Hematology Flashcards

Question

WBC **Normal Range** 1. High levels = 2. Low levels =

Answer 1

**4-11K/uL** 1. **High** = Infection, inflammation, acute and chronic leukemias, polycythemia vera, anaphylaxis, smoking, COPD/emphysema, obesity, etc 2. **Low** = Cancer (liquid and solid tumor), chemotherapy/radiation, aplastic anemia, bone marrow failure, HIV/AIDS, TB, autoimmune disease, nutritional deficiencies and malnutrition

Answer 2

**3.8-5.3 M/uL** 1. 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. 2. 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.

Answer 3

**Males 14-18 g/dL** **Females 12-16 g/dL** 1. 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. 2. 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.

Answer 4

**Males 40-54%** **Females 37-47%** % of RBCs per sample of blood 1. **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. 2. **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.

Answer 5

**150-400 K/uL** 1. **High =** Infection, inflammation, cancers, polycythemia, essential thrombocytosis 2. **Low** = TTP, ITP, BM failure

Answer 6

**8-12 fL** Mean size of platelets, older platelets generally smaller 1. **Low MPV** = BM failure, renal disease, aplastic anemia, cancers, inflammation/infection, some drugs

Answer 7

**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

Answer 8

**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

Answer 9

**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

Answer 10

**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

Answer 11

**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*

Answer 12

1. Neutrophils = first line immune response, shapes early host response 2. Lymphocytes = antibody production, direct cytotoxicity of cells infected by viruses or abnormal cells, directors or adaptive immune response 3. Monocytes = Boosts immune response, engulfs pathogens, cleans up foreign material and tissue debris after injury 4. Eosinophils = regulates inflammation, traps and kills pathogens 5. Basophils = Facilitates immune response of other cells by making environment favorable; often involved in parasite response

Answer 13

* 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**

Answer 14

Increased nRBCs represent stress on the marrow and need for fast RBC turnover; more severe than increased reticulocytes; consider **severe infection or BM infarction**

Answer 15

WBC x [(PMN% + Bands%)/100] 1. Mild Neutropenia \<1500 2. Moderate Neutropenia \<1000 (risk of infection) 3. Severe Neutropenia \<500 (high risk of infection, may need prophylaxis) 4. Agranulocytosis \<100 (critical risk of infection)

Answer 16

* **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)*

Answer 17

**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

Answer 18

**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

Answer 19

**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)*

Answer 20

* 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?

Answer 21

* **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?

Answer 22

* Mosquito borne illness → malaria, dengue, etc.. * Tick borne illness → babesiosis (hikers or agricultural workers) * Hemorrhagic fevers → ebola, nippah, hantavirus

Answer 23

May mask anemias in those who are symptomatic but CBC is otherwise WNL

Answer 24

1. **General appearance** - listless in advanced cases 2. **Vitals** - ↑HR and/or ↓BP in advanced cases *(may have wide pulse pressure 120/50)* 3. **Skin** - pallor, jaundice, mucous membrane pallor, spoon nails, cold to touch 4. **HEENT** - conjunctival pallor, scleral icterus, glossitis, angular cheilitis 5. **Heart**- tachycardia, flow murmurs 6. **Abdomen** - hepatosplenomegaly 7. **Neuro** - acroparesthesias 8. **MSK** - weakness 9. **Psych** - depression, poor memory and concentration; dementia like symptoms in severe anemia

Answer 25

1. CBC → Hb levels and red cell indices 2. Retic’s → enough production? appropriate to degree of hemolysis? 3. BMP → renal function 4. LFT → bilirubin and transaminases 5. LDH → hemolysis/necrosis 6. Ferritin → iron stores; beware inflammatory processes 7. TIBC→ ↑ may reflect iron deficiency; ↓ acute phase reaction, chronic illness or iron overload 8. TSAT → ↑ iron overload; ↓ IDA or chronic illness

Answer 26

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)

