Hematological Disorders

Healthcare providers are seldom summoned as a direct result of a chronic hematological disorder. More often, an acute exacerbation or event has led to our being called. Many of these patients have complicated medical histories; therefore, knowing about the diseases we may encounter can enhance our assessment skills and provide a better understanding of treatment for those patients.

This article presents a brief review of blood and its components, followed by some common red and white blood cell disorders and platelet disorders. Signs and symptoms associated with these diseases are reviewed, as well as prehospital treatment.

Blood Components

Blood is composed of plasma and the formed elements. Plasma, the “sticky” substance in blood, is about 92% water and contains important proteins (albumin, globulins and fibrinogen), as well as salts, lipids and glucose and makes up about 55% of the blood. Formed elements consist of erythrocytes, leukocytes and platelets.

Erythrocytes or red blood cells (RBCs) make up about 45% of blood and are produced primarily in the bone marrow. RBCs outnumber white blood cells approximately 600:1, which means there are 4.2–6.2 million RBCs per mm3 of blood.1 They are biconcave anucleate discs when mature, and are made of water and the red protein hemoglobin. Their primary responsibility is tissue oxygenation and removal of carbon dioxide and waste products. After a lifespan that can reach 120 days, RBCs are destroyed by macrophages. Each RBC contains about 270 million hemoglobin molecules; each hemoglobin molecule carries 4 molecules of oxygen. Hemoglobin is expressed in grams per 100 mL of blood. A normal hemoglobin level in males is 13.5–18 g/100 mL and 12–16 g/100 mL in females.1 The percentage of RBCs in whole blood is referred to as the hematocrit and it averages about 45%, or 40%–54% in males and 38%–47% in females.1

Leukocytes, or white blood cells (WBCs), make up about 1% of the blood. WBCs are categorized into broad groups: granulocytes, monocytes and lymphocytes. Three types of granulocytes exist: neutrophils, basophils and eosinophils. Neutrophils comprise 55%–65% of the WBCs and are responsible for phagocytizing and digesting engulfed materials. Basophils (0%–1%) release histamine and other inflammation-causing chemicals from their granules. Eosinophils (2%–4%) participate in inflammatory reactions and immunity to some parasites. Monocytes (3%–8%) leave the bone marrow and develop into either macrophages or dendritic cells upon migrating into tissues. Macrophages phagocytize and digest engulfed materials, while dendritic cells act as scouts in various tissues, gathering antigen from the tissues then presenting it to the lymphocytes that congregate in the secondary lymphoid organs in a process called antigen presentation. Lymphocytes (25%–35%) include B cells, T cells and natural killer (NK) cells, which are important in immune responses.

Platelets are fragments arising from larger cells called megakaryocytes and are important for blood clotting. When bleeding occurs, platelets migrate to the site in the platelet phase of hemostasis. Once there, they adhere to the endothelial wall of the vessel causing other platelets to stick to them in a process called platelet aggregation, which forms a platelet plug. Platelets are present at 150,000–400,000/mm3 of blood.1 Less than 50,000/mm3 may leave a person in danger of bleeding disorders.

Red Cell Blood Disorders

Anemia

Anemia is not a disease, but rather a symptom of an underlying disease process. It is a condition in which the concentration of hemoglobin or erythrocytes in the blood is below normal, thus impairing the ability of the RBCs to transport oxygen and carbon dioxide. Nearly 100 different types of anemia have been identified. Causes of anemia include an increased destruction of RBCs (hemolytic anemia), increased blood loss, either chronic or acute, and inadequate production of RBCs (aplastic anemia) by the bone marrow. A diagnosis of anemia can be confirmed through routine blood work, but in the prehospital setting, one must rely on signs and symptoms.

Signs and symptoms of anemia include pale skin, nail beds, conjunctiva and mucous membranes; weakness, vertigo, headache, irritability, fatigue, sore tongue, drowsiness, general malaise, dyspnea, tachycardia, palpitations, angina, GI disturbances, amenorrhea, loss of libido and fever.

Those at most significant risk for anemia include the elderly and people with chronic kidney disease, diabetes, heart disease and patients with cancer, rheumatoid arthritis, inflammatory bowel disease and HIV.

