Preface

The estimated total number of symptomatic venous thromboembolism (VTE) events per annum within six European communities was 465,715 cases of DVT; 295,982 cases of PE and 370,012 VTE related deaths and almost three quarters of all VTE-related deaths were hospital–acquired deaths.

Across the Atlantic, VTE is a major health problem in the USA with the annual incidence of VTE of 108 per 100,000 person/year among Caucasians, with 250,000 incident cases occurring annually among the Caucasians in the United States. Among African Americans, the incidence appears to be similar or higher, but among the Asian and native-Americans, the incidence is lower.

In the Far East, VTE is not as common in Chinese as in Caucasians but is certainly not rare. The incidence of DVT and PE was reported to the 17.1 and 3.9 per 100,000 populations, respectively.

Understanding the etiology and pathogenesis of thrombosis is important for developing management strategy including preventive. In this book, we have selected two important etiological aspects of venous thrombosis to highlight microparticles and homocysteine. Flowcytometry has shown that the levels of platelet-derived microparticles and endothelial-derived microparticles to be elevated in deep vein thrombosis and cardiovascular disease can constitute to hypercoagulability due to circulating procoagulant microparticles. To that end, Dr. Enjeti from Australia assembled a very informative account, chapter 1, on the role of microparticles in hemostasis and venous thromboembolism and concluded that there are three potential areas where measuring the microparticles with respect to VTE may be relevant: diagnostic, prognostic and therapeutic.

Hyperhomocysteinemia is a known risk factor for VTE. The risk of VTE recurrence in patients with hyperhomocysteinemia is unknown and so is the management of those patients after acute event of VTE. Dr. Plazar and Dr. Jurdana from Slovenia, Chapter 2, present a detailed updated account on this important topic including diagnosis and management.

VTE is an important clinical problem because of the associated morbidity and mortality and its negative impact on the Healthcare System. The medical literature is

#### VIII Preface

very rich in publications on the subject, epidemiology, etiology, pathogenesis, risk stratification, VTE in different groups of medical and surgical conditions, diagnosis, management, guidelines for thromboprophylaxis and management. As it is not possible to have a comprehensive book that covers all aspects of VTE, in this book we have elected to address certain etiological aspects of venous thrombosis: VTE in neonates, children, chronic renal disease and VTE in cancer patient with special reference to anti-cancer agents associated with high risk of VTE, especially in tertiary care settings.

Preface IX

(1996 - 2010), Dr. Christoffersen and Dr. Hove describe situations where VTE may be judged to be a patient injury and the cases cited from the database all emphasize the need for healthcare practitioner to be aware of the medico-legal aspects of VTE cases,

The medical practice guidelines are usually prepared by standing Task Force/Committees and approved by Executive and/or Council. These evidence-based guidelines reflect emerging clinical and scientific advances in the specific clinical discipline and related specialties as to the date of issue. However, they are subject to change and local institutions are advised that they may modify the guidelines for their own use with full documentation of those modifications. Moreover, the guideline are not meant as dictating an exclusive line of treatment or procedure to be followed and

are not intended to substitute the clinical judgment of the attending physician.

The American Public Health Association issued a white paper in 2003, entitled "Deep Vein Thrombosis: Awareness to protect patient lives" and issued a call for action stating that DVT and PE constitute major health problem in the USA and more people die of PE than motor vehicle accidents, breast cancer or AIDS, and physicians, healthcare providers, public heath advocates and consumers must be aware of the

For patients with a high/very high risk of VTE combined pharmacological and mechanical prophylaxis should be ordered. However, failure of physicians and healthcare providers to adhere to VTE prophylaxis guidelines/protocols in high/very high-risk patients remains a problem in many countries. Hospitals with adequate electronic information systems may consider implementation of electronic alerts to enforce adherence to thromboprophylaxis guidelines/protocols. However, the same strategy can be implemented by institutions without electronic systems if the awareness and willingness of the healthcare providers to cooperate on this important aspect of patient's safety is ensured. In the near future, the voluntary aspects of ordering thromboprophylaxis is very likely to be replaced with an obligatory one, as regulating authorities and insurance companies demand that VTE is a preventable

Senior Consultant Hematologist, Head of Pathology & Laboratory Medicine;

Head of King Abdullah International Medical Research Center

**Dr Mohamed A. Abdelaal** 

Jeddah, Saudi Arabia

and use updated approved guidelines on VTE prophylaxis.

preventability of this epidemic and act accordingly.

patient injury.

Several national and international registries have helped to define the epidemiology, risk factors for VTE in different age groups and demonstrated the important differences between VTE in adults and pediatric patients and called for evidencebased guidelines for management and prevention of VTE in neonates and children. In chapter 3, Dr. Lazaro and colleagues described the magnitude of this problem including diagnosis and management.

The same authors also gave a detailed account of VTE in patients with chronic renal disease, with special reference to epidemiology, pathogenesis, and treatment in this important group of patients with a special reference to unfractionated heparin, low molecular heparin, the pentasaccharide and some of the novel oral anticoagulants.

Although cancer has been clearly associated with venous thromboembolism, many aspects of this relation are still not well understood, including the cancer sites most associated with VTE and the risk for cancer development during follow-up of patients with idiopathic VTE. In chapter 4, the authors have depicted an informative updated account on the epidemiology, pathogenesis, patient-related factors, cancer-related factors and treatment related factors and their impact on the risk of VTE in cancer patients with special emphasis on some chemotherapeutic agents associated with VTE. The authors also put up some practical information on thromboprophylaxis in cancer patients at different clinical settings.