Answer 27

CBC, Ferritin, TIBC and TSAT

Answer 28

○ 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

Answer 29

○ **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.*

Answer 30

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

Answer 31

* **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

Answer 32

* 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 * 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****.*

Answer 33

MCV \> 100 MCV 80-100 MCV \<80

Answer 34

**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)*

Answer 35

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

Answer 36

1. Suspect malignancy → referral to HemeOnc or ED based on presentation 2. Nutritional deficiency, vegan diet or GI/Bariatric surgery → supplement folate and vitamin B12 3. Positive screen for AUD → link to care; supplement thiamine, folate and vitamin B12

Answer 37

* Repeat testing after supplementation * Poor response or worsening → referral to Heme * Ongoing supplementation * Ongoing linkage to outside referrals. * Even if there is an explanatory cause to macrocytosis, if the patient is still anemic continue work up or referral * IE: Hb 8g/dL and MCV 104 even if taking PPIs → still anemic and should be further explored

Answer 38

1. CKD → ↓retics 2. Blood loss (early/acute) → ↑ retics 3. Chronic disease/inflammation 4. Autoimmune → possibly emergent! 5. Infection → hemolysis markers 6. Hemoglobinopathies (SCD) → cell morphology and hemolysis markers 7. G6PD → diet recall and hemolysis markers 8. Spherocytosis → cell morphology 9. Hypothyroidism *Anemia of chronic disease may become microcytic/iron deficient overtime*

Answer 39

* Obtain repeat CBC and peripheral smear with review (some labs do this), BMP, LFT, Retics, LDH, TSH, Ferritin * Review family history and recent diet recall * Screen appropriate candidates with colonoscopy

Answer 40

1. Suspect CKD→ referral to Renal or Heme for consideration of ESA 2. Blood loss→ find source and correct 3. Infection → treat as appropriate or refer to ID 4. G6PD → list sulfa allergy, referral to RD for dietary counseling, consider referral to Heme 5. Hypothyroidism → work up and referral as appropriate 6. AIHA (autoimmune hemolytic anemia), SCD, Spherocytosis → if clinically unstable referral to Heme; otherwise referral to ED

Answer 41

* Repeat testing after intervention. * Poor response or worsening → referral to Heme for co-management * MCV falls for low Ferritin → consider IDA or bleeding has not fully been corrected * Ongoing linkage to outside referrals

Answer 42

**Iron Deficiency Anemia** **Thalassemias (usually MCV \<70fL)** **Sideroblastic Anemia** **Chronic blood loss** **CU deficiency** **Pb (lead), Al, Zn poisoning**

Answer 43

* Obtain iron panel (including ferritin, TIBC, and TSAT) * Review family history, occupational/environmental exposures and recent diet recall * Screen appropriate candidates with colonoscopy

Answer 44

1. IDA → to be discussed further but generally replete 2. Thalassemias/Sideroblastic anemia → referral to Heme 3. Blood loss → stop bleeding and replete iron as needed 4. Metal deficiency/Toxicity → referral to Heme

Answer 45

* Repeat testing after supplementation. * Poor response or worsening * Consider EGD in addition to colonoscopy * Consider IV iron preparations * Referral to Heme for co-managment * Ongoing supplementation

Answer 46

* **Causes**: blood loss, nutritional deficiencies, poor absorption * **S/S**: Fatigue, weakness, SOB, craving ice, pica, restless legs * **PE**: tachycardia, glossitis, pallor, koilonychia (spoon nails) * **Labs**: CBC, Ferritin, Iron, TIBC, TSAT; consider CMP if broader differential * **Colonoscopy for FIT test**: Microcytic, hypochromic anemia

Answer 47

* **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

Answer 48

Beef, pork, chicken (Organ meat and blood) Shellfish (Bivalves) Fish Eggs

Answer 49

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.*

Answer 50

**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 Newer forms of PO iron on the horizon with improved absorption and tolerability but hard to obtain coverage

