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148 Cards in this Set
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Initial Laboratory evaluation of suspected bleeding disorder
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CBC w/platelet count (detects shortage of platelets)
Peripheral blood smear (helps r/o pseudothrombocytopenia and look for abnormally shaped platelets) PT (measures the factors of the extrinsic and common pathways) PTT (Measures the factors of the intrinsic and common pathways) Platelet Function Analyzer-100 (stimulates platelet plug formation by passing blood through aperture w/collagen/epi and collagen/ADP; Screens for von Willebrand's DZ) |
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Peripheral Blood Smear
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helps r/o pseudothrombocytopenia and look for abnormally shaped platelets
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PT
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Measures the factors of the extrinsic and common pathways
Deficiencies (most notably factor VII) will prolong the PT - may be Vitamin K deficient* |
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PTT
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Measures the factors of the intrinsic and common pathways
Deficiencies of these factors, including F VIII (Hemophilia A) and F IX (Hemophilia B) prolong the PTT. Factor VIII = low in von Willebrand's Disease --> Prolonged PTT Presence of Inhbitiors (autoantibodies) prolong PTT --> attach to factor --> rendered useless for clot formation --> MC inhibitors are the Factor VIII inhibitors and the Lupus Anticoagulant. |
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Factor VIII Inhibitor
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Should be suspected in anyone who has no h/o bleeding, but develops significant bleeding and has a prolonged PTT
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MC Factor Inhibitors
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Factor VIII Inhibitor and Lupus Anticoagulant
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Platelet Function Analyzer (PFA)-100
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Stimulates platelet plug formation by passing blood through aperture w/collagen/epi and collagen/ADP.
(+) von Willebrand's/Plate Function d/o's: Time required for aggregation is prolonged Prolonged time JUST to collagen/epi - suggests a drug effect, ex aspirin. Screens for von Willebrand's DZ *SUPERIOR to bleeding time in detecting von Willebrand's disease * A negative result should not preclude further testing for von WIllebrand's DZ |
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Mixing Study
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Determines if the patient has a clotting factor deficiency or an inhibitor to a factor.
One part pt's blood + 1 part normal blood --> Inhibitor in pt's blood --> disables the Factor in normal blood PTT stays prolonged --> does NOT "correct" * Then...perform Inhibitor assay - determine which Inhibitor is present If the mixing study --> PTT normalizes/corrects --> indicates Factor deficiency! ** Then.... perform Factor Assay to identify which factor is deficient. |
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Inhibitor Assays
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Performed after a mixing study that shows positive for the presence of an Inhibitor to a Factor. (Prolonged/Didn't correct)
Determines which Inhibitor is present. |
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Factor Assay
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Performed after a mixing study that shows positive for the presence of an Factor Deficiency. (Corrects/Normalized w/mixing)
Used to identify which factor is deficient. |
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Indications to Refer for a bleeding d/o
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1) Lab work-up non-diagnostic for bleeding d/o, but high suspicion from person/FHX --> Hematologist
2) IF von Willebrand's DZ, a Factor VIII Inhibitor, or Factor Deficiencies are discord --> Referral is based on diagnosis and severity, as well as comfort level of the PROVIDER. 3) If pre-op History/PE/Routine Labs = abnormal --> delay surgery --> refer/work-up for cause |
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MC inherited bleeding d/o
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Von Willebrand's Disease
Use bleeding score system to screen for this disease. Results from a qualitative or quantitative defect in von WIllebrand's factor, which is required for platelet aggregation. |
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Quantitative Platelet Disorders
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Findings: Bleeding, bruising, petechia, or purpura
Consider ITP, TTP, Malignancy, Viral DZ |
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Functional Platelet Disorders
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Consider in a patient w/lifelong h/o bleeding despite (-) lab workup
Consider Glycoprotein d/os, Von Willebrand's DZ |
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Hemophilia A or B
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Classically presents w/joint or soft-tissue bleeding
FHX of bleeding in men (skips generations) Factor VIII or IX defiencies |
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Factor Inhibitors
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Presenatation similar to hemophilia,
Onset is typically sudden w/no pt or FHX of bleeding |
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Leukemia Labs (General)
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Abnormal CBC or peripheral blood smear
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Disseminated Intravascular Coagulation - Lab results
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Bleeding from multiple sites; prolonged PT and PTT
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Normal Pt, Normal PTT
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--> perform Platelet Function Analyzer 100
Prolonged aggregation w/PFA100? Yes: eval for von Willebrand's No: Further eval based on clinical suspicion -> if only prolonged w/collagen/epi -> drug effect |
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Normal PT, Abnormal PTT
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--> Perform Mixing Study w/PTT
Does PTT correct? Yes: Factor VII, IX, XI assays; if VIII low, work up for Von Willebrand's No: Screen for Inhibitors (Lups and Factor VII Inhib) |
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Abnormal PT, Abnormal PTT
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Consider DIC
--> Then consider factor assays for factor deficiencies *Verify no use of warfarin/heparin and no liver disease |
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Severely Microcytic Anemia
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[MCV] < 70
d/t either Iron Deficiency (dec ferritin), Anemia of Chronic Disease (inc ferritin) or Thalassemia |
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Severely Macrocytic Anemia
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MCV > 125 fL
Almost always d/t Megalobastic Anemia (alcoholism) or myelodysplasia or Vitamin B12/Folate deficiency |
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Iron Deficiency Anemia
