Hematology Flashcards
Define Erythrocyte
carries oxygen from lungs to peripheral tissues
Define Reticulocyte
immature erythrocyte
Define Neutrophil
granulocyte integral in innate immunity; main cell in acute inflammation
Define Eosinophil
involved in response to parasites (especially helminths) and allergic response
Define Basophil
granulocyte mainly involved in allergy and parasitic infection
Define Lymphocyte
integral cell in adaptive immunity
Define Monocyte
involved in innate immunity; can differentiate into macrophage or dendritic cell
Define Platelet
Mediator of primary hemostasis
Define Plasma
Liquid component of blood containing water, proteins, coagulation factors and immunoglobulins
Define Serum
Equivalent of plasma minus clotting factors and fibrinogen
What three precursor cells come off of the Hematopoietic Stem cell?
- Megakaryocyte/erythrocyte precursor 2. Myeloid precursor 3. Lymphoid precursor
Describe the process from the megakaryocyte precursor to a platelet
megakaryocyte precursor > megakaryoblast > megakaryocyte > platelet
Describe the process from an erythrocyte precursor to an erythrocyte
erythrocyte precursor > pro erythroblast > polychromatic erythroblast > erythrocyte
Describe process from myeloid precursor to macrophage
myeloid precursor >monoblast > monocyte > macrophage
Describe process from myeloid precursor to granulocytes (basophil, eosinophil, neutrophil)
myeloid precursor > myeloblast > progranulocyte > basophil, eosinophil, neutrophil
Describe process form lymphoid precursor to T cell/B cell
Lymphoid precursor > lymphoblast > T cell/ B cell
what are three sites of hematopoiesis in adults
pelvis, sternum, vertebral body
what is the life span of mature cells in blood: 1. erythrocytes 2. neutrophils 3. platelets 4. lymphocytes
- erythrocytes (120d) 2. neutrophils (1 d) 3. platelets (10 d) 4. lymphocytes (varies; memory cells for years)
What is the role of the spleen
Spleen; part of reticuloendothelial system; removes aged RBCs, removes antibody coated bacteria/cells, site of antibody production
What is the role of the thymus?
Thymus; site of T cell maturation, involutes with age
What is the role of lymph nodes?
sites of B and T cell activation (adaptive immunite response)
What is RBC Count
RBC; # of RBCs per volume of blood
What is Hgb
Hgb; amount of oxygen carrying protein in blood
What is hematocrit (Hct)
Hct; % of a given volume of whole blood occupied by PRBCs
What is Mean Corpuscular Volume (MCV)
MCV; measurement of size of RBCs
What is Mean Corpuscular Hgb (MCH)
MCH; amount of oxygen carrying Hgb inside RBCs
What is Mean Corpuscular Hgb Concentration (MCHC)
MCHC; avg concentration of hub inside RBCs
What is RDW (RBC Distribution Width)
RDW; Measurement of variance in RBC size
What is WBC Count
WBC; # of WBCs per volume of blood
What is a WBC Differential
WBC Differenital; include neutrophils, eosinophils, basophils, lymphocytes and monocytes
What is a platelet count
of platelets per volume of blood
What is Mean Platelet Volume (MPV)
MPV; measurement of platelet size
What are reticulocytes
Retic Count; Immature RBCs that contain no nucleus but have residual RNA
What to consider if all of CBC is low?
pancytopenia
What do you consider if RBCs and platelets are low?
microangiopathic hemolytic anemia (MAHA)
What measure define size of RBC? 1. Microcytic 2. Normocytic 2. Macrocytic
- Microcytic (MCV 100)
What is anisocytosis?
RBCs with increased variability in size (increased RDW)
What are 4 causes anisocytosis? (RBCs with increased variability in size (RDW))
- Iron deficiency anemia 2. Hemolytic anemia 3. Myelofibrosis 4. Blood Transfusion
What is a hypo chromic RBC?
increase in size of central pallor (normal =
What are 3 causes of hypo chromic RBC’s?
- Iron deficiency anemia 2. Anemia of Chronic Disease 3. Sideroblastic Anemia
What is polychromasia?
Increase reticulocytes (pinkish-blue cells)
What causes polychromasia?
increased RBC production by bone marrow
What is Poikilocytosis?
increased proportion of RBCs of abnormal shape
What are two causes of Poikilocytosis?
- Iron deficiency anemia 2. Myelofibrosis
Discocyte; definition and associated conditions
Define; Biconcave disc Normal RBC
Spherocyte; definition and associated conditions
Spherical RBC (due to loss of membrane) Hereditary spherocytosis, Immune hemolytic anemia
