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Hematology Flashcards

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1
Q

Anemia definition?

A

Low hemoglobin (M: <130g/L, F: <120g/L), normal MCV 80-100fL

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2
Q

What are the symptoms of anemia?

A

Symptoms of anemia: fatigue, headache, SOB, light-headedness, malaise, weakness, decreased exercise tolerance, dyspnea, palpitations, dizziness, tinnitus, and syncope

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3
Q

What should be your physical exam for anemia?

A

o HEENT: pallor in mucous membranes and conjunctiva at Hb <90g/L (<9g/dL), ocular bruits at Hb <55 g/L (<5.5 g/dL), angular cheilitis, jaundice
o Cardiac: tachycardia, orthostatic hypotension, systolic flow murmur, wide pulse pressure, signs of CHF
o Dermatologic: ecchymosis, petechiae, pallor in palmar skin creases at Hb <75 g/L, jaundice (if due to hemolysis), nail changes (spooning - koilonychia), and glossitis
o Splenomegaly, lymphadenopathy

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4
Q

What should be asked on history for anemia?

A

o Acute vs. chronic, bleeding, systemic illness, diet (Fe, B12 sources), alcohol, and family history
o Menstrual history: menorrhagia, menometrorrhagia
o Rule out pancytopenia (recurrent infection, mucosal bleeding, easy bruising)

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5
Q

Define microcytic anemia

A

If MCV <80

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6
Q

Clinical features of microcytic anemia

A

 Iron deficiency may cause fatigue before clinical anemia develops
 Signs/symptoms of anemia
 Brittle hair, nail changes (brittle, koilonychia)
 Pica (appetite for non-food substances e.g. ice, paint, and dirt)
 Restless leg syndrome

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7
Q

Ddx of microcytic anemia

A

TAILS: thalassemia, anemia or chronic disease, iron deficiency*, lead poisoning, sideroblastic anemia

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8
Q

Lab results of iron deficiency anemia

A

low serum iron, high TIBC and low ferritin. High RDW

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9
Q

Etiology of iron deficiency anemia?

A

Increased demand
 Increased physiological need for iron in the body (e.g. pregnancy)
 Decreased supply: dietary deficiencies - Cow’s milk (infant diet), “tea and toast” diet (elderly), absorption imbalances, post-gastrectomy, malabsorption (IBD of duodenum, celiac disease, autoimmune atrophic gastritis, and H.pylori infection)

Increased losses
 Hemorrhage - menorrhagia, abnormal uterine bleeding, and frank GI bleed. Occult: peptic ulcer disease, GI cancer
 Hemolysis - Chronic intravascular hemolysis (e.g. PNH, cardiac valve RBC fragmentation)

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10
Q

Sequence of iron deficiency

A

Decrease in iron – increase TIBC – decrease Hb – decrease MCV - hypochromia

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11
Q

What is anemia of chronic disease

A

Hepatic hepcidin production is increased in inflammatory processes, trapping iron in enterocytes and macrophages (via ferroportin inhibition).

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12
Q

Lab results of anemia of chronic disease

A

Low serum iron, low TIBC and high/normal ferritin. Inflammatory markers (CRP)

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13
Q

Etiology of anemia of chronic disease

A

o Infection, malignancy, inflammatory, and rheumatologic disease
o Chronic renal and liver disease
o Endocrine disorders (e.g. DM, hypothyroidism, hypogonadism, and hypopituitarism)

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14
Q

Lab results of thalassemia

A

Normal iron, high RBC, very low MCV, historically low MCV

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15
Q

What is thalassemia?

A

Condition characterized by ineffective synthesis of globin chains due to inherited mutations in the alpha or beta globin genes; alpha or beta thalassemia depending on which chain is affected;

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16
Q

If 4/4 alpha globing genes deleted?

A

Incompatible with life

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17
Q

What is thalassemia trait?

A

Thalassemia trait→ carrier state, mild anemia with microcytosis

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18
Q

Beta thalassemia disease treatment?

A

Severe transfusion dependent anemia

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19
Q

Diagnostic hallmark of sideroblastic anemia?

A

Ringed sideroblasts

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20
Q

Etiology of sideroblastic anemia?

A 
o	Hereditary (rare): X-linked; median survival 10yr
o	Idiopathic (acquired) 
- Refractory anemia with ringed sideroblasts: a subtype of MDS 
- Preleukemic phenomenon (1-2% transform to AML) 
o	Reversible: drugs (isoniazid, chloramphenicol), alcohol, lead, copper deficiency, zinc toxicity, and hypothyroidism
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21
Q

What is sideroblastic anemia?

A

Erythrocytes with iron- containing (basophilic) granules in the cytoplasm

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22
Q

Explain the “ring” - The hallmark of sideroblastic anemia

A

“ring”: iron deposits in mitochondria, forming large, abnormal granules that surround the nucleus

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23
Q

Lab results of sideroblastic anemia?

A

Increased serum Fe2+, normal TIBC, increased ferritin

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24
Q

Treatment of sideroblastic anemia?

A

o X-linked: high dose pyridoxine (vitamin B6) in some cases
o Acquired: EPO and G-CSF
o Reversible: remove precipitating cause

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25
Q

Distinguishing features between Iron deficiency and thalassemia?

A

 RDW red cells in thalassemia tend to have a narrower distribution than in iron deficiency
 MCV red cells in thalassemia tend to be smaller than in iron deficiency
 RBC high or normal if thalassemia but tend to decrease proportionally to Hb in iron deficiency
 THALASSEMIA INDEX MCV/RBC. Suggests thalassemia if <13 and iron deficiency if >13

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26
Q

Basic lab investigations for microcytic anemia?

A

CBCD, peripheral smear, reticulocyte count, serum iron, serum ferritin, TIBC (transferrin), % sat, Hb electrophoresis (thalassemia), fecal occult blood (if suspect GI bleed), CRP (anemia of inflammation)

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27
Q

Who should receive endoscopy (gastroscopy and/or colonoscopy) for microcytic anemia?

A

Symptoms in any man or post-menopausal woman with iron deficiency or in anyone with suspected GI bleeding

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28
Q

IV iron indications

A

o Intolerant of oral iron
o Inflammatory bowel disease
o Chronic kidney disease on hemodialysis

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29
Q

Treatment of iron deficiency anemia?

A

Iron deficiency (iron gluconate 300 mg PO TID - It may take up to 6 weeks to correct anemia and 6 months to replete iron stores. Oral iron should be taken with citrus juice (vitamin C) to enhance absorption

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30
Q

Definition of normocytic anemia?

A

Definition: If MCV 80-100

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31
Q

Clinical features of normocytic anemia?

A

 Can present acutely or insidiously
 Symptoms of anemia
 Thrombocytopenia and/or infection
 Splenomegaly and lymphadenopathy

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32
Q

Ddx of normocytic anemia with increased RBC loss or destruction?

