Hematology Flashcards
1) Review of Blood Physiology
Blood is a ______ tissue
Blood components (2) %
Where is each component produced (3),(4)?
Blood is a connective tissue
-
Plasma 55% (proteins)
- Liver* reticuloendothelial cells of adults
- Spleen
- Bone marrow
-
Blood Cells 45%
- Bone marrow*
- Thymus
- Lymph nodes
- Spleen at diff points in development and under stress
In some pathological conditions spleen and bone marrow can take over to some extent – of producing proteins of plasma
Blood Functions
- ____ exchange
- H_____ and n____ transport
- Adaptive and innate ______
- Co_______
- W_____ elimination
- T______ regulation
Takeaway =
- Gas exchange
- Hormonal and nutrient transport
- Adaptive and innate immunity
- Coagulation
- Waste elimination
- Temperature regulation (vasodilation/vasoconstriction)
Blood disorders have the potential to impact every other organ system!
Cell Lines
All cells originate from (1)
Myeloid Cells (4)-(1)
Lymphoid Cells (3)
Multipotential Hematopoietic Stem Cell (MHSC)
Myeloid Cells = RBC, Platelets, Mast Cells, Granulocytes (Neutrophils, Basophils, Eosinophils, Monocytes)
Lymphoid Cells = NK cells, T and B Lymphocytes, Plasma Cells
Erythropoesis
- RBCs are produced in BM in response to (1)
- EPO is released from _______ in response to sensing low _______ of blood and tissues.
- As oxygenation increases, EPO is _____regulated
- As cells mature from progenitor cells they ____ organelles and their nucleus
- Mature RBCs live approx. ____ days
- Seeing an increase in early forms in blood and/or earlier stages of differentiation can indicate stress on BM from hyp____, inf_____, hemo_____ and/or BM nec______
- RBCs are produced in BM in response to EPO
- EPO is released from kidneys in response to sensing low oxygenation of blood and tissues.
- As oxygenation increases, EPO is downregulated
- As cells mature from progenitor cells they lose organelles and their nucleus
- Mature RBCs live approx. 120 days
- Seeing an increase in early forms in blood and/or earlier stages of differentiation can indicate stress on BM from hypoxia, infection, hemolysis and/or BM necrosis
Hemoglobin (Hb)
=
- Used to carry _____ in the blood
- Consists of 4 subunits =
- Missing or altered subunits can result in a number of pathological conditions affecting (1
- Destruction of RBCs either through standard or accelerated processes releases ______ into the blood stream
Metalloprotein in RBC’s
- Used to carry oxygen in the blood
- Consists of 4 subunits (2 𝞪 and 2𝜷)
- Missing or altered subunits can result in a number of pathological conditions affecting oxygen transport
- Destruction of RBCs either through standard or accelerated processes releases bilirubin into the blood stream
Iron
Role of iron?
- Iron required typically obtained from _____
- No efficient physiological means of ______ iron other than from cell _____, therefore?
Necessary for heme synthesis and provides strength and stability to the hemoglobin molecule
- Iron required typically obtained from diet
- No efficient physiological means of removing iron other than from cell shedding from the GI tract, therefore iron supplementation not a harmless therapy bc of effects of iron overload
Clotting
- Tissue injury results in potential blood loss
- Release of tissue ____ stimulates initial platelet ____ and clotting ______ which stabilizes plug with a cross linked ____ clot
- Objective is to ____ bleeding and prevent entry of _____
- Tissue injury results in potential blood loss
- Release of tissue factor stimulates initial platelet plug and clotting cascade which stabilizes plug with a cross linked fibrin clot
- Objective is to stop bleeding and prevent entry of microbes
Clotting Notes
- Intrinsic pathway factors (5)
- Extrinsic pathway factors (2)
- Common pathway – (4)
- PT (INR) – asctd with ______ pathway
- PTT –asctd with ______ pathway
- Intrinsic pathway – 12, 11, 8, 9, 10 (common pathway technically) TENANT
- Extrinsic pathway – tissue factor and lucky number 7
- Common pathway – you go to the bank and get small bills 10, 5, 2, 1
- PT (INR) – asctd with extrinsic pathway
- PTT –asctd with intrinsic pathway
Immunity
-
(1)- 1st line of defense; non specific
- Monocytes/Dendritic cells function (1)
- Granulocytes/Mast cells function (1)
-
(1)- specific to pathogen
- B lymphocytes function (1)
- T lymphocytes function (3)
-
Innate - 1st line of defense; non specific
- Monocytes/Dendritic cells - phagocytosis
- Granulocytes/Mast cells - degranulation
-
Adaptive - specific to pathogen
- B lymphocytes - antibody production
- T lymphocytes - direct cytotoxicity, production of cytokines, recruitment and de-escalation of immune response
Big Picture
about blood disorders =
- Because blood is relevant to every system in the body, you can expect to see some pathology in every system when there is a blood disorder.
- Correction of hematological abnormalities will directly impact other systemic disorders; don’t be afraid to be assertive and treat or refer.
2) The peripheral blood smear mini “atlas”
What should be the relative size of an RBC?
Should be around the size of a small lymphocyte - so in this pic the RBC’s are microcytic
Red Cell Line
(1) → (1) → (1)
nRBC’s → Reticulocytes → Erythrocytes
Red Cell Lines
-
Erythrocyte
- Functional unit of _____ transport
- What does it look like?
- Lives how long?
-
Reticulocytes
- What are they?
- What does it look like?
- Any central pallor?
