SEMINAR ON HEMATOLOGIC

DISORDER

PRESENTED BY MR. VIRENDRA JAIN

ANATOMY OF BLOOD•

•Blood is a fluid connective tissue circulating through the heart, veins, capillaries carrying nourishment, electrolytes, hormones, vitamins, antibodies heat and oxygen to the tissues and taking away waste matter and carbon- dioxide.

COMPOSITION OF BLOOD:

Blood is composed of two portions:

•Plasma-Blood is composed of 55% plasma, a straw colored transparent fluid.

•Formed elements-45 % of blood is composed of formed elements

PLASMAThe constituents of plasma are

water (90-92%) and dissolved substances containing:

• plasma proteins:– albumins– potassium– globulins– fibrinogen– clotting factors

Cont…• inorganic salts:

– sodium chloride– sodium bi-carbonate– magnesium– potassium– iron – copper – calcium– cobalt

Cont…

nutrients:1.amino-acids2.glycerol3.monosaccharide4.vitamins

Organic waste materials• uric acid• urea• Creatinine

HormonesGases:• oxygen• carbon-dioxide

•FORMED ELEMENTS:

Blood cells

• 1.) Erythrocytes (R.B.C’S) 2.) Leukocytes (W.B.C’S)

Granular Leukocytes Agranular Leukocytes

Neutrophils * T Lymphocytes Eosonophils

* B LymphocytesBasophils * Monocytes

3) Thrombocytes (Platelets)

•FUNCTIONS OF BLOOD

• 1. Respiratory•2. Nutritive•3. Excretory•4. ‘Homeostatic’ for water, pH

and electrolyte concentration•5. Regulation of body

temperature • 6. Chemical for communication

and protection.• 7. Plasma proteins functions

•RED BLOOD CELLS (R.B.C’S)

•Red blood cells are bi-concave non-nucleated discs with a diameter of 8 microns.

•they contain oxygen carrying pigment called heamoglobin,which is responsible for their red color of whole blood.

Production of R.B.C’s• RED BLOOD CELLS (R.B.C’S)• Proerythroblast

• Early erythroblast

• Intermediate erythroblast

• Late Erythroblast

• Reticulocyte

• BONE MARROW

• Blood stream

• Red Blood cells

LIFE SPAN OF RED BLOOD CELLS

• The lifespan of RBC’s is about 120 days because of wear and tear on their plasma membranes as they squeeze through the blood capillaries.

• Without a nucleus and other organelles,RBC”s cannot synthesise new components to replace damaged ones

• As a result the plasma membrane becomes more fragile with age and cells are more likely to burst

• Worn-out cells are removed from the circulation by phagocytic macrophages in the spleen and liver

• After the breakdown of R.B.C’s,bilirubin is formed which is further forms apart of the bile formed by the liver.

FORMATION OF HEAMOGLOBIN

•Heamoglobin is acomplex protein,consisting of globin and iron containing substance called haem and is synthesized inside developing erythrocytes in red bone marrow

Function of hemoglobin

: •Transport of oxygen•Haemoglobin in mature RBC’S

combine with oxygen in the lungs to form oxyhaemoglobin and this oxyhaemoglobin further dissociates to supply oxygen to the tissues.

Blood grouping and

Typing• Individuals have different types of antigens

on the surfaces of their red blood cells.• These antigens which are inherited

determine the blood group of the individual

• Therefore individuals with the respective antigens on their blood cell,then the individual’s blood group is determined by the respective antigen.

• The most commonly followed system of blood grouping is the ABO syatem

THE ABO SYSTEM•The ABO system classifies blood

grouping into 4 different typesblood group-A(A-type antigen)blood group-B(B-type antigen)blood group-AB (both A&B-type

antigens presentblood group-O (neither A nor B

type antigen present)

The Rhesus system

• The individuals possessing Rh antigen on their surfaces of red blood cells are called as Rh +ve individuals. (eg.A+ve)

• The individuals who do not possess Rh antigen on their surfaces of red blood cells are called as Rh -ve individuals. (eg. A-ve)

LEUKOCYTES(W.B.C’S)

•Leucocytes are nucleated blood cells which are further divided into

•Granular Leukocytes•Neutrophils•Eosonophils•Basophils

•Agranular Leukocytes•Lymphocytes

--T Lymphocyte --B Lymphocytes

•Monocytes

THROMBOCYTES(PLATELETS)

• Thrombocytes are very small non-nucleated discs,(2-4micro-m) in diameter,derived in the cytoplasm of megakarocytes in the red bone marrow.

• They contain a variety of substance which promote blood clotting,which causes hemostasis

• Normal blood platelet Count:(200,000-350,000/mm3)

• Control of platelet production in the bone marrow is controlled by Thrombopoeitin

• Life span:8-11 days

•There are 4 main steps involved in the process of hemostasis:

• Vasoconstriction• Platelet plug formation• Coagulation• Fibrinolysis

•MANAGEMENT OF

HEMATOLOGIC DISORDERS

1.ANEMIA

•Introduction•It is by far the most common hematologic condition.

•Anemia, a condition in which the hemoglobin concentration is lower than normal, reflects the presence of fewer than normal RBCs within the circulation.

Causes of anemia

• Loss of RBCs— occurs with bleeding, potentially from any major source, such as the gastrointestinal tract, the uterus, the nose, or a wound.

