MoD session 5: haemostasis and thrombosis Flashcards
What is haemostasis?
Physiological host defence response to blood vessel injury and bleeding-to stop blood loss
What factors determine successful haemostasis?
Vessel wall-constricts to limit blood loss
Platelets-form a platelet plug
Coagulation cascade-ends in formation of fibrin
Fibrinolysis-to break down fibrin so not excess clotting. Plasminogen activators convert plasminogen to plasmin
Endothelium-produces anti-thrombotic factors (plasminogen activators, prostacyclin, nitric oxide, thrombomodulin)
What is the platelet release reaction?
Once stuck, platelets release molecules to expand the plug and activate coagulation
ADP and thromboxane A2 cause platelet aggregation. 5HT and PF3 are also released
What are platelets?
Subcellular fragments of megakaryocytes that are made in the bone marrow
Outline the coagulation cascade
Extrinsic and intrinsic pathways
Prothrombin–>thrombin so thombin can convert fibrinogen–>fibrin
Tightly regulated to balance pro- and anti-coagulants
Review MGD
What is thrombosis?
The formation of a solid mass of blood within the circulatory system/heart DURING LIFE (if after death isn’t a thrombus)
Describe Virchow’s triad, which explains the causes of thrombosis
- ABNORMAL VESSEL WALL: atheroma/direct injury/inflammation
- ABNORMAL BLOOD FLOW: stagnation/turbulence
- ABNORMAL BLOOD COMPONENTS: smokers/post partum/post operative (more coagulants to prevent bleeding in latter two is natural)
Appearance of arterial thrombi?
Pale, granular, lines of Zahn (alternating pale pink bands with fibrin, and red bands of RBCs), low cell content
Appearance of venous thrombi?
Soft, gelatinous, deep red colour, high cell content
Describe the possible outcomes of thrombosis
LYSIS: complete dissolution more likely if small, by fibrinolytic system
PROPAGATION: spread of thrombus in direction of blood flow (i.e. distally in arteries and proximally in veins); veins get bigger towards heart so thrombus starting in small vein gets bigger
ORGANISATION: reparative ingrowth of fibroblasts and capillaries, lumen remains obstructed and connective tissue becomes more scar-like
RECANALISATION: mix of fibrinolysis and organisation. Blood flow incompletely reestablished, 1 or more channels formed through organising thrombus
EMBOLISM: part of thrombus breaks off, travels through bloodstream and lodges at a distant site
Effects of an arterial thrombus?
Ischaemia
Infarction
(depends on site and collateral circulation)
Effects of a venous thrombus?
Congestion and oedema (as veins can’t drain tissue, so increase in hydrostatic pressure so poor flow. Tissue pressure can eventually reach arterial pressure so no flow–> infarction)
Ischaemia
Infarction
Define embolism
Blockage of a blood vessel by solid, liquid or gas at a site distant from its origin
Name the different types of embolism
Thrombo-emobili (>90%) Air Amniotic fluid Nitrogen (decompression sickness when gaseous nitrogen leaves blood; can lead to avascular necrosis) Medical equipment Tumour cells
Where can thrombo-emoboli travel to and from?
Systemic veins to lungs (pulmonary emboli)
Heart via aorta to renal, mesenteric and other arteries
Atheromatous carotid arteries to brain
Atheromatous abdominal aorta to arteries of legs
Risk factors for deep vein thrombosis?
Immobility Long journey where legs compressed Surgery Pregnancy and post-partum Oral contraceptives Severe burns Cardiac failure Disseminated cancer
Prevention and treatment of DVT?
Prevention: subcutaneous heparin-based drug, leg compression during surgery to expel blood from venous circulation back to the heard to prevent stagnation
Treatment: IV heparin and oral warfarin. Stop thrombus getting bigger but don’t directly dissolve
Pulmonary embolism?
Minor PE: small peripheral pulmonary arteries blocked. Asymptomatic or minor sob, particularly in young fit people. Multiple minor PEs can lead to pulmonary hypertension
Major PE: medium-sized pulmonary vessels blocked. SOB, cough, bloody sputum
Massive PE: >60% reduction in blood flow, rapidly fatal
Cerebral embolism?
Thrombus passes through cerebral supply, causes TIA, “messenger” that there might be a stroke
Iatrogenic embolism?
Due to medical treatment
Fat embolism-from a long bone fracture?
Fat and bone marrow from site of fracture gets into circulation and stops somewhere, causing ischaemic problems.
Can cause neurological symptoms e.g. confusion in #NoF patients
Haemophilia?
X-linked recessive disorder affecting mainly males.
Haemophilia A: deficiency in factor VIII
Haemophilia B: deficiency in factor IX
Both cause spontaneous haemorrhage into joints and soft tissues, bleeding after trauma, bruising. Need treatment with clotting factor replacement therapy
Disseminated intravascular coagulation? (acquired)
Physiological generation of thrombin is unregulated, so when coagulation is activated thrombin is released into the circulation so microthrombi form in numerous organs
Fibrinolytic system is activated but unregulated, leading to haemorrhagic consequences-plasmin released into circulation
so
combination of thrombosis and haemorrhage. Consumption of clotting factors and platelets in the process of clot formation
Thrombocytopenia
Deficiency of platelets, so bleeding into tissues, bruising and slow blood clotting after injury
Causes:
-leukaemia: not enough platelets made in the bone marrow
-DIC or hypersplenism: increased breakdown of platelets in blood/spleen
Thrombophilia
Blood has increased tendency to form clots
Presentation: history of venous thromboembolism, or strong family history (can be heritable)
Other causes: heart failure, haemolytic anaemia
Predisposes to thromboembolism, may need thromboprophylaxis
Amniotic fluid embolism
A rare and severe consequence of pregnancy
Entry of amniotic fluid/hair/foetal cells into the maternal circulation via uterine veins in placental bed of uterus. Causes heart and lung collapse and massive haemorrhage
Very rare, no specific treatment
Bowel infarction
Often due to bowel obstruction or occlusion of one of the mesenteric arteries
Define aneurysm
A permanent and irreversible dilatation of a blood vessel by at least 50% of the normal diamter. Aortic aneurysms are abdominal (majority) or thoracic
How are aneurysms caused?
Degradation of the elastic lamellae, a leukocytic infiltrate, enhanced proteolysis and smooth muscle cell loss. The dilatation affects all 3 layers of the arterial wall
What is a pseudoaneurysm?
Blood leaks through arterial wall but is contained by the adventitia or surrounding perivascular structure
Seqeunce of events leading to DVT after long flight?
Immobility and compression causes stagnated flow
Thrombus forms in vein of lower limb
Clot increases venous pressure so increases hydrostatic pressure
Water leaks into vein–>oedema
Venous return in legs driving force reduced even more than usual
Symptoms often not until late as collateral venous supplies initially available to bypass clot
Why are those who have had surgery, burns or trauma particularly susceptible to DVT?
Hypercoagulative state of healing-release of procoagulant substances e.g. tissue factor
Increased hepatic synthesis of coagulation factors
Decreased tissue plasminogen activation
More platelets
What is Trousseau syndrome?
Migratory inflammation of a vein, due to an imbalance in the clotting cascade that is induced by an underlying malignancy-tumours produce clotting factors
Common in lung and pancreas adenocarcinomas. Palpable lumps in superficial veins
What is a saddle embolus?
A large PE straddling where the pulmonary artery bifurcates and extends into both the left and right pulmonary arteries (very serious as blocks both lungs)
What is a paradoxical embolus?
Venous embolus that causes systemic artery infarction by passing through an interatrial or interventricular defect
Paradox as formed in vein but goes into an artery
