leicester warwick medical school haemostasis thrombosis and embolism dr. kevin west kpw2@le.ac.uk...

Leicester Warwick Medical School

Haemostasis Thrombosis and Embolism

Dr. Kevin Westkpw2@le.ac.uk

Department of Pathology

Why don’t you bleed to death from a minor injury?

Objectives 1

• Haemostasis

Objectives 2

• Thrombosis– definition– predisposing factors– effects – outcomes – common clinical examples

Objectives 3

• Embolism– definition– thromboembolism– other types of embolism– pathogenesis of DVT and pulmonary embolism– pathophysiology of pulmonary embolism– prevention and treatment of thrombo-embolic

disease

Haemostasis

Successful haemostasis depends on

• vessel wall

• platelets

• coagulation system

• fibrinolytic system

Blood Vessels

• constrict to limit blood loss

• arteries, veins, capillaries

• mechanism not fully understood

Platelets

• adhere to damaged vessel wall

• adhere to each other

• form a platelet plug

• platelet release reaction

Platelet Release Reaction

• ATP ADP

• ADP, thromboxane A2 cause platelet aggregation

• 5HT, platelet factor 3 also released

• PF3 important in coagulation

• Platelets coalesce after aggregation

Coagulation

• Cascade

• Series of inactive components converted to active components

• Prothrombin Thrombin

Fibrinogen Fibrin

Coagulation

• 1 ml of blood can generate enough thrombin to convert all the fibrinogen in the body to fibrin

• Tight regulation therefore required

• Balance of procoagulant and anticoagulant forces

Control of Coagulation

• Thrombin destroys factors V and VIII• Thrombin inhibitors

– anti-thrombin III*– alpha 1 anti-trypsin– alpha 2 macroglobulin– protein C and S*

* inherited deficiency may thrombosis

Fibrinolysis

• Breakdown of fibrin• Plasminogen Plasmin

Plasminogen activators

• Fibrinolytic therapy widely used– streptokinase– tPA

Endothelium

• Anti-thrombotic– plasminogen activators– prostacyclin– nitric oxide– thrombomodulin

Thrombosis

• Definition

Thrombosis is the formation of a solid mass of blood within the circulatory system

Why does thrombosis occur?

• Abnormalities of the vessel wall– atheroma– direct injury– inflammation

Why does thrombosis occur?

• Abnormalities of blood flow– stagnation– turbulence

• Abnormalities of blood components– smokers– post-partum– post-op

Appearances of thrombi

• Arterial– pale– granular– lines of Zahn– lower cell content

Appearances of thrombi

Appearances of thrombi

• Venous– soft– gelatinous– deep red– higher cell content

Outcomes of thrombosis

• Lysis– complete dissolution of thrombus– fibrinolytic system active– bloodflow re-established– most likely when thrombi are small

Outcomes of thrombosis

• Propagation– progressive spread

of thrombosis– distally in arteries– proximally in veins

Outcomes of thrombosis

• Organisation– reparative process– ingrowth of

fibroblasts and capillaries (similar to granulation tissue)

– lumen remains obstructed

Outcomes of thrombosis

• Recanalisation– bloodflow re-

established but usually incompletely

– one or more channels formed through organising thrombus

Outcomes of thrombosis

• Embolism– part of thrombus breaks off– travels through bloodstream– lodges at distant site

Effects of thrombosis

• Arterial– ischaemia– infarction– depends on site and

collateral circulation

• Venous– congestion– oedema– ischaemia– infarction

Coronary artery thrombosis

Coronary artery thrombosis

Rudolf Virchow

• b. Pomerania 1821• graduated in

medicine 1843• presented work on

thrombosis 1845 but could not get it published

• founded own journal

Rudolf Virchow

• 1848 studied typhus epidemic in Prussia

• Attributed typhus to poor social conditions which upset the government

• Became a political activist and was sacked in 1849 after building barricades in Berlin uprising

Rudolf Virchow

• Appointed Professor of Pathology in Wurzburg

• Described leukaemia, pulmonary embolism and much more

• 1856 appointed Professor of Pathology in Berlin despite government opposition

Rudolf Virchow

• 1858 published ‘Cellular Pathology’ one of the most influential medical books ever written

• 1880-93 Member of Reichstag

• Died aged 81 after fracturing his hip jumping from a moving tram

Embolism

• Definition

Embolism is the blockage of a blood vessel by solid, liquid or gas at a site distant from its origin.

>90% of emboli are thrombo-emboli

Embolism

• Other types– air– amniotic fluid– nitrogen– medical equipment– tumour cells

Thrombo-emboli

• from systemic veins pass to the lungs = pulmonary emboli

• from the heart pass via the aorta to renal, mesenteric, and other femoral arteries

• from atheromatous carotid arteries pass to the brain

• from atheromatous abdominal aorta pass to arteries of the legs

Deep vein thrombosis

• predisposing factors– immobility/bed rest– post-operative– pregnancy and post-

partum– oral contraceptives– severe burns – cardiac failure– disseminated cancer

Can DVT be prevented?

• high risk patients must be identified and offered prophylaxis– heparin sub-cutaneously– leg compression during surgery

Can DVT be treated?

• intravenous heparin

• oral warfarin

Pulmonary embolism - effects

• massive PE >60% reduction in bloodflow rapidly fatal

• major PE - medium sized vessels blocked. Patients short of breath +/- cough and blood stained sputum

• minor PE - small peripheral pulmonary arteries blocked. Asymptomatic or minor shortness of breath

• recurrent minor PEs lead to pulmonary hypertension

Pulmonary embolism