A
  • Bleeding: GI, GU, pelvis/abdomen, skin, CNS
  • Hemolysis
    Acquired:
     Immune-mediated: autoimmune hemolytic anemia (warm agglutinins, cold agglutinins), drug induced hemolytic anemia, alloimmune hemolytic anemia (acute hemolytic reaction)
     Microangiopathic (MAHA): TTP, HUS, DIC, pre-eclampsia, eclampsia, malignant hypertension, prosthetic valves
     Infection: Malaria, babesiosis, Clostridium infections

Hereditary:
 Enzymopathies - G6PD deficiency, pyruvate kinase deficiency
 Membranopathies – hereditary spherocytosis, elliptocytosis
 Hemoglobinopathies – thalassemia and sickle cell disease

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33
Q

What is myelofibrosis?

A

Bone marrow replaced with collagenous deposition–scarring of bone marrow

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34
Q

Ddx of normocytic anemia with decreased RBC production?

A
  • Primary causes: Marrow hypoplasia, myelopathies, myeloproliferative diseases, red cell aplasia
  • Secondary causes: chronic renal failure, liver disease, anemia of chronic disease
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35
Q

Basic lab investigations for normocytic anemia?

A

CBCD, peripheral smear, reticulocyte count, iron, ferritin, TIBC, % sat, Cr, TSH, AST, ALT, ALP, bilirubin, INR, PTT, haptoglobin, LDH, direct and indirect Coombs test, serum protein electrophoresis (MM), fecal occult blood (if suspect GI bleed)

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36
Q

What is included in a hemolytic workup?

A
  • LDH (enzyme found in RBCs, released when broken up)
  • Bilirubin (Hb released from RBCs metabolized to bilirubin), unconjugated bilirubin – liver is overwhelmed and is unable to keep up
  • Haptoglobin (present in blood to mop up toxic free Hb) – so it will decrease rapidly
  • Blood film (changed RBC shape)
  • DAT (direct antiglobulin test/Coomb’s test: look for antibodies bound to red cell surface supporting immune cause of hemolysis) DAT positivity suggests immune rather than non-immune causes of hemolysis
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37
Q

What is intravascular hemolysis?

A

Severe damage to RBC membrane such that immediate lysis occurs in the circulation - schistocytes

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38
Q

What is extravascular hemolysis?

A

RBCs are destroyed outside of the vessels - membrane alterations by the macrophages of the spleen and liver

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39
Q

What are the findings of intravascular hemolysis?

A

Schistocytes. Low haptoglobin and hemoglobinuria - pink or brown serum and dark urine

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40
Q

Diagnosis of immune-mediated hemolytic anemia?

A

Antibodies to red blood cell surface antigens. Diagnosis: Spherocytes and positive DAT

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41
Q

Ddx of normocytic anemia with overexpansion of plasma volume?

A

Pregnancy, Overhydration

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42
Q

What is warm antibody hemolytic anemia?

A

Polyclonal IgG bind to protein Ag on RBC surface at 37C

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43
Q

Etiology of autoimmune hemolytic anemia?

A

Etiology: Most cases are idiopathic, lymphoproliferative disorders (e.g., chronic lymphocytic leukemia, non-Hodgkin’s lymphoma), antibiotics (penicillin, sulfa drugs, cephalosporins), HIV
o Warm: SLE
o Cold: Infections (M. pneumonia, EBV mono),

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44
Q

What is cold antibody hemolytic anemia?

A

IgM bind to polysaccharide Ag on RBC surface at <37C

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45
Q

Treatment of warm antibody hemolytic anemia?

A

Warm: RBC transfusions (test for co-existing allo-antibodies), reduce Ab production (prednisone), supportive therapy (folic acid, bisphosphonates, Ca and vit D replacement), treat underlying cause (malignancy, rheumatological condition, d/c offending medication)

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46
Q

Treatment of cold antibody hemolytic anemia?

A

Cold: usually supportive (does not respond to steroids or splenectomy). If transfusion needed (warm prior to infusion), avoidance of cold, treatment of underlying malignancy if present

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47
Q

What is the most severe alloimmune hemolytic anemia?

A

ABO incompatibility

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48
Q

What are examples of microangiopathic hemolytic anemia (MAHA)?

A

TTP, HUS, DIC, pre-eclampsia, eclampsia, malignant hypertension, prosthetic valves

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49
Q

How to diagnosis microangiopathic hemolytic anemia (MAHA)?

A

Schistocytes

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50
Q

What are the events that can causes hemolysis in G6PD deficiency?

A

Hemolytic events caused by infections, drugs, ingestion of fava beans

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51
Q

Diagnosis of hereditary spherocytosis?

A

Spherocytosis noted on peripheral smear, a family history (in 75 percent of cases), and a negative DAT

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52
Q

Treatment of hereditary spherocytosis?

A

Treatment: splenectomy

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53
Q

What is sickle cell disease?

A

Autosomal recessive sickling disorders arise due to a mutant globin chain, most commonly caused by a Glu - Val substitution at position 6 (chromosome 11) resulting in HbS variant

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54
Q

Pathophysiology of sickle cell disease?

A

At low pO2, deoxy HbS polymerizes leading to rigid crystal-like rods that distort membranes → ‘sickles’

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55
Q

Clinical features of HbAS (sickle cell trait)?

A

Patient will be asymptomatic except during extreme hypoxia or infection - increased risk of renal medullary carcinoma

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56
Q

Clinical features of HbAS (sickle cell trait)?

A

Patient will be asymptomatic except during extreme hypoxia or infection - increased risk of renal medullary carcinoma

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57
Q

Clinical features of SCD-SS (HbSS)?

A

Chronic hemolytic anemia, jaundice in the first year of life, retarded growth and development ± skeletal changes, splenomegaly in childhood; splenic atrophy in adulthood

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58
Q

Investigations for sickle cell disease?

A
  • Sickle cell prep (detects sickling of RBCs under the microscope in response to O2 lowering agent): determines the presence of a HbS allele, but does not distinguish HbAS from HbSS
  • Hb electrophoresis distinguishes HbAS, HbSS, HbSC, and other variants
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59
Q

Treatment of vaso-occlusive crisis in sickle cell disease?

A

Supportive care: oxygen, hydration (reduces viscosity), correct acidosis, analgesics/opiates

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60
Q

Treatment of sickle cell disease?

A
  • Folic acid to prevent folate deficiency

* Hydroxyurea to enhance production of HbF

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61
Q

Prevention of crises of sickle cell disease?

A
  • Establish diagnosis
  • Avoid conditions that promote sickling (hypoxia, acidosis, dehydration, fever)
  • Vaccination in childhood (pneumococcus, meningococcus, H. influenzae b)
  • Prophylactic penicillin (age 3 mo-5 yr)
  • Good hygiene, nutrition, and social support
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62
Q

Definition of macrocytic anemia?

A

Definition: If MCV >100→ macrocytic anemia

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63
Q

Ddx of macrocytic anemia?