-
nRBCs
- What are they?
- What does it look like?
- Will we see these in a smear?
-
Erythrocyte
- Functional unit of oxygen transport
- Enucleated biconcave disc
- Lives approx 120 days
-
Reticulocytes
- Immature erythrocytes
- Loose condensed chromatin without clear nuclear envelope (reticular network)
- No central pallor
-
nRBCs
- Immature erythrocytes
- Clear nucleus and condensed chromatin
- Abnormal in smear; body is desperate for RBCs
- Loosely condensed chromatin – remnants of nuclear material*
- More reticulocytes = more demand*
- In bottom right pic – the erythrocytes are a bit hypochromic indicating problems with oxygen*
Red Blood Cell Morphology
Tear drops can arise from ___ deficiency, bone marrow _____, however if all the tear drops facing the same way =
Schistocytes indicative of ______ (some hemolysis is normal but shouldn’t see more than 3-4 shistocytes) – pretty much are cell fragments (cells that have died), increased in sickle cell/small blood vessel clotting disorders
Agglutination – can be seen in (1) reactions – foreign blood attacking host blood, neoplasms/cancer, ehler’s danlos, infection, inflammation
Tear drops can arise from b12 deficiency, bone marrow fibrosis, however if all the tear drops facing the same way – lab person just smeared the blood sample too aggressively and squished the cells
Schistocytes indicative of hemolysis (some hemolysis is normal but shouldn’t see more than 3-4 shistocytes) – pretty much are cell fragments (cells that have died), increased in sickle cell/small blood vessel clotting disorders
Agglutination – can be seen in blood transfusion reactions – foreign blood attacking host blood, neoplasms/cancer, ehler’s danlos, infection, inflammation
Platelet cell lines
- Platelet
- Small cell fragments (~__% size of RBC)
- Life approx __-__ days
- _________
- Large precursor cell
- ______ up into smaller fragments to create platelets (~1000)
- Should we see platelets in a peripheral blood smear?
- Platelet
- Small cell fragments (~20% size of RBC)
- Life approx 7-10 days
- Megakaryocyte
- Large precursor cell
- Breaks up into smaller fragments to create platelets (~1000)
- Should not be present in peripheral blood, lives in bone marrow
Which Granulocyte (white cell line) does this describe?
- Regulate inflammation
- Trap and kill parasites (mostly multicellular)
- Increase during allergic reactions, parasites, pernicious anemia
- Decrease with certain infections, corticosteroids
Eosinophils
Which Granulocyte (white cell line) does this describe?
- Trap and kill pathogens (mostly bacterial)
- Bands- continuous nucleus; bandlike
- Mature -lobulated
- Can increase with infection, granulocyte leukemias, and burns
- Can decrease due to certain drugs/environmental exposures, viruses, or in aplastic anemias
Note: marrow stress from infection can results in “left shift” meaning there is a high number of immature granulocytes in blood
Neutrophils
Which Granulocyte (white cell line) does this describe?
- Cytokine, histamine and heparin release
- Facilitate immune response of other cells by making environment favorable
- Often involved in parasite response
- Poorly understood
- Secretory function to mediate function of other cells but also drive anaphylaxis
- Increase in CML, PV
Basophils
Which Agranulocyte (white cell line) does this describe?
- Engulfs pathogens, cleans up foreign material and tissue debris after injury
- Further differentiation to macrophage or dendritic cell in tissues
- Large well stained nuclei with blue-gray “ground glass” cytoplasm
Monocytes
Monocytes that differentiate into dendritic cells also function as antigen presenting cells
Can increase in monocyte leukemias, TB, connective tissue diseases, chronic infections/ inflammation
Which Agranulocyte (white cell line) does this describe?
- Antibody production, direct cytotoxicity of cells infected by viruses or abnormal cells
- Directors or adaptive immune response
- Large well stained nucleus with very little, blue staining cytoplasm
Lymphocytes
-T cell matures in thymus, B cell matures in bone marrow
Can increase in infection, TB and lymphocytic leukemias
3) Review of the CBC
Why do I need this Test?
- Screening/Prognosis
- Determine r___
- E____ intervention
- D_____
- Include or exclude possibility of disease
- Consider the possibility of alternate diagnosis
- M______
- How severe is the disease?
- How far has the disease progressed?
- Is our treatment working?
- What drugs are appropriate in treatment?
- Screening/Prognosis
- Determine risk
- Early intervention
- Diagnosis
- Include or exclude possibility of disease
- Consider the possibility of alternate diagnosis
- Management
- How severe is the disease?
- How far has the disease progressed?
- Is our treatment working?
- What drugs are appropriate in treatment?
- Remember that you are responsible for following up on any test which you order*
- Only order a test that you can reliably interpret and decide a treatment for*
- Take in the full clinical picture available and don’t panic about isolated abnormalities or expected abnormals.*
Sensitivity and Specificity
- Sensitivity → “true _____”
- _____ → ↑Sensitivity rules OUT → negative test, no disease
- Specificity → “true _____”
- _____ → ↑Specificity rules IN → positive test, has disease
- Notes:
- Sensitivity and specificity can vary with respect to screening or diagnosis
- Ie: PSA testing for screening vs monitoring
- Same test can have variable sensitivity and specificity for different _____
- Ie: EKGs baseline vs acute chest pain
- T_____ of test is important
- Ie: COVID swabs and HIV testing
- Sensitivity and specificity can vary with respect to screening or diagnosis
- Sensitivity → “true positives”
- SnOUT → ↑Sensitivity rules OUT → negative test, no disease
- Specificity → “true negatives
- SpIN → ↑Specificity rules IN → positive test, has disease
- Notes:
- Sensitivity and specificity can vary with respect to screening or diagnosis
- Ie: PSA testing for screening vs monitoring
- Same test can have variable sensitivity and specificity for different purposes
- Ie: EKGs baseline vs acute chest pain
- Timing of test is important
- Ie: COVID swabs and HIV testing
- Sensitivity and specificity can vary with respect to screening or diagnosis
General Approach to Heme Labs
-
Is the value _____?
