hematology Flashcards
Composition of blood
92% water and 8% solutes
Plasma
50%–55% of the blood volume
Aqueous liquid with organic and inorganic elements (electrolytes)
Serum
Component of plasma
Clear liquid that remains after blood clots
What is hematopoiesis?
Process of blood cell production in adult bone marrow or in the liver and spleen of the fetus
Two stages:
Maturation which is the cell’s function and proliferation which is the cells division
Hematologic Neoplasms
Leukemia (neoplastic proliferation of blood cells
Lymphoma (proliferation of B or T lymphocytes in lymphoid tissue)
-lymphomas are more common than leukemia
Symptoms: anemia, leukopenia, thrombocytopenia, bone pain, enlarged lymph node, and splenomegaly
Acute Lymphocytic Leukemia (ALL)
Aggressive, more common in children than adults (survival rate is over 80% for children)
- The faster the response to treatment the better the prognosis
Many chromosomal and genetic alterations
- Ph chromosome
Immature T or B cells (lymphoblasts)
Signs and symptoms
- May be nonspecific, anemia, increased bleeding, lymph node enlargements, splenomegaly, increased infection risk, bone pain
- May migrate to CNS
Chronic Lymphocytic Leukemia (CLL)
Most common leukemia type in US
Individuals over 70 years of age, male
Etiology
- Any agent that can disrupt DNA
- Occupational history important
Zeta-chain-associated protein tyrosine kinase 70 (ZAP-70)
- Positive: indicates worse prognosis
- Negative: better prognosis
B cell malignancy
- B-CLL cells: express proto-oncogene bcl2 allowing constant proliferation
- Do not synthesize functional Igs
Typical signs and symptoms of leukemia
Diagnosis
- Lymphocytosis with WBC greater than 20,000/microliter
- Bone marrow biopsy: “smudge cells”—abnormal lymphocytes
Acute Myelogenous Leukemia
Proliferation of undifferentiated myeloid blast cells
Myeloid blasts can invade other tissues
- Skin, lungs, spleen, liver
Risk increased with previous chemotherapy and radiation treatments for other cancers
Commonly: activation of oncogenes such as FLT3, c-KIT
Diagnosis
- CBC, genetic translocation between chromosome 8 and 12 is common
Typical signs and symptoms of leukemia
Chronic Myelogenous Leukemia CML
Overproduction of mature myeloid cells
Age 65 years or older
95% of adults with CML have PhC
Clinical course: 3 phases
- Chronic : Neutrophils begin to lose differentiation
- Accelerated : Neutrophils more undifferentiated
- Blast crisis phase : Myeloid blast cells do not differentiate, large clusters of blast cells spread to other tissues
Usual symptoms of leukemia
- Anemia, increased infection, increased bleeding
- WBC count greater than 100,000 cells per microliter
Diagnosis
- CBC, PCR
Non-Hodgkin’s Lymphoma (NHL)
B, T, or NK cells
Middle aged or older adults; more common in men
Chromosomal translocations (chromosomes 14 and 18)
Some pathogens (HIV, Hep C, H. pylori) associated with NHL development
Immunosuppressive treatment may increase NHL risk
Enlarged, painless lymph node is often first sign
Diagnosis
- Lymph node biopsy
Hodgkin’s Lymphoma
B cell
Most common lymphoma in young adults and children over 10 years of age
Unknown cause, but EBV may play a role
Diagnosis
- Reed-Sternberg cells : malignant B cell with two nuclei (appear as owl eyes),
Signs and symptoms
- No dramatic symptoms, Enlarged lymph node may be present .
Diagnosis
- Lymph node biopsy
Anemia
Major pathophysiologic condition of RBC’s
- Insufficient oxygen delivery to tissues due inadequate healthy, mature RBC’s
- In United States, 6.6% of men and 12.4% of women have anemia
- Some races and ethnic groups have increased risk of some forms of anemia
Example: Sickle cell anemia (SCA) is common in poor socioeconomic countries.
