Leicester Warwick Medical School Department of Pathology Haemostasis Thrombosis and Embolism Dr. Kevin West kpw2@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 Venous 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