Anemia is a common complication of chronic kidney disease. As the kidneys deteriorate, their ability to produce adequate erythropoietin is impaired, resulting in decreased production of new red blood cells and anemia. Remember that erythropoietin in a healthy functional kidney is produced when the renal cells sense hypoxia, which then stimulates the bone marrow to produce more RBCs. Another factor affecting RBCs is toxin buildup resulting from overall renal deterioration, which can shorten the lifespan of existing RBCs. This decrease in the number of RBCs forces the heart to work harder to pump oxygen-rich blood throughout the body, resulting in unwanted tachycardias, possible irregularities and left ventricular hypertrophy.

Diabetes can, over time, damage tiny blood vessels throughout the body, including blood vessels in the kidneys, causing diabetic nephropathy. This can cause slow but progressive loss of kidney function and a related decrease in RBC production.

Anemia in cancer patients results from many factors, including chemotherapy, radiation treatment, gastrointestinal blood loss and iron deficiency. Chemotherapy and radiation treatment are both designed to kill cancer cells, but in the process kill or damage healthy cells as well, including RBCs. Because of its toxicity, chemotherapy can suppress RBC production in the bone marrow and can also affect kidney function, including the production of erythropoietin.

Heart disease, including hypertension, is the second-leading cause of kidney failure. Hypertension makes the heart work harder, which over time can damage blood vessels throughout the body, including those in the kidneys. Randomized trials with recombinant human erythropoietin therapy in anemic patients with chronic kidney disease and concomitant heart disease have demonstrated a reduction in left ventricular hypertrophy (LVH) but variable effects on clinical outcome.2 Preliminary clinical trials in anemic patients with chronic heart failure demonstrate that erythropoietin therapy is well tolerated and associated with short-term clinical improvement.2 Further study is required to determine whether erythropoietin will have beneficial effects in patients with acute ischemic syndromes or chronic heart failure.

Several factors may contribute to anemia in rheumatoid arthritis, including the body’s impaired ability to use iron due to impaired intestinal iron absorption and the sequestration of iron by the reticuloendothelial system. Also, the presence of inflammatory cytokines contributes to anemia in rheumatoid arthritis. Inflammatory cytokines are proteins that cause the inflammation, pain and swelling in the joints of rheumatoid arthritis patients. These proteins can lead to reduced production of erythropoietin and result in lower RBC counts.

Anemia in inflammatory bowel disease may be related to chronic blood loss or to effects of inflammatory cytokines, and can also be a side effect of treatment with drugs that suppress bone marrow activity.

Anemia exists in 65%–95% of persons with AIDS.3 It is strongly associated with the disease progression and carries an increased risk of death. Anemia develops either as a complication of the disease process or the activity of inflammatory cytokines, which generate negative effects on erythropoietin levels and RBC production, or as a side effect of treatment with antiretroviral therapy or chemotherapeutic agents.

Studies have shown that the incidence of anemia increases above age 65, and in people over age 85, the prevalence of anemia may be as high as 45%.4 Fatigue, dizziness, loss of concentration and other symptoms of anemia may contribute to loss of independence and lower tolerance for stress and injury. One study evaluating the correlation between anemia and falls in older patients in nursing homes and the community showed that while there was no appreciative majority in the number of falls in either population, anemic patients were more likely to fall and were older (falls increased 7% per year of age after age 40).5 Anemia represented a threefold increase in the risk of falling; however, with every 1.0 g/dL increase in hemoglobin, the risk decreased by 45%.5

Other significant anemia can result from variceal bleeding, aortic rupture, ectopic pregnancy, hemophilia, hemolytic-uremic syndrome, idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura.

Hemolytic anemia

Hemolytic anemia results when RBCs are destroyed prematurely and cannot keep up with the body’s demands. Autoimmune hemolytic anemia results when the immune system mistakes RBCs as foreign and begins to destroy them. Inherited defects include sickle cell, thalassemia and glucose 6-phosphate dehydrogenase deficiency.