• Decreased production of RBCs—can be caused by a deficiency in cofactors (including folic acid, vitamin B12,and ron) required for erythropoiesis.

• Increased destruction of RBCs—may occur because of an overactive RES

(including hypersplenism)

TYPES OF

ANEMIA

1. Hemolytic anemia's

• Hemolytic anemia's stem from premature destruction of RBCs, which results in a liberation of hemoglobin from the RBC into the plasma.

• The increased RBC destruction

results in tissue hypoxia.

CLINICALMANIFESTATIONS•The metabolic requirements of

the individual other concurrent disorders or disabilities (eg, cardiopulmonary Disease)

•Special complications or concomitant features of the condition that Produced the anemia

CONT…..

•symptoms other than slight tachycardia on exertion and fatigue.

• In general, the more rapidly an anemia develops, the more severe its symptoms.

CAUSES OF HEMOLYTIC ANEMIAInherited Hemolytic AnemiaInherited Hemolytic Anemia• Abnormal hemoglobin• Sickle cell anemia• Thalassemia• Red blood cell membrane abnormality• Hereditary spherocytosis• Hereditary elliptocytosis• Stomatocytosis• Enzyme deficiencies• Glucose-6-phosphate dehydrogenase (G-

6-PD) deficiency

CONT……

Acquired Hemolytic AnemiaAcquired Hemolytic Anemia

Antibody-relatedAntibody-related• Iso-antibody/transfusion

reaction• Auto immune hemolytic

anemia (AIHA)• Cold agglutinin disease

Not antibody-relatedNot antibody-related• Red blood cell membrane defects• Paroxysymal nocturnal hemoglobinuria (PNH)• Liver disease• Uremia• Trauma• Mechanical heart valve• Microangiopathic hemolytic anemia• Infection• Bacterial• Parasitic• Disseminated intravascular coagulation (DIC)• Toxins• Hypersplenism

DIAGNOSTIC FINDINGS• hematologic studies are performed

• The hemoglobin, hematocrit, reticulocyte count, and RBC indices, particularly the mean corpuscular volume (MCV), are particularly useful.

• Iron studies (serum iron level, total iron-binding capacity [TIBC], Percent saturation, and ferritin), as well as serum.

CONT……..

• Other tests include haptoglobin and erythropoietin levels. Bone marrow aspiration may be performed.

• vitamin B12 and folate levels, are also frequently obtained.

CONT……..

Medical Management•Management of anemia is

directed toward correcting or controlling the cause of the anemia; if the anemia is severe, the RBCs that are lost or destroyed may be replaced with a transfusion of packed RBCs (PRBCs).

•HYPOPROLIFERATIVE ANEMIAS

1. IRON DEFICIENCY ANEMIA

•Iron deficiency is the most common cause of anemia.

•Results in microcytic hypochromic anemia.

Iron is used in:• Hemoglobin.• Heme enzymes, e.g., cytochromes, catalase,

peroxidase• Myoglobin• Metalloflavoprotein enzymes such as xanthine

oxidase

• The mitochondrial enzyme alpha glycerophosphate oxidase and other mitochondrial enzymes.

• Other enzymes and processes

Iron Deficiency – Common Causes

•Inadequate dietary intake of iron especially in:– Infants in the postnatal period

–Young females after menarche

–Adolescents of both sexes–During pregnancy

Iron Deficiency – Common Causes (cont)

• Partial gastrectomy due to ulcers• Blood loss due to:

– Bleeding peptic ulcers– Malignancy– Trauma in which there is excessive bleeding

(includes blood loss through extensive bruising)

• Malabsorption syndromes– Cystic fibrosis

– Celiac Disease (nontropical sprue)

Iron Deficiency – lead toxicity

•Can lead to lead toxicity from pica– Iron deficiency enhances uptake of heavy metals, including lead.

–Lead is still used in all outside house paint.

–Lead is highly concentrated in the first few inches of soil in cities – from car exhaust of 20 years or more ago.

Clinical Manifestations

•If the deficiency is severe or prolonged, they may also have a smooth, sore tongue, brittle and ridged nails, and angular cheilosis (an ulceration of the corner of the mouth).

Diagnostic Findings the diagnosis of iron deficiency

anemia is bone marrow aspiration.

The MCV, which measures the size of the RBC, also decreases. Hematocrit and RBC levels are also low in relation to the hemoglobin level.

CONT….. Typically, patients with iron

deficiency anemia have a low serum Iron level and an elevated TIBC.

The most reliable laboratory findings in evaluating iron deficiency anemia are the ferritin and hemoglobin values.

Medical Management Examination of the gastrointestinal tract

to detect ulcerations, gastritis, polyps, oral cancer.

Several oral iron preparations—ferrous sulfate, ferrous gluconate, and ferrous fumarate—are available for treating iron deficiency anemia.

In these situations, intravenous or intramuscular administration of iron dextran may be needed.

2. ANEMIAS IN RENAL

DISEASE

3.ANEMIA OF CHRONIC DISEASE

4.APLASTIC ANEMIA

DEFINITION

Aplastic anemia is a rather rare disease caused by a decrease in or damage to marrow stem cells, damage to the microenvironment within the marrow, and replacement of the marrow with fat.

Clinical Manifestations

• infection and symptoms of anemia (eg, fatigue, pallor, dyspnea).