A

BF HARM - vit B12 or folate deficiency*, hypothyroidism, EtOH/liver disease, reticulocytosis (blood loss, hemolysis), myelodysplasia

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64
Q

Investigations for macrocytic anemia?

A

CBCD, peripheral blood smear, reticulocyte count, vitamin B12, RBC folate, TSH, AST, ALT, ALP, bilirubin, INR, PTT

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65
Q

Why a peripheral blood smear for macrocytic anemia?

A

Blood smear to determine if megaloblastic or non-megaloblastic

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66
Q

What is megaloblastic anemia?

A

Megaloblastic is due to impaired DNA synthesis during RBC synthesis leading to continued cell growth without division. Pancytopenia, hypersegmented neutrophils

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67
Q

Examples of megaloblastic anemia?

A

Due to Vit B12 deficiency and folate deficiency

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68
Q

What does vitamin B12 bind to?

A

Binds to intrinsic factor (IF) secreted by gastric parietal cells

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69
Q

Where is vitamin B12 absorbed?

A

Terminal ileum

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70
Q

What is pernicious anemia?

A

IgA targets intrinsic factor or parietal cell and therefore vit B12 can’t be absorbed.

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71
Q

Etiology of vitamin B12 deficiency?

A
  • Diet - Strict vegan
  • Gastric - Mucosal atrophy (Gastritis, autoimmune), Pernicious anemia, Post-gastrectomy
  • Intestinal absorption – Malabsorption (Crohn’s, celiac sprue, pancreatic insufficiency, H. pylori), Stagnant bowel, Resection of ileum
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72
Q

Clinical features of vitamin B12 deficiency?

A

o Peripheral neuropathy (variable reversibility) - usually symmetrical, affecting lower limbs more than upper limbs
o Cord (irreversible damage) - subacute combined degeneration
 Posterior columns: decreased vibration sense, proprioception, 2-point discrimination, and paresthesia
 Pyramidal tracts: spastic weakness, ataxia
o Cerebral (common, reversible with B12 therapy) - confusion, delirium, and dementia
o Cranial nerves (rare) - optic atrophy

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73
Q

Treatment of vitamin B12 deficiency?

A

B12 1000 mcg IM: daily x 7d then weekly x 4 weeks then monthly. B12 1000 mcg PO daily (monitor for hypokalemia)

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74
Q

Etiology of folate deficiency?

A

Dietary (neglected elderly, EtOH), malabsorption (celiac, enteritis, short bowel syndrome), increased requirements (hemolysis, pregnancy), drugs (methotrexate, phenytoin)

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75
Q

Clinical features of folate deficiency?

A

Clinical Features: anemia, mild jaundice, glossitis, diarrhea, confusion, pallor

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76
Q

Treatment of folate deficiency?

A

Folate 5 mg PO

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77
Q

What is non-megaloblastic anemia?

A

Reflects membrane abnormality with abnormal cholesterol metabolism increased RBC cell membrane size, no DNA replication problems

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78
Q

Examples of non-megaloblastic anemia?

A

Due to liver disease, chronic alcohol intake, hypothyroidism, drugs, myelodysplasia

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79
Q

Treatment of pernicious anemia?

A

Transfuse fewer units and transfuse each unit slowly over 3 h since an expanded intravascular volume puts patients at risk for transfusion induced pulmonary edema.

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80
Q

Definition of localized lymphadenopathy?

A

Localized lymphadenopathy is specific to 1 lymph node region

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81
Q

Definition of generalized lymphadenopathy?

A

Generalized lymphadenopathy involves > 2 noncontiguous lymph node regions

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82
Q

Reassuring features of lymphadenopathy?

A

Reassuring: a few small (<1cm), localized, mobile, tender LNs with acute onset, associated with infectious symptoms, and no changes to overlying skin.

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83
Q

Worrisome features of lymphadenopathy?

A

Worrisome: generalized, subacute or chronic lymphadenopathy with fixed, non-tender nodes, changes to overlying skin, and associated fever, weight loss, night sweats, joint or bone pain, splenomegaly

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84
Q

Causes of localized lymphadenopathy?

A
  • Infection (bacterial more common)
  • Neoplasm - Metastatic disease
  • Local inflammation
  • Local reaction (insect bite)
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85
Q

Causes of generalized lymphadenopathy?

A

Reactive

  • Bacterial (TB, Lyme, brucellosis, cat scratch disease, and syphilis)
  • Viral (EBV, CMV, HIV, rubella) – most common
  • Parasitic (toxoplasmosis)
  • Fungal (histoplasmosis)

Inflammatory

  • Collagen disease (RA, dermatomyositis, SLE, vasculitis, and Sjögren’s)
  • Drug hypersensitivity
  • Sarcoidosis, amyloidosis
  • Serum sickness

Neoplastic (lymphoma)
- Lymphoma – especially when you see nodes enlarged above and below the diaphragm, this is less likely a metastasis from a solid tumour and more likely lymphoma

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86
Q

What should be asked on history for lymphadenopathy?

A
  • Lymph nodes – onset, duration, progression (any changes), characteristics, associated symptoms
  • Recent illnesses – URTI, rash, headache, vision changes, nausea/vomiting/diarrhea
  • Constitutional symptoms – fever, night sweats, weight loss (ask about changes in clothing sizes)
  • Skin lesions/trauma
  • Recent travel/exposures – Infectious symptoms around travel time, animal bites, ticks, cat scratch, food
  • Medications: Carbamazepine, phenytoin
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87
Q

Physical exam for lymphadenopathy?

A
  • LN
  • H&N exam: scalp infection, oropharynx (large tonsils, inflamed gums), ears (AOM), eyes (conjunctivitis), thyroid, ROM
  • Abdomen: hepatosplenomegaly, masses
  • Skin: rash, erythema, petechiae, bruising and pallor
  • Resp exam
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88
Q

Red flags for lymphadenopathy

A

Generalized lymphadenopathy, Size >2cm, not decreasing after 4 weeks, Firm, matted, rubbery consistency, Nontender, Supraclavicular location, Systemic symptoms

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89
Q

What should you comment on for lymph node exam?

A

Comment on: Location +(Non)Tender + Size (abnormal if >terminal phalanx of pinky) + Rubbery/Firm + Fixed/Mobile + Matting w/ Other Nodes + Drainage + Skin Changes (swelling/erythema/induration)

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90
Q

Investigations for lymphadenopathy

A

o CBC and differential, blood film
o If generalized, consider tuberculin test, HIV RNA, VDRL, Monospot/EBV serology, ANA, and imaging (CXR +/- abdomen CT)
o If localized and no symptoms suggestive of malignancy, can observe 3-4wk (if no resolution - biopsy)

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91
Q

Gold standard bx for lymphoproliferative disease?

A

Excisional biopsy is the gold standard

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92
Q

Most common presentation of cervical adenitis?

