The aetiology of deep venous thrombosis : a critical, historical and epistemological survey / P. Colm Malone, Paul S. Agutter.

Format:

Book

Author/Creator:

Malone, P. Colm.

Contributor:

Agutter, Paul S., 1946-

Language:

English

Subjects (All):

Thrombophlebitis--Etiology.

Thrombophlebitis.

Venous Thrombosis--etiology.

Diseases--Causes and theories of causation.

Medical Subjects:

Venous Thrombosis--etiology.

Physical Description:

xxi, 318 pages : illustrations ; 24 cm

Place of Publication:

Dordrecht ; London : Springer, 2008.

Summary:

What we now call??deep venous thrombosis??? (DVT) has been elucidated by a diversity of investigative approaches during the past four centuries. The authors of this book survey the history of the field and ask: why has one of these perspectives?? the haematological/biochemical?? come to dominate research into the causation of DVT during the past 50 years and to exclude alternatives? In answering this question, they show that the current consensus model is conceptually flawed. Building on the work of William Harvey, John Hunter, Rudolf Virchow, Ludwig Aschoff and a number of pathologists in the mid-20 th century, they offer a revised account of the aetiology of this condition. In the process they retrace and review the 160-year-old philosophical and methodological schism in biomedical research and, using DVT as an example, propose how this schism might be bridged to the benefit of both research and clinical practice.

Contents:

