Leicester Warwick Medical School Haemostasis Thrombosis and Embolism

Leicester Warwick Medical School Haemostasis Thrombosis and Embolism Dr. Kevin West kpw 2@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 A 2 cause platelet aggregation • 5 HT, platelet factor 3 also released • PF 3 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 activators • Fibrinolytic therapy widely used – streptokinase – t. PA

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 reestablished 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 postpartum – 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