Thalassemia

Thalassemia, which usually affects people of Mediterranean, African and Southeast Asian descent, is marked by abnormal and short-lived red blood cells. Thalassemia major, also called Cooley’s anemia, is a severe form of anemia in which red blood cells are rapidly destroyed and iron is deposited in the skin and vital organs. Thalassemia minor involves only mild anemia and minimal red blood cell changes.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency

This deficiency most commonly affects men of African heritage, although it has been found in many groups of people. The red blood cells of people with this condition either do not make enough of the enzyme G6PD, or the enzyme that is produced is abnormal and does not work well. G6PD plays a role in reducing harmful oxidative stress on red blood cells, resulting from the body’s interaction with oxygen as part of the energy-producing processes of cells. Red blood cells in patients with G6PD deficiency are not able to handle this stress and, consequently, hemolysis results. Due to this deficiency, oxidizing agents such as sulfonamides, furantoins, chloramphenicol, methylene blue, ascorbic acid, primaquine, quinine and other oxidizing drugs should not be given to these patients. If these patients are prescribed one of these medications, it may result in severe abdominal and back pain within 1–3 days of the initiation of treatment. -

Iron deficiency anemia

Iron deficiency anemia is a decrease in the amount of iron to meet body demands. Iron is essential for the production of hemoglobin in red blood cells. Hemoglobin is made up of four subunits called globin, which are each bound to an iron molecule called heme. This structure allows each RBC to carry four molecules of oxygen—one bound to each globin subunit. Any reduction in the amount of iron in the body will result in the RBCs’ inability to carry oxygen to the tissues adequately. Iron is normally obtained from food in the diet. Poor dietary iron intake or excessive loss of iron from the body, such as in pregnancy, growth spurts, blood loss due to heavy menstrual bleeding, or internal bleeding, can lead to iron deficiency anemia.

Pernicious anemia

Pernicious anemia is rare and results from the body not absorbing enough vitamin B12 from the GI tract. Vitamin B12, found in meat, liver, egg yolk, poultry and milk, is necessary for processing carbohydrates, proteins and fats, and to help manufacture blood cells in the body. Vitamin B12 deficiency results in inadequate production of RBCs. Pernicious anemia is most commonly inherited, but other causes include surgery of the stomach and small intestine, abnormal bacterial growth in the small intestine, Crohn’s disease and celiac disease. It may be associated with Type I diabetes and thyroid disease, and rarely attributed to a diet lacking in vitamin B12.6

Aplastic anemia

Aplastic anemia occurs when the bone marrow is unable to produce sufficient numbers of blood cells due to a decrease in the number of blood-forming stem cells. Often, aplastic anemia is caused by a viral infection, exposure to certain toxic chemicals, radiation or medications such as antibiotics, antiseizure medications or cancer medications.

Prehospital management

Prehospital management of anemias requires a thorough focused history using an acronym such as SAMPLE. ABCs should be assessed and addressed accordingly. Family members can be valuable sources of information if your patient is unable to communicate. When applicable and appropriate, ask questions regarding GI history, including stool color, consistency and frequency. Melena, the black, tarry, foul-smelling stool, is characteristic of upper-GI bleeding proximal to the ligament of Treitz. Lower-GI bleeding is characterized by maroon-colored, lumpy, irregular stools. Menstrual history should include timing, frequency and duration of bleeding.

Monitor vital signs frequently, comparing subsequent readings with the baseline determination. Be wary of the possibility of occult bleeding. Transport in a position of comfort, so long as vital signs and patient condition do not dictate otherwise.

Rarely, you may encounter a patient with religious beliefs that oppose receiving blood products. Those beliefs should be acknowledged and respected; however, they should not bias the caregiver against transporting the patient. It has been shown that administration of hemoglobin-based oxygen-carrying compound (HBOCs) in conjunction with recombinant human erythropoietin is effective in maintaining and even increasing hemoglobin levels.7

Sickle cell anemia

Sickle cell anemia is perhaps the hematological disorder that prehospital providers will encounter most frequently. Sickle cell anemia is a recessive genetic illness that primarily affects African-Americans, but also Africans, Arabs, Greeks, Italians, Latin-Americans and those from India. Caucasians, however, can also have sickle cell disease or sickle cell trait. A person must inherit two sickle cell genes—one from each parent—to develop sickle cell disease. When only one gene is present, the condition is known as a sickle cell trait. If both parents have sickle cell trait, there is a 25% chance the child will develop the disease, a 50% chance the child will have sickle cell trait, and a 25% chance that the child will have neither.8,9 Consequently, genetic counseling should be considered for carriers of the disease who plan to become parents. Many states require sickle cell screening of newborns. Approximately one in 12 African-Americans has the sickle cell trait,8,10 while more than 70,000 Americans of different ethnic origins have sickle cell disease.11 Persons with sickle cell trait generally do not experience symptoms, except occasionally under low-oxygen conditions, such as scuba diving, or at high altitudes.