Description and Causes |
- MC cause of anemia worldwide
- (10-15mg of dietary Iron daily; 10% absorbed) - Most important cause = blood loss, esp. GI --> Prolonged aspirin use, or anti-inflammatory drugs may cause it w/out even a lesion --> search for bleeding source, if other sites of blood loss are r/o (menorrhagia/uterine/blood donations, etc) - Menstrual Blood Loss, avg = 50mL --> May be 5x the average! Heavy menstruation --> Must absorb 3-4 mg from diet daily --> most likely require supplementation - Pregnancy - Requirements increased to 2-5 mg of Iron per day during pregnancy and lactation --> Normal diet can't substitute --> requires medicinal iron --> Repeated pregnancy - may cause IDA --> medicinal tx -Celiac DZ - Decreased Iron Absorption - After Surgical Resection of stomach - decreased Iron absorption - Chronic Hemoglobinuria - uncommon - Paroxysmal Nocturnal Hemoglobinuria - intravascular hemolysis |
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IDA
Labs |
3 Stages of development
Early: depletion of iron stores. --> No change in RBC size/MCV normal --> Serum Ferritin abnormally low (<12 mcg/L) ***May rise in response to inflammation --> does not exlude dx 2)RBC formation will continue w/deficient supplies of Iron --> Serum iron values decline to <30 mvc/dL --> Transferrin levels rise --> Transferrin saturation of < 15% 3) MCV falls Blood smear: hypo chromic microcytic cells -->Progression --> Anisocytosis (varied size); Poikilocytosis (varied shape; Bizarre Peripheral Blood Smear w/severely hypochromic cells, target cells, hypocrhomic pencil-shaped cells, and small #s of nucleated RBCs - Platelets usually increased! |
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IDA
Sx |
Only symptoms = those of the anemia itself -->
Easy fatigability, tachycardia, palpitations, and tachypnea on exertion. Severe deficiency causes: skin/mucosal changes. --> smooth tongue, brittle nails and cheilosis (fissuring lips/mouth angles) --> Dysphagia d/t formation of esophageal web. --> Pica -craving of non-Iron foods (ice, chips) |
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Nonmegaloblastic Anemias
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Myelodysplasia, chemotherapy
Liver disease Increased reticulocytosis Myxedema |
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Decreased Production Anemias
Hb Synthesis Lesion |
Hb Synthesis Lesion:
IDA Thalassemia ACD |
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Decreased Production Anemias
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Hb Synthesis Lesion:
IDA Thalassemia ACD DNA synthesis Anemia: Megaloblastic Anemia Stem Cell lesion: Aplastic Anemia; Myeloproliferative Leukemia Bone Marrow Infiltration: Carcinoma, Lymphoma Pure Red Cell Aplasia |
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Decreased Production Anemias
d/t: Stem Cell lesion |
Aplastic Anemia; Myeloproliferative Leukemia
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Abnormal PT, Abnormal PTT
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Consider DIC
--> Then consider factor assays for factor deficiencies *Verify no use of warfarin/heparin and no liver disease |
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Severely Microcytic Anemia
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[MCV] < 70
d/t either Iron Deficiency (dec ferritin), Anemia of Chronic Disease (inc ferritin) or Thalassemia |
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Severely Macrocytic Anemia
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MCV > 125 fL
Almost always d/t Megalobastic Anemia (alcoholism) or myelodysplasia or Vitamin B12/Folate deficiency |
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Iron Deficiency Anemia
Description and Causes |
- MC cause of anemia worldwide
- (10-15mg of dietary Iron daily; 10% absorbed) - Most important cause = blood loss, esp. GI --> Prolonged aspirin use, or anti-inflammatory drugs may cause it w/out even a lesion --> search for bleeding source, if other sites of blood loss are r/o (menorrhagia/uterine/blood donations, etc) - Menstrual Blood Loss, avg = 50mL --> May be 5x the average! Heavy menstruation --> Must absorb 3-4 mg from diet daily --> most likely require supplementation - Pregnancy - Requirements increased to 2-5 mg of Iron per day during pregnancy and lactation --> Normal diet can't substitute --> requires medicinal iron --> Repeated pregnancy - may cause IDA --> medicinal tx -Celiac DZ - Decreased Iron Absorption - After Surgical Resection of stomach - decreased Iron absorption - Chronic Hemoglobinuria - uncommon - Paroxysmal Nocturnal Hemoglobinuria - intravascular hemolysis |
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IDA
Labs |
3 Stages of development
Early: depletion of iron stores. --> No change in RBC size/MCV normal --> Serum Ferritin abnormally low (<12 mcg/L) ***May rise in response to inflammation --> does not exlude dx 2)RBC formation will continue w/deficient supplies of Iron --> Serum iron values decline to <30 mvc/dL --> Transferrin levels rise --> Transferrin saturation of < 15% 3) MCV falls Blood smear: hypo chromic microcytic cells -->Progression --> Anisocytosis (varied size); Poikilocytosis (varied shape; Bizarre Peripheral Blood Smear w/severely hypochromic cells, target cells, hypocrhomic pencil-shaped cells, and small #s of nucleated RBCs - Platelets usually increased! |
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IDA
Sx |
Only symptoms = those of the anemia itself -->
Easy fatigability, tachycardia, palpitations, and tachypnea on exertion. Severe deficiency causes: skin/mucosal changes. --> smooth tongue, brittle nails and cheilosis (fissuring lips/mouth angles) --> Dysphagia d/t formation of esophageal web. --> Pica -craving of non-Iron foods (ice, chips) |
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Nonmegaloblastic Anemias
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Myelodysplasia, chemotherapy
Liver disease Increased reticulocytosis Myxedema |
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Decreased Production Anemias
Hb Synthesis Lesion |
Hb Synthesis Lesion:
IDA Thalassemia ACD |
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Decreased Production Anemias
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Hb Synthesis Lesion:
IDA Thalassemia ACD DNA synthesis Anemia: Megaloblastic Anemia Stem Cell lesion: Aplastic Anemia; Myeloproliferative Leukemia Bone Marrow Infiltration: Carcinoma, Lymphoma Pure Red Cell Aplasia |
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Decreased Production Anemias
d/t: Stem Cell lesion |
Aplastic Anemia; Myeloproliferative Leukemia
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Serum Ferritin
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determines the amount of iron in the serum, commonly used as an index of available Iron. Normal is about 35 g/L in women and 100 g/L in men. If less than 12 g/L, iron stores in the marrow are depleted.
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TIBC
Total Iron Binding Capacity |
In the serum, a carrier (Transferrin) binds iron. This rises and falls in a diurnal pattern and is measured in the morning on a fasting patient. Normal range is 75-150 g/dL .(TIBC is a value obtained by adding the serum iron to the amount of additional iron the sample can bind.) Transferrin is normally about one third saturated and a higher TIBC is indicative of iron depletion.