- Should it be? Underlying conditions? Treatments applied and how often?
-
Is the patient s______?
- Do we actively treat? Surveillance? Referral to specialist? Referral to ED?
- Are symptoms unaccounted for by other medical conditions or history? OLDCART
-
_____ counts
- Increased destruction? Malignancy? Hemolysis? Autoimmune disorder?
- Decreased production? Hepatic or Renal compromise? Drugs impacting marrow? Infection?
-
_____ counts
- Increased production? Malignancy? Other chronic illness? Inflammation?
- Decreased destruction? Myelosuppression? Meds? Infections?
- Big picture
-
Is the value normal?
- Should it be? Underlying conditions? Treatments applied and how often?
-
Is the patient symptomatic?
- Do we actively treat? Surveillance? Referral to specialist? Referral to ED?
- Are symptoms unaccounted for by other medical conditions or history? OLDCART
-
Low counts
- Increased destruction? Malignancy? Hemolysis? Autoimmune disorder?
- Decreased production? Hepatic or Renal compromise? Drugs impacting marrow? Infection?
-
High counts
- Increased production? Malignancy? Other chronic illness? Inflammation?
- Decreased destruction? Myelosuppression? Meds? Infections?
- Big picture
Important terms
-
(1) - decrease in cell numbers
- (1) - low RBCs/ Hb
- (1) - low WBCs (broadly)
- (1) - low neutrophils (normally > half all WBCs)
- (1) - low platelets
- (1) - all cell lines low (RBC, WBC and PLTs)
-
(1) - increase in cell numbers
- (1)/(1) - high RBCs
- (1) - high WBCs (broadly
- (1) - high platelets
-
Cytopenia - decrease in cell numbers
- Anemia - low RBCs/ Hb
- Leukopenia - low WBCs (broadly)
- Neutropenia - low neutrophils (normally > half all WBCs)
- Thrombocytopenia - low platelets
- Pancytopenia - all cell lines low (RBC, WBC and PLTs)
-
Cytosis - increase in cell numbers
- Erythrocytosis/Polycythemia - high RBCs
- Leukocytosis - high WBCs (broadly
- Thrombrocytosis - high platelets
WBC
Normal Range
- High levels =
- Low levels =
4-11K/uL
- High = Infection, inflammation, acute and chronic leukemias, polycythemia vera, anaphylaxis, smoking, COPD/emphysema, obesity, etc
- Low = Cancer (liquid and solid tumor), chemotherapy/radiation, aplastic anemia, bone marrow failure, HIV/AIDS, TB, autoimmune disease, nutritional deficiencies and malnutrition
RBC
Normal Range
- High levels =
- Low levels =
3.8-5.3 M/uL
- High = Smokers, living or endurance training in high altitude, dehydration, doping in athletes, structural heart disease, heart failure, COPD/emphysema, polycythemia vera, certain solid tumors, etc.
- Low = Anemias(broadly), thalassemias, hemoglobinopathies, bone marrow failure, thyroid disease, chronic kidney disease, chronic blood loss (including GI and HMB), chronic inflammation, Pb poisoning, certain drugs, liquid and solid tumors, frequent blood donation.
Hemoglobin (Hb)
Normal Range
- High levels =
- Low levels =
Males 14-18 g/dL
Females 12-16 g/dL
- High = Smokers, living or endurance training in high altitude, dehydration, doping in athletes, structural heart disease, heart failure, COPD/emphysema, polycythemia vera, certain solid tumors, etc.
- Low = Anemias(broadly), thalassemias, hemoglobinopathies, bone marrow failure, thyroid disease, chronic kidney disease, chronic blood loss (including GI and HMB), chronic inflammation, Pb poisoning, certain drugs, liquid and solid tumors, frequent blood donation.
Hematocrit (Hct)
Normal Range
Meaning of measurement
- High levels =
- Low levels =
Males 40-54%
Females 37-47%
% of RBCs per sample of blood
- High = Smokers, living or endurance training in high altitude, dehydration, doping in athletes, structural heart disease, heart failure, COPD/emphysema, polycythemia vera, certain solid tumors, etc.
- Low = Anemias(broadly), thalassemias, hemoglobinopathies, bone marrow failure, thyroid disease, chronic kidney disease, chronic blood loss (including GI and HMB), chronic inflammation, Pb poisoning, certain drugs, liquid and solid tumors, frequent blood donation.