A

Acute Bilateral

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93
Q

History for acute bilateral cervical adenitis?

A

History: rhinorrhea, cough, sore throat, sick contacts

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94
Q

Most common etiology for acute bilateral cervical adenitis?

A

Viruses

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95
Q

Physical exam findings for acute bilateral cervical adenitis?

A

Physical: bilateral, small, mobile, LN, minimally tender, no erythema or overlying warmth
- Associated findings: +/- fever, pharyngitis, hepatosplenomegaly, rash

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96
Q

Investigations for acute bilateral cervical adenitis?

A

Clinical +/- swabs or serology

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97
Q

Treatment for acute bilateral cervical adenitis?

A

Treatment: supportive, self-limited

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98
Q

Most common etiology for acute unlateral cervical adenitis?

A

Usually bacterial

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99
Q

History for acute unlateral cervical adenitis?

A

History: viral prodrome

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100
Q

Physical exam findings for acute unilateral cervical adenitis?

A

Physical: tender, warm, erythematous and poorly mobile LN

- Associated findings: +/- fever, fluctuance, ill-appearing

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101
Q

Investigations for acute unilateral cervical adenitis?

A

Clinical +/- partial septic workup if febrile and ill-appearing, throat swab and cultures of draining skin lesions + US

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102
Q

Treatment for acute unilateral cervical adenitis?

A

Antibiotics

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103
Q

Presentation of lymphoma?

A

Presents with lymphadenopathy and/or splenomegaly, abdominal or mediastinal mass – can compress vessels or kidneys/ureters, cytopenia (Can cause ITP because the abnormal lymphoma cells can sometimes make wonky antibodies that for some reason can destroy platelets), B sx (weight loss, fever, night sweats), recurrent infections.

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104
Q

Investigations for lymphoma?

A

▪ CBC/diff + blood smear, lytes, liver function tests, creatinine, LDH (Can be high if the lymphoma is aggressive and has a high proliferation rate - for whatever reason when cells are turning over frequently LDH will elevate), urate (uric acid – marker of tumor lysis)
▪ Others: viral studies (HIV, hep B or C) - helpful because some of the drugs will cause reactivation of these infections if they’re positive, and must rule these out as causes of lymphadenopathy
▪ Blood culture and broad spectrum antibiotics
▪ Biopsy of LN or involved organ. Can do histology, immunophenotyped by flow cytometry, cytogenetics (karyotype), immunostaining

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105
Q

Classification for lymphoma?

A
  1. B-cell NHL (more common)
    - Indolent e.g. Follicular
    - Aggressive e.g. Diffuse large B cell lymphoma
  2. T-cell NHL
    - Indolent (causing little or no pain)
    - Aggressive/very aggressive
  3. Hodgkin
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106
Q

Which is more common NHL or HL?

A

NHL is more common than HL

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107
Q

Presentation of NHL?

A
  • Bimodal – elderly
  • LN – peripheral, non-contiguous spread
  • Bone marrow involvement – more frequent
  • Peripheral blood involvement sometimes
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108
Q

When treating aggressive lymphomas or lymphomas with high tumour bulk, we’ll give ______ to prevent conversion to uric acid, and keep them hydrated. ______ can break down uric acid that has already built up

A

Allopurinol

Rasburicase

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109
Q

Treatment goal with agressive NHL?

A

Treatment: Goal is cure. Treat immediately with chemotherapy with anti-CD20 monoclonal antibody if B cell lymphoma

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110
Q

Is it necessary to treat indolent NHL immediately?

A

Often asymptomatic, not necessary to treat immediately. When they become symptomatic, we then give them treatment to shrink the LNs to take away symptoms but still can’t cure them

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111
Q

Is indolent NHL or aggressive NHL more likely to result in tutor lysis syndrome?

A

Agressive NHL

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112
Q

Presentation of Hodgkin’s lymphoma?

A
  • Bimodal – peak 20-30 and then at 70-80
  • LN – central – mediastinal mass, continuous spread
  • Bone marrow involvement – rare
  • Peripheral blood involvement – cytopenias secondary to impaired production (as in the case of bone marrow replacement), to sequestration in the spleen, or to autoimmune destruction (by a dysfunctional immune system that makes antibodies against normal peripheral blood cells
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113
Q

Symptoms of Hodgkin’s lymphoma?

A
  • Pruritis and LN sensitivity on alcohol ingestion

- Can also have B symptoms

114
Q

Treatment of Hodgkin’s lymphoma?

A
  • Chemotherapy and/or radiation

- INTENT IS ALWAYS CURATIVE – High cure rate

115
Q

Presentation of mononucleosis?

A
  • Incubation 1-2 months then 2-3 days of prodrome of malaise + anorexia + younger children usually more asymptomatic or mild vs. older children who may be fatigued with fever + pharyngitis + abdominal pain (i.e. splenomegaly).
  • Presentation similar to acute tonsillitis but more chronic course. If tonsillitis not responding to antibiotics – be suspicious
  • Severe tonsillar enlargement, diffuse white/patchy exudates with palatal petechiae. More prominent posterior chain cervical lymphadenopathy
116
Q

Triad for mononucleosis?

A

Triad: fever + non-tender lymphadenopathy + pharyngitis/tonsillitis

117
Q

Investigations for mononucleosis?

A

Investigations: CBCs (lymphocytosis) + mono-spot + EBV serology is the only definitive + throat swab to r/o strep + LFT + abdominal US

118
Q

Management for mononucleosis?

A

Management: supportive management with rest + hydration + avoid contact sports for 6-8 weeks because of splenomegaly (risk of rupture)

119
Q

What is relative erythrocytosis?

A

Hemoconcentration, or an elevation of Hb and/or Hct due to a decrease in plasma volume alone (ie, without an increase of the RBC mass)

120
Q

What is primary polycythemia?

A

Refers to an increase of RBC mass caused by a mutation (either acquired or inherited) in RBC progenitor cells

121
Q

What is polycythemia (erythrocytosis)?

A

An increase in the number of RBCs: Hb>185g/L or Hct>52% (males) ; Hb>165g/L or Hct>47% (females and African males)

122
Q

Etiology of erythrocytosis?

A
  • Relative erythrocytosis: Diuretics, severe dehydration, burns
  • Primary polycythemia — Polycythemia vera (PV) or another myeloproliferative neoplasm (MPN)
  • Secondary polycythemia
    1. Hypoxemia
  • Congenital Heart Disease
  • Lung Disease; COPD, Sleep apnea, Pulmonary hypertension
  • RBC defects (Hb with increased O2 affinity, methemoglobinemia), high altitude
  • Heavy smoking, CO posioning
  1. Increased EPO
    - Exogenous EPO, steroid
    - EPO-secreting tumors/cysts: Hepatocellular carcinoma, Renal cell carcinoma, Cerebellar hemangioblastoma, Pheochromocytoma, Uterine leiomyoma, Ovarian tumour
123
Q

What is secondary polycythemia?