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Vitamin B12 and Folate
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Vitamin B12 and Folate are essential co-enzymes for the DNA synthesis portion of cell reproduction. Deficiency causes Pernicious Anemia. Vitamin B12 (Cobalamin) is found in the plasma and in the tissues. Plasma levels are measured and should be > 800 pg/ml. Deficiency is < 100 pg/ml
Folate (Folic Acid) fluctuate significantly with diet and normals are 2-14 ng/ml |
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3 Underlying diseases of Anemia
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Uremia
Liver DZ Hypothyroidism |
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Anemias from Decreased Erythropoiesis
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IDA
B12/Folate Deficiency Blood Loss (acute v. chronic) Aplastic |
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• Characteristic anemia symptoms
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– Easy fatigability
– Tachycardia and palpitations – Tachypnea on exertion |
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IDA Specific Sxs (usually occur late)
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– Atrophic glossitis (“sore tongue”) and cheilosis
Cracking along mouth lines – Brittle and ridged nails – Koilonychia (“spoon nails”) – Splenomegaly – Pica (craving for abnormal substances such as ice, starch, clay or lettuce) |
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Labs - IDA
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• CBC
– Microcytic, hypochromic cells → Hypochromic – cell loses it’s thick rim – start to fill out from middle – Anisocytosis (variation in RBC size) – poikilocytosis (variation in RBC shape –Poke the cell changes it’s shape) • Serum Ferritin – Decreased to < 12 µg/L. (*) (Highly reliable if less than 30 µg/L ) → although 30 is considered within the normal range, still assume it’s IDA! TIBC = Normal Bone Marrow - Absence of Iron |
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Pernicious Anemia
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Autoimmune d/o
Think of a caucasian female over 40yo is rare in patients <35 years old. It is most common in older, white females because of the genetics associated with its development. It is the most common cause of Vitamin B12 Deficiency • Since vitamin B12 is present in all foods of animal origin, other types of dietary vitamin B12 deficiency is extremely rare and seen only in vegans—strict vegetarians who avoid all dairy products as well as meat and fish. |
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Folate Deficiency
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• By far the most common cause of folate deficiency is inadequate dietary intake – Alcoholics, anorectics and those who do not eat fresh fruits or vegetables are at risk
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Presentation of
B12/Folate Deficiency Anemia |
• General symptoms of anemia
– weakness, malaise and light-headedness – pallor, + cyanosis • Symptoms related to abnormal DNA/RNA – Sore mouth, Cheilosis, Glossitis • “Lemon-yellow” skin (Icterus) • Neurologic Symptoms : Listed in order of progression – Paresthesias and loss of proprioception – Balance and gait problems → may bump into thins, have falls which leads to minor injuries – Confusion and dementia This is more common with Vitamin B12 |
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Labs of B12/Folate Deficiency Anemia
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• CBC
– Macrocytosis (MCV . 100) with normal hemoglobin – Decreased thrombocytes and white blood cells – Reticulocyte count is normal • Blood Smear – macrocytic, normochromic cells with variable size and abnormal shapes. (anisocytosis and poikilocytosis.) Howell-Jolly bodies, Pappenheimer bodies and nucleated RBCs can appear on blood smear. • Bone Marrow – Megaloblatic cells with variable maturation of the nucleus and cytoplasm within the cell • Schilling Test = $$$$ - test of vitamin B12 absorption over 24 hours (24 urine collection |
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Schilling Test
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test of vitamin B12 absorption over 24 hours (24 urine collection)
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Pernicious Anemia Tx
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• Pernicious Anemia is treated with B 12 injections. These are continued for life
100 mcg SQ or IM QD x first week, q. weekly x 1 month and q. monthly for life |
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Folate/B12 diet deficiency Tx
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• Those with Vitamin B12 or Folate deficiency due to diet receive oral supplementation.
B12 defic Oral or sublingual 1mg QD x life, once intial defic is corrected Neuro sxs will reverse if present < 6 mos |
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ACD
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• The clinical presentation is that of the underlying disease plus feature consistent with anemia
– weakness, malaise and light-headedness – pallor, + cyanosis |
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ACD Labs
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CBC
normocytic, Retic count is not sig increased or decreased Hct rarely < 60% (except in CKD) Blood smear = normal |
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Tx of ACD
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Tx the underlying cause
If SEVERE - Parenteral recombinant erythropoietin - RBC transfusion Tricky: May present like secondary to Iron deficiency Elderly may not eat as well or lose their appetite → Don't assume the microcytic anemia is due to IDA This is often missed. |
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Blood Smear
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Blood smears review the whole blood on a slide in order to evaluate the shape of the erythrocyte as well as look for evidence of cell destruction or increased red cell production.
The blood smear also will demonstrate various inclusions within the cell when stained which may be useful diagnostically. |
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Bone Marrow Bx
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• Since most of the cells which differentiate into blood cells are in the bone marrow, examination of the marrow can be revealing of a multitude of conditions such as atrophy or loss of stem cells, iron deposition or malignancies.
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TIBC
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– Total Iron-Binding Capacity - In the serum, a carrier (Transferrin) binds iron. This rises and falls in a diurnal pattern and is measured in the morning on a fasting patient. Normal range is 75-150 g/dL .(TIBC is a value obtained by adding the serum iron to the amount of additional iron the sample can bind.) Transferrin is normally about one third saturated and a higher TIBC is indicative of iron depletion
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CBC
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For evaluation of red blood cells, the CBC uses:
– Red Blood Cell Count – Hematocrit – Hemoglobin – Red Cell Indices • Mean Corpuscular Volume (MCV) Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC) – Reticulocyte Count |
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Blood Loss Anemia LABS
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• The CBC Results depend on the Rapidity of development.
– Acute • May be normal initially, then dilution from fluid shifts to the vascular network causes a dilution effect. • Reticulocyte count rises – Chronic • Looks like Iron deficiency anemia! |
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Aplastic Anemia
Etiology |
Injury to or suppression of the hematopoietic stem cell →
→ Hypoplastic bone marrow fails to produce mature blood cells → Pancytopenia = all cell lines are down |
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Pancytopenia (Aplastic Anemia)
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Anemia caused by destruction or disruption of the bone marrow is characterized by loss of erythrocytes and all other cell types (including granulocytes and platelet) - this is termed pancytopenia.