Platelets (PLT)
Normal Range
- High levels =
- Low levels =
150-400 K/uL
- High = Infection, inflammation, cancers, polycythemia, essential thrombocytosis
- Low = TTP, ITP, BM failure
MPV
=
Normal Range
- Low MPV =
8-12 fL
Mean size of platelets, older platelets generally smaller
- Low MPV = BM failure, renal disease, aplastic anemia, cancers, inflammation/infection, some drugs
MCV
=
Normal Range
- High MCV =
- Low MCV =
86-98 um3/cell
(Mean Corpuscular Volume) = Ave size of RBCs
High:Low B12/B9, AUD, hypothyroid, liver disease, pernicious anemia, AIHA, Leukemia, some drugs
Low: IDA, chronic disease/inflammation, thalassemia, low Cu, low Vit A, Pb poisoning
MCH
=
Normal Range
- High levels =
- Low levels =
27-32 uug/RBC
(Mean Corpuscular Hemoglobin) Ave concentration of Hb per cell
High: Low B12/B9, AUD, hypothyroid, liver disease, pernicious anemia, some drugs, MDS
Low: IDA, hemoglobinopathies, thalassemia
MCHC
=
Normal Range
- High levels =
- Low levels =
31-37 g/dL
Mean corpuscular hemoglobin concentration = ave concentration of Hb per unit volume
High: early ID, hemolytic anemias, hereditary spherocytosis
Low: IDA or anemia of chronic illness
RDW
=
Normal Range
Generally larger indicates? what could cause this?
11.5-14.5%
Red cell distribution width = Range in variation in RBC size
Generally larger indicates more rapid turnover from
Anemias (including hemoglobinopathies and thalassemias), chronic illness/inflammation/blood loss, nutritional deficiencies
CBC Differential (WBC Differential) Normal Ranges
Never Let Monkeys Eat Bananas
Neutrophils 55-70% (~60%)
Lymphocytes 20-40% (~30%)
Monocytes 2-8% (~6%)
Eosinophils 1-4% (~3%)
Basophils 0.5-1% (~1%)
- Note: look at the big picture, if one value is super high, it will automatically lower the other values*
- Remember to consider both the absolute counts (vary by lab) and the %; they both give insights into what may be occurring*
WBC Differential Functions
- Neutrophils =
- Lymphocytes =
- Monocytes =
- Eosinophils =
- Basophils =
- Neutrophils = first line immune response, shapes early host response
- Lymphocytes = antibody production, direct cytotoxicity of cells infected by viruses or abnormal cells, directors or adaptive immune response
- Monocytes = Boosts immune response, engulfs pathogens, cleans up foreign material and tissue debris after injury
- Eosinophils = regulates inflammation, traps and kills pathogens
- Basophils = Facilitates immune response of other cells by making environment favorable; often involved in parasite response
Reticulocytes
- Increase in retics may indicate?
- Normal retics in setting of _____ may be inappropriate (ARC>120)
- Low levels or retics may indicate insufficiency due to?
- Increase in retics may indicate high RBC turnover
- Normal retics in setting of hemolysis may be inappropriate (ARC>120)
- Low levels or retics may indicate insufficiency due to CKD/Low Epo
nRBCs
What does an increased # of nRBCs indicate? (2), relative to high reticulocytes?
Increased nRBCs represent stress on the marrow and need for fast RBC turnover; more severe than increased reticulocytes; consider severe infection or BM infarction
ANC levels
Calculation for ANC?
At what point do you need prophylaxis?
- Mild Neutropenia
- Moderate Neutropenia
- Severe Neutropenia
- Agranulocytosis
WBC x [(PMN% + Bands%)/100]
- Mild Neutropenia <1500
- Moderate Neutropenia <1000 (risk of infection)
- Severe Neutropenia <500 (high risk of infection, may need prophylaxis)
- Agranulocytosis <100 (critical risk of infection)
Highlights of BMP and other lab studies
-
sCr
- (1) may be cause of low Epo production
- Also important to know with respect to Rx of any (1)
-
LDH
- Measure of tissue _____/cell _____ → consider _____ but less specific
-
Ferritin
- Reflects whole body iron _____
- Can be (1) during acute inflammatory states
-
sCr
- CKD may be cause of low Epo production
- Also important to know with respect ot Rx of any medication
-
LDH
- Measure of tissue damage/cell necrosis → consider hemolysis but less specific
-
Ferritin
- Reflects whole body iron stores
- Can be artificially inflated during acute inflammatory states (Bc ferritin is an acute phase reactant so will be artificially high during infection)
Highlights of BMP and other lab studies
Bilirubin
○ ↑͢direct (conjugated) →
○ ↑͢indirect (unconjugated) →
Transaminases
○ ↑͢AST - may indicate (1)
○ ↑͢ALT - may indicate (1)
○ ↑͢ALP - bone marrow _____ or ______ disease
Bilirubin
○ ↑͢direct (conjugated) → may indicate hepatocellular injury
○ ↑͢indirect (unconjugated) → likely from hemolysis
Transaminases
○ ↑͢AST - may indicate hemolysis
○ ↑͢ALT - may indicate hepatocellular injury
○ ↑͢ALP - bone marrow necrosis or metastatic disease
- Anemia
=
- Decrease in one of the (3) major RBC indices
- WHO criteria in males and females =
- Always treat anemias as a ______ rather than a disease entity and work to correct the underlying disorder
Mismatch between oxygen supply to the tissues carried by RBCs and metabolic need
- Decrease in one of the three major RBC indices: RBC, Hct or Hb
- WHO criteria: Hb <13 (males), Hb <12 (females)
- Always treat anemias as a symptom rather than a disease entity and work to correct the underlying disorder
General Pathologic Causes of Anemia
(3)
- Other causes: physiological anemia of ____ in women, ath_____
- Anemia masks: sm______, de______, living at (1)
Blood loss/Inflammation
Low production of RBCs
High destruction of RBCs (hemolytic anemias)
- Other causes: Physiological anemia of pregnancy, Athletes
- Anemia masks: Smoking, Dehydration, Living at high altitude (all are hemoconcentrated states)
Smoking – deoxygenates (dt many factors but also inhaling carbon monoxide impairs oxygen transport)
Anemia General Medical History
- Known medical conditions & medications → HMB = , N___/A__ use, last E___/C___ screen, Chronic ____ Disease, C__ Hx?