A

Secondary polycythemia refers to an increase of RBC mass caused by elevated serum erythropoietin (EPO)

124
Q

Clinical features of erythrocytosis?

A
  • Secondary to high red cell mass and hyperviscosity
  • Headache, dyspnea, dizziness, tinnitus, visual disturbances, hypertensive symptoms, and numbness/tingling
  • Symptoms of angina, congestive heart failure, and aquagenic pruritus (only in MPNs)
  • Thrombosis (venous or arterial) or bleeding (seen with acquired vWD or acquired platelet dysfunction in MPNs)
125
Q

Physical findings of erythrocytosis?

A

Physical findings: splenomegaly ± hepatomegaly, facial plethora/ruddy complexion (70%) and/or palms, gout

126
Q

Investigations of erythrocytosis?

A
  • CBCd
  • O2 sat, ABG Pulmonary function test, sleep study, P50 oxygen dissociation curve
  • Serum erythropoietin (EPO): differentiates primary (low/normal) from other etiologies (elevated)
  • Search for tumour as source of EPO as indicated (e.g. abdominal U/S, CT head)
  • JAK-2 mutation analysis: positive in >96% of cases of PV
  • Ferritin (iron deficiency can mask the diagnosis; if iron deficient with reticulocytosis, suggestive of PV)
127
Q

Treatment of erythrocytosis?

A
  • If secondary: treat underlying cause

- O2 for hypoxemia, CPAP for sleep apnea, surgery for EPO-secreting tumours

128
Q

Definition of polycythemia vera?

A

Stem cell disorder characterized by elevated RBC mass (erythrocytosis) ± increased white cell and platelet production

129
Q

Diagnosis of polycythemia vera?

A
  • Requires meeting either all 3 major criteria, or the first 2 major criteria and the minor criterion
  • Major Criteria
    1. hemoglobin >165 g/L in men, >160 g/L in women, OR Hct >49% in men or >48% in women, OR increased red cell mass (>25% above mean normal predicted value)
  1. bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation
  2. presence of JAK2 V617F or JAK2 exon 12 mutation
  • Minor Criterion
    1. serum erythropoietin level below reference range for normal (must have at least two major criteria if using erythropoietin level)
130
Q

Physical findings of polycythemia vera?

A
  • Plethora (ruddy complexion) of face (70%), palms

- Splenomegaly (70%), hepatomegaly (40%)

131
Q

Clinical features of polycythemia vera?

A
  • Symptoms are secondary to high red cell mass and hyperviscosity
  • Thrombotic complications: DVT, PE, Budd-Chiari (hepatic vein thrombosis), portal vein thrombosis, thrombophlebitis, increased incidence of stroke, and MI
  • Bleeding complications: epistaxis, gingival bleeding, ecchymoses, and GI bleeding. If high platelet counts: associated with acquired vWD
  • Erythromelalgia (burning pain in hands and feet and erythema of the skin). Associated with platelets >400 x 109/L. Pathognomonic microvascular thrombotic complication in PV and ET
  • Pruritus, especially after warm bath or shower (40%) due to cutaneous mast cell degranulation and histamine release
  • Epigastric distress, PUD - Due to increased histamine from tissue basophils, alterations in gastric mucosal blood flow due to increased blood viscosity
  • Gout (hyperuricemia), due to increased cell turnover
132
Q

Treatment of polycythemia vera?

A
  • Phlebotomy to keep hematocrit <45%
  • Hydroxyurea (prior thrombosis or symptoms, severe coronary artery disease, refractory to phlebotomy)
  • Low-dose Aspirin (for antithrombotic prophylaxis, will also treat erythromelalgia)
  • Allopurinol: as needed
133
Q

What is a pulmonary embolism?

A

Pulmonary embolus (PE) refers to obstruction of the pulmonary artery or one of its branches by material (eg, thrombus, tumor, air, or fat) that originated elsewhere in the body (DVT)

134
Q

Risk factors for VTE?

A

Genetic (Thrombophilia): Factor V Leiden + Protein C&S Deficiency + ATII + Homocysteine

Acquired:

  • Provoking - recent surgery, trauma, immobilization, initiation of hormone therapy, active cancer
  • Non-provoking - obesity, heavy cigarette smoking
135
Q

Clinical presentation of PE?

A

Sudden onset, persistent pleuritic chest pain/SOB, preceding DVT sx. Tachy/cyanosis/right-side HF. Rarely: hemoptysis, syncope, shock, sudden death.

136
Q

Clinical presentation of DVT?

A

Unilateral calf tenderness/pain + red/purple discolouration + warmth + veins protruding + swelling (measure @10cm below tibial tuberosity)

137
Q

Pathogenesis of VTE?

A

Virchow’s triad - consists of venous stasis, endothelial injury, and a hypercoagulable state

  • Stasis: immobility >6h, hospitalization, lymph node compression, obesity, venous insufficiency from varicose veins, venous obstruction from gravid uterus.
  • Vascular trauma: any surgery, prev vasc injury, indwelling cath or line.
  • Hypercoag states: cancer, preg/OCP, inflamm/sepsis, inherited/acquired condition.
138
Q

Findings of PE on ECG?

A

Sinus tachycardia (S1Q3T3 - A large S wave in lead I, a Q wave in lead III and an inverted T wave in lead III)

139
Q

Findings of PE on CXR?

A

Hampton’s Hump – infarcted lung, or Westermark Sign – darker = edema = obstruction

140
Q

Basic labs that should be ordered with VTE?

A

CBC + Urea/Cr (GFR! Is it safe to give contrast?) + CRP + LDH + liver panel + troponin/CK + ABG in hypoxic

141
Q

Two most important investigations for DVT?

A
  • D-dimer -Useful when it’s negative because you cannot have D dimers without forming a clot first
  • U/S Doppler for clot (DVT)
142
Q

____ should be used to determine the risk score for DVT.

A

Well’s criteria

143
Q

For low or moderate risk DVT: Negative D-dimer, should you get an US?

A

No

144
Q

Only if ___ and ___ are positive for low or moderate risk DVT should anticoagulation therapy be initiated?

A

D-Dimer, U/S

145
Q

For high risk DVT order both D-Dimer + U/S to rule out DVT, If (+)(+) or (-)(+)

A

Anticoagulate/treat

146
Q

For high risk DVT order both D-Dimer + U/S to rule out DVT, If (+)(-)

A

Repeat U/S in 1 week’s time

147
Q

For high risk DVT order both D-Dimer + U/S to rule out DVT, If (-)(-)

A

Discharge

148
Q

For pretest probability of pulmonary embolism, use?

A

Well’s criteria

149
Q

If low probability of pulmonary embolism determined on Well’s criteria, then apply ____ to determine whether or not diagnostic evaluation with D-dimer is indicated?

A

PERC

150
Q

If low probability of pulmonary embolism: For patients who fulfill all eight PERC criteria?