Answer 51

* Considered in severe IDA, patients who are bloodless (*religion*) /untransfusable (*lots of past transfusions, increased alloimmunity*), or anemic during pregnancy and near EDD * Preparations vary by maximum dose frequency of administration, immunogenicity and insurance coverage. * Risk of allergic reactions in trials is generally small: 1:1 million to 1:3 million * Highest risk among those with multiple allergies * Allergy is to conjugate material most times; can rechallenge with other irons if allergy to one formulation

Answer 52

* **Iron dextran** → oldest, most easily covered, highest immunogenicity; requires test dose 1st * **Iron sucrose** → smaller more frequent doses; generally well covered; only IV iron used in pregnancy * **Iron carboxymaltose** → biggest single dose; sometimes difficult to cover with insurance

Answer 53

Common and secondary to inflammation → enough iron but not free for Heme (*all the iron is bound up dt inflammation)* * **Causes**: chronic inflammation (autoimmune dz, collagen vascular dz, malignancy, or infection) * **S/S**: Fatigue, weakness, SOB, weight loss, pallor, and findings consistent with primary cause of inflammation * **PE:** tachycardia, pallor, findings consistent with primary cause of anemia

Answer 54

Connective tissue diseases: Ehlers Danlos Autoimmune disease: RA, SLE Thyroid disease IBD: UC and Crohn’s Chronic infection: TB, osteomyelitis, subacute bacterial endocarditis Cancer CKD

Answer 55

* **Labs**: CBC, CMP Ferritin, TSH; primary disorder labs and markers; colonoscopy * Normocytic normochromic but may progress to microcytosis if occult blood loss * WBC and platelets are normal or elevated; ferritin normally elevated * **Rx**: Treat primary disorder; usually do not need iron unless there is source of occult blood loss; some conditions require **ESAs** if patient becomes hypoproliferative * **F/U**: as per primary cause of inflammation but monitor CBC for changes in MCV *Erythropoiesis-stimulating agents – for hypoproliferative ie CKD*

Answer 56

Secondary to chronic renal disease; may co-exist with IDA or chronic inflammation * **Causes**: chronic renal disease from various causes (often CKD4 or CKD5) * **S/S:** Fatigue, weakness, SOB, weight loss, pallor, edema, oliguria/anuria * **PE**: tachycardia, hypertension, pallor or hyperpigmentation, xerosis, itching

Answer 57

* **Labs:** CBC, CMP, Ferritin, Vit B12 and folate, colonoscopy * Normocytic normochromic but may progress to microcytosis if occult blood loss * **Higher threshold for ferritin** to reflect adequate iron stores due to chronic inflammation; Defer to nephrology but generally desire **ferritin ≥ 300-500** (KDIGO, 2012). * **Rx:** Often will trial PO iron as tolerated; Often require ESAs due to hypoproliferation due to low EPO. * **F/U**: Nephrology co-management; monitoring of CBC per KDIGO guidelines depending on CKD stage and whether or not on HD.

Answer 58

**Causes**: due to **diet, EtOH use or malabsorption** **S/S:** fatigue, weakness, **poor memory or concentration, acroparasthesias; severe cases may present with dementia-like symptoms** **PE**: tachycardia, pallor, **glossitis, angular cheilitis, poor mini-cog performance** * Malabsorption – often autoimmune or secondary to drugs* * More mental symptoms*

Answer 59

**Labs:** CBC, CMP, vitamin B12 and folate levels, ferritin; consider A**UDIT or other EtOH screening and mini-cog testing** **Rx:** PO or IM supplementation of **vitamin B12 and PO folate; if EtOH is factor referral to treatment and PO thiamine** **F/U:** Depending on severity but generally 2-4 weeks post start of supplementation for symptom check and linkage to other referrals and Q3months after; monitor for correction of macrocytosis in CBC