Elliptocyte/Ovalcytes; definition and associated conditions
Oval shaped, elongated RBCSs * Elliptocytes; the RBC long axis is > 2x the lengths of the short axis * Ovalcytes; the RBC long axis is
Schistocytes;definition and associated conditions
Fragmented cells (r/t traumatic disruption of the membrane) Microangiopathic hemolytic anemia (HUS/TTP, DIC, Preeclampsia, HELLP, malignant HTN), vasculitis, glomerulonephritis, prosthetic heart valve
Sickle Cells;definition and associated conditions
Sickle shaped RBC (due to polymerization of hemoglobin S) Sickle cell disorders; HbSC, HbSS
Codocyte (target cell); definition and associated conditions
“bulls eye” on dried film Liver disease, hemoglobin SC, thalassemia, Fe Deficiency, asplenia
Dacrocyte (teardrop cell); definition and associated conditions
Single pointed end, looks like a teardrop myelofibrosis, thalassemia major, megaloblastic anemia
Acanthocyte (spur cell); definition and associated conditions
Distorted RBC with irregularly distributed thorn-like projections (due to abnormal membrane lipids) Severe liver disease (spur cell anemia), starvation/ anorexia, post splenectomy
Echinocyte (burr cell);definition and associated conditions
RBC with numerous regularly spaced, spiny projections Uremia, HUS, burns, cardiopulmonary bypass, post transfusion, storage artifact
Rouleaux formation; definition and associated conditions
Aggregates of RBC resembling stacks of coins due to increased plasma concentration of high molecular weight proteins Pregnancy; most common cause; due to physiological increase in fibrinogen inflammatory conditions; due to polyclonal immunoglobulins Plasma cell dyscrasias; due to monoclonal paraproteinemia (e.g. multiple myeloma, macroglobinemia, storage artifact)
RBC Inclusions definition and associated conditions; Nucleus
Present in erthyroblasts (immature RBCs) Hyperplastic erythropoiesis (seen in hypoxia, hemolytic anemia), BM infiltration disorders, Myeloproliferativve neoplasm (myelofibrosis)
RBC Inclusions definition and associated conditions; Heinz Bodies
Denatured and precipitated hemoglobin G6PD deficiency (post exposure to oxidant), thalassemia, unstable hemoglobins
RBC Inclusions definition and associated conditions; Howell-Jolly Bodies
Small nuclear remnant resembling a pyknotic nucleus Post splenectomy, hyposplenism (sickle cell disease), neonates, megaloblastic anemia
RBC Inclusions definition and associated conditions; Basophillic Stippling
Deep blue granulations indicating ribosome aggregation Thalassemia, heavy metal (Pb, Zn, Ag, Hg) poisoning, megaloblastic anemia, hereditary (pyrimidine 5’ nucleotidase deficiency)
RBC Inclusions definition and associated conditions; Sideroblasts
Erythrocytes with Fe containing granules in the cytoplasm Hereditary, idiopathic, drugs, hypothyroidism
Lymphocytes comprise _____% of WBCs
30 - 40
Reed Sternberg Cell; definition and associated conditions
giant multinucleate B lymphocyte Hodgkin lymphoma, other lymphoproliferative disorders
Smudge Cell; definition and associated conditions
Lymphocytes damaged during blood smear preparation indicating cell fragility chronic lymphocytic leukemia (CLL) and other lymphoproliferative disorders
What kind of neutrophils are found in the blood?
Normally; - only mature neutrophils (2 - 4 lobed nucleus) and bands (immediate precursor with horsehoe shaped nucleus)
What are hyper segmented neutrophils?
>5 lobes suggests megaloblastic process (b12 or folate deficiency)
What is a left shift
increase in granulocyte precursors (bands, metamyelocytes, myelocytes, promyelocytes and blasts) in circulation
When is a left shift seen?
in leukemoid reactions; - acute infections, pregnancy, hypoxia, shock, chronic myeloid leukaemia (CML)
What are blasts and when are they seen?
immature, undifferentiated precursors associated with acute leukaemia, MDS, severe infection
Auer Rods; definition and associated conditions
clumps of granular material that form long needles in the cytoplasm of myeloblasts pathognomonic for acute myeloid leukaemia (AML)
What do platelets look like?
small purple a nuclear cell fragments
What are the 2 sites for bone marrow aspiration and biopsy
Posterior iliac crest sternum
What is the difference between bone marrow aspiration and biopsy
