As you can imagine, there is significant overlap of clinical manifestations between anemia and leukemia since they both involve the impaired synthesis and distribution of red blood cells.  Thus, we present clinical manifestations to anemia first as it represents the signs and symptoms of decreased RBCs which can also be seen in leukemia – whether the leukemia targets the erythrocyte stem cell (i.e. myeloid) or the leukemia significantly decreases normal hematopoiesis as leukemic cells replace normal mature blood cells within the bone marrow. 

Clinical Manifestation of Anemia

Red blood cells are responsible for carrying oxygen from the lungs to all over the body, where the oxygen is used in energy metabolism and various cellular processes. In anemia, the number of hemoglobin within functional red blood cells is decreased, resulting in clinical manifestations related to the decreased distribution of oxygen throughout the body – typically tiredness, shortness of breath, and pale appearance. However, as anemia may arise from a number of underlying causes, there are several other signs and symptoms that may accompany the classic manifestations depending on the source of the red blood cell deficiency.

Generally, anemia is caused by lack of production (e.g. deficiencies of iron, certain vitamins/nutrients, or erythropoietin), loss (i.e. bleeding), or destruction (i.e. something is targeting the RBCs and removing them from circulation). A full discussion of the manifestations for each cause of anemia is beyond the scope of this book, we will focus on the most common causes of poor RBC production (i.e. iron deficiency) and RBC loss (i.e. hemorrhage)

Manifestations Due to Reduced Oxygen Distribution (e.g. iron deficiency)

Red blood cells contain hemoglobin, a red iron-containing protein unit which binds oxygen, giving red blood cells their colour and allowing the red blood cells to carry oxygen to distribute throughout the body. In iron-deficiency anemia, red blood cells have low amount of hemoglobin, thus reducing their oxygen-carrying capacity and resulting in a pale appearance. Oxygen is used for cellular respiration, the metabolic pathway that produces energy in the form of ATP. With anemia, the reduced number of red blood cells leads to a reduction in the amount of oxygen that reaches cells to be used in cellular respiration, and there is a resulting decrease in the amount of energy being produced by cells. This manifests as tiredness and shortness of breath in the individual. A pale appearance may also be observed due to reduced blood cells flowing to the skin. Since low red blood cells are the defining characteristic of anemia, these clinical manifestations can be seen in all types of anemia

Manifestations Due to Blood Loss

The most common cause of anemia in North America is bleeding. Blood loss can occur in a number of ways such as hemorrhage, trauma, menstrual bleeding, or blood donation. Anemia due to blood loss exhibits classic clinical manifestations of anemia – paleness, tiredness, shortness of breath – in addition to several other clinical manifestations related to sympathetic nervous system activation.  Bleeding activates the sympathetic nervous system, triggering a fight-or-flight response. This has several effects:

• Heart rate increases. The sympathetic nervous system activates beta-1 receptors on the heart which raises heart rate to more efficiently transport the reduced volume of blood throughout the body.

• Respiratory rate increases. The sympathetic nervous system activates beta-2 receptors in the smooth muscles of the respiratory system, causing them to relax and open up airways to deliver more oxygen to cells.

• Diaphoresis. Also known as a ‘cold sweat’ which occurs regardless of warm environment. Chemical messengers released by the sympathetic nervous system  activate sweat glands to cool down the body when under stress, perhaps in anticipation to cool down the muscles needed for “fight or flight”.

Figure 11.16  Summary of clinical manifestations of anemia

Clinical Manifestations of Leukemia

Leukemia can generally be divided into four different types – Acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia. While the four have varying characteristics under the microscope and pathophysiology, they can share similar manifestations. With leukemia being a blood disease, most of these symptoms can be understood by investigating leukemia’s effect on our blood cells.

Manifestations Due to Missing Blood Cells

Hematopoietic stem cells in bone marrow are multipotent cells, meaning that they differentiate into a variety of cells:  red blood cells, platelets and granulocytes are derived from the common myeloid  progenitor whereas lymphocytes are derived from the common lymphoid progenitor cells. 