Normal hemoglobin is called hemoglobin A. Sickle cell anemia produces an abnormal type called hemoglobin S, which has an inferior oxygen-carrying capacity. It results when the amino acid valine is substituted for normal glutamic acid in the sixth amino acid position of the betaglobin chain of hemoglobin from both parents.12 When hemoglobin S is exposed to low-oxygen states, it crystallizes, distorting the RBCs into a sickle shape. The sickle-shaped cells are fragile and easily destroyed. The lifespan of the RBCs is reduced to 10–20 days. They also are unable to pass easily through tiny blood vessels, and block flow to various organs and tissues, causing a vaso-occlusive sickle cell crisis that can be life-threatening.

Sickle cell crisis may occur for no apparent reason or be triggered by conditions like dehydration, infection, stress, trauma, exposure to extreme temperatures, lack of oxygen or strenuous physical activity. Frequency of pain varies with each person. Recurrence of these crises can be disabling and lead to blindness, leg ulcers and other health problems, depending on where in the body the blood flow blockage occurs. There are four types of sickle cell crisis: aplastic, hemolytic, sequestration and vaso-occlusive. This article only covers vaso-occlusive sickle cell crisis.

As fewer RBCs pass through congested vessels and blood sludges, tissues and joints become starved for oxygen and other nutrients, causing excruciating pain from the buildup of waste products in the hypoxic area. Common areas of blood sludging are the extremities, back, chest and abdomen. This is the classic sickle cell vaso-occlusive crisis. Sickle cell crisis can occur in any part of the body and can vary in intensity from one person to the next and from one crisis to the next. Pain may range from mild transient attacks lasting about five minutes to excruciating pain lasting days to weeks and requiring hospitalization.

Other signs and symptoms can be attributed to occluded blood flow and include increased weakness, aching, pain, shortness of breath, sudden severe abdominal pain, bony deformities, icteric sclera, fever and arthralgia. Blockage of blood vessels in hands or feet can result in hand-foot syndrome, producing pain, swelling and fever. This may be the first symptom of sickle cell anemia in infants. If a vaso-occlusive crisis involves abdominal organs, an acute abdomen may be mimicked. Acute chest syndrome can result if the vaso-occlusive crisis involves the lungs, and is life-threatening. CNS effects of vaso-occlusive crisis may range from TIA/CVA to seizures and coma. Skin ulcerations may be present over bony prominences. Eye problems may also develop, as the retina can deteriorate when there are insufficient RBCs to properly nourish it. Severe retinal damage may result in blindness. Rapid hemolysis of RBCs may manifest in the sclera of the eyes and in skin as jaundice. Vaso-occlusion may also involve the corpus cavernosum, preventing blood return from the penis and resulting in priapism. Finally, growth may be stunted or slowed due to overall shortage of RBCs.

Hematologic crises are caused by a sudden exacerbation of anemia and a corresponding decrease in hemoglobin. This is attributed to sickled cells blocking either splenic or hepatic blood flow. Over time, sickle cell crises can destroy the spleen, kidneys, gallbladder and other organs, leaving the body more susceptible to infection from organisms like S. pneumoniae, H. influenzae, M. pneumoniae, Salmonella typhimurium, S. aureus and E. coli.9 Sickle cell disease in children also leads to splenic infarcts, which leaves them susceptible to many types of infections.

Prehospital management of sickle cell crisis should include management of pain as in any other severe, acute pain-producing disease, tailoring analgesics and dosages to the level of pain experienced by the patient. Pain intensity should be assessed routinely to monitor response to treatment, using a 1–10 scale or other recognized form. Treatment of pain crisis includes administration of analgesics, including narcotics and NSAIDs, intracellular hydration with hypotonic fluids, bed rest, and antibiotics to treat underlying infection and other precipitants.13 Oxygen should always be administered to sickle cell patients to fully oxygenate all normal RBCs and to decrease the sickling of RBCs that occurs during hypoxic states.