Although it is uncommon, it is a serious condition if which remains untreated death occurs from hemorrhage (low platelet) or infection (low white cells) within a few months |
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Presentation of Aplastic Anemia
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• General symptoms of Anemia
– weakness, malaise and light-headedness – pallor, + cyanosis, “cold” • Symptoms of Leukopenia – Infection • Symptoms of thrombocytopenia – Purpura and petechiae Should NOT have symptoms of bone pain, enlarged liver or spleen or lymphadenopathy |
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Labs for Aplastic Anemia
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• CBC = PANCYTOPENIA
– severe normochromic to macrocytic anemia – Leukopenia and thrombocytopenia – Reticulocytes are absent The hallmark of aplastic anemia is pancytopenia. However, early in the evolution of aplastic anemia, only one or two cell lines may be reduced. • Blood Smear – No special abnormalities • Bone Marrow – HYPOCELLULAR (STEM CELLS NOT WORKING) – few cells, no stem cell colonies and replacement of the marrow by fat. |
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Mgmt for Aplastic Anemia
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• MILD
• SUPPORTIVE CARE • RBC AND PLATELET TRANSFUNSIONS WHEN NECESSARY • ABX FOR INFXN • SEVERE • YOUNG ADULTS – BONE MARROW TRANSPLANT (TX of CHOICE) • ADULTS > 60 YO = IMMUNOSPRESSION • UNTREATED = DEATH - Depend on cause and severity - Replacement of the stem cell or suppression of the autoimmune response are the mainstays of treatment (along with supportive care) - Bone marrow transplantation - Immunosuppression with antilymphocyte globulin - Administration of androgens AVOID: toxins; aspirin, platelet aggregates Tx infections aggressively. Platelet transfusions = possible; but rare. |
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Reticulocytosis
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Demonstrates accelerated loss of RBCs
Autoimmune Hemolytic Aneima Warm Hemolytic Cold Agglutinin Sickle Cell Syndromes Thalassemia Syndromes Will demonstrate liver and spleen symptoms |
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Hemolytic Anemia
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• Decrease of the life span of the normal erythrocyte, without increased bone marrow production leads to anemia. There are multiple causes.
• Hemolysis is the process of erythrocyte breakdown, therefore these are termed Hemolytic anemia |
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Intrinsic Hemolytic Anemia
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resulting from a defect in the erythrocyte itself, usually hereditary
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Extrinsic Hemolytic Anemia
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- normal erythrocyte which acquires an external destructive factor
– Causes are generally due to immunoglobins • “Warm Type” is related to IgG or idiopathic and the spleen destroys the tagged cells (Key disease -Autoimmune Hemolytic Anemia) • “Cold type” is related to IgM (infections) or an idiopathic version seen with chronic disease in patients > 50 y/o (Key disease - Cold Agglutinin Disease) |
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Presentation of Hemolytic Anemia
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- Same for Warm and Cold types
- Anemia features – weakness, malaise and light-headedness – pallor, + cyanosis - Hemolytic features – + mild jaundice, abdominal pain and fever – Dark colored urine Rapid onset Fatigue and dyspnea May present w/angina or CHF! On PE - In severe “Cold Type” - livedo reticularis and acrocyanosis with exposure to cold |
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Labs: Hemolytic Anemia
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•CBC
–Hct varies, but may be life threatening (<10%) –low hematocrit and RBC count –Reticulocytosis –Spherocytes SEVERE Nucleated RBCs •Coombs Test ***** (antiglobulin) = Basis for Dx Direct test = Positive = AIHA Indirect = AIHA May or may not be +; Cold - only the Complement is +. |
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Coombs' Test
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Used to show Ag-Ab runs, differentiation of types of hemolytic anemias, testing for erythroblastosis fettles and RBC sensitization by drugs or blood transfusions.
Cired: adding antihuman globulin serum to a client's washed RBC's and observing for agglutination. --> signals the presence of previously undetected IgG Abs, Complement, or Immunoglobulins on the surfaces of their RBCs. The Ab's are left over from incomplete Ag-Ab runs and are present, but invisible, on the RBC surface. Coomb's test: causes complete rxn of the Ag-Ab Direct Test +: AIHA (Warm Hemolytic) Indirect Test + :Cold Hemagluttinin (ONLY the Complement rxn will be +) (-): Nonautoimmune Hemolytic Anemia Direct IgG - Antiglobulin containing only anti-IgG = specific to AIHA than Indirect Coombs Test: Tests for unexpected Ab's to group O RBCs; or ags to RhDu, Kell, Duffy, pre-transfusion testing; and rare Ab's. |
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Hemolytic Anemia Referral
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Tx of underlying Dz + Protective measures for spleen:
Refer ASAP Get them started on Prednisone Pack - to suppress immune system If prednisone = ineffective --> Splenectomy |
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Cold Agglutinin Anemias
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Mostly idiopathic
Looks the same as other hemolytics Jaundice - in response to cold temp Mottled or numb fingers Coombs: Positive for Complement only Keep them out of the cold! |
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Sickle Cell DZ v. SC Trait
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- Sickle Cell Anemia results from a genetic disorder with the production of an abnormal hemoglobin. It is recessive and occurs when both parents carry the gene. This occurs in 0.1-0.2% of Blacks in the United States.