•Purpura (bruising) may develop

later .

CONT…

Retinal hemorrhages are common.

•throat infections, cervical lymphadenopathy may be seen.

Diagnostic FindingsA bone marrow aspirate shows an extremely hypoplastic or even aplastic (very few to no cells) marrow replaced with fat

Medical Management

•bone marrow transplantation (BMT)

•peripheral stem cell transplantation (BSCT).

•immunosuppressive therapy.

Medical Management CONT….. A combination of antithymocyte globulin

and cyclosporine is used most commonly.

Supportive therapy plays a major role in the management of aplastic anemia.

transfusions of RBCs and platelets as necessary.

5. MEGALOBLASTIC ANEMIAS

DEFINITION In the anemias caused by

deficiencies of vitamin B12 or folic acid, identical bone marrow and peripheral blood changes occur, because both vitamins are essential for normal DNA synthesis.

FOLIC ACID DEFICIENCY•The folate stores in the body are much smaller than those of vitamin B12, and they are quickly depleted when the dietary intake of folate is deficient (within 4 months).

CONT……

•women who are pregnant, because the need for RBC production is increased in these conditions.

• Folate is found in green vegetables and liver.

VITAMIN B12 DEFICIENCY

A deficiency of vitamin B12 can occur in several ways. Inadequate dietary intake is rare but can develop in strict vegetarians who consume no meat or dairy products.

Another cause is the absence of intrinsic factor, as in pernicious anemia.

CONT……..

• patients with pernicious anemia have a higher incidence of gastric cancer than the general population; these patients should have endoscopies at regular intervals (every 1 to 2 years) to screen for early gastric cancer.

• This occurs in conditions such as Crohn’s disease, or after ileal resection or gastrectomy.

Clinical Manifestations

• The hematologic effects of deficiency are accompanied by effects on other organ systems, particularly the gastrointestinal tract and nervous system.

• Weakness• listlessness, • Fatigue

CONT……

•pernicious anemia develop a smooth, sore, red tongue and mild diarrhea. They are extremely pale, particularly in the mucous membranes.

Diagnostic Findings

• The classic method of determining the cause of vitamin B12 deficiency is the Schilling test, in which the patient receives a small oral dose of radioactive vitamin B12, followed in a few hours.

The intrinsic factor antibody test.

Medical Management

Folate deficiency is treated by increasing the amount of folic acid in the diet and administering 1 mg of folic acid daily.

Folic acid is administered intramuscularly only for people with malabsorptions problems.

Vegetarians can prevent or treat deficiency with oral supplements through vitamins or fortified soy milk.

•NURSING PROCESS: THE PATIENT WITH A CONDITION OF THE ESOPHAGUS

•MYELODYSPLASTIC SYNDROMES (MDS)

DEFINITIONThe MDSs are a group of disorders of the myeloid stem cell that cause dysplasia (abnormal development) in one or more types of cell lines.

CAUSES The most common feature of MDS— dysplasia of the RBCs—is manifested as a macrocytic anemia; however, the WBCs (myeloid cells, particularly neutrophils) and platelets can also be affected.

CONT…

•exposure to chemicals, including chemotherapeutic medications (particularly alkylating agents).

Clinical Manifestations

•Fatigue is often present. Many patients are

asymptomatic, with the illness being discovered incidentally when a CBC is performed for other purposes.

Diagnostic Findings

The CBC typically reveals a macrocytic anemia; WBC and platelet counts may be diminished as well.

Serum erythropoietin levels may be inappropriately low, as is the reticulocyte count.

Medical Management

•allogeneic bone marrow transplantation (BMT), there is no known cure for MDS.

•Chemotherapy is used.•transfusions of RBCs are

required to control the anemia.

CONT…..

platelet transfusions to prevent significant bleeding.

Chelation therapy is a process that is used to remove excess iron acquired from chronic transfusions.

•SICKLE CELL

ANEMIA

DEFINITION Sickle cell anemia is a severe

hemolytic anemia that results from inheritance of the sickle hemoglobin gene.

This gene causes the hemoglobin molecule to be defective. The sickle hemoglobin (HbS) acquires a crystal-like formation when exposed to low oxygen tension.

Clinical Manifestations Patients are always anemic, usually with hemoglobin values of 7 to 10 g/dL.

Sometimes leading to enlargement of the bones of the face and skull.

CONT…..

tachycardia, cardiac murmurs, and often an enlarged heart (cardiomegaly).

Dysrhythmias and heart failure may occur in adults.

Diagnostic Findings

• hemoglobin level, a normal hematocrit, and a normal blood smear.

• sickle cell anemia has a low hematocrit and sickled cells on the smear.

• diagnosis is confirmed by

hemoglobin electrophoresis.

Medical Management

• antiadhesion treatment for vasoocclusive crises.

• sickle cell diseases: BMT, hydroxyurea, and longterm RBC transfusion.

• Hydroxyurea (Hydrea), a chemotherapy agent,

CONT…..

Transfusion therapy may be effective in preventing complications from sickle cell disease.

•chelation therapy.

CONT…..•supportive therapy•sickle cell anemia require daily folic acid replacements

•Infections must be treated promptly with appropriate antibiotics.

CONT…..• intravenous hydration with dextrose

5% in water (D5W) or dextrose 5% in 0.25 normal saline solution (3 L/m2/24 hours)

• Aspirin is very useful in diminishing mild to moderate pain.

• Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful for moderate pain

•NURSING PROCESS: THE PATIENT WITH A SICKLE CELL ANEMIA

•THALASSEMIA

DEFINITION The thalassemias are a group of

hereditary disorders associated with defective hemoglobin-chain synthesis.

highest prevalence is found in people of Mediterranean, African, and Southeast Asian ancestry.

CONT….. Thalassemias are characterized

by hypochromia, extreme microcytosis, destruction of blood elements, and variable degrees of anemia.

The thalassemias are classified into two major groups according to the globin chain diminished: alpha and beta.

CONT…..

The alpha thalassemias occur mainly in people from Asia and the Middle East.

the beta-thalassemias are most prevalent in Mediterranean populations but also occur in people from the Middle East or Asia.

CONT…..

Patients with mild forms have a microcytosis and mild anemia. If left untreated, severe beta-thalassemia (thalassemia major or Cooley’s anemia) can be fatal within the first few years of life.

β Thalassemia Major

• Most severe form. Also known as Cooley’s anemia.• Lab findings: Hgb electropheresis would show

increase in Hgb A2 and F and no normal Hgb A• Signs and symptoms usually present in infants

prior to 6 months of age including irritability, poor feeding, pallor

• Physical findings: severe anemia, jaundice and hepatosplenomegaly, as well as growth retardation

• Management includes life long chronic blood transfusions to replace abnormal Hgb with normal Hgb. Chronic transfusions lead to iron overload which must be removed from the body with chelation therapy to avoid liver and heart failure.

β Thalassemia Minor• Definition: less severe form of Thalassemia

whereby pt does produce some normal Hgb A• Labs: Hgb electropheresis shows decreased

Hgb A and increased Hgb A2 and F. Peripheral smear often shows target cells and basophilic stippling. Iron studies are normal

• Signs and Symptoms are usually absent• Physical exam: normal or may show

splenomegaly• Management: no specific therapy is required.

Iron supplements are not recommended unless iron studies confirm iron deficiency with low Ferritin

Thalassemia• Definition: Genetic disorder of the A-globin chain. 4 loci

of alpha globin and severity of disease depends on number of alpha globin chains genetically affected.

• Incidence: Most common thalassemia with highest incidence in those of Southeast Asian, Mediterranean and African decent.

• Labs: Microcytic RBC, with or without anemia. May have elevated RBC count. Hgb electropheresis may be normal

• Signs and Symptoms: none to mild symptoms of anemia including pallor, fatigue to most severe form causing fetus with hydrops fetalis and stillbirth.

• Physical findings: none to more severe form of disorder causing splenomegaly to most severe form in which all 4 alpha globin chains are affected. This is not compatible with life

• Management: most often –no specific therapy. Genetic counseling recommended for families with history of thalassemias prior to pregnancy

•NAYA BANANANA

Hemolytic anemia• Hemolytic anemia – occurs when the bone

marrow is unable to make up for premature destruction of red blood cells by increasing their production. Hemolysis can be triggered by infection, medications, auto-immune responses, inherited disorders (hemoglobinopathies)

• Treatment depends on cause• Folate is used in all hemolytic anemias to help

stabilize the RBC membrane and decrease destruction

Hemolytic Anemia• Auto-immune hemolytic anemia - Cause is often unknown• Signs and Symptoms: usually very acute and serious with sudden

rapid drop in Hgb leading to fatigue, weakness, SOB. Patient is usually hospitalized

• Exam findings: pallor, tachycardia, tachypnea, jaundice, splenomegaly

• Labs: low Hgb/Hct, + direct Coombs, elevated bilirubin, elevated LDH, low serum haptoglobin, elevated retic count

• Diff Dx: anemia secondary to blood loss, hemoglobinopathy• Treatment is Prednisone at high dose (1mg/kg) to help suppress

the immune system with gradual taper over weeks to months. Splenectomy is often considered followed by other types of immune modulation if hemolysis is not improving. Blood transfusions can be used to off set severe anemia however there is increased risk for antibody development and reactions

• This can be a chronic relapsing disease

Hemoglobinopathies• Hemoglobinpathy: defined as a genetic defect

that results in an abnormal structure of one or both of the globin chains of the hemoglobin molecule

• These disorders are hereditary and some such as sickle cell and G6PD deficiency offered an evolutionary advantage over time by providing immunity to malaria

• There are hundreds of types of hemoglobinopathies and most are not clinically apparent

Sickle cell anemia• Sickle cell anemia – genetic disorder whereby red blood cells

become abnormally shaped like a sickle and cause hemolysis, anemia and veno-occlusion leading to end-organ damage in the spleen, kidneys and liver.

• Incidence: More than 70,000 Americans have sickle cell anemia. And about 2 million Americans - and one in 12 African Americans - have sickle cell trait

• Ethnic groups with sickle cell anemia are usually African American although those of Mediterranean decent can also be affected.

• Labs: CBC showing anemia, adult sickle cell anemia patient usually has elevated WBC and platelet count, elevated retic, elevated bilirubin, Hgb electropheresis shows abnormal Hgb SS (more severe disease) or SC or S-beta Thalassemia

• Signs and symptoms: anemia occurs as abnormal RBC have a shortened life span of only about 15 days compared to the usual 120 days. The RBC are also fragile and lack flexibility leading to veno-occlusion and resulting pain crises, as well as risk for CVA and priapism. Sickle cell veno-occlusive crises can be triggered by infection, dehydration, temperature changes and other stressors to the body.