Answer 60

Inherited group of Hemolytic Anemias Results from substitution of VAL for GLU in the **B subunit** of Hb at the 6th position → HB polymerization → RBC destruction Most commonly HbSS but variants include HbSC, HbS𝛃+, HbS𝛃0, HbSE, etc..., Standard part of newborn screen in USA

Answer 61

Microvascular occlusion and ischemia 1. **Anemia** 2. **Painful episodes/ chronic pain** 3. **Immuno-compromise** 4. **Multisystem organ dysfunction**

Answer 62

Autosomal Recessive Inheritance HbAA SCD = 2 dysfunctional genes for Hb production SCT = 1 dysfunctional gene

Answer 63

* **FMHx**: parent with SCD or SCT; unexplained anemia * **S/S:** * **General :** fatigue, weakness, weight loss, acute/chronic pain * **Skin:** pale or yellow mucous membranes or palms, yellow eyes, edema, non-healing wounds * **CV/Pulm:** palpitations, SOB *Usually thin bc metabolism needs them to constantly put out blood*

Answer 64

* **General appearance** - acutely distressed during (1) * ****_Vital_**s** - ↑HR in crisis and/or normotensive with wide pulse pressures * **Skin** - jaundice, mucous membrane pallor, open/non-healing ulcers on shins/ankles * **HEENT** - conjunctival pallor, scleral icterus, * **_Heart_**- tachycardia, flow murmurs * **Abdomen** - hepatomegaly, absent spleen (HbSS) or splenomegaly (HbSC) * **Neuro** - mild cognitive impairments in those with history of stroke or silent cerebral infarcts; hyperalgesia/allodynia * **Psych** - depression, poor memory and concentration

Answer 65

Normocytic anemia with evidence of hemolysis * CBC + **Retics**, BMP, LFT (total and direct **bili**), **LDH** → routine monitoring or during crisis * **HbEP, Ferritin** → q3-6 months depending on clinical presentation * **Dilated eye exam with MD** → annually due to risk of SCD retinopathy * **Echo** → q1-2years for screening in those with baseline SOB *hbEP = hemoglobin electrophoresis*

Answer 66

* **Hydroxyrurea** → ↑Hb F which ↓ polymerization; only therapy proven to ↓ mortality * **L-glutamine** → ↓ oxidative stress and ↓ frequency of pain crises * **Voxelotor** → ↓ polymerization, ↓ hemolysis and ↑ Hb levels * **Crizanlizumab** → ↓ frequency of pain crisis and hospitalizations *Very appropriate to use opiates in acute pain crises in SCD*

Answer 67

* HCM→ PCP updates i**mmunizations (asplenic schedule)** & routine screenings; coordinate MDT * Heme → **DMTx,** CBC monitoring, acute crisis, disease specific **HCM** * Pain → sometimes Heme but may be managed by other pain specialists

Answer 68

* 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 *Known risk factors: other heme disorders, chemical exposures, some medications, ionizing radiation, viral infections, heredity*

Answer 69

* S/S: Fatigue, weakness, dizziness, palpitations (see anemia) * PE: fever, pallor, bruising, petechiae, tachycardia *Symptoms are vague and may vary according to progression of disease. Symptoms are similar to those with anemia but may not have anemia on CBC.*

Answer 70

1. Active surveillance 2. Symptom management 3. Induction, Consolidation chemotherapy 4. HSCT (allo or haplo) *Treatment is super variable as well depending on specific symptoms, disease progression and findings*

Answer 71

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

Answer 72

* Diverse group of malignancies * Originate from immature and/or mature lymphocytes; sometimes NK cells * May present with anemias or other cytopenias * Traditionally have high cure rates

Answer 73

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*

Answer 74

* Age \> 60 * ♂\>♀ (slight and variable by subtype) * Caucasian * Exposure to benzene, insecticides, or herbicides * Ionizing radiation * Autoimmune disease (SLE, RA, etc) * Viral infections which directly impact lymphocytes (EBV, HTLV-1) * Chronic immunosuppression * HIV infection * Inherited immune disorders

Answer 75

* Enlarged painless lymphadenopathy * Hepatosplenomegaly * Cytopenias * Systemic symptoms : fever, night sweats, unintentional weight loss (aggressive cases) * Symptoms may also be system specific if affected lymph nodes are localized ( ie: GI symptoms of anorexia, early satiety, N/V, abdominal pain, GI obstruction, perforation, hemorrhage, etc.).

