ITP Conference 2007

Presentations

Julie A. Birkofer
“IVIg Production and Safety”

The Plasma Protein Therapeutics Association (PPTA) is the primary advocate for the world's leading source plasma collectors and the producers of plasma-derived therapies. These therapies produced by PPTA members are used in treating life-threatening disorders and serious medical conditions including bleeding disorders, immune system deficiency, alpha-1 antitrypsin deficiencies, burns and shock. Working cooperatively with consumer groups, policy makers and other key stakeholders, PPTA addresses critical issues that affect patients who depend on plasma protein therapies. PPTA and its members take an active role in the areas of product quality, pathogen safety, health policy advocacy and standards setting. Ms. Birkofer will discuss the process plasma goes through starting at the plasma collection facility until it is infused into a patient.

Patricia M. Brady, Ed.D.
”Coping with ITP”

The diagnosis of chronic disease, while a medical event, can set off an acute psychological crisis and major social upheavals. We define ourselves in many ways and usually think and live as if these definitions have some sort of stable, permanent reality. It is therefore extraordinarily difficult for anyone to adjust to a diagnosis such as ITP as the confrontation with the disease negatively and unexpectedly changes how each person thinks when answering the question "who am “I”?"

The normal reactions to the abnormal events of the disease and its treatments often include anxiety, depression, anger and a sense of social isolation. Additionally a loss of confidence can occur when fatigue, clouded thinking and the emotional roller coaster of treatment make previously easy tasks nearly impossible. Family and friends whose practical and emotional support are critically necessary, often become angry and frightened themselves as their lives are impacted by the illness of the patient. These emotional and social difficulties are problems in themselves and can potentially have a negative effect on the course of the disease.

Psychological benefits are derived by the patient who becomes an active collaborator in treatment decision-making. In addition, the practical and emotional support of family and friends who understand the disorder and its treatments can strengthen these relationships and ease the treatment journey. Alternative treatments and lifestyle changes, chosen and implemented by the patient, often help restore the sense of control and repair wounded self-confidence. While one would not choose to have a platelet disorder, there can be tremendous emotional growth and increased clarity about life and values as an outcome of the struggle with the disease.

In addition to expanding on the psychological issues of the patient, attention will be given to the parallel journey of caretakers, friends and families. Some of the special difficulties of sick children will also be discussed.

James Bussel, MD
"Novel Treatment Approaches"

ITP has had an explosion of new therapies or of new developments in pathophysiology that are likely to lead to new therapies. A number will be covered in this talk.

1. There have been new developments in the mechanism of effect of IVIG over the past 3-5 years. It is likely that these could result in new ways of providing the "same" effect.
2. the thrombopoietic agents have undergone the greatest degree of testing. These will mainly be covered by Dr Gernsheimer in her talk.
3. There are new developments in the use of rituximab and anti-CD20's relating to: a) better definition of long term effects, and b) new forms humanized and optimized of anti-CD20.
4. There is a monoclonal anti-FcRIII in trial
5. There is a syk kinase inhibitor in trial

Other new developments may be covered as well.

Nichola Cooper, MD
"UK Treatment Guidelines"

The UK guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy were published in the British Journal of Haematology in 2003. As with all guidelines for ITP, they are limited by a lack of controlled clinical trials. Some of the salient points from the guidelines are that a bone marrow is not recommended if patients are under 60 years and there are no abnormal features, but should be done before splenectomy. PAIg is not helpful in acute diagnosis but helicobacter pylori screening may be appropriate. Importantly patients should be treated for symptoms and not for the platelet count. Splenectomy is still recommended as second line therapy, although this may need updating. Children are different. Most (80%) have acute ITP and will remit within 6-8 weeks. Serious bleeding is rare, with intracranial haemorrhage occurring in children on or off treatment. Side effects to treatment are however common. Therefore, treatment is not advocated in children unless there is severe bleeding. Bone marrow examination is advised if steroids are contemplated, if there are other suspicious symptoms or there is no response to treatment. Finally, it is clear that more randomised controlled trials are needed.