Sickle Cell Disease

•

Parasite

Sickle cell anemia cont…

• Exam findings: scleral icteris, jaundice, splenomegaly in children (adults usually have either required splenectomy in childhood or have infarcted the spleen causing loss of spleneic function by adult age).

• Diff Dx: other hemoglobinopathies• Treatment: no cure for sickle cell disease other than allogeneic bone

marrow transplant which carries significant risk for morbidity and mortality. Management of this chronic disease includes avoidance of known triggers of veno-occlusive crisis, daily folic acid. Analgesics for painful crisis – patients are often hospitalized for pain crisis for IV narcotic analgesics, hydration with D5W (need free water), anti-inflammatories. Hydrea sometimes used to decrease frequency of pain crises. Vaccination with pneumococcal vaccine q5 years in adults is recommended. Blood transfusions with exchange transfusion is used in serious cases of acute chest syndrome or priapism and are also used in children with sickle cell as prophylaxis to reduce risk of CVA.

•

G6PD deficiency• Glucose-6-phosphate dehydrogenase deficiency – hereditary

enzyme deficiency that leads to hemolysis when certain drugs are ingested that induce oxidant stress on RBCs.

• Incidence - Most common human enzyme deficiency affecting 400 million people worldwide. X-linked recessive disorder with more males affected than females. Occurs more often in blacks

• Signs and symptoms: none unless hemolysis occurs causing anemia with fatigue, SOB, dark urine

• Exam findings: none specific unless having hemolysis• Drugs to be avoided with G6PD def: • Elitec (rasburicase), Methylene blue, Pyridium, Sulfacetamide,

Sulfasalazine, Isobutyl nitrite, Nitrofuratoin, Primaquine, Sulfamethoxazole (Bactrim), Toluidine blue

• *G6PD deficient patient are also allergic to fava beans

G6PD deficiency• Labs: show evidence of hemolysis• Elevated bilirubin levels • Elevated serum LDH • Low serum haptoglobin• hemoglobinuria • Elevated retic count• Low RBC count and hemoglobin • Heinz bodies present on examination of the peripheral

blood smear using special stains • Methylene blue test• Methemoglobin reduction test – used for diagnosis

Anemia of Chronic Disease

• Definition: anemia caused by inflammatory processes occuring due to long-standing infection, neoplastic disease and other inflammatory disorders including rheumatoid arthritis, SLE. These processes block iron transportation from storage sites to the bone marrow factory. Can also be associated with renal failure and decreased erythropoetin production

• Incidence: second most common anemia behind iron deficiency anemia

• Lab findings: CBC showing anemia, low or normal MCV, normal iron studies or low % iron saturation with normal to low TIBC, Elevated CRP or sed rate. Elevated BUN/creatinine

• Signs and Symptoms: fatigue, pallor or asymptomatic if patient has long standing history of RA, SLE, other inflammatory disease, chronic renal failure

• Physical findings: none specific

Anemia of Chronic Disease

• Management: Treat underlying disease

• If unable to determine causative factor refer to hematology for bone marrow biopsy

Sideroblastic Anemia• Definition: anemia characterized by ringed-sideroblasts. Caused by an

enzyme disorder in which the body has adequate iron but is unable to incorporate it into hemoglobin. Iron enters the developing red blood cell; here iron accumulates in the mitochondria giving a ringed appearance to the nucleus (ie: ringed sideroblast). Can be caused by genetic defect, toxin exposure or idiopathic.

• Lab findings: microcytic anemia, basophilic stippling on peripheral smear, usually normal iron studies. Bone marrow biopsy needed if this anemia is suspected based on presentation and peripheral smear. Check blood ETOH, lead levels

• Signs and Symptoms: depend on cause. May have history of ETOH abuse, have altered mental status, abdominal pain or neuropathy, history of treatment for TB, fatigue, pallor, family history

• Physical findings: pallor, abnormal neuro exam with decreased sensory perception, tender abdomen, evidence of ETOH, enlarged spleen or liver, cardiac arrhythmia

• Management: refer to hem for management. Sometimes treated as a Myelodysplastic syndrome with epo growth factors. May progress to aplastic anemia requiring bone marrow transplant

Macrocytic Anemias• Definition: macrocytosis or megaloblastic

anemia is charactized by anemia with elevated MCV

• Incidence: fairly common, seen more in the elderly and those with history of GI pathology or surgeries

• Differential Diagnosis:B12 deficiency, folate deficiency, history of GI disorder or surgery, chemotherapy, chronic alcoholism, hypothyroidism, liver disease (hepatitis), splenectomy (loss of filtration through spleen leads to larger RBCs)

B12 deficiency anemia• Definition: anemia caused by inadequate B12. Can be

due to inadequate dietary intake in vegans or more commonly as a result of loss of intrinsic factor which leads to inability to absorb B12 (pernicious anemia)

• Lab findings: anemia on CBC, MCV elevated usually > 95. Normal or low serum B12 with elevated methylmalonic acid, normal or elevated homocysteine, anti-intrinsic factor antibodies

• Signs and Symptoms: fatigue, pallor, neuropathy, dizziness, hair loss, memory loss/dementia in elderly, history including chronic gastritis, bariatric surgery, auto-immune disorder.

