1.1 Introduction
Hemostasis is the physiological process by which bleeding is stopped following vascular injury. It involves a highly regulated interplay between blood vessels, platelets, and plasma clotting factors to form a stable blood clot and maintain circulatory integrity (Hoffbrand et al., 2019). Leukaemia, a group of hematological malignancies characterized by the uncontrolled proliferation of abnormal white blood cells, disrupts normal bone marrow function, thereby impairing the production of red blood cells, white blood cells, and platelets (Cheson, 2001). As a consequence, leukaemia significantly affects the hemostatic system. Thrombocytopenia (a reduced platelet count), dysfunctional platelets, and abnormal levels of clotting factors are frequently observed in patients with leukaemia, predisposing them to bleeding or thrombotic complications (Tallman et al., 2005).
This chapter will address the background information that motivated this study, the challenges that prompted it, its aim, and its objectives as a preface to subsequent sections of the study. Additional factors include the study's significance, scope, limitations, research questions and hypotheses, and the definition of technical terms.
1.2 Background of Study
The exploration of hemostasis parameters in leukaemia patients has evolved alongside advancements in hematology and oncology. Hemostasis as a biological concept was first systematically understood in the 19th and early 20th centuries, with discoveries surrounding clotting factors and platelet function providing the foundation for diagnosing and treating bleeding disorders. As laboratory techniques improved, especially with the advent of coagulation assays, scientists began to investigate how various diseases including cancers impact hemostasis.
Leukaemia, first identified as a distinct hematological malignancy in the 1840s, was later found to significantly disrupt the blood's ability to clot. According to Bain (2006), early observations of leukaemia patients frequently described spontaneous bleeding, petechiae, and prolonged bleeding times, which pointed to abnormalities in the clotting system. These signs prompted clinical researchers to delve deeper into the mechanisms through which leukaemia alters hemostasis (Bain, 2006). Hemostasis, the body's mechanism to prevent and control bleeding, involves a complex and well-orchestrated interaction between blood vessels, platelets, and coagulation factors. It plays a critical role in maintaining vascular integrity and ensuring a balance between bleeding and clot formation. However, disruptions in this system are commonly observed in hematological malignancies such as leukaemia, leading to significant clinical complications.
According to Hoffbrand et al. (2019), hemostasis is tightly regulated, and any imbalance whether due to thrombocytopenia, defective coagulation, or platelet dysfunction can result in either excessive bleeding or unwanted clot formation. In the context of leukaemia, this balance is often compromised due to the infiltration of malignant leukocytes in the bone marrow, which interferes with the normal production of blood components, including platelets and clotting factors (Hoffbrand et al., 2019).
Cheson (2001) reported that patients with acute forms of leukaemia are especially prone to hemostatic abnormalities due to their rapid disease progression and the aggressive treatment regimens they undergo. The reduced number of functional platelets and the presence of abnormal white blood cells can severely impair clot formation. Tallman et al. (2005) asserted that in cases such as acute promyelocytic leukaemia (APL), there is a high incidence of disseminated intravascular coagulation (DIC), which presents a dual threat of thrombosis and severe hemorrhage.
De Stefano et al. (2006) stated that chemotherapeutic agents, although necessary for controlling leukemic cell proliferation, contribute to hemostatic disorders by inducing bone marrow suppression and endothelial damage. These complications make it essential for clinicians to monitor hemostasis parameters throughout the treatment process. Additionally, Lechner and Obermeier (2008) affirmed that cancer-associated coagulopathies are underdiagnosed in clinical practice, particularly in low-resource settings, where diagnostic capabilities are often limited. This study is set against the backdrop of addressing the knowledge gap regarding hemostasis parameters among leukaemia patients.
1.3 Statement of Problems
Investigation revealed that leukaemia, a malignant disorder of the blood and bone marrow, is known to significantly alter the normal physiological functions of hematologic systems, particularly hemostasis. Hemostasis, the process that prevents and stops bleeding, is a delicate balance involving platelets, coagulation factors, and vascular integrity. In patients with leukaemia, especially acute forms, this balance is often disrupted due to the infiltration of abnormal leukemic cells in the bone marrow, leading to reduced production and function of platelets and clotting factors (Hirsh et al., 2001).
There is also a lack of comprehensive data on how these hemostatic parameters interact with the clinical stage of leukaemia or influence patient prognosis. On the other hand, existing studies tend to focus more on the treatment of the disease itself, paying less attention to the associated hematologic complications such as bleeding diathesis or thrombosis, which are equally life-threatening if left unmanaged.
Additionally, the complexity of the hemostatic alterations in leukaemia is exacerbated by the disease's heterogeneity. For example, some types of leukaemia are associated with hypercoagulability and thrombotic events, while others predominantly present with hemorrhagic complications (Falanga & Marchetti, 2012).