Aspiration; takes fluid marrow sample for histology, flow cytometry, cytogenetics, molecular studies, microbiology (C&S, AFB) Biopsy; takes a sample of intact bone marrow to assess histology
What are 8 indications of Bone marrow aspiration or biopsy
- unexplained CBC abnormalities 2. dx and evaluation of plasma cell disorders and leukemias 3.diagnosis and staging of lymphoma or solid tumours 4. evaluate iron metabolism and stores 5. evaluate suspected deposition and storage disease (amyloidosis, Gaucher’s disease) 6. Evaluate fever of undetermined origin, suspected mycobacterial, fungal, or parasitic infections or granulomatous disease 7. unexplained splenomegaly 8. confirm normal bone marrow in potential allogenic hematopoietic cell donor
What are the absolute contraindications for bone marrow aspiration or biopsy
untreated haemophilia, severe DIC, infection over skin site, DIC with uncontrolled bleeding
Is thrombocytopenia a contraindication of bone marrow biopsy or aspirate
No but may need platelet transfusion prior to procedure
What is anemia?
a decrease in RBC mass that can be detected by hgb concentration, hct and RBC count
What defines low MCV
MCV
What are causes of Low MCV?
iron deficiency, thalassemia, anemia of chronic disease, sideroblastic anemia, lead poisoning
How is normal MCV measured?
MCV = 80 - 100
How do you classify normal MCV?
high retic and low retic
what percent of retics is considered high?
>2 - 3%
What are some causes of high retic counts
increased destruction (divided into hemolysis and bleeding)
What percent of retics is considered low?
What is the cause of low retics?
decreased production (divided into pancytopenia and non pancytopenia)
What are 7 causes of pancytopenia (low retic, normal MCV)
- aplastic anemia 2. MDS 3. Myelofibrosis 4. Leukemia, 5. TB 6. Amyloidosis/sarcoidosis 7. Drugs (chemo)
What are two causes of non pancytopenia (low retic, N MCV)
- Anemia of chronic disease 2. Renal/liver diseae
What are two categories is hemolysis divided into? (high retic, N MCV)
- inherited 2. acquired
What are the three causes of Inherited Hemolysis (high retic, N MCV)
- hemoglobinopathy (sickle cell disease, thalassemia, unstable hb) 2. Membrane (spherocytic) 3. Metabolic (HMP shunt, glycolytic pathway)
What are the 4 causes of Acquired Hemolysis? (high retic, N MCV)
- Immune (+coombs, drug related cold agglutinin) 2. Infection (malaria) 3. Microangiopathic hemolytic anemias (DIC, TTP, HUS, HELLP) 4. Oxidative/ drug related
What defines a high MCV and what are the two categories associated with high MCV?
MCV >100 Megaloblastic/ Non-megaloblastic
What are three causes of megaloblastic anemia (high MCV)
- B12 deficiency 2. Folate deficiency 3. Drugs that impair DNA synthesis (methotrexate, sulfa, chemo)
What are the 5 causes of non megaloblastic anemia?
- Liver disease 2. Alcoholism 3. Reticulocytosis (see high retic) 4. Hypothyroidism 5. Myelodysplasia
What are 10 sx of anemia?
fatigue, malaise, weakness, dyspnea, decreased exercise tolerance, palpitations, headache, dizziness, tinnitus, syncope
What are things you need to inquire about in Hx of anemia?
- menstrual hx (metorrhagia, menometrorrhagia, dysfunctional uterine bleeding) 2. r/o pancytopenia (recurrent infection, mucosal bleeding/easy bruising) 3. acute vs chronic, bleeding, systemic illness, diet, alcohol, family hx
What are HEENT physical signs of anemia?
- pallor in mucous membranes and conjunctiva at hgb
What are Cardiac physical signs of anemia?
tachycardia, orthostatic hypotension, systolic flow murmur, wide pulse pressure, signs of CHF
What are dermatologic physical signs of anemia?
pallor in palmar skin creases at hub
What 5 investigations should you do for anemia?
- rule out dilution anemia 2. CBC with differential 3. retic count 4. blood film 5. r/o gastro disease in Fe defiency anemia
Define Polycythemia
an increase in the number of RBCs 1. Hgb >185 or Hct >52% (males) 2. Hgb >165 or Hct >47% (females/ African Males)
What are the two umbrella aetiologies for polycythemia?
Relative/ spurious erythrocytosis (decreased plasma volume) Absolute Erythrocytosis
What are the causes of relative erythrocytosis (Decreased plasma volume)?
diuretics severe dehydration burns “stress” (Gaisbock’s Syndrome)
What are the three umbrella causes of absolute erythrocytosis?