• Physical findings: pallor, tachycardia, abnormal sensory neuro exam, tachypnea

B12 deficiency• Management:• Cyanocobalamin 1000mcg IM

weekly x 4 then monthly usually for life

• B12 is poorly absorbed by the oral route

Pernicious anemia

Folate Deficiency anemia

• Definition: macrocytic anemia caused by lack of folic acid. Common in alcoholics

• Lab findings: CBC with anemia, macrocytic with MCV > 95. Elevated homocysteine with low or normal serum folate

• Signs and Symptoms: fatigue, pallor, unusual diet (no uncooked fruits and vegetables), alcoholism

• Physical exam: none specific• Management: Folic Acid 1mg po qd• Repeat homocysteine in 3 months and if remains

elevated, may increase folic acid to 2mg daily. Treatment usually long term.

Macrocytic RBC

•

Increased marrow production

• Elevated blood cells due to over production in the marrow. Can see overproduction of RBC, WBC, Platelets

Erythrocytosis• Definition: Over production of red blood cells

in the bone marrow. Possible causes are:• Polycythemia Vera (PV)– myeloproliferative

disorder which leads to over production of red blood cells (possibly also in WBC and Platelets) in the bone marrow.

• Incidence in the US: PV is relatively rare, occurring in 0.6-1.6 persons per million. Occurs more in men.

• Work up should be triggered for Hgb > 15 in women and > 17 in men

Polycythemia

•

Polycythemia Vera• Lab tests would include RBC mass, serum

erythropoetin levels –decreased, ABG, bone marrow biopsy usually performed

• History and Exam findings: splenomegaly, red complexion, fatigue, headache, dizziness, assess for clotting

• Diff Dx: elevated RBC from smoking, chronic cardiac or lung disease, high altitude, dehydration

• Treatment – therapeutic phlebotomy 500ml weekly until Hct < 45%, then usually maintenance phlebotomy every 1-3 months

Secondary Erythrocytosis

• Definition: elevated RBC count without other blood cell abnormality. Most common causes are smoking, dehydration and environment of chronic hypoxia

• Lab findings: Elevated RBC with otherwise normal WBC, platelet count. Bone marrow biopsy would show normal erythrocyte precursors, normal epo level

• Diagnosis is often one of exclusion if polycythemia is ruled out

• Signs and symptoms depending on cause. May have symptoms of chronic hypoxia, SOB, oxygen requirement, current tobacco use. High altitude living

• Management: treat underlying cause

Thrombocytosis• Definition: elevated platelet count > 500,000. • Differential diagnosis includes: bone marrow

myeloproliferative disorder as in essential thrombocythemia (ET) or secondary to iron deficiency, splenectomy, infection, malignancy or inflammatory disease

• Incidence: little data• Lab findings: CBC showing elevated platelet count. Iron

studies may show iron deficiency.• Signs and Symptoms: often asymptomatic and found on

routine CBC. In ET patient may experience headaches, TIAs

• Physical findings: eval for evidence of infection, lymphadenopathy, bleeding, thrombosis

Thrombocytosis• Bone marrow needed to evaluate for ET• Usually referred to hematology for work up• Management: treat underlying cause as

applicable• For ET: usually no treatment unless patient is

symptomatic with headaches, TIAs, thrombosis. Treatment usually consists of Anagrelide and or Hydroxyurea. May consider at least ASA for asymptomatic patient with platelet count > 1 million.

Platelets

Thrombocytopenia• Definition: platelet count < 100,000.• Differential Diagnosis: bone marrow dysfunction, malignancy, auto-

immune response, medication, chemotherapy, acute bleeding, acute thrombosis, DIC, HIT, lab error

• Incidence: ITP 100 cases per million people per year with children accounting for half of those. Females more likely to be affected.

• Lab/diagnostic studies: check CBC for other cytopenias, HIT assay, platelet aggregation studies, anti-platelet antibodies, bleeding time, bone marrow biopsy would show elevated megakaryocytes (platelet precursors) in destruction problem however low megakaryocytes in bone marrow production disorder. Check DIC panel. Check cultures of blood, CSF if evidence of infection. Radiographic studies for evidence of DVT/PE. Splenic ultrasound to eval for sequestration

• Signs and symptoms: bruising, bleeding, infectious symptoms, abd pain, fever, recent history of heparin, medication use including recent chemo, thiazides, ethanol, estrogen, sulfonamides, quinine, quinidine, methyldopa, anti-epileptics

Thrombocytopenia• Physical findings: ecchymoses, bleeding, splenomegaly with LUQ pain, SOB,

hemoptysis (with PE), unilateral lower ext edema, + homan’s sign (with DVT), erythema, swelling or other evidence of infection, petechiae

• Management: depending on cause• For ITP (idiopathic thrombocytopenia pupura) need to suppress immune

system since this is an auto-immune response. Usually treat with Prednisone 1mg/kg qd until platelet count back to normal range then slowly taper. Often have relapse. Can also use IVIG, Monoclonal ab therapy with Rituxan.