A

No further testing is required

151
Q

If low probability of pulmonary embolism: For patients who do not fulfill all eight criteria?

A

Further testing with sensitive D-dimer measurement is indicated

152
Q

An elevated D-dimer alone is insufficient to make a diagnosis of PE, but a normal D-dimer can be used to rule out PE in patients with a _____ or ______ probability of PE?.

A

Low or intermediate

153
Q

In low-risk patients for PE where PERC cannot be applied (eg, inpatients, critically-ill patients) or PERC is positive, ____ testing is indicated.

A

D-dimer

154
Q

In low or moderate-risk patients for PE, when the D-dimer level is <500 ng/mL (fibrinogen equivalent units)?

A

No further testing is required

155
Q

In low or moderate-risk patients for PE, when the D-dimer level is ≥500 ng/mL (fibrinogen equivalent units), diagnostic imaging should be performed, preferably with ____

A

CTPA

156
Q

Intermediate probability of pulmonary embolism — For most patients in whom the suspicion for PE is intermediate, a sensitive ____ level should be measured.

A

D-dimer

157
Q

For patients in whom the risk of PE is thought to be high, a normal D-dimer is not as helpful for excluding the diagnosis and does not need to be performed. Go straight to ___

A

CTPA

158
Q

For hemodynamically unstable PE, ie, high-risk or “massive” PE is that which presents with hypotension what should be your initial approach and resuscitation?

A
  • Initial support should focus upon restoring perfusion with intravenous fluid resuscitation and vasopressor support, as well as oxygenation and, if necessary, stabilizing the airway with intubation and mechanical ventilation.
  • For most patients who become hemodynamically stable following resuscitation and in whom the clinical suspicion for PE is high, we prefer immediate anticoagulation with unfractionated heparin and prompt imaging for definitive diagnosis (usually computed tomographic pulmonary angiography [CTPA]).
159
Q

For hemodynamically stable PE what should be your initial approach and resuscitation?

A
  • Peripheral intravenous access with or without intravenous fluids - small volumes of intravenous fluid (IVF), usually 500 to 1000 mL of normal saline, followed by vasopressor therapy (norepinephrine) should perfusion fail to respond to IVF
  • Oxygen supplementation - Supplemental oxygen should be administered to target an oxygen saturation ≥90 percent. Severe hypoxemia, hemodynamic collapse, or respiratory failure should prompt consideration of intubation and mechanical ventilation.
  • Empiric anticoagulation
160
Q

What are the absolute contraindications to thrombolytics?

A

h-CVA + i-CVA (within 3 months) + structural CVD (e.g. AVM) + CNS neoplasm + CNS surgery + known/active bleeding or bleeding diathesis + recent head trauma with fracture or injury

161
Q

Disadvantages of low molecular weight heparin (LMW heparin)?

A
  • Only partially reversible by protamine, long-term use associated with osteoporosis, costly!
  • Renally cleared - must adjust dose in patients with renal dysfunction
162
Q

Advantages of unfractionated heparin

A

Rapidly reversible by protamine

163
Q

Disadvantages of unfractionated heparin

A

Must monitor aPTT or heparin levels with adjustment of dose to reach therapeutic level (~2x normal value); monitor platelet counts for development of HIT

164
Q

Advantages of DOACs

A

PO, no monitoring (predictable effect), no drug interactions, no food interactions, safe 1-2% loading dose

165
Q

Disadvantages of DOACs

A

Failed in mechanical heart valves, costs, antidote is quite expensive, and can’t use in those with renal dysfunction, pregnant patient, non-compliance

166
Q

Indications of DOACs

A

DVT prophylaxis post hip or knee replacement surgery, non-valvular a fib stroke prevention, lower extremity DVT and/or PE acute and extended treatment

167
Q

Duration of anticoagulant treatment for provoked VTE with transient risk factor

A

3 mo

168
Q

Duration of anticoagulant treatment for provoked VTE with ongoing risk factor

A

Consider indefinite therapy with annual reassessment

169
Q

Duration of anticoagulant treatment for first unprovoked VTE?

A

At least 3 mo, subsequent reassessment

170
Q

Duration of anticoagulant treatment for unprovoked proximal DVT or PE?

A

Consider indefinite therapy with annual reassessment

171
Q

Duration of anticoagulant treatment for second unprovoked VTE

A

Consider indefinite therapy

172
Q

Long term treatment options for DVT/PE?

A
  • DOACs
  • Warfarin:
  • LMWH
173
Q

Long term DVT/PE anticoagulation option for cancer patients?

A

LMWH

174
Q

Antidotes to warfarin

A

Vitamin K + fresh frozen plasma (FFP) + PCC (expensive, but quick)

175
Q

Standard treatment of warfarin should be initiated with ____ overlap: dual therapy for at least 48 hours with INR >2, due to initial prothrombotic state secondary to warfarin’s inhibition of natural anticoagulants protein C/S, half-life of vitamin K factors and risk of warfarin-induced skin necrosis

A

Heparin

176
Q

Advantages of warfarin?

A

Use in those with any GFR or obese patients, quick reversibility

177
Q

Warfarin dosed to maintain INR at ___, monitor twice weekly for 1-2 wk - discontinue heparin after ___ for 2 consecutive days

A

2-3

INR>2.0

178
Q

Duration of anticoagulant treatment for cancer-associated DVT

A

At least 3 mo, longer if continued evidence of cancer

179
Q

_____ indicated only if acute DVT (<4 wk) with significant contraindications to anticoagulant therapy (i.e. active bleeding) or if require interruption of anticoagulation (i.e. for urgent surgery)

A

Temporary filter

180
Q

Stages of primary hemostasis?

A
  1. Endothelial injury – smooth muscle cells provide reflexive contraction (vascular spasm), endothelin is released which causes smooth muscle contraction.
  2. Exposure – damaged endothelial cells exposes collagen and von Willebrands factor binds.
  3. Adhesion (PLT GpIB + vWF + collagen)
  4. Activation of platelet (thromboxane A2, ADP, serotonin) which activates/amplifies other platelets. This is a positive feedback loop, however undamaged endothelial cells are releasing prostaglandins and nitric oxide which are platelet inhibitors
  5. Aggregation (PLT GpIIb/IIIa + fibrinogen)
181
Q

Stages of hemostasis?

A
  • Primary hemostasis
  • Secondary hemostasis
  • Fibrin Stabilization: Conversion from soluble to insoluble and stable clot
  • Fibrinolysis: Once healing initiated, clot dissolution via action of the fibrinolytic system
182
Q

Stages of secondary hemostasis?

A

Activated PLTs are foundation, sequential activation of coagulation factors (extrinsic and intrinsic pathways→ common), thrombin IIa generation

183
Q

Signs and symptoms of primary hemostasis disorders?

A

Primary: excessive/prolonged surface cuts, immediate after injury, usually superficial (petechiae, purpura, mucosal bleeding).