- Primary (low or normal erythropoietin) 2. Secondary (elevated erythropoietin) 3. Inappropriate production of erythropoietin
What is the cause of primary absolute erythrocytosis?
polycythemia vera (PV)
What are the 6 causes of secondary (elevated erythropoietin) absolute erythrocytosis?
- poor tissue oxygenatoin/hypoxia 2. pulmonary disease; COPD, sleep apnea, pulmonary HTN 3. CV Disease; R–>L Shunt (eisenmenger syndrome) 4. RBC Defects (Hgb with increased O2 affinity, methemoglobinemia) 5. CO poisoning (heavy smoking) 6. HIgh altitude
What are the 6 causes of inappropriate production of erythropoietin?
- Renal cell Ca 2. Cerebellar hemangioblastoma 3. hepatocellular ca 4. uterine leiomyomas 5. ovarian tumour 6. other (PKD, post kidney transplant, hydronephrosis, androgens, exogenous erythropoietin)
What are the clinical features secondary to high red cell mass/ hyper viscosity of polycythemia?
headache, dizziness, tinnitus, visual disturbances symptoms of angina, CHF
Is thrombosis, bleeding or both associated with polycythemia?
both - thrombosis (venous/arterial) - bleeding (abnormal platelet function)
What are the physical findings of polycythemia?
splenomegaly +/- hepatomegaly, facial plethora (ruddy complexion (70%) and/or palms, gout
What investigation is important to do for polycythemia?
Serum erythropoietin (EPO); increased EPO suggests autonomous production or hypoxia, and is used to r/o PV
What is a cause you have to r/o for polycythemia when there is increased epo
search for tumour as source of epo (abdo US/CT head)
What test for polycythemia vera needs to be done when low/normal EPO?
Jak-2 mutation analysis (positive in >96% of cases of PV)
What is the tx for secondary polycythemia?
treat underlying disease 02 for hypoxemia, CPAP for sleep apnea, surgery for EPO secreting tumours
What is factitious thrombocytopenia?
platelet clumping (secondary to EDTA antibodies from collection tube)
Define Thrombocytopenia
platelet count
What are the four categories thrombocytopenia can be divided into?
- Decreased production 2. Sequestration 3. Increased Destruction 4. Hemodilution
What are the three categories that cause decreased production of platelets?
Nutritional (B12/folate deficiency) Congenital (Alport’s, Fanconi’s) Marrow Damage (Aplastic anemia, chemo, rads, drug induced, malignancy, myelodysplasia)
What is the cause of platelet sequestration in Thrombocytopenia?
Splenomegaly - liver diseases - malignancy - myelofibrosis
What are the two broad categories that cause increased platelet destruction (in thrombocytopenia)?
Immune Non Immune
What are the 6 immune causes of platelet destruction (in thrombocytopenia?)
- Idiopathic thrombocytopenic purpura 2. Viral (HIV) 3. Systemic (SLE) 4. Alloimmune 5. Heparin induced thrombocytopenia 6. Drug Induced
What are the 6 Non immune causes of platelet destruction (in thrombocytopenia?)
- Disseminated intravascular coagulation 2. Thrombotic thrombocytopenic purpura 3. Hemolytic uremic syndrome 4. Preeclamspia 5. HELLP (hemolysis, elevated lived enzymes, low platelet count) 6. APS (antiphospholipid antibody syndrome)
What are the two causes of thrombocytopenia caused by demodulation?
- Massive transfusion cardiopulmonary bypass
What is the history associated with thrombocytopenia?
bleeding gums, epistaxis, post surgical bleeds, metromenorrhagia
What are physical exam findings consistent with thrombocytopenia?
bruising, petechiae, ecchymoses, non palpable purpura
Are Hermarthrosis and deep muscle hematomas initial signs in patients with primary hemostatic disorders?
rarely
What investigations are appropriate for thrombocytopenia?
CBC/Diff Blood film work up for nutritional deficiencies (B12/folate) LFTs
What are you looking for on blood film for thrombocytopenia?
- r/o platelet clumping 2. decreased production = other possible cell line abnormalities, blasts, hyper segmented PMNs, leukoerythroblastic changes 3. Increased destruction; large platelets, schistocytes (seen in MAHA)
What is the tx for life threatening thrombocytopenia?
platelet transfusion
What is the tx for secondary thrombocytopenia?
tx underlying disease
Define Thrombocytosis
platelet count >500
What causes primary thrombocytosis?
due to myeloproliferative neoplasms (CML, primary myelofibrosis, polycythemia vera) rarely MDS