• For HIT (heparin induced thrombocytopenia) must discontinue all Heparin use (considered Heparin allergic). This response causes patient to be hypercoagulable despite low platelet count so patient must be anti-coagulated with Refludan/Argatroban in hospital setting and then Warfarin as out patient for 3-6 months under care of hematologist

• For medication related drop – discontinue offending medication and platelets should recover rapidly. May be expected drop post chemotherapy if being treated for cancer

• For consumption from acute thrombosis, patient needs to be anti-coagulated and platelets should recover

Thrombocytopenia• Lab Error: can have platelet clumping due to EDTA tube

causing platelet count to appear low – peripheral smear examination can confirm normal platelet count. Blood can be collected in NA citrate tube and re-run to confirm normal count

• For TTP (thrombotic thrombocytopenia purpura) patient will require plasmapheresis to remove inhibitors of VW factor and FFP (fresh frozen plasma) to replace normal VW factor. This is a rare but serious disease that requires care under hematologist.

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Bleeding Disorders• Hemophilia • Definition: genetic disorder characterized by lack of blood

clotting factors. • Hemophilia A: lack of factor VIII (most common). Sex linked

occurring in 1:10,000 males• Hemophilia B: lack of factor IX (Christmas factor) occurring in

1:100,000 males• Labs/diagnostic testing: diagnosed by checking factor activity

levels, CBC, PT/PTT, bleeding time• Signs and symptoms: easy bruising, prolonged bleeding,

painful joints due to hemarthrosis. Older hemophiliacs likely to be infected with HIV due to receiving contaminated factor products

• Physical findings: Ecchymoses, bleeding, edematous painful joints

Hemophilia• Management:• Patients with hemophilia require

replacement of factor when bleeding occurs or sometimes daily based on severity of disease.

Bleeding Disorders• von Willebrand’s disease• Definition: bleeding disorder caused by lack of von

Willebrand’s factor which interferes with platelet function thereby increasing risk for bleeding. Most forms of vW are mild

• Incidence: most common blood clotting disorder occurring in 1 in 800-1000 people

• Labs: normal CBC, bleeding time (prolonged), von Willebrand’s factor assay (reduced), platelet aggregation study (reduced), Ristocetin co-factor (reduced)

• Signs and symptoms: easy bruising, prolonged bleeding after surgery, dental procedure, menorrhagia, epistaxis

• Physical findings: may be normal or may see ecchymoses, petechiae, bleeding

von Willebrand’s Disease

• Management: • Desmopressin (DDAVP) nasal

spray – helps to increase factor VIII and vW factor in the blood

• Fresh frozen plasma/Cryoprecipitate in acute bleeding or surgery

White blood cells• Definition: blood cells that fight

infection. Produced in the bone marrow.

• Elevated = leukocytosis• Decreased = leukopenia.

Leukopenia• Definition: total WBC < 4,300• Differential diagnosis: Infection including bacterial or viral,

chemotherapy, other medications (anti-epileptics, penicillins, sulfonamides, cephalosporins, thiazides, cimetidine, ethanol, immunosuppressants), hematologic malignancy, aplastic anemia, hypersplenism, auto-immune disorders, Felty’s syndrome. Low WBC can be normal in certain populations

• Lab studies/diagnostic testing: CBC, differential, CMP, bone marrow biopsy

• Signs and Symptoms: symptoms of infection, fever, lymphadenopathy, weight loss, night sweats. Check medications

• Physical findings: lymphadenopathy, splenomegaly, may be asymptomatic

Leukopenia• Management: determine

underlying cause• African Americans can have

asymptomatic leukopenia as baseline

Leukocytosis• Definition: WBC > 10,800• Differential Diagnosis: Infection, Chronic inflammation,

Medications (steroids), Recovery post chemotherapy, WBC growth factors (Neupogen, Leukine, Neulasta) used in cancer therapies, hematologic malignancy (leukemia) or bone marrow dysfunction

• Lab/diagnostic tests: CBC with diff, UA/cx if urinary symptoms, CXR if resp symptoms, blood cultures, LAP (leukocyte alkaline phosphotase – elevated in leukomoid reaction, decreased in leukemias)

• Signs and Symptoms: may be asymptomatic, fever, infectious symptoms, cough, SOB, dysuria, skin infection/abcess, rash, weight loss, fatigue, night sweats

• Physical findings: may be none. Erythema, edema, skin rash, lymphadenopathy, cachexia, hepatosplenomegaly, abnormal heart sounds, adventitious lung sounds

Leukocytosis• Management: determine

underlying cause.• If unable to determine cause or if

leukocytosis persists or is rising after treating for infection, hematology consult for bone marrow biopsy

Leukemia• Definition: hematologic malignancy of the

bone marrow whereby abnormal immature cells crowd out normal cells. WBC can be elevated or decreased in leukemia. RBC and platelets can be normal or decreased

• Types of leukemia: most common• Acute Myelogenous Leukemia• Acute Lymphocytic Leukemia• Chronic Myelogenous Leukemia• Chronic Lymphocytic Leukemia

Acute Leukemia• Incidence: about 7000 cases per year in US. 80% are AML,

20% ALL• Etiology is unknown for the most part. Risk factors include

exposure to benzene, radiation exposure and prior treatment with cytotoxic chemotherapy

• Lab findings: CBC can show elevated, normal or low WBC count. Often see anemia at presentation as well as thrombocytopenia. Differential often shows circulating blasts (very immature WBCs). Elevated LDH usually seen. Bone marrow biopsy diagnostic