David Dayya, D.O., M.P.H.
“Environmental Exposures and Autoimmune Disease”

The role of toxins in our environment and their role in chronic diseases has been the subject of great interest and offers significant research opportunities. The national goal-setting Healthy People 2010 report issued by the U.S. Department of Health and Human services concluded that research on environmental health and its impact on disease was one of its key priorities. The public has voiced great concerns with respect to a causal link between toxins and diseases such as autoimmune diseases such as Systemic Lupus Erythematosis, cancers, autism and other neuro-development diseases, neuro-degenerative conditions such as multiple sclerosis and Lou Gherig’s disease. Many links have already been well established yet many researchers feel that the associations made to date are only the tip of the iceberg. Their currently exists huge potential in facilitating the environmental toxicology researcher’s efforts to further investigate these concerns. The lecture will focus primarily on environmental exposures and their association with autoimmune diseases in order to help illustrate the research challenges, potentials and controversies posed. The lecture will treat the various autoimmune diseases as a family of diseases as has been advocated by experts for purposes of research and as a general overall approach to this subject and it’s relationship to environmental exposures.

Joel Fuhrman, M.D.
“Nutritional care of autoimmune disorders”

This presentation will offer a nutritional and dietary protocol for the treatment of autoimmune diseases, including medical studies lending support, and case histories. Autoimmune diseases is the fourth leading cause of disability among women and about 75% on average of autoimmune diseases occur in women. Autoimmune diseases include the common lupus, psoriasis and rheumatoid arthritis, but there are about 80 other autoimmune diseases.

Genetic inheritance is not the central determinant for autoimmune diseases; rather the skyrocketing increase in autoimmune illnesses in America is a result of environmental and dietary challenges, which have implications for both prevention and treatment. Such factors such as oxidative stress, free radicals, fatty acid imbalances, bacterial challenges, and Vitamin D deficiency are implicated as causative factors and can be addressed nutritionally.

And most importantly, nutritional excellence can offer a person with autoimmune disease an opportunity to achieve a complete and drug-free recovery. Over the last 15 years, having treated hundreds of patients with autoimmune diseases I have found that remission is achievable in the majority of cases when treated in the early stages of illness. Sample menu plans and recipes for the high cruciferous diet to achieve the high level of beneficial phytochemicals directed against autoimmune illness will be reviewed.

Amy E. Geddis MD PhD
”How platelets are made and what happens in ITP”

All blood cells, including platelets, are derived from a common stem cell in the bone marrow. Under the influence of thrombopoietin, a platelet growth factor, a portion of these stem cells differentiate into cells that will form platelets, called megakaryocytes. Thrombopoietin levels are regulated by megakaryocyte and platelet numbers; when platelet counts are low, thrombopoietin levels in the blood increase and stimulate greater megakaryocyte and platelet production. Developing megakaryocytes become very large, and once they have attained sufficient size, they develop long, branching processes called proplatelets. Proteins important in platelet function collect at the ends of these processes where platelets will ultimately be formed and released into the blood.
In ITP, antibodies attach to platelets, targeting them for destruction by macrophages in the spleen. Despite low platelet counts, thrombopoietin levels are not greatly increased, probably because platelets are able to bind thrombopoietin before they are destroyed, and thus new platelet production is not optimally stimulated. Microscopic examination of megakaryocytes from the bone marrow in ITP also indicates that megakaryocytes may be damaged. Thus, low platelets in ITP are due not only to increased antibody-mediated platelet destruction as once thought, but also due to decreased production.

