Why Blood Remains So Special

In her wonderful text, History of Medicine: A Scandalously Short Introduction, Dr. Jacalyn Duffin entitles the chapter on the history of hematology (her own subspecialty) "Why is Blood Special?". Of the four "humours" of ancient medicine, blood alone remains a vital substance. Dr. Duffin explains how simple it is to understand why blood is so important. Everybody is acquainted with blood; of the internal substances, it is the one that surfaces regularly, and all are aware of how essential blood is to maintain life. From a medical point of view, both points are still valid.

Blood also is relatively easy to study (particularly if it is not your own blood being drawn), and its importance in human physiology and in maintaining life is still very obvious. In fact, in recent decades we have learned that functions once considered related to blood only (clotting and platelet function, among many) have widespread effects on function in many other organs as well, and are of profound biological significance. In the era before widespread invasive procedures in internal medicine, there was a unique satisfaction in examining a blood film or a bone marrow preparation, and being able to make or confirm a diagnosis. Those satisfactions, although no longer unique, are still present, and bone marrow and blood film preparations can be quite beautiful to examine.

The focus of this month's issue is benign hematological disorders, for which we have a superb collection of articles. I really feel my age when I see that former residents have written four of the featured articles. Drs. Shabbir Alibhai and Sudeep Gill have collaborated on two articles, folate deficiency in the elderly, and the controversial topic of diagnosing vitamin B12 deficiency in the elderly. Dr. Anne McLeod discusses inherited and acquired coagulopathies, while Dr. Vikas Gupta writes about hypercoagulable states, an extremely common circumstance in the elderly. Drs. Anne Grand'Maison and William Geerts review the appropriate use of traditional anticoagulants, as well as highlighting the newer agents. The renowned amateur Gilbert and Sullivan singer (and hematologist), Dr. Richard Wells, reviews the myelodysplastic syndromes. I have fond memories as a resident of reviewing Block's initial article in JAMA in the early 1950s on this topic while preparing a presentation. At that time, the term was "preleukemic" syndrome, but shortly after Block's article it became clear that not everybody with this syndrome went on to develop leukemia. We also have a patient information page focusing on anemia from Dr. Durhane Wong-Rieger.

Our usual collection of column articles includes sun-induced skin damage by Dr. G. Daniel Schachter (I feel guilty, having just returned from Florida the day before writing this editorial), while Dr. Wilbert Aronow outlines the pharmacological management of acute non-ST-elevation coronary syndromes in the elderly. Dr. Chris MacKnight outlines the diagnosis and management of Creutzfeld-Jakob disease, and Drs. Robert Chen and Guillermo Paradiso focus on a common and very troublesome problem in the elderly, restless legs syndrome.

Enjoy this issue.

An Approach to the Evaluation of Thrombocytopenia in the Elderly

D'Arcy Little, MD, CCFP
Director of Medical Education,
York Community Services, Toronto, ON.

Introduction
Thrombocytopenia is a common hematologic problem in the elderly.¹ A classic survey indicated that over 50% of patients with thrombocytopenia were over 50 years of age, and 25% were over 70 years of age.² The elderly patient with thrombocytopenia presents the clinician with both diagnostic and management challenges. Because the disorders and mechanisms that lead to decreased numbers of platelets in the circulation are varied, the spectrum of differential diagnoses is broad and includes decreased platelet production and accelerated destruction.³ In addition, the clinical implications of thrombocytopenia fall into a wide spectrum, from a benign condition picked up incidentally in an asymptomatic patient to a life-threatening disorder.⁴ The following article will present an approach to the evaluation of thrombocytopenia in the elderly patient (Figure 1).

Definition and Clinical Significance
Thrombocytopenia is a condition in which there is a deficient number of circulating platelets. The cutoff for diagnosis is 150 x 10⁹/L of blood, which represents the platelet count two standard deviations below the mean obtained when sampling a large number of persons from the general population.

Management of Complications of Hematologic Malignancies in the Elderly

Jeffrey Zonder, MD
Ulka Vaishampayan, MD
Division of Hematology/Oncology,
Department of Medicine
Wayne State University School of Medicine/Barbara Ann Karmanos Cancer Institute
Detroit, MI, USA.

Introduction
The incidence of hematologic malignancies, especially lymphoma, is steadily rising in the elderly. These diseases and their complications pose specific problems for older patients. Factors that contribute to increased toxicity in the elderly include diminished marrow reserve, impaired renal and hepatic metabolism and, perhaps most importantly, poor performance status as a result of comorbidities.¹ This article will focus on the management of common complications of hematologic malignancies, particularly as they pertain to older patients.

Febrile Neutropenia

Risk of Neutropenia in the Elderly
The incidence of life-threatening neutropenia (absolute neutrophil count, ANC, <0.5x 10⁹/L) in elderly patients following chemotherapy for hematologic malignancies is 40% or higher.² The risk of infection is affected by the duration and severity of neutropenia with a steep rise in infection incidence at a neutrophil count of less than 0.5x 10⁹/L.