184
Q

Signs and symptoms of secondary hemostasis disorders?

A

Secondary: prolonged or normal surface cuts, delayed issue, often presents with deep hematogenous bleeds into joints/muscle/skin/GI/GU. Ecchymosis.

185
Q

History to be asked for bleeding disorders?

A
  • Is the patient stable? How urgently is treatment and testing required? Major or minor bleeding? Hx of iron deficiency anemia. Women – take a detailed menstrual history
  • Narrow the differential diagnosis for etiology. Has this been a lifelong issue? FHX? Was it provoked or spontaneous? Try and pinpoint a defect in primary or secondary hemostasis (where is the bleeding – deep or superficial and timing of bleeding after the insult?
  • Rule out non hematologic causes: PMHx (liver disease, renal disease, CT disease)?
  • Rule out offending medications: Meds (ASA, antiplatelet, herbals, anticoags)?
186
Q

Investigations to order for bleeding disorders?

A
  • Primary: PLTs (#, size/morphology, special tests of function) and vWF (factor level and function)
  • Secondary:
    Prothrombin time (PT) - Extrinsic pathway (factor VII)
    INR - Used to monitor warfarin therapy and for assessment of hepatic function
    Partial thromboplastin time (aPTT) - Intrinsic pathway (factors XII, XI, VIII, IX)→, PT + PTT→ common pathway (factors X, V, II, I)

-Others: fibrinogen, D-dimer, lupus anticoagulant

187
Q

Ddx for primary hemostasis disorders?

A
  1. Platelets:
    - Low Platelets (thrombocytopenia): ↓production, ↑destruction/consumption, or sequestration.
    - Normal platelet count (platelet dysfunction)
  2. Vascular
    - Acquired: Purpura simplex (easy bruising), Senile purpura, Dysproteinemias, HSP, Scurvy, Cushing’s syndrome, Infections, Drugs
  3. vWD
188
Q

Ddx for low platelets (thrombocytopenia)?

A
  • ↓production: Aplastic anemia
  • ↑destruction/consumption: immune-mediated (idiopathic (ITP), SLE, lymphoma), consumptive (TTP/HUS, DIC).
  • Sequestration: splenomegaly, dilutional.
189
Q

Ddx for normal platelet count (platelet dysfunction)?

A
  • Hereditary - Bernard Soulier syndrome (GPIb deficiency), Glanzmans syndrome (GP IIb/IIIa deficiency)
  • Acquired - Drugs (ASA, EtOH, NSAIDs), Uremia/CRF, Myeloproliferative disorders
190
Q

Definition of thrombocytopenia?

A

Thrombocytopenia is a lab diagnosis of platelets <140 x 109/L

191
Q

Definition of primary immune thrombocytopenia?

A

Primary: isolated thrombocytopenia (platelet count <100 x109/L) with no other cause of thrombocytopenia

192
Q

Definition of secondary immune thrombocytopenia?

A

Secondary: thrombocytopenia associated with another condition (e.g. HIV, HCV, SLE, CLL)

193
Q

Definition of drug-induced immune thrombocytopenia?

A

Drug-induced: drug-dependent platelet antibodies causing platelet destruction

194
Q

Pathophysiology of immune thrombocytopenia?

A
  • An acquired immune-mediated disorder (pathophysiology incompletely understood)
  • Anti-platelet antibodies bind to platelet surface → increased splenic clearance
  • Impaired platelet production
  • Helper T-cell and cytotoxic T-cell activation also implicated in platelet destruction
195
Q

Clinical presentation of a child with ITP?

A

Otherwise well afebrile child post viral illness with sudden onset petechiae + purpura +/- epistaxis/bloody stool; no lymphadenopathy or hepatosplenomegaly

196
Q

Clinical features of ITP?

A
  • Variable presentation: asymptomatic, fatigue, minimal bruising, mucocutaneous bleed (e.g. purpura, ecchymoses, petechiae, continuous epistaxis, menorrhagia), and intracranial bleed
197
Q

Investigations for ITP?

A
  • CBC and reticulocyte count: thrombocytopenia
  • PT and aPTT: normal
  • Peripheral blood film: decreased platelets, giant platelets (rule out platelet clumping)
  • HIV, HCV, H.pylori serology
  • Vitamin B12, ANA, C3, C4, depending on clinical symptoms
  • Bone marrow aspirate and biopsy: increased number of megakaryocytes
198
Q

Emergency treatment (active bleeding [CNS, GI, or GU] or in need of emergency surgery) for ITP?

A
  • General measures: stop drugs that reduce platelet function, control blood pressure, minimize trauma
  • Corticosteroids: prednisone (1 mg/kg/d) or dexamethasone (40 mg PO/d x 4 d)
  • Antifibrinolytic: tranexamic acid (1 g PO tid or 1 g IV q6h) if mucosal bleeding
  • IVIg 1 g/kg/d x 2 doses (raises platelet count faster than corticosteroids)
  • Platelet transfusion: for refractory, major bleeding or need for urgent surgery (expect that platelet recovery will be diminished)
  • Emergency splenectomy: may be considered, vaccinations prior if possible (pneumococcus, meningococcus, H. influenzae b)
  • Management of intracranial bleeding: IV steroids, IVIg, platelets
199
Q

Non-urgent treatment for ITP?

A
  • Typically, no treatment as >70% will recover spontaneously within 6 months – advise to avoid contact sports and blood thinner
  • 1st-line: corticosteroids (dexamethasone 40 mg PO qd x 4 d x 1-4 cycles (not wk) or prednisone x 3 wk then slow taper), IVIg, anti-D: appropriate for Rh+ non-splenectomized patients, but can cause hemolysis (avoid if low Hb at baseline or if DAT is positive)
  • 2nd-line: splenectomy (need vaccinations prior to splenectomy: pneumococcus, meningococcus, and H. influenzae b), rituximab
200
Q

Pathophysiology of heparin-induced thrombocytopenia?

A
  • Immune mediated
  • Ab recognizes a complex of heparin and platelet factor 4 (PF4) leading to platelet activation via platelet Fc receptor and activation of coagulation system
201
Q

Diagnosis of heparin-induced thrombocytopenia?

A
  • Suspected with intermediate or high probability HIT Score

- Confirm with ELISA testing and Serotonin Release Assay testing

202
Q

Clinical features of HIT?

A
  • Venous thrombosis: DVT, PE, limb gangrene, cerebral sinus thrombosis
  • Arterial thrombosis: MI, stroke, acute limb ischemia, organ infarct (mesentery, kidney)
  • Heparin-induced skin necrosis (with LMWH)
  • Acute platelet activation syndromes: acute inflammatory reactions (e.g. fever/chills, flushing, etc.)
  • Transient global amnesia (rare)
203
Q

Specific tests for HIT?