What causes reactive/secondary thrombocytosis?
acute phase reactant (e.g. surgery, inflammation, infection, trauma, bleeding, iron deficiency, neoplasms)
What is a hx consistent with thrombocytosis?
trauma, surgery, splenectomy, infection, inflammation, bleeding, iron deficiency, prior diagnosis of chronic hematologic disorder, constitutional sx (malignancy)
What are vasomotor symptoms associated with thrombocytosis?
headache, visual disturbances, lightheadedness, atypical chest pain, acral dysesthesia, erythromelalgia, lived reticular is, aquagenic pruritis
Is clotting risk or bleeding risk more rare with thrombocytosis?
bleeding more rare
What are physical exam findings for thrombocytosis?
splenomegaly can be seen in myeloproliferative neoplasms (MPNs)
what are appropriate investigations for thrombocytosis?
- CBC, peripheral blood film, serum ferritin concentration 2. non specific markers of infection or inflammation (CRP, ESR, ferritin) 3. If reactive process has been r/o, bone marrow biopsy may be required to r/o MPN/MDS
What is tx for primary thrombocytosis?
Asa +/- cytoreductive agents
What is tx for secondary thrombocytosis?
treat underlying cuase
Define Pancytopenia
A decrease in all hematopoietic cell lines
What are three clinical features of pancytopenia
- Anemia; fatigue 2. Leukopenia; recurrent infections 3. Thrombocytopenia; mucosal bleeding and ecchymoses
What investigations are appropriate for pancytopenia?
- CBC diff, blood film 2. investigate secondary causes as per hx; HIV, serum B12, RBC folate, ANA 3. Often requires bone marrow biopsy to determine cause
What are the two BM categories of pancytopenia?
Hypocellular BM Cellular BM
What are the 7 diseases associated with hypo cellular BM (in pancytopenia)?
- Acquired aplastic anemia 2. inherited aplastic anemia 3. some myelodysplasia syndromes 4. AML 5. Overwhelming infections 6. Toxic depression of BM 7. Anorexia nervosa
What are the two categories associated with cellular BM in pancytopenia?
primary BM disease secondary to systemic disease
What primary BM diseases (4) cause cellular BM in pancytopenia?
- myelodysplasia 2. paroxysmal nocturnal hemoglobinuria 3. myelofibrosis 4. lymphoma
What are 7 disease states associated with cellular BM 2 to systemic disease?
- SLE 2. Hypersplenism 3. Vit B12/Folate deficiency 4. Alcoholism 5. TB 6. Sarcoidosis 7. HIV
Define Neutrophilia
Absolute Neutrophil Count (ANC) >7.7
What are the 5 things that cause primary neutrophilia?
- hereditary neutrophilia (autosomal dominant) 2. chronic idiopathic neutrophilia in otherwise healthy patients 3. chronic myeloid leukemia (CML) 4. Other myeloproliferative disorders (PV, essential thrombocytopenia, myelofibrosis) 5. Leukocyte adhesion defiency
What are the causes of secondary neutrophilia?
- Smoking (most common for mild) 2. Infection 3. Inflammation 4. Malignancy 5. Stress/ exercise/ epinephrine 7. Meds (glucocorticoids, Beta agonists, lithium)
What are the clinical S&S of neutrophilia?
fever, inflammation, malignancy to determine appropriate further investigations exam oral caivty, peri-rectal area, genitals and skin for signs of infection
What investigations are appropriate for Neutrophilia?
CBC diff (mature neutrophils or bands >20% of total WBC suggests infection/inflammation) Blood film (Dohle bodies, toxic granulation, cytoplasmic vacuoles in infection)
What is the tx for neutrophilia?
directed at underlying cause
Define Mild, Moderate, Severe Neutropenia
Mild; ANC 1 - 1.5 Moderate; ANC 0.5 - 1 Severe; ANC
What are the three categories of causes of Neutropenia?
- Decreased Production 2. Peripheral Destruction 3. Excessive Margination (transient Neutropenia)
Describe the 6 causes of decreased production of neutrophils?
- Hematological Diseases (idiopathic, aplastic anemia, myelofibrosis, BM infiltration) 2. Infection (TB, typhoid, EBV, Malaria, Viral hepatitis, HIV) 3. Drug Induced (alkylating agents, antimetabolites, anticonvulsants, antipsychotics, anti inflammatory agents, anti thyroid drugs) 4. Toxic (high dose rads, chemicals) 5. Nutritional Deficiency (B12, folate) 6. Idiopathic (constitutional neutropenia, benign cyclic neutropenia)
What are the 5 causes of peripheral destruction of neutrophils?