- Family history of anemia → ___PD, S____ cell disease, th______, k____ disease?
- Lifestyle and diet → Sm____, Et___ use, ath____, veg___?
- Known medical conditions & medications → HMB, NSAID/ASA use, last EGD/CRC screen, CKD, Ca Hx?
- Family history of anemia → G6PD, SCD, thalassemias, kidney disease?
- Lifestyle and diet → Smoker, EtOH use, athlete, vegan?
Anemia History
- OLDCART
-
Symptoms
- General →
- IDA → (3)
- Macrocytic → (2)
- Hemolysis → (3)
- Chronicity → how quickly and for how long have symptoms persisted
- Recent travel → T____ infections or p_____?
- OLDCART
-
Symptoms
- General → Fatigue, weakness, dizziness, HA, SOB, CP, palpitations, cold extremities, weight loss, brittle nails, paleness
- IDA → Ice chewing, PICA, restless legs
- Macrocytic → poor concentration/memory loss, burning and tingling in fingers and toes
- Hemolysis → yellow skin and eyes, dark urine, worsening of other symptoms with certain foods/drugs
- Chronicity → how quickly and for how long have symptoms persisted
- Recent travel → Tropical infections or parasites?
Anemia Eval Contextual Factors
Acute or Chronic bleeding
- Bleeding from (2)
- Known ___ ulcers/tumors, stool abnormalities (2)
- Urine abnormality (1)
- Menstrual abnormality (1)
- Transfusions → acute or delayed ______ transfusion reaction
Anemia Eval Recent Travel?
- (1) borne illness → malaria, dengue, etc..
- (1) borne illness → babesiosis (hikers or agricultural workers)
- (1) fevers → ebola, nippah, hantavirus
- Mosquito borne illness → malaria, dengue, etc..
- Tick borne illness → babesiosis (hikers or agricultural workers)
- Hemorrhagic fevers → ebola, nippah, hantavirus
Anemia Eval
What can volume depletion do to underlying anemias?
May mask anemias in those who are symptomatic but CBC is otherwise WNL
S/S of Anemia
- General appearance
- Vitals
- Skin
- HEENT
- Heart
- Abdomen
- Neuro
- MSK
- Psych
- General appearance - listless in advanced cases
- Vitals - ↑HR and/or ↓BP in advanced cases (may have wide pulse pressure 120/50)
- Skin - pallor, jaundice, mucous membrane pallor, spoon nails, cold to touch
- HEENT - conjunctival pallor, scleral icterus, glossitis, angular cheilitis
- Heart- tachycardia, flow murmurs
- Abdomen - hepatosplenomegaly
- Neuro - acroparesthesias
- MSK - weakness
- Psych - depression, poor memory and concentration; dementia like symptoms in severe anemia
Anemia Lab Findings
- (1) → Hb levels and red cell indices
- (1) → enough production? appropriate to degree of hemolysis?
- (1) → renal function
- (1) → bilirubin and transaminases
- (1) → hemolysis/necrosis
- (1) → iron stores; beware inflammatory processes
- (1) → ↑ may reflect iron deficiency; ↓ acute phase reaction, chronic illness or iron overload
- (1) → ↑ iron overload; ↓ IDA or chronic illness
- CBC → Hb levels and red cell indices
- Retic’s → enough production? appropriate to degree of hemolysis?
- BMP → renal function
- LFT → bilirubin and transaminases
- LDH → hemolysis/necrosis
- Ferritin → iron stores; beware inflammatory processes
- TIBC→ ↑ may reflect iron deficiency; ↓ acute phase reaction, chronic illness or iron overload
- TSAT → ↑ iron overload; ↓ IDA or chronic illness
Iron Panel (4)
Serum Iron
Ferritin
TIBC (blood’s ability to attach itself to iron and transport it around the body, indirect measurement of transferrin, the protein transports iron)
TSAT (Transferrin saturation ie iron saturation)
If you are doing a direct look for IDA, your best labs would be? (4)
CBC, Ferritin, TIBC and TSAT
Anemia Imaging
○ Abdominal US → spleen, liver?
○ Echocardiogram → _____ heart, ______ E/E’, ____ TRJ velocity
○ CT/MRI → spleen, liver, LN?