Currently, no cure exists for sickle cell disease short of a bone marrow transplant, which is unrealistic for most patients due to lack of available donors and the multitude of significant risks. The spleen provides protection from bacterial infection; however, because of the eventual damage that occurs to the spleen, patients with sickle cell disease are at increased risk for septicemia if infected by certain types of bacteria like S. pneumoniae. Children with the disease should be current with all immunizations.

White Blood Cell Disorders

There are a variety of white blood cell disorders. Some of the more common WBC disorders are discussed below. A common complication of all WBC disorders is the patient’s increased risk of infection due to the malfunction or absence of certain types of WBCs. It is important to realize that the immune system is an orchestration of all of the WBCs through the use of cytokines and other chemical mediators, and any dysfunction or disorder that affects a type of WBC can severely inhibit the immune system from performing its function to the fullest.

Lymphoma

Lymphoma is a cancer of the lymphocytes, consisting of about 35 different subtypes. All lymphomas are characterized into one of two categories: Hodgkin’s lymphoma, also known as Hodgkin’s disease, and non-Hodgkin’s lymphoma. Hodgkin’s lymphoma and non-Hodgkin’s lymphoma have very similar symptoms and are hard to distinguish on physical exam. A microscope is needed to find the exact cell type that is being affected to differentiate the two types of lymphoma.14 Hodgkin’s lymphoma affects a specific subtype of B lymphocytes, while non-Hodgkin’s lymphoma affects other B lymphocytes or T lymphocytes.14 There are five subtypes of Hodgkin’s lymphoma and 30 subtypes of non-Hodgkin’s lymphoma, and while they may appear the same, their therapies and cure rates are different. Thus, it is important to distinguish between the different subtypes.

Signs and symptoms of lymphoma include swollen lymph nodes, enlargement of the spleen, pain from swollen lymph nodes pressing on nerves and vessels, fever, chills, unexplained weight loss, night sweats, lack of energy and itching.14

Those at risk for lymphoma include individuals who are infected with human T-lymphocytic virus type 1 (HTLV-1), Epstein-Barr virus (EBV), Helicobacter pylori and hepatitis B or C. The elderly are also at increased risk of developing lymphoma.14

Leukemia

Leukemia is a cancer of the blood-forming cells, or stem cells, located in the bone marrow. These cancerous cells may have an exaggerated proliferation or a developmental problem causing immature cells to be released from the bone marrow, which can lead to inappropriate responses when they’re stimulated. Still other leukemic cells do not die normally, causing an increase in the number of white blood cells. These cells are also functionally immature.

Stem cells differentiate into one of two cell lines: myeloid or lymphoid. Myeloid stem cells differentiate into RBCs, platelets, granulocytes and monocytes.15 Lymphoid stem cells differentiate into T-lymphocytes, B-lymphocytes and natural killer cells.15 Thus, there can be two major types of leukemia, myelogenous or lymphocytic, each of which has acute and chronic forms.16 Acute forms of leukemia have cells that proliferate quickly and do not develop properly, while the chronic forms of leukemia have cells that do not die normally.

Adults with leukemia are more likely to have acute myelogenous leukemia or chronic lymphocytic leukemia. Children are more likely to have one of the acute forms of leukemia; however, survival rates are higher for children than adults. The overall survival rate for leukemia today is about 50%.16

Signs and symptoms of leukemia include frequent infections, poor healing of minor wounds, anemia, bleeding disorders, fatigue, fevers, night sweats, weight loss, headache, confusion, balance problems, blurry vision, abdominal pain and/or swelling, pain (neck, underarms, groin, bones, joints and testicles), loss of muscle control and seizures.16

Those at risk for leukemia include patients with histories of long-term exposure to certain chemicals, prolonged exposure to radiation, previous chemotherapy, HTLV-1, myelodysplastic syndrome, Down syndrome and family history.16,17

Prehospital Management

Prehospital management of lymphoma and leukemia patients is aimed at protecting the patient from infection. It is extremely important to use aseptic technique when performing any type of invasive procedure. These patients are at an increased risk of developing infections due to their compromised immune systems. Once an infection is obtained, it is extremely difficult to cure. Not using due regard in trying to prevent infections in patients with white blood cell disorders may cause longer hospitalization or death.