Chapter 1 Introduction to the Study of Deep Venous Thrombosis 1

1.1 Incidence 1

1.2 Pathology 3

1.3 Aetiology: The Consensus Model 4

1.4 The Dominance of the Consensus Model 7

1.5 'Virchow's Triad' 8

1.6 An Alternative Viewpoint 9

Chapter 2 The Coagulation Cascade and the Consensus Model of DVT 11

2.1 The Cascade Model of Blood Coagulation 11

2.2 The Origin of the Consensus Model of DVT 13

2.3 The Coagulation Cascade Today 16

2.3.1 Platelet Activation and Congregation: Local Vasoconstriction 17

2.3.2 The Contact ('Intrinsic') System 19

2.3.3 The Tissue Factor ('Extrinsic') System 20

2.3.4 Fibrinogenesis 20

2.3.5 Fibrinolysis 23

2.3.6 Controlling Coagulation 25

2.4 Disorders of Coagulation 27

Chapter 3 Hypercoagulability 31

3.2 The 'General' Use of the Term 'Hypercoagulability' 32

3.3 Early Evidence for 'Hypercoagulability' Conditions 32

3.4 Testing the 'Hypercoagulability' Hypothesis 33

3.5 Inherited Thrombophilias 34

3.6 Acquired Thrombophilias 36

3.7 Thrombophilia and DVT 37

3.8 Testing for Thrombophilias 38

3.9 Implications for Prophylaxis and Therapy 39

3.10 Reflection 40

Chapter 4 Historical Roots 41

4.1 Two Approaches to Biomedical Research 41

4.2 Semantic Issues 42

4.3 The Ancient World 44

4.4 'Binary Oppositions' in 17th-18th-Century Medicine 45

4.5 Harvey and the 'Physiological' Approach 48

4.6 The 18th Century: Solidism, Humoralism and the Work of Boerhaave 49

4.7 Hunter and Hewson 51

4.8 Late 18th- and Early 19th-Century Studies of Blood Chemistry 54

4.9 The 18th-Century Pioneers of Haemostatics and Haemodynamics 54

Chapter 5 Coagulation and its Disorders: A History of Haematological Research 57

5.2 Phase 1: 1835-1893 58

5.2.1 Haemophilia and the Study of Coagulation 59

5.2.2 Buchanan 59

5.2.3 Buchanan's Influence: The Impact of Mechanistic Materialism 60

5.2.4 The 'Classical Hypothesis' of Blood Coagulation 63

5.3 Phase 2: 1893-1947 64

5.3.1 Prothrombin and its Conversion to Thrombin 64

5.3.2 Heparin, Vitamin K and the Dominance of In Vitro Studies 65

5.4 Philosophical and Semantic Considerations 66

5.5 Reflective Anamnesis 67

Chapter 6 Virchow and the Pathophysiological Tradition in the 19th Century 71

6.2 Cruveilhier 72

6.2.1 Previous Insights into Thromboembolism 73

6.2.2 Cruveilhier's Contribution 74

6.3 Other Formative Influences on Virchow 75

6.4 Resolving the Conflict: Virchow's Synthesis 77

6.5 Virchow on the Structure of a Thrombus 79

6.6 Virchow on Oxygen and Thromboembolism 81

6.7 Virchow versus Cruveilhier 81

6.8 The Possible Source of 'Virchow's Triad' 83

6.9 Reflective Anamnesis 84

Chapter 7 The Pathophysiological Tradition after Virchow 87

7.1 Problems of Nomenclature: 'Phlebitis' and 'Inflammation' 87

7.1.1 'Pus' 89

7.2 Leukocytes, Phagocytosis and Thrombosis 91

7.3 Platelets 93

7.4 The Persistence of the 'Phlebitis' Concept 95

7.5 Continuation of the Pathophysiological Perspective: Welch and Aschoff 96

7.6 The Role of Leukocytes Reconsidered 99

Chapter 8 Interrupted Circulation: The 'Stasis' Hypothesis and the Significance of Venous Valves 103