○ Abdominal US → enlarged or absent spleen, hepatomegaly
○ Echocardiogram → enlarged heart, elevated E/E’, high TRJ velocity
○ CT/MRI → enlarged or absent spleen, hepatomegaly, enlarged lymph nodes
Anemia Causes Direct Visualization
○ (1) → polyps, chronic gastritis, ulcers, tumors, tumors, etc…
○ (1) → polyps, colitis, fistulas, ulcerations, tumors, etc…
○ EGD → polyps, chronic gastritis, ulcers, tumors, tumors, etc…
○ Colonscopy → polyps, colitis, fistulas, ulcerations, tumors, etc…
- Do not blanket order imaging for new anemia. These suggestions are here regarding old imaging that might offer insight into a new anemia or progression of known anemia.*
- Do order colonoscopy for anyone appropriate for screening by age or investigation by symptoms. New iron deficiency anemia is an indication for colonoscopy in adults regardless of age. I would strongly consider it in anyone who is anemic and microcytic without other explanation.*
Anemia severity and progression
Can range from mild asymptomatic to severe requiring admission:
Important features for determining level of care:
● Clinical ______
● Overall _____ of health at baseline
● Pace of symptom pr________
● Pace of l___ changes
● Ability of body to com________
Important features for determining level of care:
● Clinical presentation
● Overall state of health at baseline
● Pace of symptom progression
● Pace of lab changes
● Ability of body to compensate
A note on acute blood loss
- Normal adult blood volume =
- 1 unit of blood =
- By volume loss:
○ ≤ 20% (≤1000 cc)→
○ 20-30% (1000 -1500cc) →
○ 30-40% (1500 - 2000cc)→
○ ≥50% (≥2500cc)→
- Normal adult blood volume: ~5000 cc
- 1 unit of blood = 500cc
- By volume loss:
○ ≤ 20% (≤1000 cc)→ asymptomatic at rest; tachycardia and mild SOB with activity
○ 20-30% (1000 -1500cc) → variable but symptomatic at rest and may progress rapidly
○ 30-40% (1500 - 2000cc)→ circulatory collapse and hypovolemic shock
○ ≥50% (≥2500cc)→ incompatible with life
Chronically Progressive Anemias
- Hb may drop to 50% below baseline without threat of sh___ or d____
- Compensatory mechanisms → ↑O2 delivery per RBC
- ↑(1) → ↑circulation to maintain O2 delivery
-
↑(1) → ↑ increased extraction of O2 from the blood
- ____ shift of O2 dissociation curve
-
↑(1) → ↑ anaerobic metabolism → ↓pH
- _____ shift of O2 dissociation curve
- Compensatory mechanisms → ↑O2 delivery per RBC
- Hb may drop to 50% below baseline without threat of shock or death
- Compensatory mechanisms → ↑O2 delivery per RBC
- ↑HR → ↑circulation to maintain O2 delivery
-
↑2,3DPG → ↑ increased extraction of O2 from the blood
- Right shift of O2 dissociation curve
-
↑hypoxia → ↑ anaerobic metabolism → ↓pH
- Right shift of O2 dissociation curve
- Compensatory mechanisms → ↑O2 delivery per RBC
- 2**,3 Bisphosphoglycerate -stabilizes oxygenated form of Hb*
- The RBC 2,3 BPG (also known as 2,3 DPG) molecule* stabilizes the deoxygenated form of hemoglobin by allosteric binding and facilitates oxygen release at tissue sites.
Macrocytic =
Normocytic =
Microcytic =
MCV > 100
MCV 80-100
MCV <80
Macrocytic Anemia Differentials
(4)
Vitamin B9, B12 Deficiency
(GI/bariatric surgery, chronic PPIs)
Chronic ETOH use/abuse
Increased Bone Marrow Stress
(MDS, AML, other heme malignancy, chemo, hydroxyurea, azidothymidine (AZT) antiretroviral)
Pernicious Anemia
Nutritional vs. Malabsorptive (bariatric surgery, alcohol)
Macrocytic Anemia Workup
(3)
Check VB12 and folate levels
Screen for ETOH use (consider checking LFTs)
Review diet and med list
If MCV > 110 fL → almost always folate or vitamin B12 deficiency
Iron Deficiency Anemia Treatment and FU
- Rx: Depending on severity can start with (1) iron and titrate up; (1) iron if stable but anemia profound
- F/U: Depending on severity: PO iron: _-_ weeks and Q_months after: IV iron: _ weeks (no labs) then _ weeks after for labs
- Rx: Depending on severity can start with (1) iron and titrate up; (1) iron if stable but anemia profound
- F/U: Depending on severity: PO iron: 2-4 weeks and Q3months after: IV iron: 2 weeks (no labs) then 6 weeks after for labs
Plant Sources of Iron
Legumes (5)
Iron enriched cereals (4)
Fruits (4)
Vegetables (4)
N___ and S____
Blackstrap ______
Legumes (Beans, lentils, peas, tofu, tempeh)
Iron enriched cereals (Bread, bran, oats, cornmeal)
Fruits (Figs, dates, raisins, prunes)
Vegetables (Broccoli, dark leafy vegetables, potatoes, cabbage)
Nuts and seeds
Blackstrap molasses
- While not absolutely required, animal sources of iron are generally more bioavailable and easily absorbed than than plant based sources*
- Some vegans will consume bivalves and eggs depending on their definition of veganism and how it fits into their moral framework. It’s worth asking what veganism is to them when considering dietary sources of iron.*
PO Iron Formulations
(3), dose, frequency
-
Pro’s
- ____ line for IDA
- Least in____
- Easiest to obtain
- Least risk of _____genicity
-
Con’s
- GI side effects: (2)
- Max dose: ___mg elemental iron QD
- ____ to take effect
- Timing for max absorption
- Give with (1) to boost absorption
- Rx (1) block absorption
- GI side effects: (2)
Newer forms of PO iron on the horizon with improved absorption and tolerability but hard to obtain coverage
Ferrous Sulfate, Ferrous Gluconate, Ferrous Fumarate 325 TID
- Pro’s
- First line for IDA
- Least invasive
- Easiest to obtain
- Least risk of immunogenicity
- Con’s
- GI side effects: constipation, NVD
- Max dose: 200mg elemental iron QD
- Slow to take effect
- Timing for max absorption
- Give with Vitamin C to boost absorption