Answer 76

* Bimodal distribution with regard to age: young adults (~20 yo) and older adults (~65 yo). * Previous EBV infection * ♂\>♀ (slight) * Family history of lymphoma * Higher SES * HIV infection * FHx: nodular sclerosis Hodgkin lymphoma

Answer 77

* Asymptomatic lymphadenopathy * Mostly above the diaphragm * Pel-Ebstein fever (~⅓) * cyclic about every 7-10 days * Cough, CP +/- SOB when large mediastinal mass or lung involved * Pruritis * EtOH induced pain at nodal sites * Back or bone pain

Answer 78

* **Labs**: CBC, CMP, LDH, CRP * **Imaging**: XR, US, CT, PET-CT, MRI * **Biopsy**: Lymph node, BM or now “liquid” biopsy * **Immunophenotyping**: IHC, flow cytometry * **Chromosomal**: FISH, PCR * Labs: helpful for prognosticating but do not establish the diagnosis* * Imaging: stage the disease and offer insight into prognosis; do not establish dx. MRI helpful with CNS involvement* * Biopsy: _only thing that can establish the dx_; liquid bx are relatively new but often have long turn around times so not always useful if treatment decisions need to happen rapidly*

Answer 79

* Active surveillance * Symptom management * Cytotoxic chemotherapy * Immunotherapy * Radiation * HSCT

Answer 80

* **Primary** → initial clot formation after injury from vessel elasticity and platelets * **Intrinsic** pathway - PT/INR * Warning: **mucocutaneous** bleeding * **Secondary** → development of a fibrin based clot * **Extrinsic** pathway - PTT * Warning: deep **hematomas** or **joint** bleeds * Bleeding challenges → event that causes bleeding * Surgery, vaginal delivery, dental extraction, trauma, etc… * Major bleed → event that causes fall in Hb of ≥ **2** g/dL *These are some important terms you may need in discussing bleeding disorders with members of a hematology team*

Answer 81

* Start with a good history of any specific bleeding events → OLD CART * Provoked? When and where? Age? * Any previous major bleeding challenges? → appropriate clotting at the time? * Any major bleed events? →**_Surgery, transfusions or IV iron replacement_** *History of bleeding significant enough to require surgery, transfusions or IV iron should get you thinking about an undiscovered bleeding disorder. Likewise a bleed that did not require this interventions is suggestive of not having a bleeding disorder but a basic review of CBC and coags would be advisable.*

Answer 82

* **PMH** → renal, liver or thyroid disease; connective tissue disorders; personal history of cancer * **FHx** → Cancer, VWD, hemophilias, family members with HMB * **Social Hx** → EtOH use, synthetic THC * **Medications**/**supplements** → anticoagulant and antiplatelet * ASA, NSAIDs, steroids, antibiotics, SSRI, vit E, garlic, turmeric, fish oil\*, ginko, etc * **Menstrual Hx** → onset, frequency, duration, flow, other family members * Ask about # of pads/tampons used rather than light, moderate or heavy flow * Passage of clots \> size of quarter * Renal → platelet dysfunction* * Liver → produces clotting factors and albumin* * Thyroid → acquired VWD* * \*fish oil is traditionally thought to contribute to bleeding however the evidence suggest that while platelet aggregation is affected; it did not impact perioperative bleeding in one meta-analysis (Begtrup, Krag and Hvas, 2017).*

Answer 83

* **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*

Answer 84

* **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.*

Answer 85

* Review their history and symptoms as previously stated * Any previous bleeding that needed surgery, IV iron or transfusion is a red flag * Known congenital syndromes