- If one parent does not carry the gene, the patient has Sickle Cell Trait. 8-9% of Blacks carry the gene singly. SC Trait - hetero; no sxs until late in life SC - homo; Sxs in first year of life; chronic extravascular hemolysis |
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Presentation of SC Anemia DZ
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- History = +FX
- Precipitating factors – decreased hydration, decreased oxygenation and infection ALSO extreme tempteratures - Begins in childhood - Symptoms of hemolytic anemia Acute episodes of vascular occlusion (“Attack”) = Acute painful - Ruptured spleen - Crisis |
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Complications of SC Anemia
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Osteomyelitis
Thromboembolism Ulcers in legs Heart failure Stroke Death from organ failure |
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Labs of Sickle Cell Anemia
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- CBC
– Low hematocrit, low RBC count with reticulocytosis, Hemoglobin normalizes at 6 - 9 g/dL – Elevated white count – Thrombocytosis - Blood Smear – irreversibly sickled cells, Target cells, – Howell-Jolly bodies = always think Sickle cell – , target response The abnormal shape of the cell is easily seen on blood smears, but may require a precipitating agent. - Hemoglobin Electrophoresis – hemoglobin S present Hemoglobin eletrophoriesis demonstrates the abnormality well. |
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Management of Sickle Cell Anemia
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REFER
- Control of precipitating factors - Prophylaxis – Folic Acid supplements Transfusions during crisis - Pneumococcal and influenza vaccination Keep well hydrated - Acute Painful episodes – Norco – give generous analgesics - Crisis - Oxygen - Prenatal Counseling |
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Thalassemia
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Hypocrhomic/microcytic = compare w/IDA
• Also an inherited trait or disease with hemoglobinopathy. • Commonly seen in those of Mediteranean, African or Southeast Asian ancestry • Symptoms usually begin in childhood since it is a genetic disorder. • It can co-exist with Sickle Cell anemia |
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Thalassemia Major
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occurs when both parents have the gene
– Symptoms begin in childhood, usually within the first year of life – Requires transfusions for management, usually die between ages 20-30 (also called Cooley anemia, Mediterranean anemia, or von Jaksch anemia) They are symptomatic by 12 months of age (often as early as 3 months) Severe anemia Complications are usual: M/C due to iron overload Craniofacial Features onset within the first 6 months of life represents medullary hematopoiesis mandibular prominence - prominent malar maxillary overbite eminences depressed nasal bridge - frontal bossing Extramedullary Hematopoiesis hepatomegaly/hepatosplenomegaly peripheral lymphadenopathy |
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Thalassemia Intermedia
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have a milder form of the disease.
– Symptoms are milder and occur when under stress – Also requires transfusions but not as frequently, live longer but not normal life expectancy 2-10% of Beta Thalassemics They are symptomatic by 2-4 years of age (but CBC may show anemia during the first year of life) Moderate anemia Complications are usual: hepatosplenomegaly growth failure jaundice thalassemic facies |
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Thalassemia Minor
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have only one parent with the gene
– May be asymptomatic except for a mild hemolytic anemia – Normal life expectancy The majority are asymptomatic and not anemic Women may become severely anemia during pregnancy Complications (in a minority): bone changes cholelithiasis leg ulcers splenomegaly***** |
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Presentation of Thalassemia
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- Signs of severe anemia
- Enlargement of bone marrow with bony deformities – Skull and face – thick ridge on xray – Long bones – Spine - Sign of Hemolysis – jaundice – Hepatosplenomegaly – Gallstones (cholelithiasis) - Leg ulcers |
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Complications of Thalassemia
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- The most frequent complication is due to iron overload.
– Skin darkening (iron-stimulated melanin production) – Sideroblastic Cardiomyopathy (Arrhythmias, Heart failure, recurrent pericarditis) – Hepatic fibrosis and cirrhosis (often by age 5) – endocrine disorders (diabetes mellitus, hypothyroidism, hypoparathyroidism and hypopituitarism) - Death results primarily from these complications, age varies due to the volume of transfusions needed. |
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Thalassemia: Labs
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- CBC
– anemia with microcytosis (Level of anemia and microcytosis varies by the degree of the thalassemia) – reticulocytosis - Blood Smear – hypochromia, target cells, + poikilocytosis, anisocytosis, target cells or basophilic stippling. - Hemoglobin Electrophoresis – Variable amounts of Hemoglobin F – Elevation of hemoglobin A2 |
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Thalassemia Tx
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Folate Supplementation
Oxidative Supplementation NOOO IRON! Transfusion every 2-3 wks SE: urticaria, fever, Hep B, Hypersplenism, hemosiderosis Consider splenectomy Experimental: Iron chelating agents (Desferrioxamine) over 8 hrs, min 5d/wk The goal is to achieve an iron balance in growing children and a negative iron balance in older or symptomatic patients. Ascorbic acid supplementation to keep ascorbic acid levels normal (when iron chelation is optimal) . It is initiated between 4-5 years of age when serum ferritin is greater than 1000 ng/cc and transferrin is >50% saturated – Allogenic bone marrow transplantation used since 1982 risks: mortality, chronic graft vs host disease |
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Erythrocytosis "Polycythemia"
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- It can occur as a compensatory mechanism in hypoxia (such as living at high altitude) or as a neoplasm of the bone marrow colonies. Then they will have increased WBCs and thrombocytes.
- It is characteristically found in patients over age 40. PV Acquired myeloproliferative d/o All cell lines are up, but the RBCs will STAND OUT (WAY UP) -→ ddx from the malignancies overproduction of all 3 hematopoietic cell lines In general: think blood doping → cyclists increase their RBCs 1) primary – idiopathic 2) secondary →compensatory mechanism takes place living at altitude neoplasm of bone marrow colonies |
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Presentation of Polycythemia
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• Signs and symptoms are related to excessive intravascular volume and viscosity
– Headache, blurred vision (due to retinal engorgement) Dizziniss, tinnitus, blurred vision and fatigue – Thrombosis (strokes, retinal occlusions, spleen) – Epistaxis – Generalized pruritis following a bath or shower = histamine release with too many RBCs Palpable splenomegaly Thrombosis (d/t increased viscosity and increased platelet count) |
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Polycythemia Labs
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• CBC = HALLMARK
– Hematocrit above 60% is pathognomonic if not dilutional. Men > 54% Women: Hct > 51% – Leukocytosis and thrombocytosis • Blood Smear – Normal cells with increased mass • Bone Marrow – Hypercellular with Panyhyperplasia - excessive numbers of all cell lines. – Absent Iron stores |
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Polycythemia - Tx
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• The treatment of choice is phlebotomy**** weekly until the hematocrit is < 45%.