- Antacids block absorption
- GI side effects: constipation, NVD
Newer forms of PO iron on the horizon with improved absorption and tolerability but hard to obtain coverage
Sickle Cell Disease/Trait Major Complication
(1) → (4)
Microvascular occlusion and ischemia
- Anemia
- Painful episodes/ chronic pain
- Immuno-compromise
- Multisystem organ dysfunction
Sickle cell inheritance
Type of Inheritance
Usual gene =
SCD =
SCT =
Autosomal Recessive Inheritance
HbAA
SCD = 2 dysfunctional genes for Hb production
SCT = 1 dysfunctional gene
- Leukemia
- Group of malignancies of hematopoetic tissues
- Classically associated with __creased white cells in BM or peripherally
- Etiology is largely idiopathic
- Classified by origin and chronicity of changes
-
(1) cell lines - RBC, PLT, Granulocytes and Monocytes
- Acute =
- Chronic =
-
(1) cell lines - Lymphocytes and NK cells
- Acute =
- Chronic =
-
(1) cell lines - RBC, PLT, Granulocytes and Monocytes
- Group of malignancies of hematopoetic tissues
- Classically associated with increased white cells in BM or peripherally
- Etiology is largely idiopathic
- Classified by origin and chronicity of changes
- Myeloid cell lines - RBC, PLT, Granulocytes and Monocytes
- Acute - AML
- Chronic - CML
- Lymphoid cell lines - Lymphocytes and NK cells
- Acute - ALL
- Chronic – CLL
- Myeloid cell lines - RBC, PLT, Granulocytes and Monocytes
Known risk factors: other heme disorders, chemical exposures, some medications, ionizing radiation, viral infections, heredity
Leukemia Blasts
Blasts on the smear are?
- Difficult to d_____ on your own when looking at smear
- Note ____ counts
- Hematologic e______
- ____ day referral to hematology office or send to closest ___
Blasts on the smear are not normal!
- Difficult to differentiate on your own when looking at smear
- Note WBC counts
- Hematologic emergency
- Same day referral to hematology office or send to closest ER
Lymphoma Classes
(2), (2)
Non-Hodgkins Lymphoma (NHL)
Hodgkins Lymphoma (HL) → Classic vs. Nodular lymphocyte
- NHL is much more common than HL at about a 9:1 ratio*
- Can also further differentiate type by system or tissue involved: CNS lymphoma, Primary gastric, Follicular, Cutaneous, Bone marrow*
Lymphoma Treatment
- Active ______
- S_____ management
- Cytotoxic _____
- _____therapy
- R_____
- H_ _ _
- Active surveillance
- Symptom management
- Cytotoxic chemotherapy
- Immunotherapy
- Radiation
- HSCT
Cutaneous Bleeding
- (1): small flat red discrete areas < 2mm
- (1): collections of petechiae; usually flat but sometimes palpable depending on cause.
- (1): subQ collection of blood that remains flat to skin
- (1): Collection of blood in extravascular space and may raise skin or cause pain in deep tissues
- Petechiae: small flat red discrete areas < 2mm
- Purpura: collections of petechiae; usually flat but sometimes palpable depending on cause.
- Ecchymosis: subQ collection of blood that remains flat to skin
- Hematoma: Collection of blood in extravascular space and may raise skin or cause pain in deep tissues
- A brief visual atlas of some cutaneous findings associated with bleeding*
- Generally listed as increasing in size from large to small; however, not to be confused with importance. Some larger findings like ecchymosis with a known explanation and without impediment to resolving is far less concerning than recurrent diffuse petichiae.*
- Takeaway – ecchymosis vs. hematoma*
Other cutaneous findings associated with bleeding
- (1): Dilated or broken blood vessels near surface of skin
- Perif_____ hemorrhage
- (1): Absence of melanin in skin and hair
- Telangiectasias: Dilated or broken blood vessels near surface of skin
- Perifollicular hemorrhage
- Albinism: Absence of melanin in skin and hair
- Telangictasias - on lips mouth or fingers may be associated with hereditary bleeding disorders*
- Perifolicular hemorrhage - classically associated with scurvy*
- Oculocutenous albinism - can be associated with platelet disorders*
- Other physical exam findings are certainly relevant and should be considered. Patients with recurrent bleeding may present with symptoms of anemia as they are chronically losing Hb.*
Basic Coags: PT and PTT
-
PT _____/ PTT ____ → Extrinsic pathway
- Drug toxicity (VKA), vitamin K deficiency, liver disease, DIC, plasma cell dyscrasia (MGUS, MM, etc…)
- Inherited Factor ____ deficiency is rare but also a possibility
-
PT ____ / PTT _____ → Intrinsic pathway
- DOACs (rare but possible) VWD/aVWD (severe), hemophilias, factor deficiencies,
- Antibody inhibition of pathway 2/2 pregnancy, malignancy or connective tissue disorders
-
____ PT and PTT _____ → common pathway
- Anticoagulant toxicity (VKA, Heparins or DOACs), liver disease, amyloidosis, DIC
- Factor deficiencies or inhibition
-
PT abnormal / PTT normal → Extrinsic pathway
- Drug toxicity (VKA), vitamin K deficiency, liver disease, DIC, plasma cell dyscrasia (MGUS, MM, etc…)
- Inherited Factor VII deficiency is rare but also a possibility
-
PT normal / PTT abnormal → Intrinsic pathway
- DOACs (rare but possible) VWD/aVWD (severe), hemophilias, factor deficiencies,
- Antibody inhibition of pathway 2/2 pregnancy, malignancy or connective tissue disorders
-
Both PT and PTT abnormal → common pathway
- Anticoagulant toxicity (VKA, Heparins or DOACs), liver disease, amyloidosis, DIC
- Factor deficiencies or inhibition
Remember this is just a starting point for investigations and you should be thinking what picture fits these symptoms and what disorders do I not want to miss to guide testing.