Clinical manifestation of leukemias are more about the lack of mature blood cells in circulation due to it’s ‘replacement’ by leukemic blast cells which crowd out normal hematopoiesis.  Regardless of the lineage the leukemia is affecting (i.e. myelogenous vs lymphoid), signs and symptoms will relate to lack of one or more mature blood cell. Thus, symptoms can vary.

Anemia

• as discussed above,  low red blood cell count will result in fatigue, pallor, and cardiovascular adaptations to the reduced oxygen carrying capability of the blood. 

Leukopenia

• A decrease in white blood cells is known as leukopenia. White blood cells protect against infection and leukopenia will results in reduced immune function,  manifesting as fever, cough, persisting sores/ulcerations, and concurrent infections.

Thrombocytopenia

• Platelets are derived from fragments of megakaryocytes and are responsible for clotting. When a blood vessel is damaged, platelets are activated and clump together to form a blood clot to cover the hole and control bleeding.  With thrombocytopenia, there is reduced clotting ability due to the platelet deficiency, which can lead to bleeds to ordinary traumas (e.g.  nosebleeds when sneezing, bleeding gums from brushing teeth, bruising)  and wounds that keep re-opening leading to prolonged periods of bleeding.
• Tiny multiple bleeds, known as petechiae and purpura, can  occur as tiny blood vessels have torn or experienced a burst, leaking within the skin while platelet cells are unable to effectively clot and stop bleeding. Hence, tiny red pinpoint spots (petechiae) or <1cm bruises (purpura) are visible on the skin. Ecchymoses, on the other hand, are bruises due to larger rupture in blood vessels, they tend to be visibly larger, greater than 1 cm.

Persistent fatigue, weakness

• Most cancer patients – including leukemic patients – experience fatigue and weakness of varying degree,  known as cancer-related-fatigue. In the case of leukemia, it can be the direct result of reduced RBC number and hence, reduced oxygen carrying capacity; thus, a lowered amount of red blood cells, and hence oxygen, leads to  decreased energy production for cellular processes. Hence, fatigue is a very common symptom for cancer.

Swollen lymph nodes, enlarged liver or spleen (hepatosplenomegaly)

• Swollen lymph nodes usually appear around neck and armpit area. Sometimes, these swelling are just indications that one’s body is actively fighting against infections. With leukemia/lymphoma have swollen lymph nodes that are mainly caused by the replacement of abnormal malignant cells. As liver and spleen are also lymphatic organs, they can also enlarge and cause discomfort and dysfunction.

Losing weight without trying

• Unintentional weight loss can be observed in chronic leukemias patients regardless of whether one is eating sufficiently, as their energy storage gets consumed by cancer. On the other hand, enlarged liver and or spleen  can sometimes occur and places limit of stomach expansion, leading to possible lower appetite. Tumor cells take a lot of nutrients to feed its metabolism leaving the body with little nutrients.

Bone pain or tenderness at area of bone pain

•  It is speculated that the massive accumulation of malignant leukemia cells causes an expansion of cellular marrow space that may cause the bone pain.

Section Review

• The clinical manifestations of anemia can vary depending on the underlying cause of the decrease in red blood cell levels.
• Tiredness, and shortness of breath are classic clinical manifestations of anemia due to reduced delivery of the oxygen necessary for cells to generate ATP through cellular respiration. Anemia patients may also appear pale due to reduced blood flow to the surface of the skin.
• Red blood cells in iron-deficiency anemia lack hemoglobin, which leads to the individual being pale and tired.
• Anemia due to blood loss may cause several clinical manifestations from the activation of the sympathetic nervous system such as increased heart rate, increased respiratory rate, and diaphoresis
• If the red blood cell deficiency is accompanied by deficiencies of other blood cell types, manifestations related to the missing blood cells may be seen
• Leukemia will manifest as reduced number of mature red blood cells. Thus clinical manifestations will appear as anemia (lack of RBCs), frequent severe infections (lack of white blood cells), and/or abnormal bleeding (lack of platelets).
• Being a cancer, leukemia will manifest with common cancer manifestations such as fatigue, unintentional loss of weight, decreased appetite, and swollen lymph nodes and organs.  Bone pain is sometimes associated with leuekmia.

Review Questions