The use of immunomodulatory agents thalidomide and, lately, its second generation Lenalidomide, has revolutionized the management of multiple myeloma patients. However, their use carries a significant risk of thrombosis. Dr. Mateos and Dr. Gonzalez-Porras, chapter 5, assembled an excellent account on those agents in a practical format, which helps the practicing oncologists and hematologists in handling those effective agents to minimize the risk of the VTE associated with the use of those agents.

Dr. Agutter and Dr. Malone from Theoretical Medicine and Biology Group, UK, argued elegantly for a rational approach for mechanical thromboprophylaxis in chapter 6. The authors summarized the valve cusp hypoxia hypothesis, discussed its clinical implications and suggested a sound approach to prophylaxis based on this hypothesis.

In their descriptive account in Chapter 7, titled Venous Thromboembolism as a Preventable Patient Injury - Experience of the Danish Patient Insurance Association (1996 - 2010), Dr. Christoffersen and Dr. Hove describe situations where VTE may be judged to be a patient injury and the cases cited from the database all emphasize the need for healthcare practitioner to be aware of the medico-legal aspects of VTE cases, and use updated approved guidelines on VTE prophylaxis.

VIII Preface

care settings.

including diagnosis and management.

patients at different clinical settings.

very rich in publications on the subject, epidemiology, etiology, pathogenesis, risk stratification, VTE in different groups of medical and surgical conditions, diagnosis, management, guidelines for thromboprophylaxis and management. As it is not possible to have a comprehensive book that covers all aspects of VTE, in this book we have elected to address certain etiological aspects of venous thrombosis: VTE in neonates, children, chronic renal disease and VTE in cancer patient with special reference to anti-cancer agents associated with high risk of VTE, especially in tertiary

Several national and international registries have helped to define the epidemiology, risk factors for VTE in different age groups and demonstrated the important differences between VTE in adults and pediatric patients and called for evidencebased guidelines for management and prevention of VTE in neonates and children. In chapter 3, Dr. Lazaro and colleagues described the magnitude of this problem

The same authors also gave a detailed account of VTE in patients with chronic renal disease, with special reference to epidemiology, pathogenesis, and treatment in this important group of patients with a special reference to unfractionated heparin, low molecular heparin, the pentasaccharide and some of the novel oral anticoagulants.

Although cancer has been clearly associated with venous thromboembolism, many aspects of this relation are still not well understood, including the cancer sites most associated with VTE and the risk for cancer development during follow-up of patients with idiopathic VTE. In chapter 4, the authors have depicted an informative updated account on the epidemiology, pathogenesis, patient-related factors, cancer-related factors and treatment related factors and their impact on the risk of VTE in cancer patients with special emphasis on some chemotherapeutic agents associated with VTE. The authors also put up some practical information on thromboprophylaxis in cancer

The use of immunomodulatory agents thalidomide and, lately, its second generation Lenalidomide, has revolutionized the management of multiple myeloma patients. However, their use carries a significant risk of thrombosis. Dr. Mateos and Dr. Gonzalez-Porras, chapter 5, assembled an excellent account on those agents in a practical format, which helps the practicing oncologists and hematologists in handling those effective

Dr. Agutter and Dr. Malone from Theoretical Medicine and Biology Group, UK, argued elegantly for a rational approach for mechanical thromboprophylaxis in chapter 6. The authors summarized the valve cusp hypoxia hypothesis, discussed its clinical implications and suggested a sound approach to prophylaxis based on this hypothesis.

In their descriptive account in Chapter 7, titled Venous Thromboembolism as a Preventable Patient Injury - Experience of the Danish Patient Insurance Association

agents to minimize the risk of the VTE associated with the use of those agents.

The medical practice guidelines are usually prepared by standing Task Force/Committees and approved by Executive and/or Council. These evidence-based guidelines reflect emerging clinical and scientific advances in the specific clinical discipline and related specialties as to the date of issue. However, they are subject to change and local institutions are advised that they may modify the guidelines for their own use with full documentation of those modifications. Moreover, the guideline are not meant as dictating an exclusive line of treatment or procedure to be followed and are not intended to substitute the clinical judgment of the attending physician.

The American Public Health Association issued a white paper in 2003, entitled "Deep Vein Thrombosis: Awareness to protect patient lives" and issued a call for action stating that DVT and PE constitute major health problem in the USA and more people die of PE than motor vehicle accidents, breast cancer or AIDS, and physicians, healthcare providers, public heath advocates and consumers must be aware of the preventability of this epidemic and act accordingly.

For patients with a high/very high risk of VTE combined pharmacological and mechanical prophylaxis should be ordered. However, failure of physicians and healthcare providers to adhere to VTE prophylaxis guidelines/protocols in high/very high-risk patients remains a problem in many countries. Hospitals with adequate electronic information systems may consider implementation of electronic alerts to enforce adherence to thromboprophylaxis guidelines/protocols. However, the same strategy can be implemented by institutions without electronic systems if the awareness and willingness of the healthcare providers to cooperate on this important aspect of patient's safety is ensured. In the near future, the voluntary aspects of ordering thromboprophylaxis is very likely to be replaced with an obligatory one, as regulating authorities and insurance companies demand that VTE is a preventable patient injury.