Phlebotomy = cornerstone of mgmt → REFER for phlebotomy schedule • DO NOT give iron supplementation → d/t reticulocytosis • Symptomatic treatment of complications such as thrombosis. • Suppression of the bone marrow may be attempted. |
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Thalassemia
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Microcytosis disproportionate to the degree of anemia!
Hypochromic-microcytic Falls into the hypoproliferative; hemolytic; and Abnormal Hb Anemias! |
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Thalassemia Trait
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Lab features w/out clinical impact
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Thalassemia Intermedia
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There is a RBC transfustion requirement or other moderate clinical impact.
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Thalassemia Major
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The d/o is life threatening!
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Alpha Thalassemia
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D/t gene deletion --> reduced alpha-globin chain synthesis.
Since all adult Hb's are alpha containing, alpha-thalassemia produces no change in percent distribution of Hb A, A2 and F. Severe forms: excess Beta chains may form a B4 tetramer --> Hemoglobin H |
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Beta Thalassemias
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Usually d/t point mutations.
Result: premature chain termination/transcription problems. Numerous molecular defects. B0 = defects that result in absent globin chain expression B+ = reduced synthesis Reduced = results in relative increase in %age of Hb A2 and F compared to A (substitute for missing B chains) --> Unstable - excess chains precipitate --> damage of RBC membranes --> intramedullary and peripheral hemolysis. Bone Marrow = hyperplastic d/t anemia and ineffective erythropoiesis (d/t inramedullary destruction of erythroid cells) Severe: marked expansion of bone marrow --> bony deformities |
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Alpha Thalassemia: clinical presentation
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Usually southeast Asians and Chinese
L/C blacks 3 globin alpha = silent carrier 2 = alpha thal. trait (1 of 2 minor forms) --> mild microcytic anemia; but clinically normal; norm life expectancy 1 alpha = Hb H Disease --> chronic hemolytic anemia - variable severity: minor v. intermedia PE: pallor, splenomegaly; usu. don't require transfusions; but possible during hemolytic exacerbation d/t infxn/stress 0 Alpha = stillborn/hydrops fetalis |
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B Thalassemia Major
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Mediterranean origin (italian/greek), asians, blacks
Homozygous = Major Normal at birth 6 mos = switches from Hb F - Hb A Severe anemia requiring transfusion Growth failure, bony deformities, hepatosplenomegaly, jaundice Transfusion therapy Transfusional iron overload (hemosiderosis) results in clinical picture similar to hemochromatosis w/heart failure, cirrhosis, and endocrinopathies. D/t inability to excrete the iron from the transfused red cells. |
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Thalassemia Intermedia
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Mediterranean origin (italian/greek), asians, blacks
Homozygous for a milder form of B-Thalassemia (allowing a higher rate of globin gene synthesis). Chronic hemolytic anemia, but do not require transfusions except under stress. May develop iron overload (d/t transfusion) Survive into adult life, but w/hepatosplenomegaly and bony deformities. Clinically insignificant |
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Silent Carrier of Thalassemia A
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3 globin alpha = silent carrier
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Alphat Thalassemia Trait
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= alpha thal. trait (1 of 2 minor forms) --> mild microcytic anemia; but clinically normal; norm life expectancy
2 alpha-globin chains. Mild anemia w/hct btwn 28-40% MCV is strikingly low despite the modest anemia RBC count is normal/increased Peripheral blood smear - microcytes, hypochromia, target cells and acanthocytes (cells w/irreg. spaced bulbous projections. Reticulocyte count and iron parameters = normal Hb electrophoresis - no increase in % of Hb A2 or F, and no Hb H. Usually diagnosed by exclusion! |
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B- Thalassemia Minor
Labs |
Modest Anemia (similar to a-trait)
Hct 28-40% MCV = 55-75 RBC count is norm/increased Periph blood smear = mildly abnl BASOPHILIC STIPPLING Retic count norm/elevated Hb electrophoresis - elevated A2; occasional elevations of HbF |
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B Thalassemia Major
Labs |
Severe anemia
Hct < 10% Peripheral blood smear = bizarre --> severe poikilocytosis, hypochromia, microcytosis, target cells, basophilic stippling, nucleated RBCs Little or no HbA Variable HbA2 The major Hb present = Hb F |
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DDX: Thalassemia
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Mild - compare with IDA
- thal = lower MCV; normal RB count; anbml perish blood smear at modest levels of anemia. Iron = normal Severe thalassemia: Confused w/other Hb-opathies --> Dx w/ Hb electrophoresis --> elevated levels of Hb A2 and F Alpha Thal = dx made by exclusion --> since no change in percentage of Hb's. |
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Thalassemia Txs:
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Mild (a or b): no tx, but identify d/o
Hb H DZ = folic acid supplementation; Severe: regular transfusion; folic acid supplement; splenectomy prn; and iron chelation if regular transfusion requirements --> prevents life-limiting organ damage from iron overloaded --> Oral agent Deferasirox Allogenic Bone marrow transplat = TX OF CHOICE FOR B Thalassemia MAJOR |
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Vitamin B12 Deficiency Anemia
3 General Identifiers |
Macrocytic anemia
Macro-ovalocytes and hypersegmented neutrophils on peripheral blood smear Serum B12 < 100pg/mL |
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Vitamin B12 Deficiency Anemia
General |
Daily B12 absorption = 5 mcg
Dialy losses 3-5mcg/d Sufficient stores - deficiency devleps > 3 yrs after absorption ceases Dietary defic: extremely rare; seen only in strict vegans. CAUSES: Abdominal surgery: Gastrectomy - eliminates the site of IF production Blind Loop Syndrome - cause compeitition for Vita B12 by bacterial overgrowth in lumen Surgical resection of ileum = dec SA Fish tapeworm Pancreatic insufficiency Severe Crohn DZ |
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Presentation of Vitamin B12 Deficiency Anemia
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Hallmark: Megaloblastic anemia --> referred to as Pernicious Anemia
Advanced: Severe Low Hct (10-15%) Leukopenia; thrombocytopenia Changes in mucosal cells --> glossitis GI: anorexia, diarrhea Neuro syndrome: Peripheral nerves first - paresthesias Posterior Columns - balance cerebral fx - dementia/neuropsych changes |
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Vitamin B12 Deficiency Anemia
Labs |
MCV strikingly elevated