Many of these patients may be complaining about the nausea, vomiting and weakness that follow chemotherapy and/or radiation treatments. Perform a thorough patient assessment, looking for signs of dehydration and altered mental status. If the patient is dehydrated, treat with fluid therapy and transport to the hospital. All patients with altered mental status should be treated according to your local protocol for altered mental status and transported. If the patient is in a stable condition, transport in a position of comfort to the hospital for evaluation of their chief complaint. Consider analgesics for those patients in significant pain.

Platelet Disorders

Thrombocytosis

Thrombocytosis is an increase in the number of platelets produced. Most of these patients are asymptomatic; however, thrombocytosis can complicate other disorders like chronic myelogenous leukemia.18 Thrombo-cytosis is sometimes seen as secondary to other primary diseases, such as malignant diseases, hemolytic anemias, acute hemorrhage and autoinflammatory diseases.18 Thrombocytosis can lead to formation of emboli, which can affect the extremities and lead to deep vein thrombosis; the heart, causing an embolic MI; the lungs, leading to a pulmonary embolus; and the brain, causing a TIA or CVA. Prehospital management of thrombocytosis is supportive only.

Thrombocytopenia is a decrease in the number of platelets caused by one or more of three processes: decreased platelet production; sequestration of platelets in the spleen; or destruction of platelets by the immune system.18,19

Decreased platelet production is normally caused by chemotherapeutic drugs, myelophthisic disease (a type of bone marrow failure due to fibrosis of the hematopoietic stem cells), or the direct effects of alcohol and thiazides on the bone marrow.19 Increased sequestration of platelets in the spleen can be caused by hematologic malignancy, portal hypertension or disorders that cause an increased destruction of RBCs in the spleen.19 The destruction of platelets by the immune system can be seen in systemic lupus erythematosus (SLE), leukemia and lymphoma, in which an antiplatelet antibody has been produced.19 Drug-induced platelet destruction can be caused by the platelet being coated with the drug, thus forming a drug-antibody complex, which is then destroyed by the complement system and lysis of the platelet occurs. Common drugs that cause platelet destruction are quinidine, quinine, heparin, digitoxin, sulfonamides, phenytoin and aspirin.19

Idiopathic thrombocytopenic purpura (ITP)

ITP is an autoimmune disease that is seen when an IgG antiplatelet antibody is formed. This antiplatelet antibody then forms immune complexes with the platelet, and the platelet is destroyed. There are acute and chronic forms of this disease. The acute form is most often seen in children ages 2–6 years, who have usually had a viral infection within the past three weeks.19 This form is limited in nature, there is usually full recovery within a few weeks of onset, and only supportive treatment is necessary. The chronic form is seen in adults, is more common in women than men, and occurs without a previous infection.19

Signs and symptoms of chronic ITP are bruising, prolonged menses, mucosal bleeding, petechiae or purpura, and platelet counts between 30,000/mm3 and 100,000/mm3.19 Spontaneous remission in this disease is rare.

Thrombotic thrombocytopenic purpura (TTP)

TTP leads to the production of hyaline thrombi, which are made up of platelets and fibrin. These thrombi occlude arterioles and capillaries, leading to multisystem destruction of the heart, brain, kidneys and pancreas. Other organs are involved as well, but to a lesser extent.

Signs and symptoms of TTP are thrombocytopenia, renal dysfunction, microangiopathic hemolytic anemia, neurological abnormalities, fever, stroke and heart failure.

Prehospital management of thrombocytopenia, ITP and TTP is aimed at controlling any bleeding, even if it is minor. These patients’ bleeding time will be increased due to the decrease in platelets. Oxygen should be administered to any patient with significant blood loss. All other treatment is supportive.

Conclusion

Patients with a hematological disorder may have a complicated medical history, which requires EMS providers to perform a thorough assessment and physical exam. Remember, these patients may require oxygen, even in minor medical or trauma emergencies, or they may require analgesics for pain. Hematological disorders are rare in the prehospital arena; however, it is important to understand the physiology behind these disease states. Increased knowledge will enable healthcare providers to conduct an improved assessment and better understand treatment for those patients.