Answer 86

* **Skin**: * Evidence of bleeding → thrombocytopenias * Pallor → bleeding leading to anemia * Skin elasticity → EDS * **Chest**: systolic murmur → bleeding causing anemia? VWD (harsh murmur) * **Abdomen**: hepatosplenomegaly → liver disease? * **MSK**: joint laxity → EDS

Answer 87

* Start with the basics → obtain CBC, PT/INR and PTT * Do we have enough platelets? Do they appear normal? * Is there a problem in the intrinsic, extrinsic or common pathway? * How fast and sever are the changes occurring? Do I need to refer to a higher level of care? * No specific testing or work up exist for general bleeding disorders but general starting points include* * CBC → platelet function and morphology* * PT/PTT → intrinsic and extrinsic pathways*

Answer 88

* Common inherited bleeding disorders → **VWD, Hemophilia A (Factor VIII deficiency) and Hemophilia B (Factor IX deficiency)** * Drug toxicities → **overdose on anticoagulation**; change in **renal or hepatic function** affecting dosing * In general: bleeding emergencies are determined on history and clinical presentation; no need to wait for an extensive work up * Defer to Heme to order unless confident of a particular diagnosis and intend to initially manage it. → PFA, Mixing studies → deficiency of factors vs inhibition of factors, Thrombin, Fibrinogen, Factor assays, VWF antigen, Vitamin K , levelsAnticoagulant levels* * Refer early and often to Heme for suspected bleeding disorders*

Answer 89

* **Liver disease** → TPO production of liver drops * **APLS (antiphospholipid syndrome)** → history of thrombosis or recurrent pregnancy loss; associated with Rheum dz’s * **ITP** → antibody mediated platelet destruction

Answer 90

* **DIC** → use up all platelets and clotting factors in small vessel resulting in disseminated bleeding; associated with sepsis * **TMA**→ aHUS, TTP, (associated with MAHA); emergent * **HIT** → prior heparin exposure (usually UFH or LMWH) * **VIITT** → 5-30 days post vaccination with J&J or AZ covid vaccines; rare/emergent * Also think broadly like infections and medications as these may present either acutely or chronically* * Please do not wait until platelest are critically low to refer*

Answer 91

* \<100k - hold high risk surgeries (cardiac, ortho, neuro); obtain heme clearance for other surgeries * \<50k - hold all surgeries; high risk of surgical bleed and mortality * \<20k - risk of spontaneous brain bleed and death; send to ED

Answer 92

* **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.*

Answer 93

**Von Willebrand Disease (VWD)** **Most common inherited bleeding disorder** * Commonly HMB in menstruating persons, mucocutaneous bleeding, post-op bleeding, and/or easy bruising, * Typically has normal platelet counts, PT and PTT but some variation according to severity * Consider testing and referral to heme → Factor VIII, VWF antigen, Ristocetin cofactor + collagen binding * Will need support prior to elective surgeries such as DDAVP and tranexamic acid depending on findings and severity Beyond this → strongly advise referral to Heme for stable patients You are never wrong to consult/refer a stable patient

Answer 94

**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.*

Answer 95

**Vessel wall damage** **Turbulent flow (Venous stasis)** **Hypercoagulability**

Answer 96

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)

Answer 97

S/S: * **Unilateral swelling** below suspected thrombus (~70%); rare but can be bilateral * **Pain** at site of thrombus (~50%) * **Redness** below thrombus PE: * Limb edema; bilateral if high enough to affect pelvic circulation * Limb erythema, warmth and dilation of blood vessels * +/- tenderness to palpation * Homans test is not particularly useful

Answer 98

**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**

Answer 99

* 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

Answer 100

* Pallor/cyanosis * Tachypnea * Tachycardia * Decreased breath sounds * Distended neck veins * PE findings of DVT