Reticulocytes
Less than 1% of reticulocytes live in the blood
More than 1% of reticulocytes is normal in the bone marrow
More than 1% of reticulocytes in the blood is abnormal
Erythropoietin
In states of hypoxia:
- Kidney releases erythropoietin (EPO)
- EPO simulates bone marrow to produce RBC’s
- Increased RBC’s to compensate for the hypoxia
low oxygen in arterial blood —-> kidney —> erythropoietin stimulates bone marrow —–> bone —-> synthesis of erythrocytes —-> RBC —-> increase oxygen carriage in the blood
RBC Formation and Breakdown
RBC synthesis
- Protein, iron, vitamin B12, folic acid
Hemoglobin
- Composed of heme and globin component
- Metabolized to biliverdin (pigmented)
- Biliverdin broken down to bilirubin (yellow pigment)
Hyperbilirubinemia
- Accumulation of bilirubin in blood
- Can lead to jaundice
-Iron is the main substrate for synthesis of hemoglobulin
RBC —–> Heme + Globin
| |
Iron |
Porphyrin
Biliverdin
Bilirubin
Jaundice
Anemia
Possible etiologies
- Deficiencies (Iron, vitamin B12, folic acid)
- Blood loss (Chronic and acute)
- Hemoglobinopathies
- Medications
- Hemolysis
Signs and Symptoms
- Can be asymptomatic
- GI tract blood loss
- Heavy menstrual periods (menorrhagia)
– Tachycardia
- Jaundice
- Splenomegaly
- Nutritional anemias can cause glossitis, cheilitis, koilonychia, or pica
Anemia Diagnosis
Diagnosis
- Complete blood count: Hb, Hct, RBC count
- Peripheral blood smear: size, shape, color of RBC’s
- Bone marrow aspiration
- Echocardiogram/electrocardiogram
- Nutritional status assessment
Anemia Caused by Decrease in RBC Mass
Adult total blood volume: 5 liters
Can lose 500 mL of blood without serious effects
Loss of 1,000 mL or more:
- Serious adverse effects
- Hypovolemic shock
- Cerebral hypoperfusion
Anemia of Acute Blood Loss
Trauma, hemorrhage, clotting disorder
Diagnosis
- NCNC with reticulocytosis
- FOBT to determine GI blood loss
Signs and symptoms depend on loss of blood volume
- Less than 15%: Orthostatic hypotension and anxiety
- 15%–30%: SNS activity, increased HR; activation of RAAS; release of ADH; restlessness and change in consciousness
- 30%–40%: HR greater than 120 bpm, hypotension, urine output 5 to 15 ml/hr
- Greater than 40%: severe hypotension, decreased consciousness, HR greater than 140 bpm, no urine output
Anemia Cause by Chronic Blood Loss
Causes
- GI bleed (melena—dark stool), menorrhagia, hemolysis
- Medications (NSAID’s may lead to GI bleeding)
Signs and symptoms
Because blood loss is slow, patient may report no noticeable changes
Diagnosis
- Iron depletion often occurs
- Microcytic and hypochromic anemia
- Low iron, low ferritin, increased TIBC
- Low Hgb and Hct
Hemolytic Anemia
Erythrocyte destruction outpaces replacement
Various causes:
- Hemoglobinopathies (Inherited disorder of Hgb)
- Autoimmune disorders, blood transfusion reactions, hemolytic disease of the newborn (HDN), and lead poisoning
- Antibody Reactions
- Warm agglutinin syndrome (IgG antibodies, hemolysis any temperature)
- Cold agglutinin syndrome (IgM antibodies, hemolysis at low temperatures)
- Alloimmune hemolysis (Antibodies against RBC antigens: ex) transfusion reactions, hemolytic disease of newborn)
Signs and symptoms : Typical anemia signs and plus jaundice, dark urine, enlarged spleen
Sickle Cell Anemia
Autosomal hemoglobinopathy- HbS formation problems
Signs of SCA do not appear until fetal Hgb levels begin to decline
After age 10 years, complications increase (Renal disease is a major concern)
SCA causes RBC’s to be fragile and misshapen (Sickle-cell appearance noted on peripheral blood smear)
Misshaped RBC can lodge in capillaries, causing hypoxia in tissue
Chronic damage to liver, spleen, kidneys, and eyes
Hand-foot syndrome (Decreased blood flow to extremities)
Spleen may become damaged, requiring removal
-most common type of hemolytic anemia
Blood Transfusion Reactions
Known as hemolytic transfusion reactions
- Recipient blood-type antibodies attack transfused cells
Mandatory that 2 clinicians double check donor-recipient blood types
If transfusion reaction suspected, stop transfusion
Nonhemolytic febrile reactions (without hemolysis) and mild allergies are the most common transfusion reactions
Anaphylactic reactions can occur
Severe cases
- Hypotension, oozing from the IV site, diffuse bleeding, oliguria, shock, and renal failure
Fever, chills, flushing, burning at IV line, joint pain, tachycardia
Iron Deficiency Anemia
Most common cause of anemia worldwide
Women of childbearing age, infants and children, elderly, vegetarians, and those with GI bleeding
Most common cause: menorrhagia, GI bleed, inadequate iron intake