Normal if coexistant IDA/Thalassemia Periph Blood Smear: anisocytosis, poikilocytosis Macro-ovalocytes Neutrophils = hypersegmeneted (> 6 lobes) Retic count = reduced Severe: WBCs and Platelets reduced --> pancytopenia Bone Marrow morphology: abnml Marked erythroid hyperplasia - d/t defective RBC production Abnormally large cell size and asynchronous maturation of nucleus/cytoplasm Giant metamyelocytes Elevated serum LDL Modest increase in indirect bilirubin DX: Low B12 serum level Overt - < 170 Sxs - < 100 Confirmation of Dx: elevated serum methylmalonic acid (may also be d/t kidney insufficiency) |
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Ddx: B12 deficiency
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DDX from Folic Acid deficiency (low folic acid) - common cause of megaloblastic anemia -
IDENTICAL except has normal B12/low Folic Acid Myelodysplasia - common cause of macrocytic anemia w/abnormal morphology --> Dx B12 Deficiency based on characteristic morphology and low B12 and elevated methylmalonic acid levels |
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Folic Acid Deficiency
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DDX:
Alcoholic pts who often have a nutritional deficiency may also have anemia of liver DZ --> macrocytic doesn't have megaloblastic changes --> produces target cells in peripheral blood Hypothyroidism - mild macrocytosis, but w/PA |
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Folic Acid Deficiency Causes
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MC = inadequate dietary intake
Alcoholic, anorectic (don't eat fresh fruit/veggies), overcooked veggies Reduced absorption = RARE d/t absorption throughout entire GI tract Phenytoin, Trimethoprim-Sulfamethoxazole, or sulfasalazine may interfere w/absorption. |
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Anemias w/diminished RBC production
(reticulocytopenia) |
IDA
B12 or Folate DeficiencyAnemia Blood Loss ACD Aplastic Anemia |
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Anemias w/accelerated loss of RBC's
(reticulocytosis) |
Autoimmune Hemolytic Anemia
Cold Agglutinin Sickle Cell DZ Thalassemia |
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Classification of Anemias by RBC Size
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Microcytic:
IDA Thalassemia Normocytic Anemia of Chronic DZ Macrocytic B12 and Folate Deficiency Cold Agglutinin |
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Hyperleukocytosis
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Most dramatic presentation in leukocytosis of acute leukemia
Markedly elevated circulating blast count (>200,000/mL) Leads to impaired circulation Presents as HA, Confusion, and Dyspnea Require: Emergent leukapheresis and chemotherapy Later: other organs become involved. |
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Acute Leukemia Presentation
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Abrupt presentation w/in days - weeks
--> anemia, infxn, bleeding Gum hypertrophy and bone pain (d/t expansion of marrow and periosteum infiltration) hyperleukocytosis --> impaired circulation --> HA, confusion and dyspnea (req. emergent leukophoresis and cheo) Dissemination to other organs Brain T cell: mass in anterior mediastinum Death = usually d/t hemorrhage (cerebral, GI) and/or infxn (neutropenia, chemo) and/or complications of bone marrow transplant HALLMARK: pancytopenia w/circulating blasts |
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Chronic Lymphocytic Leukemia
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Disease of older pts
Indolent course Sxs: Fatigue Lymphadenopathy Hepatosplenomegaly Labs • Isolated lymphocytosis – The WBC count is usually greater than 20,00/mL – often >75% of the WBC count • Mature cells (no bands) |
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Chronic Myelogenous Leukemia
Labs |
Overgrowth of normally-maturing myeloid stem cells.
High counts of neutrophils and their precursors High Basophil count (almost ALWAYS) --> Cells = Normal functionally and morphologically, but lack cyotplasmic alkaline phosphatase |
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Chronic Myelogenous Leukemia
Presentation |
• Characteristically seen in middle age.
• Common symptoms include – General symptoms of fatigue, night sweats and low-grade fever – Bone tenderness (usually sternal) – Splenomegaly – often huge, often with small infarcts – Leukostasis if counts are > 100,000 • Blurred vision, brain infarcts, respiratory distress – Blast crisis • Bleeding and infection due to loss of other cell lines |
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Lymphatic Disease
Key Sx |
Key Sx is PAIN!
Differentiates from malignant (not painful) – Lymphangitis – Lymphadenopathy – Lymphedema |
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Lymphadepenitis
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Type of Lymphatic DZ
•Inflammation of a lymph channel (“Lymphangitis) is most commonly the result of a local wound or cellulitis. –Hemolytic Streptococci or Staphlyococci are the usual bacteria •Bacteria gain access to the lymphatic channels by direct extension or through phagocytosis by Neutrophils. The resulting inflammation leads to the characteristic “red streak”. |
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LAD
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Primary fx = filtration
--> lymph node filter bed: narrow sinus tracts and macrophages near the sinuses --> result of lymphadenitis or malignant process Multiple reactive changes of lymph nodes May be local effects - confined infxn - swelling of node near cat scratch Common sign in viral infxns (mumps, measles) Local bacterial infxn (cervical LAD in strep) General infxns can affect multiple nodes |
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Lymphangitis-adenopathy
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• The primary symptom is inflammation of the lymph veins and nodes.
• Usually the lymphatic channels are NOT tender or indurated, which distinguishes this from thrombophlebitis. • The lymph nodes are tender and swollen. • Systemic manifestations of the infection include fever, chills, tachycardia, and malaise. • An ascending red streak indicates the inflammation of the lymphatic channel. (Thrombophlebitis) |
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Mgmt of Lymphangitis-adenopathy
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AB - tx underlying disease
If dry: hot compresses if draining: heating pad Elevation above the heart, Restriction of movement of affected part Acute: usually resolves w/infxn May progress to chronic --> remain enlarged (Tb) Refer to surgeon if developed abscesses AND: 1) septic 2) it is on the neck 3) draining significant pus. |
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Lymphedema
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Painless edema at lower extremities
Usually involves the dorsum of foot and toes Primarily YOUNG WOMEN Initially: pitting edema Becomes: brawny, nonpitting w/time Episodes of lymphangitis and cellulitis Underlying cause: obstruction of lymph channels --> inflammation of local stressed areas --> possible early Sx of malignancy (breast cancer) |
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Splenomegaly
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• Filtration of foreign particles occurs through the red, reticular tissues with patches of white lymphoid tissues containing phagocytes.