Terry Gernsheimer, MD
“Thrombopoietic Agents”

Autoimmune thrombocytopenia is characterized by the presence of anti-platelet antibodies and immune platelet destruction. Bone marrow megakaryocytes, appearing morphologically normal and present in normal or increased numbers, have historically been believed to be producing large numbers of platelets but unable to keep up with the severe shortening of platelet survival in the circulation. Over the last 10 to 15 years our understanding of the kinetics of this disorder has gradually changed with evidence that platelet survival is not as abbreviated as previously thought. In addition, thrombopoietin levels are only minimally elevated if at all in the patient with ITP and megakaryocyte physiology appears to be altered. This session will review evidence of impaired platelet production and discuss current developments in the treatment of ITP with thrombopoietic agents.

Paul Kempisty MSTOM, L.Ac
“Traditional Chinese Herbal Medicine in the treatment of ITP”

I will discuss the application of botanical medicines for the treatment of ITP in the context of Traditional Chinese Medicine. An important aspect of understanding alternative approaches in the treatment of established western medical disease models is to maintain a firm grasp of the unique theoretical framework that forms the basis of these traditions. For this reason, aside from introducing various useful herbal preparations for
the patient with ITP, an introduction to the anatomy and pathomechanisms of bleeding disorders according to Traditional Chinese Medical theory will be presented. This is intended to provide greater depth and a fresh perspective to those who are interested in making highly effective botanical choices.

Alan H. Lazarus, PhD
“How are Platelets Destroyed and How Do We Interrupt It: Mechanisms of Effects of IVIgs”

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by the production of proteins called antibodies which bind to platelets and induce platelet clearance resulting in thrombocytopenia. Platelet clearance appears to occur mainly (though not necessarily exclusively) via the engulfment (phagocytosis) of the platelets by a type of cell called a macrophage. The macrophages which engulf the platelets are found mainly in the the spleen and sometimes the liver. Macrophages have receptor proteins on their cell surface called ‘Fc receptors’ that bind the ‘Fc region’ of these antibodies which are found on the platelets in ITP. When the antibody-coated platelet passes by a macrophage, it binds to the macrophage through this Fc receptor and the antibody-coated platelet is consequently removed from the body. One efficacious treatment for ITP and many other autoimmune diseases is intravenous immunoglobulin (IVIg), an antibody or IgG fraction prepared from large pools of ‘healthy’ plasma, typically from 10,000-60,000 blood donors. Anti-D is another type of IVIg product which contains antibodies directed to the RhD antigen on red blood cells. Anti-D has also been successfully used to treat immune thrombocytopenia in RhD+ patients. Although the exact mechanism(s) by which IVIg and anti-D work is still uncertain, many valid theories have been postulated, Dr. Lazarus will discuss how platelets are destroyed in ITP and how IVIg and anti-D may help normalize the platelet counts in ITP.

Howard Liebman, MD
“Secondary ITP: What are some of the causes of ITP”

Immune thrombocytopenic purpura (ITP) is classified as primary or as secondary to an underlying disorder. Malignant and non malignant disorders can be associated with ITP. Within the non malignant disorders a great variety of conditions such as infections, immunodeficiency states, drug treatments and autoimmune diseases are included.
The American Society of Hematology (ASH) issued guidelines for a rational approach to patients with ITP. The secondary causes of ITP were only mentioned when the diagnostic criteria of primary ITP were addressed. More recent studies have produced information that expanded our understanding of secondary ITP. Knowledge of the secondary causes of ITP can be of particular importance for the consultative hematologist assessment of patients with chronic thrombocytopenia. Autoimmune disorders including systemic lupus erythematosis (SLE), Antiphospholipid Antibody Syndrome (APS) and immune mediated thyroid disease are known to be associated with secondary ITP. Management of thrombocytopenia in these patients must be integrated into the primary management of the autoimmune disease. Secondary ITP can be associated with chronic infection with the Human Immunodeficiency Virus (HIV). Between 6 and 15% of HIV infected patients may develop thrombocytopenia. ITP patients with risk factors for HIV infection should be screened for the virus. The approach to the treatment of HIV-related ITP should be directed toward antiviral therapy with HAART regimens containing Zidovudine. Hepatitis C viral infection can also be associated with chronic thrombocytopenia even in the absence of overt liver disease. While HCV-related thrombocytopenia is less severe compared to patients with primary ITP, these patients appear to have a greater risk of major bleeding. Sustained suppression of HCV virus with interferon-ribavirin therapy can improve platelet counts. Screening for HCV infection should be considered in ITP patients with risk factors for infection, from regions with high rates of infection or patients with unexplained mild elevations of their liver enzymes. Studies demonstrated that Helicobacter pylori infection can be associated with the development of ITP. After eradication of infection with antibiotic treatment, 40 to 60% of patients will have improvement in their platelet count. Since testing for H.pylori is noninvasive and since treatment has few side effects, routine screening for H.pylori in newly diagnosed patients with ITP is recommended.