Furthermore, the administration of chemotherapeutic agents, often essential in the treatment of leukaemia, is also known to aggravate hemostatic abnormalities, further complicating patient outcomes. It is against this backdrop that this study seeks to investigate hemostasis parameters among leukaemia patients.
1.4 Purpose of the Study
The purpose of this study is to investigate the hemostatic parameters among leukaemia patients and determine how these parameters are affected by the presence of the disease and its treatment, with the aim of improving clinical outcomes through better diagnosis and management of coagulation disorders.
1.5 Aim and Objectives of Study
The aim of the study is to evaluate the hemostatic parameters in patients diagnosed with leukaemia. In achieving this aim, the following specific objectives were laid out as follows:
- To determine the levels of platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen in leukaemia patients.
- To compare the hemostatic parameters between leukaemia patients and healthy individuals.
- To evaluate the effects of chemotherapy on the hemostatic profile of leukaemia patients.
- To assess the relationship between type/stage of leukaemia and degree of hemostatic abnormality.
1.6 Research Questions
The study came up with research questions so as to be able to ascertain the above stated objectives. The specific research questions for the study are stated below as follows:
- What are the levels of platelet count, PT, aPTT, and fibrinogen in leukaemia patients?
- How do the hemostatic parameters in leukaemia patients differ from those in healthy individuals?
- Is there a significant relationship between the type or stage of leukaemia and hemostatic abnormalities?
- What effect does chemotherapy have on the coagulation profile of leukaemia patients?
1.7 Research Hypotheses
In order to pursue the objective of this study, the following generalized statements have been designed to guide and aids in obtaining the result for the experiment to be conducted. For this work, the null hypothesis will be represented with H0 while the alternative hypothesis will be represented with hypothesis H1.
Hypothesis One
- H0: There is no significant difference in the hemostatic parameters between leukaemia patients and healthy individuals.
- H1: There is a significant difference in the hemostatic parameters between leukaemia patients and healthy individuals.
Hypothesis Two
- H0: Hemostatic parameters are not significantly altered in patients with leukaemia compared to healthy individuals.
- H1: Hemostatic parameters are significantly altered in patients with leukaemia compared to healthy individuals.
Hypothesis Three
- H0: Chemotherapy does not significantly affect the coagulation profile of leukaemia patients.
- H1: Chemotherapy significantly affects the coagulation profile of leukaemia patients.
1.8 Significance of Study
It is believed that at the completion of the study, the findings will contribute to improved diagnosis and management of hemostatic complications in leukaemia patients. This research will also provide useful data to guide clinical protocols and treatment regimens for better patient outcomes.
Additionally, the research will enhance the monitoring protocols of platelet counts, clotting times, and other coagulation markers during and after chemotherapy, or reducing the risks of life-threatening bleeding.
Furthermore, the findings will help clinicians and hematologists better understand the relationship between leukaemic progression and alterations in coagulation profiles, enabling them to make informed decisions on patient care.
Lastly, the outcome of this study will serve as a reference point for researchers interested in hematological complications of cancer. It will also provide useful data to guide clinical protocols and treatment regimens for better patient outcomes.
1.9 Scope and Limitations of the Study
The scope of this study is limited to patients attending the Hematology Unit of University College Hospital (UCH), Ibadan, where both diagnostic and therapeutic services for leukaemia are provided. It includes patients of different age groups and types of leukaemia. The study does not include patients with other co-existing malignancies or those already on anticoagulant therapy.
The limitations include restricted access to advanced diagnostic equipment, possible variation in treatment regimens, delay in sample processing due to laboratory workload, and limited funding which affects the volume of samples processed.
1.10 Definition of Terms
Hemostasis:
Hemostasis is the process through which the body stops bleeding by forming clots involving vascular constriction, platelet aggregation, and coagulation cascade activation (Hoffbrand et al., 2019).
Leukaemia:
Leukaemia is a cancer of the blood-forming tissues, including the bone marrow and lymphatic system, characterized by an abnormal increase in white blood cells (Cheson, 2001).
Platelets:
Platelets are small, disc-shaped blood cells essential for clot formation. They help stop bleeding by clumping and forming plugs in blood vessel injuries (Hoffbrand et al., 2019).
Prothrombin Time (PT):
PT is a blood test that measures how long it takes for blood to clot, used to assess the extrinsic pathway of the coagulation system (Hoffbrand et al., 2019).
Activated Partial Thromboplastin Time (aPTT):
aPTT is a test that evaluates the intrinsic and common coagulation pathways, often used to detect clotting factor deficiencies (Lechner & Obermeier, 2008).
Fibrinogen:
Fibrinogen is a plasma protein that is converted into fibrin during blood clot formation. Low levels indicate a risk of bleeding, while high levels may suggest inflammation or clotting risk (Tallman et al., 2005).
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