Our Enduring Fascination with Blood

When I started my residency program in internal medicine, one of my favourite rotations was in hematology/oncology. Not only did one care for sick patients and make a positive contribution to their care, there was the added bonus of blood film and bone marrow examination. The teaching sessions at the microscope were highly educational and incredibly fun. It made me feel like a 'real doctor' to peer down the eyepieces, even though I was pretty weak at interpreting what I saw.

My first presentation on the service was on Preleukemia. In those pre-computer times, I labouriously hunted down references by hand, including Block's original article in the 1953 volume of JAMA (1953:152:1018-29). Today, we would call these preleukemic states myelodysplastic syndromes, and the science and taxonomy has progressed tremendously. However, the fascination with blood remains. Since my internship days, I have learned that this fascination with blood is endemic in medicine, and in society as a whole. This topic is particularly well covered in Professor Jacalyn Duffin's wonderful text on medical history, entitled: History of Medicine: A Scandalously Short Introduction. Not surprisingly, Professor Duffin is a hematologist, as well as a historian. My personal involvement with the 'preleukemic syndrome' continued in 1990 when my mother-in-law developed a myelodysplastic syndrome that rapidly evolved into fatal acute myelogenous leukemia. In an incredible bit of foreshadowing, my initial presentation in internship turned out to be on a topic that is predominantly geriatric, and one that would have a significant impact on my personal life.

In the United States, the predominance of the elderly in the field of oncology has resulted in the insertion of geriatric teaching modules in hematology/oncology training programs. One hopes that Canada will soon follow suit. In any event, there is no shortage of important hematology or oncology topics to discuss in the elderly. As noted in a previous editorial by our Senior Editor, Shabbir Alibhai, there may be many explanations for the poorer outcome for cancer in the elderly. Some of these are failure to correct for comorbidity, inadequate treatment, delay in diagnosis, and presentation at a later stage of disease. Another concern is that the elderly are prone to complications arising from cancer therapy that may not be well managed. Dr. Jeffrey Zonder and Dr. Ulka Vaishampayan, both of Wayne State University School of Medicine, address this issue in their article. Dr. D'Arcy Little covers the issue of thrombocytopenia in the elderly, and Dr. Ahmed Galal and Dr. Jeffrey Lipton from Princess Margaret Hospital discuss the topic of chronic myelogenous leukemia. Our understanding and treatment of this disease has certainly changed dramatically in the past few years. Living with cancer can be enormously stressful, and Dr. Jennifer Jones and Dr. Gary Rodin, also from Princess Margaret Hospital, discuss psychological adjustment to cancer: normative responses as well as psychopathology and treatment.

We also have articles on management of venous ulcers (Dr. Morris Kerstein and Dr. Ernane Reis from Mount Sinai School of Medicine, in New York), genetic counselling and testing for Alzheimer disease (Dr. Wendy Meschino, Toronto), rehabilitation of unilateral neglect (Dr. Gail Eskes and Dr. Beverly Butler, Dalhousie University), the impact of clinical pharmacy in nursing homes (Professor Michael Roberts, University of Queensland, Australia), and the impact of caloric restriction in the aging process (Dr. Isao Shimokawa, Nagasaki University School of Medicine, Japan).

Life is a risky business, and may become even riskier as we age. Many health care providers are intent on making sure our patients are completely 'risk free' in their living arrangements, clearly an impossibility. Harold Parker and Dr. Laura Diachun from the University of Western Ontario look at caregiver responses to the elderly living at risk.

Please do not take any risk that you might miss something important in this issue! Read and enjoy all of the articles.

Chronic Myelogenous Leukemia November 2001

Ahmed Galal, MD, MSc, FRCPC
Fellow in Allogeneic Bone Marrow Transplant,
University Health Network
Princess Margaret Hospital,
Toronto, ON.

Jeffrey Lipton, PhD, MD, FRCPC
Chief, Allogeneic Bone Marrow Transplant Program,
Princess Margaret Hospital,
Head, Chronic Myeloid Leukemia Group,
Associate Professor of Medicine,
University of Toronto,
Toronto, ON.

Introduction
Chronic myelogenous leukemia (CML), in addition to polycythemia rubra vera and essential thrombocytosis, are the most commonly diagnosed forms of the myeloproliferative disorders.^1-5 These diseases share several distinct features:

• They are clonal disorders of hema-topoiesis that arise in a hematopoietic stem or early progenitor cell;
• They are characterized by the dysregulated production of a particular lineage of mature myeloid cells with fairly normal differentiation;
• They exhibit a variable tendency to progress to acute leukemia.

Cytogenetic studies of bone marrow and peripheral blood in the benign myeloproliferative disorders are usually normal. However, CML is invariably associated with an abnormal chromosome known as the Philadelphia chromosome.⁶ CML accounts for 15-20% of adult leukemias. It has an annual incidence of 1 to 2 cases per 100,000, with a slight male predominance.