Epidemiology and Diagnosis of Hematologic Diseases - An Overview

Introduction

Epidemiology is the study of diseases in a particular population (neighborhood, locality, district, city, state, country, or global). It covers the determinants of a disease like risk factors, the prevalence in a particular group or place, etiology, prognosis, and also the emergence of new diseases. Epidemiology studies also involve research of clues that predispose to disease. Researchers and clinicians use the available data to diagnose pathologies and to formulate strategies to reduce the risk and morbidity of disease in the community.

What Are Hematologic Diseases and How Are They Classified?

Hematologic diseases are a broad spectrum of blood disorders that are related to cellular components of blood and blood-synthesizing tissues. Though there are numerous classifications of hematologic disorders, epidemiologists have organized them into groups concerning their clinical manifestations and causes of occurrence.

Anemias and Hemoglobinopathies

• Nutritional deficiency anemia (iron, folate, vitamin B12).

• Hemolytic anemia.

• Aplastic anemia.

• Sickle cell anemia.

• Thalassemia (alpha, beta, major, and minor variants).

Hematologic Malignancies

• Lymphoma (malignant proliferation of lymphocytes).

• Leukemia (tumor of blood-forming tissues including bone marrow).

• Myeloma( plasma cell tumors).

• Immunoproliferative neoplasms (hypergammaglobulinemia).

Hemorrhagic Disorders and Coagulopathies

• Hemophilia.

• Von Willebrand disease.

• Clotting factor XII deficiency.

• Deficiency of other clotting factors and mediators (alpha-2-plasmin deficiency).

• Thrombosis.

• Vascular diseases (vasculitis).

• Disseminated intravascular clotting (DIC).

Secondary Hematologic Dysfunctions

• Drug-induced (hemolysis, thrombosis).

• Secondary to infections (viral - Ebola virus, parasite - malarial parasite).

• Transfusion reactions.

What Are the Diagnostics Available for Hematologic Diseases?

Routine blood tests are the first line of diagnostics prescribed to detect any underlying disease condition. However, deviations from normal values in a blood test are not indicative of only hematological disorders since abnormality in blood parameters could also result from non-hematological pathologies or any other treatment interventions. Therefore, blood test results should always be correlated with clinical examination, past medical history, and history of travel and medications. Demographic details (age, gender, ethnicity, income, employment, etc.) also play a crucial role in deciding the subsequent diagnostic interventions.

The diagnostic approach in a hematologic disorder includes,

• Preliminary Screening Tests - These tests are available even in inadequately equipped laboratories and could be performed in make-shift lab setups. They give exact clues about underlying pathology and direct to the next set of diagnostics. Hemoglobin concentration (Hb), total blood cell count, platelet count, peripheral blood film examination, and red cell indices are the major hematological screening tests.

• Physiological Conditions - Pregnancy, extreme exercise, and dehydration are to be taken into consideration while interpreting screening test results.

• Interpretation of Screening Tests - Involves both quantitative (change in number) and qualitative (change in cell morphology) assessment of cellular components of blood (white blood cells, red blood cells, and platelets).

• Increase in the Number of Cells - Erythrocytosis, leukocytosis, thrombocytosis.

• Decrease in the Number of Cells - Anemia, leucopenia, thrombocytopenia.

• Abnormal changes in cell shapes of red blood cells indicate hemoglobinopathies and those of white blood cells are suggestive of reactive changes and lymphoma.

Interpretation of screening tests reveals the defective components in blood. The subsequent specific tests orient towards the particular cellular component that is affected in hematological disorders.

Red Cell Disorders

• Serum ferritin levels, transferrin assay.

• Aspiration of bone marrow.

• Hemoglobin electrophoresis.

• Stool examination and gastrointestinal endoscopy to detect occult blood.

• DNA analysis (in suspicion of thalassemia).

• Vitamin B12 and folate assays.

• Detection of viruses like hepatitis, and HIV (real-time PCR).

• Flow cytometry.

• Urine analysis to detect hemosiderin particles.

White Cell Disorders

• Full blood count and peripheral blood film.

• Immunophenotyping of bone marrow and blood.

• Bone marrow aspiration (lymphoma).

• Trephine biopsy (chronic lymphocytic leukemia).

• Cytogenetic analysis

• Fluorescence in situ hybridization (FISH) analysis to identify acute lymphoblastic leukemia.

• Autoantibody screening.

• Flow cytometry.

• Serum protein electrophoresis to assess immunoglobulin concentrations.

• Serological screening to detect infectious mononucleosis, cytomegalovirus infection, HIV infection, and toxoplasmosis.

• Imaging techniques (to detect abnormality in bone marrow, and organs like liver and spleen).

Platelet Disorders

• Bleeding time (BT), clotting time (CT).

• Prothrombin time (PT).

• Activated partial thromboplastin time (aPTT).

• Immunological assays to detect clotting factors deficiencies.

What Is the Epidemiology of Hematologic Diseases?

There are a multitude of facets in hematologic diseases like etiology, prevalence, diagnosis, and prognosis, which remains challenging for epidemiologists to comprehend the vast available data. The incidence and prevalence of hematologic diseases keep changing globally. Recent studies have shown that international travel and the migration of people have greatly affected disease distribution. The epidemiological data related to hematologic diseases are as follows,

• Nutritional deficiency anemias are common in developing or low-economic countries. Low income has a negative impact on morbidity and prognosis of anemias in these regions.

• The prevalence of thalassemia is mainly seen in areas from the coastal areas of the Mediterranean Sea to the Middle East and throughout Southern and Southeast Asia, and it is often referred to as the thalassemia belt.

• Hematologic diseases like hemophilia and certain clotting disorders are hereditary and genetically inherited. Epidemiological studies help identify and analyze the pattern of inheritance of such diseases.

• The prevalence of sickle cell anemia in certain ethnic groups of Africa has rendered them immune to malarial parasitic infections.

• Though leukemias and lymphomas are prevalent in all age groups, there is much difference in prognosis between children and adults.

• Immunoproliferative disorders are more common in America and Western Europe.

How Does Epidemiology Influence the Diagnosis of Hematological Diseases?

Epidemiological studies include clinical, pathological, diagnostic, and therapeutic facets of hematologic diseases that affect almost all of the global population. Epidemiology and diagnostics are interdependent in the following ways,

• Clinical data acquired through epidemiological studies help to assess the severity of disease and enhance the knowledge in diagnostics and treatment interventions of hematologic disorders.

• Improve the understanding of the etiology of cancer conditions and hematological diseases.

• Help scientists and clinicians formulate advanced preventive strategies.

• To establish multidisciplinary research programs to investigate unknown and rare hematologic disorders.

• To assess the change and global impact in disease expression and transformation due to global travel and migration of people.

• Epidemiological studies on hematologic disorders also bring out the enormous gaps in diagnostic techniques between developed and developing countries.

• There is a greater risk of missing out on a hematological finding in a particular area or population due to a lack of well-equipped laboratories.

• Socio-economic burden also impacts the affordability of diagnostics and therapeutics, particularly for blood malignancies in countries with minimal resources.

Conclusion

Epidemiology of hematological disease provides a wide knowledge of various aspects of disease pathology and a new perspective in diagnostics that helps to prevent adverse medical complications. Strategies for collaboration between hematologists and epidemiologists are needed to optimize diagnostics and therapeutics of hematologic disorders. Subsequently, the collected information would be disseminated to all appropriate medical faculties through authenticated channels to maximize the full potential of the available resources.