Nancy Russell
“Improving Your Health with Energy Therapy”

After choosing the most appropriate medical care, everyone with any type of disorder, especially an encompassing disease like ITP, is helped by an understanding of healing in a broader sense. While Western or allopathic medicine focuses on cure, Energy Therapy supports healing by fostering relaxation and balance. Energy Therapy, as used and explained by Nancy Russell, is an integrative experience that clears energetic blockages called cellular memory thereby allowing and encouraging balance. This session will cover historical perspectives, explain the process and address many of the options for complimentary healing support. Be prepared to think about the whole body having a symbolic life experience and the importance of relaxation in healing journeys.

John Semple, PhD
”ASH Highlights”

Dr. Semple will discuss and highlight several selected basic and clinical science abstracts related to ITP submitted to the 2006 annual meeting of the American Society of Hematology. He will particularly focus on new discoveries that may have important ramifications for patients with ITP.

Michael Tarantino, MD
“ITP Treatment Guidelines”

Since the publication of ITP management guidelines from the American Society of Hematology (1996) and the British Committee for Standards in Haematology (2003), issues surrounding the diagnosis and treatment of ITP in children continue to evolve. Few data support a change in the diagnostic approach to childhood ITP. Specifically, the need for testing beyond a complete blood count and blood smear examination are not indicated. Recent publications have again challenged the need to treat minimally symptomatic children with severely low platelet counts and confirmed that anti-D immune globulin is now an established front-line treatment option. The management of chronic ITP in children is essentially the same as in acute ITP that becomes persistent or refractory to treatment. During the past 3 years, non-controlled studies have suggested that rituximab may be useful for persistent ITP. Elsewhere, encouraging evidence suggests that the effect of splenectomy for children is durable for the long term. The decision to treat or only observe the minimally symptomatic child with severe thrombocytopenia remains controversial. This ongoing debate has served as a mandate to develop and implement clinical scoring and quality of life tools in treatment and clinical trial design. Meanwhile, experiences with adult ITP have introduced new drug treatment options for children, especially those with chronic ITP and significant bleeding.

Jeffrey Wasser, MD
“Practice Guidelines and ITP”

In 1993, the Executive Committee of the American Society of Hematology authorized the development of a practice guideline for the diagnosis and management of primary immune thrombocytopenic purpura (ITP). This topic was selected because of the lack of diagnostic certainty, perceived variations in management and uncertainty regarding the relative effectiveness of diagnostic tests and treatments.

ITP is frequently encountered by both adult (incidence of approximately 6 cases/100,000 adult/year) and pediatric hematologists, with an incidence of 4-5 cases/100,000/children/year.

The Guideline Development Committee consisted of 13 hematologists from both academic and community-based practices. One member had expertise in clinical epidemiology, and another had expertise in practice guideline methodology.

The 1996 ASH guidelines have served as the foundation for guidelines done by others, specifically, the 2000 guidelines by Italian pediatric hematologists, the 2003 British guidelines and the 2006 Japanese pediatric guidelines.

Since the diagnosis and clinical management of ITP are based on a few controlled studies, this talk will focus on diagnostic criteria using historical, clinical, and laboratory findings.

Newer treatment and management alternatives will be briefly discussed.