• Signs and Symptoms: pallor, fatigue, fever, anorexia, weight loss, weakness, palpitations, dyspnea on exertion, infection, rash, bleeding, bruising

Acute Leukemia• Physical findings: Ecchymoses, bleeding,

pallor, tachycardia, tachypnea, hepatosplenomegaly, petechiae, scleral hemorrhage

• Management: Rapid recognition of symptoms as those of leukemia is crucial in acute leukemia as patients can decline rapidly and die from infectious complications or hemorrhage. Referral to hematologist for work up and chemotherapy

Acute Leukemia

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Bone Marrow Biopsy

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Chronic Leukemia• Definition: differs from acute leukemia in that symptoms have

lasted more than 3 months. For CML, the natural history of the disease usually includes a chronic phase lasting 2-4 yrs. Accelerated phase can then occur leading to progressive leukocytosis, anemia and thrombocytopenia. Eventually a blast crisis may ensue in which the disease may behave more like AML requiring aggressive therapy and having a poor prognosis

• Incidence: 4000 cases in US per year for CML• Lab/diagnostic testing: CBC with diff shows elevated WBC often

with basophilia. Anemia often present. Platelets may be normal or low. Usually no peripheral blasts. Marrow blasts elevated or normal. LDH increased. With very high WBC may see hyperkalemia and hypoglycemia. Ultrasound of spleen often done as well as CT scans to help differentiate between leukemia and lymphoma

• Signs and Symptoms: may be subtle easy fatigability, malaise, anorexia, abd discomfort and early satiety from enlarged spleen.

Chronic Leukemia• Physical findings: may be none, or hepatosplenomegaly,

pallor, ecchymoses• Diagnosis made with bone marrow biopsy • Management:• CLL: many times a watch and wait approach is taken and only

treated if WBC doubling time is < 6m or pt becomes symptomatic with progressive abnormal blood counts. At that point chemotherapy would be offered, usually IV therapy depending on pts age and performance status

• CML: Most cases of CML have a genetic 9:22 translocation (termed Philadelphia Chromosome). This type of CML is treated at this time with an oral targeted chemotherapy agent called Gleevec taken daily. There are also new agents being studied for CML that work similar to Gleevec if Gleevec fails.

Lymphoma• Definition: Hematologic malignancy involving

lymphadenopathy as well as possible bone marrow and other solid organ involvement.

• Types: Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma (NHL)

• Incidence: About 8000 new cases of Hodgkin’s disease are diagnosed each year. Usually occurring in young adults. NHL has an incidence of up to 90,000 new cases per year

• Differential Diagnosis: infections causing lymphadenopathy, cat scratch fever, viral infections (HIV), auto-immune disorders, endocrine disorders, sarcoidosis

• Lab/diagnostic testing: CBC with diff, CMP, LDH, Beta 2 microglobulin, lymph node biopsy, bone marrow biopsy, CXR, CT scans, PET scan

Lymphoma• Risk factors for development of lymphoma: EBV, HHV-8,

HTLV-1 viruses have a strong association with development of lymphoid tumors. h.Pylori is a risk factor for development of gastric MALT (mucosa associated lymphoid tissue) lymphoma. Inherited or acquired immunodeficiency disorders also predispose individuals to lymphoma. Increase incidence of NHL in farmers and meat workers. Increased Hodgkin’s disease in wood workers.

• Signs and symptoms: Painless adenopathy, fever, night sweats, weight loss, fatigue (B-symptoms)

• Physical findings: lymphadenopathy in one or more lymph node chains, hepatosplenomegaly, pallor

Lymphoma• Staging: based on number of lymph node

chains involved and location above and or below diaphragm, bone marrow status, extra nodal sites of disease, absence or presence of B-symptoms

• Stages from IA-IVB• Histiologic subtypes also important in

determining aggressiveness of disease which guides treatment plan offered to patient

• Less aggressive NHL: follicular center cell• More aggressive NHL: diffuse large cell

Lymphoma• Management:• Based on stage, and subtype for Hodgkin’s

disease usually IV chemotherapy +/- radiation therapy

• NHL treatment can range from watch and wait approach to very strong IV chemotherapy for the aggressive subtypes. Bone marrow transplant is sometimes needed if patient fails initial chemotherapy for aggressive NHL.

WBC Differential• Five subtypes of WBC noted in differential include:• Neutrophils (segs + bands) AKA granulocytes• these are immature WBC. Important in fighting bacterial infections.

Elevated neutrophils can be caused by acute infection, chemotherapy, stress reaction, burns, tissue necrosis, chronic inflammatory disorders. Decreased neutrophils = neutropenia. Increased risk for infection if neutrophils < 1000. Severe risk for infection if < 500.

• Lymphocytes – elevated or decreased levels can be caused by infection – bacterial or viral, most common cause of increased level >10,000 is CLL. Lymphopenia can be caused by acute stressfull illness (MI, pneumonia) as well as steroid therapy and lymphoma

• Monocytes – increased in infection, granulomatous disease (sarcoid), collagen vascular disease. Decreased in acute stress reaction, pt on steroids, leukemia, chemo and immunosuppressant therapies

• Eosinophils – Increased in allergic diseases, parasitic infections, collagen vascular diseases, from certain medications, leukemia. Decreased in acute stressful illness, steroids

• Basophils – Increased in allergic diseases, CML, chronic inflammatory disorders.

WBC differential cells

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