Signs and symptoms
- Typical anemia signs and symptoms plus : Hair loss, nail changes (koilonychias: spoon-shaped), pica (craving of ice, clay, starch, dirt)
Diagnosis
- CBC, Peripheral blood smear, Serum iron and ferritin are decreased
- FOBT should be done to rule out GI bleed
Vitamin B12 Deficiency (Pernicious Anemia)
Deficiency may develop due to:
Lack of intrinsic factor (IF)
IF needed for B12 absorption
Pernicious anemia: can not absorb needed B12
Dietary deficiency, gastric atrophy, chronic Helicobacter pylori infection, chronic alcoholism, gastric bypass surgery, Crohn’s disease
Folic Acid Deficiency
Risk foctors: pregnant and lactating women, alcohol abusers, elderly, celiac disease sufferers
Deficiency causes megaloblastic anemia
- Folate along with vitamin B12 needed for RBC DNA synthesis
Patients may be asymptomatic
Important to note both folic acid levels and vitamin B12 levels with megaloblastic anemia (as adequate B12 needed for successful folate metabolism)
Lack of Bone Marrow Production of RBC’s
Lack of erythropoietin (EPO)
- Usually due to kidney failure, hypothyroidism may also decrease EPO
Aplastic anemia
Bone marrow fails: anemia, leukopenia, and thrombocytopenia
Caused by infection, radiation, chemicals (benzene), certain drugs or immune disease
Signs and symptoms may develop gradually Diagnosis begins with CBC
Blood transfusions necessary
Hemostasis
Three major steps
1. Vasoconstriction
2. Platelet plug formation
3. Blood coagulation
Thrombus (clot) formation can occur in response to injury or sluggish/stagnant blood flow
- Thrombosis: generation of an occlusive clot
- Clot formation is balanced by process of clot dissolution (fibrinolysis)
Platelet
Megakaryocytes give rise to platelets
- Thrombopoietin: from liver, stimulates platelet formation
- Lifespan 7–10 days, Many platelets sequestered in spleen
Endothelial injury exposes collagen and releases vWF (von Willebrand factor), which attracts platelets
Glycoprotein (GP) IIb/IIIa receptor
- Binds fibrinogen and enhances platelet aggregation
- Some antiplatelet agents work to block this receptor
Thromboxane A2
- Released by platelets, promotes platelet aggregation
Coagulation Factors
Coagulation is a cascade reaction
Calcium and vitamin K also needed
Two pathways
- Intrinsic: damage to vessel
- Extrinsic: damage outside vessel
Both pathways terminate at same steps
- Activation of factor X
- Conversion prothrombin to thrombin
- Conversion fibrinogen to fibrin
Increased Platelet Number and Activity
Some causes of increased platelet number:
- Splenectomy
- Myeloproliferative disorder
Paradoxical bleeding may occur if platelets are dysfunctional
Increased platelet activity results from endothelial injury and sluggish blood flow
- Smoking, hyperlipidemia, diabetes increase risk
Primary thrombocytosis- bone marrow issue
Secondary thrombocytosis- cancer, inflammation, infection
Increased Coagulation Activity
Stasis of blood flow
- Immobile, sedentary, atrial fibrillation
- DVT: deep vein thrombosis that may travel to lungs and may cause pulmonary embolism
Increase coagulation factors
- Estrogen: Women age 35 years and older may need to consider other alternatives to oral contraceptives
- Cancer: tumor cells may secrete prothrombotic factors
Decrease antithrombotic factors
- Estrogen
- Some types of cancer tumor cells secrete antithrombic factors
Antiphospholipid Syndrome
Multiple clots form with unknown etiology
Autoimmune diseases increase risk
Antiphospholipid antibodies are present
Increased risk of stroke, MI, renal failure, miscarriage
Catastrophic antiphospholipid syndrome - Multiple organ failures due to multiple clots
Decreased Platelet Number and Activity
Decreased platelet production
- Suppression of bone marrow (aplastic anemia, leukemia, radiation exposure)
Excessive pooling of platelets in spleen
Decreased platelet survival
- Antiplatelet antibodies
- Mechanical injury
Assessment of Bleeding and Clotting Disorders
Bleeding : Nosebleeds, bruising, etc.
Clotting: DVT, pulmonary embolism
Review medications for possible effects
Increase clotting : Some cancers, atherosclerosis, atrial fibrillation
Decrease clotting
Leukemia, recent infection, autoimmune disease
Lifestyle choices: Smoking, alcohol abuse
Hemostasis Disorders and Diagnsosis
CBC, peripheral blood smear, PT, INR, aPTT
- Anticoagulants prolong clotting time, so PT, INR, and aPTT should be higher than normal
- Normal INR = 1, so anticoagulant usage should have INR greater than 1 (usually 2 to 3)
Anticoagulants
Unfractionated heparin, Unfractionated heparin, Fondaparinux (Factor Xa inhibition ), Warfarin, Thrombolytic Agents