References

1. Nester E, Anderson D, Roberts CE Jr., et al. Microbiology: A Human Perspective, 4th Ed. New York, NY: McGraw Hill, 2004.
2. Katz SD. Mechanisms and treatment of anemia in chronic heart failure. Congestive Heart Failure 10(5):243–247, Sep–Oct 2004.
3. www.anemia.com/anemia/anemiahiv.html.
4. www.anemia.com/anemia/anemiaother.html.
5. Dharmarajan TS, Norkus EP. Mild anemia and the risk of falls in older adults from nursing homes and the community. J Amer Med Dir Assoc 5(6):395–400, Nov–Dec 2004.
6. www.mamashealth.com/blood/peranemia.asp.
7. Gannon CJ, Napolitano L. Severe anemia after gastrointestinal hemorrhage in a Jehovah’s Witness: New treatment strategies. Crit Care Mag 30(8):1893–1895, Aug 2002.
8. Mayfield E. New hope for people with sickle cell anemia. FDA Consumer. U.S. Food and Drug Administration 30(4), May 1996. www.fda.gov/fdac/features/496_sick.html.
9. Taher, Tali, Kazzi Z. Sickle Cell Anemia. Updated January 2005. www.emedicine.com/emerg/topic26.htm.
10. American Institute for Preventive Medicine: Sickle cell anemia, 1995. www.healthy.net/hwlibrary-books/healthyself/sicklecell.htm.
11. Hemophilia Health Services: About hemophilia, 1999. www.hemophiliahealth.com/Hemophilia/hemophilia.html.
12. The Sickle Cell Information Center; The Georgia Comprehensive Sickle Cell Center at Grady Health System; The Sickle Cell Foundation of Georgia, Inc., Emory University School of Medicine, Department of Pediatrics, Atlanta Georgia; Morehouse School of Medicine. www.scinfo.org/prod05.htm.
13. www.scinfo.org/prod05.htm.
14. Lymphoma Overview. www.emedicinehealth.com/Articles/25799-1.asp
15. Lydyard P, Grossi C. Cells involved in the immune response. Immunology 5th Edition, Roitt, Brostoff, Male, eds. Philadelphia, PA: Mosby, 1998.
16. Lymphoma Overview. www.emedicinehealth.com/articles/25755-1.asp.
17. What is leukemia? www.mdanderson.org/departments/leukemia/dIndex.cfm.
18. Bledsoe B, Kufs D, Soltis C. Hematology. Paramedic Care: Principles & Practice 2nd Edition, Bledsoe, Porter, Cherry, eds. Upper Saddle River, NJ: Pearson Prentice Hall, 2006.
19. Hamilton G, Janz T. Disorders of hemostasis. Emergency Medicine: Concepts and Clinical Practice. 4th Edition, Vol III, Rosen, Barken, eds. Baltimore, MD: Mosby, 1998.

Glossary

• Acute chest syndrome: A common complication of sickle cell disease that is associated with a high mortality rate. Symptoms are fever, cough, sputum production, dyspnea and hypoxia. Incidence is higher in children ages 2–4.
• Cytokine: A cell-signaling protein that is released by cells to interact or communicate with other cells to influence their behavior.
• Hemolytic-uremic syndrome: A condition characterized by lysis of RBCs and kidney failure. It is caused by the aggregation of platelets in the small blood vessels of the kidney.
• Left ventricular hypertrophy (LVH): Enlargement of the left ventricle of the heart.
• Lysis: Breakdown or destruction of a cell.
• Myelodysplastic syndrome: A group of disorders characterized by low WBC count, low platelet count and increased monocyte count.
• Oxidative stress: Physiological stress on the body caused by a high intracellular level of free radicals that have not been neutralized by antioxidants.
• Oxidizing agent: A substance that accepts electrons from another substance.
• Recessive gene: A gene that is expressed only when another recessive gene is present or if the other gene is missing.
• Reticuloendothelial system: Pertaining to the phagocytic system of the body, including the liver and spleen.
• Sequestration: Withdrawing fluid or cells from the circulating volume.
• Stem cells: Undifferentiated cells that are capable of differentiating into one of several cell types.