrombosis Damage to the endothelial cell layer

of blood vessel Changes to the flow of blood Alteration to the constituents of blood

Endothelial factors

Normal vascular tree is lined by endothelial cells

Endothelium prevents elements of blood coming into contact with the subendothelial connective tissue which is highly thrombogenic.

Endothelial cell surface is resistant to thrombus formation normally

Endothelial cells can initiate both thrombogenic and antithrombogenic stimuli

Thrombotic and antithrombotic mechanisms

Thrombotic ThromboplastinFactor VPAFvWF

Anti-thromboticThrombomodulinAnti thrombin IIIAlpha 2 macroglobulintPA

Normally these two groups are finely balanced to prevent thrombus formation. Damage to endothelium however will favour thrombosis.

Most significant in arterial thrombosis

Damage to the endothelium

This is of most importance in arterial thrombosis.

The endothelial cell damage could be in the form of

Endothelial cells loss Hydrodynamic stresses causing metabolic

damage eg. Prolonged Hypertension, Turbulance

Toxins and immune mediated mechanisms and radiation

Endothelial cells loss Atheromatous plaques: ulceration Damage by surgery Arteritis Indwelling vascular catheters Infusion of sclerosing chemicals

Hydrodynamic forces Prolong hypertension Turbulance

Toxins and immune mediated damage

Bacterial toxins Cigarette smoke Immune mediatd: transplant rejection,

immune complex disease Radiation

Regardless of the cause of endothelial damage, the end results include

Exposure of subendothelial collagen

Adherence of platelets Exposure to tissue factor Local depletion of prostacyclin and

plasminogen activator

Arterial thrombosis

Seen in coronary arteries, circle of Willis, small arteries of limbs and digits.

Common in aorta due to atherom a or arteriosclerosis

Due to high pressure and rapid flow , these are often platelet variety, exception is laminated thrombus in aneurisms

Coronary thrombosis

Occlusive coronary atherosclerosis

Cardiac thrombosis Thrombi of pale variety

occur on the heart valves in rheumatic endocarditis

Thrombi can be seen on the surface of the infarctions

In SABE, ABE the thrombi are larger, mixed, friable and contain bacteria

In atrial fibrillation thrombi can be seen in the auricular appendage

Rheumatic vegetations

Venous thrombosis

Common due to slower flow, lower pressure with easy compressibility and eddy formation around valves

Usually start in the deep veins of the calf, frequently a propagating thrombus extending in to femoral and iliac veins

Common in patients who are immobilized

Sites of venous thrombosis

Leg veins:immobiliity, post surgery, hypercoagulability

Pelvic veins: pueperal sepsis,post partum, pelvic surgery,

IVC: Tumour, extension from leg

Renal vein: Tumour compression

Portal/hepatic vein: Local sepsis, tumour

Cavernous sinus: Facial sepsis

SVC:Mediastinal tumour Axillary vein: Rucksac,

surgery

Deep Vein thrombosis

Deep vein thrombosis

Preventing deep vein thrombosis

Patients are encouraged to move their legs regularly when confined to bed

Leg muscles are stimulated to contract during long operations using electrodes

Anticoagulants like heparin is used in patients with a risk.

Venous thrombosis

Abdominal operations,child birth, cardiac disease, varicose veins, inflammation may potentiate the condition.

These are attached to vein wall only in few places

Hence chances of detachment and embolism are common

Can lead to pulmonary embolism

Capillary thrombosis

Form when capillaries are damaged usually in acute inflammatory processes

Capillaries can be occluded by fibrin thrombi in cases of disseminated intravascular coagulation

Varieties of thrombosis

White: mainly platelets, mainly seen in arteries where circulation is rapid. Often non occlusive

Red: Start as small platelet aggregate, and then produces fibrin strands entrangling the blood cells

Mixed and laminated: alternate layers of red and white thrombi. Common in aneurisms.

Effects of thrombosis

Arterial: Infarction Ischaemia No effects if there are adequate

anastomoses

Venous: Anastomoses developed frequently to by

pass the obstruction

Collateral circulation in venous thrombosis

Arterial venous

Risk factors Atheroma Immobility

Pathogenesis

Turbulant flowDamaged endothelium

StasisHypercoagulability

Symptoms Sudden onset Slow onset

Complications

InfarctionArterial embolism

Pulmonary embolism

Arterial & Venous thrombi

In propagation the tail builds up retrograde to the flow

Embolization is manly due to detachment of entire or almost the entire thrombus

The tail extends in the direction of flow (towards heart)

The loosely attached tail can fragment creating an embolus

Sequels of thrombosis

Propagation

Resolution

Organisation

Recanalisation

Incorporation

Embolism

Propagation of thrombus If the rate of flow is slow as

in a vein red cells are entrangled in the coagulum

In front and behind the platelet mass blood stagnates. Further formation of fibrin occurs and thrombus extends to the nearest junction

At the junction more platelets get deposited on the end of the mass. This gives the head of the thrombus a pale colour

Resolution The thrombus is completely removed

leading to complete recanalisation. Occurs commonly in the small veins of

the lower limb as the venous intima contains more plasminogen activator than arterial intima.

By giving streptokinase we can enhance the process of thrombolysis.

But it should be given early after thombosis as the effect is going to be less on polymerised fibrin

Organization

When the thrombus has formed PMNL and macrophages begin to degrade and digest fibrin

Later granulation tissue grows into the base of the thrombus and is converted into a mass of small blood vessels separated by connective tissue.

This can lead to complete block or partial block

In partial block, ultimately the thrombus shrinks and is covered by endothelial cells

Recanalisation

Involves production of new endothelium lined channels that convey blood through the occlusive thrombus.

Clefts are produced by shrinkage and digestion of thrombus and are lined by endothelium

Differences of antemortum thrombi and postmortum clots

Antemortum thrombi

Firm Dry granular

appearance Has lines of Zahn Has a point of

attachment to wall

Post mortum clots Cast of the vein Rubbery gelatinous Red current

jelly/chicken fat Not attached to

vein wall

Antemortum / Post mortum clots

Antemortum Post mortum

clot clot

Clinical problems 1 A 65 year old female patient was

admitted to accident and emergency ward with fracture of neck of R femur. Internal fixation was planned in three days time. Two days after the fracture patient complained of pain & swelling in the L calf & ankle.

What is the likely condition? How do you proceed with the

diagnosis?

Clinical problem 2

A 55 year old female patient who underwent debulking surgery for carcinoma of cervix. On 5 th day of operation she developed sudden chest pain with difficulty in breathing.

ECG showed classical pulmonary embolism changes

What is the likely condition? What measures would have taken to

prevent this incident.

Clinical problem 3 A 58 year old female patient

complained of swelling & redness in the left foot. On questioning she gives history of travelling from USA 4 days back. On examination she was afebrile.

What is the likely condition? What investigations are needed for

diagnosis? How do you prevent this? What is the management of this

patient?

A 23 yr old man met with a road traffic accident and was admitted to accident service. He was found to have fractures of R femur, tibia, left femur and left radius. 24 hrs after admission he developed dyspnoea, tachycardia and restlessness. In few hours time patient progresses to a coma. He was found to have a petechial rash.

What is the likely condition? How would you confirm the diagnosis? Explain the pathogenesis of the signs and

symptoms.