8.2 The Maturation of the Circulation Hypothesis 104

8.3 Connections with the Revolution in Mechanics 106

8.4 The Discovery of Venous Valves 107

8.5 The Significance of Venous Valves 109

8.5.1 The Venous Valves and DVT 110

8.6 The Persistence and Misleading Character of the 'Stasis' Concept 111

8.6.1 Inherent Difficulties in the 'Stasis' Dogma 111

8.6.2 The Survival of the 'Stasis' Dogma in the 19th Century 112

8.6.3 'Stasis' and the Consensus Model of DVT Aetiology 113

8.6.4 Sevitt on the Aetiology of DVT 114

8.6.5 The Consensus Model and the VVP as Sites of Thrombogenesis 115

8.7 Is the Current (Mis)Use of 'Blood Stasis' Equivalent to Virchow's 'Interrupted Circulation'? 116

8.7.1 Pulsatile Blood Movement in Veins 116

8.7.2 Compression of Veins in the Soles of the Feet 117

8.7.3 Effects of Standing, Sitting and Lying on the Dynamics of Lower Limb Veins 118

8.8 Towards the Valve Cusp Hypoxia Hypothesis: I - Altered Blood Movement 119

Chapter 9 Underperfusion of Valve Pockets and the Initiation of DVT 121

9.2 Thrombi Originate in the Venous Valve Pockets 122

9.3 The Morphology and Pathology of Venous Valves 125

9.3.1 Venous Valve Morphology 127

9.3.2 Valve Pathology: The Formation of Nascent Thrombi within VVP 129

9.3.3 Can the Venous Return Circulation and Valve Function be Correlated? 132

9.4 The Valve Cycle and the Effects of Non-Pulsatile Flow 133

9.5 Relevance of Venous Blood Rheology 134

9.5.1 Relevance of the Vasa Venarum 135

9.5.2 Flow Patterns within VVP 137

9.5.3 Implications for the Formation of Pro-Thrombotic Nidi 137

9.6 Implications for Compression Prophylaxis 138

9.7 Towards the Valve Cusp Hypoxia Hypothesis: II-VVP Hypoxaemia 139

9.7.1 Hypoxic Injury to the VVP Cusp Endothelium Is Potentially Thrombogenic: a Proposal 139

9.7.2 VVP Hypoxaemia and Hypoxic Injury to the Parietalis Endothelium 143

9.7.3 Testing the Predictions 145

9.8 The Lesson of History 145

Chapter 10 The Role of Endothelial Hypoxia in DVT 147

10.1 Oxygen, the Venous Endothelium and Thrombosis 147

10.2 Hypoxaemia, the Vascular Endothelium and Thrombosis 148

10.2.1 Association of DVT with Endothelial Hypoxia 149

10.2.2 Endothelial Hypoxia and Thrombus Formation in VVP 151

10.2.3 The Significance of Ostial Valves 152

10.2.4 Interpreting Micrographs of Venous Thrombi: The Tendency of Thrombi to Embolise 154

10.3 Carbon Monoxide Poisoning and Anaemia 162

10.4 Endothelial Hypoxia and Leukocyte Margination 164

10.5 Aschoff on the Coagulation of Cadaver Blood 165

10.6 Hypoxaemia and 'Traveller's Thrombosis' 166

10.7 Overview: Articulating the Valve Cusp Hypoxia Hypothesis 168

Chapter 11 The Valve Cusp Hypoxia Hypothesis 169

11.1.1 Criteria for an Aetiological Hypothesis 170

11.2 The General Aetiological Sequence: The 'Trinity' 171

11.2.1 'Interrupted Flow' and Underperfusion of VVP 172

11.2.2 The Specific Involvement of the Valve Cusp Parietalis Endothelium 173

11.2.3 Blood Cell Congregation and Blood Coagulation 174

11.2.4 Pathological Consequences 177

11.3 Experimental Support for the VCHH 178

11.3.1 Polarographic Demonstration of VVP Hypoxaemia during Non-Pulsatile Flow 178

11.3.2 Experimental Venous Thrombi Induced by a Non-Invasive Technique 178

11.4 Clinical Implications 183

11.4.1 The Risks of Sleeping for Long Periods in the Sitting Position 183

11.4.2 Simpson's Cases 185

11.4.3 Anaesthesia 187

11.4.4 Crucifixion 188

11.4.5 Varicose Veins 188

11.5 'Risk Factors' for DVT Reconsidered in the Light of the VCHH 189

11.6 Prophylaxis 190

11.6.1 Our Theory-Based Estimate of 1.5-3 h 191

11.6.2 Lister's Experience 191

11.6.3 Normal Tourniquet Practice 191

11.6.4 Published Traveller's Thrombosis Data 192

11.6.5 Intermittent Positive Pressure Compression (IPPC) of Feet or Legs 192

11.6.6 The Animal Experiments of Hamer and Malone (1984) 194

11.7 Reflection 194

Chapter 12 Molecular Changes in the Hypoxic Endothelium 195

12.1 Endothelial Cell Physiology 195

12.2 The VCHH and the Molecular Responses of EC to Hypoxia 197

12.3 Phenotypic Changes in EC under Hypoxic Conditions 197

12.3.1 Phenotypic Changes Consequent on Egr-1 Induction 199

12.3.2 Elk-1 and SRF 200

12.3.3 Other Regulators of Egr-1 Expression 202

12.4 Erg-1, Hypoxia and DVT 204

12.5 Thrombin and the PARs 204

12.6 Interactions Between Platelets and the Hypoxic Endothelium 206

12.6.1 Platelet Congregation and Implications for DVT 206

12.6.2 Leukocyte-Platelet Complexes in the Circulation and their Association with the Hypoxic Endothelium 207

12.7 Endothelial Hypoxia and the Congregation of Leukocytes 208

12.7.1 Monocytes and

Macrophages 209

12.7.2 Neutrophils 210

12.7.3 Effects of Leukocytes on Injured Endothelium 211

12.8 The Endothelium and Coagulation 212

12.9 The Endothelium and Vasomotor Tone 216

12.10 A Further Comment on 'Risk Factors' 218

12.11 The Unification of Approaches 218

Chapter 13 Cadaver Clots or Agonal Thrombi? 221

13.1 Can Blood Coagulate in a Cadaver? 221

13.2 An Early 20th-Century Debate 222

13.3 Aschoff on 'Post-Mortem Clots' 224

13.4 The Debate Reconsidered in the Light of the VCHH 226

13.4.1 Death from Acute Respiratory Failure 226

13.4.2 Death from Circulatory Failure 227

13.4.3 Summary: The Condition of the Blood Post-Mortem Depends on the Mode of Death 228

13.5 Consequences of Positing that All Thrombi Are Agonal 228

13.5.1 Possible Post-Mortem Changes 229

13.5.2 Summing up the Argument: Judicial Implications 229

13.6 Therapeutic and Prophylactic Implications 230

Appendix Science, Medicine and Philosophy 233

A.1 The Two Approaches to Medical Biology 233

A.2 The Philosophical Background to the Schism of the 1840s 234

A.2.1 The Aftermath of the Scientific Revolution 235

A.2.2 The Empiricist Tradition 235

A.2.3 Hume: The Achilles' Heel of Empiricism 236

A.2.4 Kant 237

A.2.5 Naturphilosophie and its Influence on Philosophy and Science 238

A.2.6 Schopenhauer 239

A.2.7 Significance for 19th-Century Physiology and Pathology 239

A.2.8 The Opening of the Schism 240

A.2.9 The Origin and Development of Mechanistic Materialism 241

A.3 Mechanism Versus Vitalism: The Distinctiveness of Vital-Materialism 243

A.3.1 The Mechanism-Vitalism Debate and its Implications 243

A.3.2 Alternatives to Mechanism are Often Misrepresented 245

A.3.3 'Extreme' Mechanism: The 19th-Century German Materialists 245

A.4 The Modern Dominance of the Mechanistic Approach 247

A.4.1 The Metaphysical Dichotomy in Early 20th-Century Biology and Medicine 247

A.4.2 Some Contributing Factors to the Hegemony of Mechanism 248

A.4.3 Molecular Motion Versus Bulk Transport: The 'Newtonianism' of Biochemistry 249

A.5 Rapprochement between the Mechanistic and Vital-Materialist Approaches 251.

Notes:

Includes bibliographical references (pages 255-294) and indexes.

ISBN:

9781402066498

140206649X

1402066503

9781402066504

OCLC:

173499372