Venous Thromboembolism (VTE)
=
- (1) → large vessels of upper or lower extremities
- (1) → migration of clot to lungs impairing gas exchange.
_____ threatening and need immediate intervention even when a_____.
Abnormal clotting of deep venous system with threatened or actual migration of clots to lungs.
- Deep vein thrombosis (DVT) → large vessels of upper or lower extremities
- Pulmonary embolism (PE) → migration of clot to lungs impairing gas exchange.
Life threatening and need immediate intervention even when asymptomatic.
Clot formation in venous sinus, portal vein, renal and mesenteric supplies are also possible but much more rare and managed differently.
DVT Risk Factors
Every 1/____ adults
- Constitutional: ____ age, ob___, pr_____, sm____, imm____, IV__U
- PMH: recent tr____/s___, any ca___, sep___, O__ use, previous DVT, recent venous access, hypercoagulable genetic disorder, APLS =
Every 1/1000 adults
- Constitutional: older age, obese, pregnancy, smoker, immobility, IVDU
- PMH: recent trauma/surgery, any cancer, sepsis, OCP use, previous DVT, recent venous access, hypercoagulable genetic disorder, APLS (antiphospholipid syndrome)
DVT Workup
Imaging (1)
Labs (2) - useful to guide tx if no baseline
Labs (1) not too useful in practice, don’t use to guide decision making
(1) Score
Venous Duplex US
CBC, PT/PTT - useful to guide tx if no baseline
D-Dimer not too useful in practice, don’t use to guide decision making
Well’s Score
Pulmonary Embolism
- Epidemiology: 50-100/100k adults
- Risk factors: similar to DVT
- Mechanism: Virchow’s Triad
- m____ of DVT; can arise de novo
- S/S
- D____
- Pl_____ CP
- Cough → Hemo____
- Weak/Dizzy
- Syn____/Pre-syncope
- Sudden D_____ Anxiety
- Epidemiology: 50-100/100k adults
- Risk factors: similar to DVT
- Mechanism: Virchow’s Triad
- migration of DVT; can arise de novo
- S/S
- Dyspnea
- Pleuritic CP
- Cough → Hemoptysis
- Weak/Dizzy
- Syncope/Pre-syncope
- Sudden Death Anxiety
Pulmonary Embolism Workup
If unstable →
- EKG → tachy to brady or ____ complex tachycardia with (1)
- (1) scan (CXR has little utility)
- Echo → ____ heart strain
- Labs (3)
- (1) score
Send to ED if unstable
- EKG → tachy to brady or wide complex tachycardia with RBBB
- CTPE (CT pulmonary angiogram)/ VQ scan (CXR has little utility)
- Echo → right heart strain
- D-dimer, BNP, Troponin
- Well’s score
Polycythemia Vera Presentation
- S/S: H__, d___ess, v____ disturbances, pr____ especially after (1), early s____
- PE: f____ plethora, spleno_____, exc_____, gouty tophi
- PMH: hyper____, arterial ______ (MI/CVA), V__
- CBC will show?
- S/S: HA, dizziness, visual disturbances, pruritus after a warm bath, early satiety
- PE: facial plethora, splenomegaly, excoriations, gouty tophi
- PMH: HTN,arterial thrombosis (MI/CVA), VTE
- CBC will show elevated H/H
- Pruritis - after a warm bath; described as unbearable/burning and commonly on chest, back, medial arms and ventral legs.*
- Facial plethora - fullness and redness; thing cushingoid with flushing*
Anemia in Children
What is the most common cause of anemia in children?
- Screen at __-__ months, draw (2)
- Consider excessive consumption of (1) in children 1-3yo, why?
- Ask about (1) exposure in the home (paint, dust, pipes, parental employment, live near airport)
- Menstruating young adults may also have heavy ____ bleeding evaluated as a cause
Iron Deficiency Anemia
- Screen at 9-12 months, draw iron panel*, lead*
- Consider excessive consumption of cow’s milk in children 1-3yo, Ca+ can displace Fe+ absorption
- Ask about lead exposure in the home (paint, dust, pipes, parental employment, live near airport)
- Menstruating young adults may also have heavy menstrual bleeding evaluated as a cause
- Please ignore racialized data; look at this as a range of normals and always consider symptoms even if someone has a classically appropriate Hb to further explore.*
- Screening at birth for SCD and G6PD; repeat at 4 months of age*
Anemia in Children
Differences in Racial and Ethnic Groups
- (1) → X linked; Southern Med, SWANA and African ancestry
- (1) →Variable depending on genotype; African and Latino ancestry most commonly in USA (also known to those of South Asian, Southern Med and SWANA ancestry)
- (1) → African, Southern Med, SWANA, and South Asian ancestry
- G6PD → X linked; Southern Med, SWANA and African ancestry
- Hgbpathies→Variable depending on genotype; African and Latino ancestry most commonly in USA (also known to those of South Asian, Southern Med and SWANA ancestry)
- Thalassemias → African, Southern Med, SWANA, and South Asian ancestry
Anemia in Pregnancy -Iron Supplementation
Anemia Ranges in Newborns