Answer 101

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

Answer 102

**Supportive Therapy** **Anticoagulation** 1. Acute = UFH or LMWH, sometimes VKA or DOAC 2. Chronic = DOAC preferred on a taper schedule, duration depends → VKA if unable to tolerate DOAC 3. Pregnant = LMWH **Reperfusion** (limb threatening or life threatening PE) 1. Thrombolysis 2. Thrombectomy 3. Surgical Embolectomy

Answer 103

Aplastic Anemia Myleoproliferative Neoplasms (MPNs) Polycythemia Vera (most common MPN)

Answer 104

**Bone marrow failure →** **Pancytopenia asctd w injury to hematopoetic stem cells → Reticulocytopenia** Life threatening, High mortality Same day referral to Heme or ED if unable or hemodynamically unstable Will need BMBx and depending on depth of cytopenia, immediate admission for HSCT * Patients with AA are at high risk fo sepsis* * Please do not refer a septic patient to Heme; we are just going to send them to the ED*

Answer 105

Causes = cancer tx, meds, environmental exposures, infection, immune d/o, etc… Presents with **recurrent infections, mucosal hemorrhages and profound progressive anemia**

Answer 106

**Essential Thrombocythemia** **Myelofibrosis** **Polycythemia Vera** *MPNs arise from a mutation in the hematopoetic stem cells*

Answer 107

BM produces too many platelets ↑ risk of VTE and arterial clots (MI and CVA) * JAK2, CALR gene mutations * \>60yo, female \> male **Symptoms** = are vague and may mimic anemias, may also present with bleeding **Treatment** = may include observation, antiplatelet/anticoagulation, or Hydroxyurea

Answer 108

BM becomes fibrotic with abnormal cells * JAK2, CALR, MPL, TET2 gene mutations most commonly associated **Symptoms** (may be asymptomatic but gradually progressive, may present with) * extreme anemia * bleeding symptoms and frequent infections * abdominal pain * hepatosplenomegaly due to extramedullary erythropoiesis **Treatment** = depends on progression and may include observation, PO small molecule inhibitors (-nibs) and/or eventual HCST

Answer 109

Clonal proliferation of myeloid cells → not all mature or functional Different from other MPN as the RBC mass is distinctly elevated (not enough to establish Dx) _Risks_ * \>50yo more common (~75% of cases) * ionizing radiation and benzene exposure * 2/2 JAK2 mutation not clearly inheritable but some family predispositions are known _Treatment_ (Treated can be managed for years) * Requires close supervision due to risk of conversion to MF, AML, MDS

Answer 110

* **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*

Answer 111

* **Hb \> 18.5 g/dL** (73%), WBC \> 10.5k/uL, Plt\>450k/uL * **Elevated LDH** (50%) * **JAK2 +** (98%) * **Low Epo** (81%) * Criteria listed here are to help you when in suspicion of PV; _I would not recommend ordering genetic testing in primary care setting_ as it will not likely be paid for, is very expensive, not diagnostic and will not be managed in primary care setting.* * This is more so a guide on who to refer to hematology based on previous testing. You do not need to draw any additional labs to refer if you have an elevated H/H. If you have a good relationship with them get a peripheral smear you can send them otherwise the will just make one in the office. Diagnosis can get complicated due to the differentials but will likely include red cell mass study and some may order BM biopsy to rule out other pathology.*

Answer 112

**Therapeutic phlebotomy** **Low dose ASA** **Cytoreductive therapy (Hydroxyurea)**

Answer 113

Anemia in Pregnancy, Newborns, Children, Older Adults

Answer 114

**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*

Answer 115

* **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

Answer 116

Majority is due to **absent iron stores** Please remember to screen and treat **iron deficiency anemia** in pregnancy! * 40% of reproductive age women globally are anemic (WHO, 2018) * Many have iron deficiency WITHOUT anemia * Also do not close the diagnosis on IDA or PhysA if anemia has unexplained factors. *SCREEN ALL PREGNANT PATIENTS FOR IDA/other anemias\* get cbc and iron panel*