- Antineutrophil antibodies 2. Spleen or lung trapping 3. Autoimmune disorders (RA, SLE) 4. Wegener’s granulomatosis 5. drugs; haptens (methyldropa)
What are the 4 causes of excessive margination (transient neutropenia)
- Idiopathic 2. Overwhelming bacterial infection 3. Hemodialysis 4. Racial variation (african or Ashkenazi Jewish Descent)
What are the clinical features of neutropenia?
- Fever, chills 2. Infection by endogenous bacteria 3. painful ulceration on skin, anus, mouth, and through following colonization by opportunistic organisms 4. avoid digital rectal exam
What investigations must be done for neutropenia?
ranges depending on neutropenia
What tx is required for neutropenia?
- Regular dental care; chronic gingivitis and recurrent stomatitis major sources of morbidity 2. febrile neutropenia 3. In severe immune mediated neutropenia, G CSF may increase neutrophil counts
Define Lymphocytosis
Absolute lymphocyte count >4
What are the 5 main categories of causes of lymphocytosis?
- infection (viral majority; mono) 2. Physiologic responses to stress (trauma, status epilepticus) 3. Hypersensitivity (drugs, serum sickness) 4. Autoimmune (RA) 5. Neoplasm (ALL, CLL, Lymphoma)
What investigations need to be done for lymphocytosis?
peripheral smear?
What are would be found on a peripheral smear for lymphocytosis?
- Smudge cells; suggestive of lymphoproliferative disorder if persistently elevated above 5 x 3 months 2. Atypical lymphocytes; suggestive of viral infection (EBV or others)
Define Lymphopenia
absolute lymphocyte count
What are the causes of lymphopenia? (6)
- Idiopathic CD4+ lymphocytopenia 2. Chemotherapeutic Agents 3. Radiation 4. HIV/AIds, Hep B, HepC, Autoimmune (SLE) 5. Malignancy 6. Malnutrition
What are the clinical features of lymphopenia?
opportunistic infections
What is the treatment for lymphopenia?
tx underlying disease tx opportunistic infections
Define Eosinophilia?
Absolute eosinophil count >0.5
What is the primary cause of eosinophilia?
Clonal bone marrow disorder - if no primary aetiology identified classified as hypereosinophlic syndrome (when other detectable causes r/o)
What are the most common causes of secondary eosinophilia?
parasitic (usually helminth) infections and allergic reactions
what are 5 less common causes of eosinophilia?
- polyarteritis nodosa 2. cholesterol emboli 3. hematologic malignancy (CML, hodgkin lymphoma) 4. adrenal insufficiency 5. medications
What is the tx for eosinophilia?
treat underlying disease
What can basophilia and/or eosinophilia be an indictor of?
CML or other myeloproliferative disease, associated with pruritus due to excessive histamine production
Define agranulocytosis
severe depletion of granulocytes (neutrophils, eosinophils, basophils) from the blood and granulocyte procurers from bone marrow
Define Agranulocytosis
Severe depletion of granulocytes (neutrophils, eosinophils, basophils) from the blood and granulocyte precursors from bone marrow
What is the main cause of agranulocytosis (70%)
Medications (clozapine, thionamides, sulfasalazine and ticlopidine
How do medications cause agranulocytosis
immune mediated destruction of circulating granulocytes by drug induced antibodies or direct toxic effects upon marrow granulocytic precursors
What are signs and symptoms of agranulocytosis
abrupt onset of fever, chills, weakness, and oropharyngeal ulceres
True or False; Agranulocytosis has a high fatality without vigorous tx
TRUE
What are 4 investifations/tx that need to be done in agranulocytosis?
- d/c offending drug 2. culture/screen for infection 3. consider bone marrow aspirate 4. consider GCSF
Define Leukemoid Reactions
blood findings resembling those seen in certain types of leukemia which reflect the repsonse of healthy BM to cytokines released due to infection or trauma
What are the lab values that are consistent with Leukemoid reactions?
leukocytosis (>50), marked left shift (myeloctyes, metamyelocytes, bands in peripheral blood smear
What are the two main differential categories for leukemoid reactions?
myeloid progenitors and lymphoid progenitors
What is important to r/o with leukemoid reactions?
CML
What are 7 different myeloid progenitors that can cause leukemoid reactions?
pneumonia, other acute bacterial infections, intoxications, burns, malignant disease, severe hemorrhage, hemolysis