• Splenomegaly can be acute or chronic and occur from infections, circulatory disturbances, neoplasia and blood disorders such as leukemias and hemolytic anemias. |
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Non-Hodgkin's Lymphoma
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malignant cells are derived from lymphocytes they are widely scattered throughout the lymph nodes, spleen, liver and bone marrow.
• Depend on aggressiveness • Indolent – painless soft lymphadenopathy, usually deep therefore non-palpable – + hepatosplenomegaly (mild to moderate) • Intermediate or High-grade – painless, soft lymphadenopathy, extra-lymph node enlargement (is skin or GI tract) – + abdominal fullness – hepatosplenomegaly – In immunsuppressed patieints - possibly brain lesions. |
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Hodgkin's Lymphoma
General |
Common, curable, typically affects young adults
Second peak: older adults --> more aggressive Malignant cell: Early = Reed-sternberg cell Late = tumor masses = primarily inflammatory cells --> responding to the cancer |
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Hodgkin's Lymphoma
Presentation and Management |
• The most common presentation is painless lymphadenopathy, usually the neck.
– Other common sites are axilla, inguinal nodes and retroperitoneal nodes. – For some patients the node can become painful with alcohol ingestion. • It spreads contiguously, node by node until late in the course. • This is useful both diagnostically and in treatment • Nearly half have general “constitutional” symptoms – fever, weigh loss, night sweats or generalized pruritis • Managed by Hematologist-Oncologist – Radiation therapy – Chemotherapathy if radiation fails • Potentially curable for most patients – Those who are older, or have disseminated “bulky disease have a poorer prognosis |
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Causes of Neutrophilia
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May be reactive or malignant:
>50,000-75,000- acute infxn >100,000 - possible malignancy >55,000/90% --> BAD Infection CTSD therapy Polychythemia Vera Malignancies (Leukemias) |
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Neutropenia
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Decrease in circulating neutrophils below 1500/microL
-Overwhelming infections - peripheral sequestration (fictitious - in lymph) -May be part of pancytopenia, nutritional d/o, alcoholism, chemo, extreme dieters, Blacks (physic), menses --> MC cause - drug-induced bone marrow suppression - Cause of a massive neutropenia = INFECTION Sepsis/Cellulitis/PNA/Stomatitis HOSPITALIZE ASAP |
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Idiopathic Hypereosinophilic Syndrome
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Ag-Ab complexes
Double/Triple normal amount Diffuse tissue damage: endocardium and CNS May not survive --> High EOS release products that perpetuate the inflammatory response Tx: ADMIT ASAP CTSDs or Antimetabolites (Hydroxyurea) |
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Eosinophilia
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MC cause is allergic or atopic state
Also parasites, autoimmune, inflammatory conditions, malignancy Hodgkins - Eosinophilia and Basophilia |
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Basophils
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Least abundant circulating cells
Active in allergic reactions and release histamine Controlled by IgE |
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Basophilia
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Defined as >150/microL
Causes: allergic rxns associated w/urticaria (drugs and foods) --> THICK raised swelling of lips if it reaches the face -Other causes (anything that perpetuates infxns) - viral infxn - chronic infxn - Chronic inflammatory states (RA) - Malignancy (Hodgkins w/EOS) |
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Monophilia
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MC cause = Malignancy
-->myelogenous leukemia and Hodgkins --> constant turnover - compression of spleen Also: Neutropenia - compensatory --> transient for 1-2 days before increase in neutrophils after chemo Chronic inflammation Thalassemia/Sickle Cell Infectious Mono |
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Lymphocytosis
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Acute Infxn:
- viral infections, usually transient --> EBV Chronic Infxn: TB, Syphillis, Lyme DZ WORST: LYMPHOCYTIC LEUKEMIA ***Only thing that's high is the lymphocytes |
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Acute Leukemias
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Overgrowth of blast cells
Death in weeks - months Also a major increase in lymphocytes Dx: Requires more than 30% blasts in the bone marrow sample AML in older pts; better prognosis Presentation: Abrupt: days - weeks as one of the cytopenias (usu. appears as anemia, infxn or bleeding) Gum hypertrophy and bone pain (D/t expansion of marrow) Hyperleukocytosis - (>200,000 blasts) - HA/confusion/dyspnea --> emergent leukapheresis and chemo Later: brain, mediastinum (T cells) Death - d/t hemorrhage (cerebral, GI) and/or infxn (neutropenia, chemo) or marrow transplants. Hallmark = pancytopenia w/circulating blasts |
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Hyperleukocytosis
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Dramatic presentation of Acute Leukemia
- marked elevated circulating blast count (>200,000) - leads to impaired circulation Presents as: HA/confusion/dyspnea Tx: EMERGENT leukapheresis and chemo |
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Chronic Leukemia
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Well differentiated, mature or almost mature cells
May present w/cytopenia OR Leukostasis (Hi count), OR LAD/Organomegaly, OR hi WBC count as incidental finding on routine lab |
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Chronic Lymphocytic Leukemia
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DZ of older pts
Indolent course Asymptomatic in early stages Sxs: Fatigue, LAD hepatosplenomegaly Labs: Isolated lymphocytosis (>75%/20,000) Mature cells, no bands |
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Chronic Myelogenous Leukemia
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Cancer of myeloid stem cells
-RF: radiation and chemicals, usually random - High counts of neutrophils and their precursors, and BASOPHILS - lack cytoplasmic alkaline phosphatase - Middle age - Fatigue, night sweats, low-grade fever Bone tenderness (sternal) Splenomegaly (huge w/infarcts) Leukostasis (if >100,000) - blurred vision, brain infarcts, resp distress --> Blast Crisis (bleeding and infxn due to loss of other cell lines) |
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Key Sx w/lymphatic DZ
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Pain
Infectious cause = painful Malignancy - no pain |