Answer 117

Pregnancy increases demand for iron and other nutrients (Vit B12/B9) for fetal tissue and rbc production * **Expanding blood volume** → physiological anemia * **Blood loss** associated with NSVD

Answer 118

Folic Acid Supplementation * Standard dose = 400-800ug daily * Hemolytic states dose = 5mg daily IV Iron Sucrose\* (only formulation allowed in pregnancy) * Folic acid supplementation should start prior to conception whenever possible* * Folic acid 5mg daily is weakly evidence based but fairly representative of what is the standard recommendation among those in hematology. Very little risk of harm as Vit B’s are water soluble and excess will just be urinated out.*

Answer 119

**Prematurity** **Blood Loss** **Hemolytic Anemias**

Answer 120

* Rh or ABO incompatibility * Twin to twin transfusion * Congenital infection * G6PD, spherocytosis, etc * Hemoglobinopathy

Answer 121

* NBs are screened for SCD and SCT at birth in the US; however, this is not always the case when patients are born abroad so don't assume that they screened negative if you don't have specific documentation stating a negative screen* * NBs and infants are not as likely to have a nutritional cause to anemia before 6 months of age; thus screening for nutritional causes begins around 9 months.* * Children with SCD may not present as anemic until around 6 months as they are born with high levels of HbF which prevents sickling of RBCs*

Answer 122

* Anemia in older adults has significant morbidity and mortality associated with it. * Likelihood of anemia of chronic disease goes up but IDA does not go down * **Annual exam**: BMP and ferritin at least * **HCM**: colonoscopy should be up to date * Low threshold to send for repeat labs and GI consult for new unexplained anemias * Morbidity: decreased mobility, QOL, neuropsychiatric effects and risk of falls* * Mortality: both community dwelling and those in nursing facilities; especially problematic in those preparing for surgery and those with underlying chronic renal or cardiac disease*

Answer 123

* Serum ferritin can be useful in guiding exploration of anemia * \<46 ng/mL → suspect IDA; GI referral and start PO iron; consider other iron studies but don't wait to treat * 46-100 ng/dL → get iron panel and BMP; refer to GI * If iron studies confirm IDA → treat * BMP indicates CKD → send to renal * No CKD, no IDA, no GIB → refer to heme * \>100 ng/dL → suspect hemoglobinopathies; HbEP and/or referral to heme * Macrocytic anemias → review nutrition, EtOH use, and chronic PPI use but generally helpful to consider at Heme consult *Ferritin and BMP screening are personal recommendations; not based on extensive literature review or society recommendations to my knowledge; HOWEVER, are very important if evaluating a new unexplained anemia* * *BMP assess for CKD by looking at sCr and any electrolyte or metabolic derangements* * *Increased risk of GIB due to Ca or ulcers from NSAID use as patients age* * Likely anemia will be normocytic to microcytic but this is not something to split hairs about as the timing and rate of any blood loss will impact these; more important to thoroughly investigate this fully when noted.* * There are cases of macrocytic anemias and these can be concerning for processes such as chronic EtOH use, nutritional deficiencies and MDS. You may want to consider a Heme consult even with a known cause for macrocytic anemia in older adults due to the concern for heme malignancies as people age.* * *Especially important to correct folate and B 12 deficiencies as this may mimic dementia*

Answer 124

* Do not be afraid to call/email with questions about whether to refer or not (curbsiding is common and will likely get you a faster appointment). * When referring to general hematology send records over with at least a: * **CBC with differential and Retic’s** * **Iron studies, ferritin, vitamin B12, folate** * **Peripheral smear (depends on internal vs external referral)** * Do not change anticoagulant/antiplatelet medications without speaking with us first if already an established Hematology patient. * Useful resources * American Society of Hematology “How I Treat” series * American Society of Hematology Pocket Guides App *Send all the labs – want to trend!*

Hematology Flashcards

(151 cards)