What are 3 different lymphoid progenitors that can cause a leukemoid reactions?
pertussis, TB, infectious mononucleosis
What is an example of a monocytic progenitor that can cause a leukemoid reaction?
TB
What are 5 things important to ask in Hx r/t Lymphadenopathy
- B Sx 2. Exposures (cat scratch, ticks, high risk behaviours) 3. Joint pain/swelling, rashses (CT disorder) 4. pruritis (seen in Hodgkin lymphoma) 5. Medications (serum sickness –> lymphadenopathy
What are 13 drugs that can cause lymphadenopathy?
Allopurinol, Atenolol, Captopril, Carbamezapine, Cephalosporings, Gold, Hydralazine, Penicillin, Phenytoin, Primidone, Pyrimethamine, Quinidine, Sulfonamides
What are typical causes of cervical lymphadenopathy?
bacterial/mycobacterial infections, ENT, malignancies, metastatic cancer
What are typical causes of right supraclavicular lymphadenopathy?
Mediastinal, bronchogenic, esophageal cancer
What are typical causes of left supraclavicular lymphadenopathy?
gastric, gall bladder, pancreas, renal, testicular/ovarian ca
What are typical causes of axillary lymphadenopathY?
cat scratch fever, breast ca, metastatic ca
What are typical causes of epitrochlear lymphadenopathy?
infections, sarcoidosis, lymphoma
What are typical causes of lower/inguinal lymphadenopathy?
STDs, Skin, cervic, vulva/ penis, rectum/anus ca
What is usually the issue if there is localized lymphadenopathy?
reactive or neoplastic
What are the three major categories associated with generalized lymphadenopathy?
reactive, inflammatory, neoplastic
What are 4 differentials of reactive generalized lymphadenopathy?
- Bacterial (TB, lyme, brucellosis, cat scratch disease) 2. Viral (EBV, CMV, HIV) 3. Parasitic (toxoplasmosis) 4. Fungal (histoplasmosis)
What are 4 differentials of inflammatory generalized lymphadenopathy
- Collagen disease (RA, dermatomyositis, SLE, vasculitis, Sjorgen) 2. Drug hypersensitivity 3. Sarcoidosis, amyloidosis 4. serum sickness
What are 3 differentials of neoplastic generalized lymphadenopathy?
- lymphoproliferative disorder/lymphoma 2. metastatic cancer 3. histiocytosis X
What are the consistency, mobility, tenderness, and size of inflammatory and neoplastic lymph nodes?
Inflammatory (rubbery,mobile, tender, 2cm)
What are the 3 main differential categories for splenomegaly?
Increased demand for splenic function (hematological, infectious, inflammatory), Congestive (cirrhosis), Infiltratic (malignant/non malignant)
What are 6 hematological differentials for splenomegaly (increased demand >hematological)
spherocytosis, hemoglobinopathies, hemolysis, sequestration crisis, nutritional anemias, elliptocytosis
What are 8 infectious causes of splenomegaly (increased demand for splenic function >infectious)
CMV, Bacterial endocarditis, TB, HIV/AIDS, EBV, Malaria, Histoplasmosis, Leishmaniasis
What are 4 inflammatory causes of splenomegaly? (Increased demand > Inflammatory)
Felty Syndrome, Still’s Disease, SLE, Sarcoidosis
What are 3 congestive (cirrhosis) causes of splenomegaly?
splenic vein thrombosis, portal vein obstruction, portal HTN (right heart failure)
What are 4 non malignant (infiltrative) causes of splenomegaly?
benign metaplasia, amyloidosis/sarcoidosis, lysosomal storage diseases (Gaucher’s, Niemann-Pick), Glycogen storage diseases
What are 5 malignant (infiltrative) causes of splenomegaly?
Leukemia (CML), Lymphoproliferative disease, hodgkin lymphoma, myeloproliferative disorders, metastatic tumour
What are 5 hx questions important for splenomegaly?
- Constitutional Sx 2. S&S of infection or malignancy 3. hx of liver disease 4. hemolytic anemia 5. high risk exposures
7 things to do on physical exam of splenomegaly
- jaundice/petechiae 2. stigmata of liver disease 3. associated lymphadenopathy/ hepatomegaly 4. signs of CHF 5. palpation and percussion of castell’s sign, traubes space
What investigations need to be done for splenomegaly?
CBC/Diff, blood film, LFT, retic count, monospot, haptoglobin, LDH, infection/autoimmune workup. Imagine
How does ferritin trend with a) Iron Def Anemia b) Anemia of Chronic Disease c) Sideroblastic Anemia and d) Thalassemia
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How does serum iron trend with a) Iron Def Anemia b) Anemia of Chronic Disease c) Sideroblastic Anemia and d) Thalassemia

How does TIBC trend with a) Iron Def Anemia b) Anemia of Chronic Disease c) Sideroblastic Anemia and d) Thalassemia

How does RDW Trend with a) Iron Def Anemia b) Anemia of Chronic Disease c) Sideroblastic Anemia and d) Thalassemia

What shows up on blood film for a) Iron Def Anemia b) Anemia of Chronic Disease c) Sideroblastic Anemia and d) Thalassemia

What happens to dietary iron when it is absorbed in the GI tract?

What are the differentials for approach to splenomegaly?

What is the differentials for generalized lymphadenopathy?

What are the differences between inflammatory and neoplastic lymph nodes?

What is an approach to pancytopenia?

What is an approach to thrombocytopenia

What is an approach to anemia ?

What are the definitions and associated conditions with RBC Nucleus

What are the definitions and associated conditions with Heinz Bodies

What are the definitions and associated conditions with Howell- Jolly Bodies

What are the definitions and associated conditions withBasophilic Stippling

What are the definitions and associated conditions with Sideroblasts

What do spherocytes, elliptocytes, schistocytes, sickel cells, target cells, teardrop cells, spurr cells, burr cells, roleaux formation, nucleated RBC, Heinz body, Basophilic stippling, Auer Rods, Reed Sternberg cells, Smudge cells

What are the definitions and associated conditions with Discocytes, spherocytes and Elliptocytes/ Ovalcytes?

What are the definitions and associated conditions with Schistocytes (helmet cells) and sickle cells

What are the definitions and associated conditions with Codocytes (target cells), Darocyte (teardrop cell)

How do you write a CBC in a chart?

What is the clinical use of RDW?

What are the definitions of common terms found on CBC (RBC, Hgb, Hct, MCV, MCH, MCHC, RDW, WBC, Platelet Count, MPV

How does the cell lineage work from Hematopoetic Stem Cells to Platelets and Erythrocytes?

How does the cell lineage work from Hematopoetic Stem Cells to Erythrocytes, Macrophages, and Granulocytes (basophils, eosinophils, neutrophils)?

How does the cell lineage work from Hematopoetic Stem Cells to T Cells and B cells?

What is a Left Shift?

What are some common features of reticulocytes?

What do you have to rule out in Thrombcytopenia?

What are 5 causes of microcytic anemia?

what does the pneumonic TAILS stand for, in causes of microcytic anemia?
Thalassemia, Anemia of chronic disease, iron deficiency, Lead poisoning, Sideroblastic anemia
Define microcytic anemia
MCV
How much iron does the average north american adult diet have/
10 - 20mg
How much iron gets absorbed (%) ?
5 - 10%
What enhances iron absorption?
citric acid, abscorbic acid (vit C)
What reduces iron absorption?
polyphenols (tea), phytate (in bran), dietary calcium, soy protien
Do males have a positive of negative Fe balance
positive balance
up to ____% of menstruating females have a negative Fe Balance?
20%
Dietary iron is absorbed where?
duodenum (impaired by IBD, celiac disease)
what is non heme iron bound to in circulation?
transferring
what does transferring do?
transfers iron from enterocytes and storage pool sites (macrophages/hepatocytes) to RBC precursors in the bone marrow
What is ferritin (molecularly)?
ferric iron complexed to a protein called apoferritin (hepatocytes are the main ferritin storage site)
Where is ferritin present?
small quantities are present in plasma in equilibrium with intracellualr ferritin
What kind of reactant is ferrition
acute phase reactant
When can ferritin be high spuriously?
when it is an acute phase reacting, spuriously elevated despite low FE stores
What is hemosiderin?
aggregates or crystals of ferritin with the apoferritin partially removed
What is the main source of hemosiderin storage?
macrophage, monocte system
What is the gold standard test for iron stores?
bone marrow aspirate
What is the single most important blood test for iron stores?
serum ferritin
when is serum feritin decreased?
iron deficiency anemia
when is serum ferritin elevated?
infection, inflammation, malignancy, liver disease, hyperthyroidism, iron overload
What is serum iron?
measure of all non-heme iron present in blood
What is all serum iron bound to?
transferrin, only a trace is froo or complexed in ferritin
does serum iron vary significantly daily?
yes
What is Total iron binding capacity?
total amount of transferring present in blood
How much TIBC is saturated with iron normally?
one third
what is TIBC specific for?
highly specific for decreased iron, low sensitivity
What is iron saturation
serum Fe divided by TIBC, expressed as a proportion or a percentage
when is iron saturation low?
low in iron deficiency anemia
what does soluble transferring receptor (sTfR) reflect?
the availability of iron at the tissue level
where is the transferring receptor in soluble transferring receptor expressed?
on the surface of erythroblasts and is responsible for iron uptake; some is cleaved off and is present in circulation as sTfR
is there an increase in sTfR or decrease in iron deficient states or a decrease and why
more and transferrin receptor is expressed on erythroblasts, leading to an increase in sTfR
When is sTfR low?
in reduced erythropoiesis and iron overload
when is sTfR useful?
in determining iron deficiency in the setting of chronic inflammatory disorders