A
  • Pre-test clinical scoring models can help rule-out HIT: 4-Ts and the HIT Expert Probability (HEP) score 14C serotonin release assay (tests the functional ability of patient’s plasma to activate platelets)
  • ELISA for HIT-Ig (more sensitive, less specific than serotonin assay, faster turnaround time, high negative predictive value)
204
Q

Management of HIT?

A
  • Clinical suspicion of HIT should prompt discontinuation of heparin and LMWH (specific tests take several days)
  • Initiate anticoagulation with a non-heparin anticoagulant: e.g. argatroban, danaparoid, fondaparinux, bivalirudin unless there is a strong contraindication (duration of treatment at least 2-3 mo if no thrombotic event, and at least 3-6 mo if thrombotic event has occurred) Warfarin should only be restarted when platelet count >150 x 109/L
  • Allergy band and alert in patient records
205
Q

What are microangiopathic hemolytic anemias characterized by?

A
  • Primary platelet activation and consumption – activation of coagulation cascade with fibrin deposition in vessels leading to intense microvascular thrombosis
  • Hemolytic anemia – Hb drops, RBCs are sheared (schistocytes) across the microthrombi
206
Q

Who does TTP typically occur in?

A

Predominantly adult

207
Q

Etiology of TTP?

A

Deficiency of metalloproteinase that breaks down ultra-large vWF multimers: ADAMTS13

  • Congenital (genetic absence of ADAMTS-13)
  • Acquired (drugs, malignancy, transplant, and HIV-associated, idiopathic)
208
Q

Clinical features of TTP?

A
  1. Thrombocytopenia
  2. MAHA/TMA
  3. Neurological symptoms: headache, confusion, focal defects, and seizures
  4. Renal failure, fever
209
Q

Pathophysiology of TTP?

A

Depletion of vWF cleaving metalloprotease (ADAMTS13). VLVWF (very long von Willebrand’s factor) - Normally vWF is a very long protein. When you injure yourself, you expose vWF and this attracts platelets. ADAMTS13 is the protease that degrades the vWF to make it smaller so you get normal clotting. When you don’t have the protease, platelets will stick to the long vWF and cause lots of clotting. Red blood cells passing through these clots get sheared as well causing increased bili/LDH/retics but lower haptoglobin.

210
Q

Investigations of TTP?

A
  • CBC and blood film: decreased platelets and increased schistocytes
  • PT, aPTT, fibrinogen: normal
  • Markers of hemolysis: increased unconjugated bilirubin, increased LDH, and decreased haptoglobin Negative Coombs test
  • Creatinine and urea to follow renal function (TTP has nearly no kidney injury vs. HUS/drug mediated TTP which induces severe injury that is sudden in onset)
  • ADAMSTS-13 gene, activity or inhibitor testing (TTP)
211
Q

Who typically gets HUS?

A

Predominantly children and elderly

212
Q

Etiology of HUS?

A

Shiga toxin (E. coli serotype O157:H7) in 90% Other bacteria, viruses, genetic causes, and drugs

213
Q

Clinical features of HUS?

A
  1. Severe thrombocytopenia
  2. MAHA/TMA
  3. Acute kidney injury
  4. Bloody Diarrhea
  5. GI prodrome
214
Q

Management of HUS?

A
  • Supportive therapy (fluids, RBC transfusion, nutrition, etc.)
  • Some evidence for plasma exchange
  • Possible role of Eculizumab (C5 antibody blocks complement activation) for neurologic symptoms
215
Q

Management of TTP?

A
  • Medical emergency
  • Plasma exchange ± steroids
  • Platelet transfusion avoided unless life- threatening bleed (associated with microvascular thrombosis)
  • Plasma infusion if plasmapheresis is not immediately available
  • *Caplacizumab in certain cases of acquired TTP TTP mortality ~90% if untreated
  • When platelets recover, give DVT prophylaxis.
216
Q

Pathophysiology of von Willebrand disease?

A
  • Usually autosomal dominant (type 3 is autosomal recessive)
  • Qualitative defect or quantitative deficiency of vWF depending on type
  • vWF needed for platelet adhesion/aggregation and acts as chaperone for Factor VIII (extending its half-life in circulation), therefore abnormality of vWF can affect both primary and secondary hemostasis
217
Q

Classifications of von Willebrand disease?

A
  • Type 1: mild quantitative defect (decreased amount of vWF and proportional decrease in vWF activity) - 80% of cases
  • Type 2: qualitative defect (vWF activity disproportionally lower than quantity) - 20% of cases
  • Type 3: severe total quantitative defect (virtually no vWF produced) – 1 per million
218
Q

Clinical features of von Willebrand disease?

A
  • Mucocutaneous bleeding (easy bruising, epistaxis (>10min), heavy menstrual bleeding, peripartum bleeding, post-dental extraction bleeding, excessive post-operative bleeding, and unexplained gastrointestinal bleeding)
  • Type 3 vWF patients can experience musculoskeletal bleeding due to significant deficiency in FVIII due to lack of FVIII chaperoning as vWF is absent
  • Family history of a bleeding disorder
219
Q

Most common inherited bleeding disorder (prevalence of 1%)

A

von Willebrand disease

220
Q

Ddx of secondary hemostasis disorders?

A
  1. Hereditary:
    - Factor VIII: Hemophilia A, vWD
    - Factor IX: Hemophilia B (Christmas Disease)
    - Factor XI
  2. Acquired: Liver disease, DIC, Vitamin K deficiency
221
Q

Investigations for von Willebrand disease?

A
  • CBC, platelet, vWF:Antigen (determine how much vWF is present), vWF:Ristocetin cofactor activity (determine how well vWF binds to platelet), Factor VIII (determine how well vWF chaperones with FVIII), and PTT
  • Tests to further categorize type/subtype of vWD: multimer analysis, ristocetin induced platelet agglutination, and genetic studies
222
Q

Treatment for von Willebrand disease?

A
  • Desmopressin (DDAVP) is effective treatment for 85-90% of patients with type1 vWD. Causes release of vWF and Factor VIII from endothelial cells
  • Tranexamic acid (Cyklokapron ,antifibrinolytic) to stabilize clot formation
  • vWF:FVIII concentrate (Humate P, Wilate) if DDAVP¬ unresponsive/clinically ineffective or for severe bleeding episode. Need to monitor vWF and factor VIII levels (very high factor VIII level can be prothrombotic)
  • Gynecologic focused care for heavy menstrual bleeding (NB estrogens have the added benefit of increasing vWF levels)
223
Q

Pathophysiology of hemophilia A (Factor VIII Deficiency)?

A

X-linked recessive, 1/5000 males

224
Q

Investigations of hemophilia A (Factor VIII Deficiency)?

A
  • Prolonged aPTT, normal INR (PT)

- Decreased Factor VIII (<40% of normal)

225
Q

Treatment of hemophilia A (Factor VIII Deficiency)?

A
  • Desmopressin (DDAVP) in mild hemophilia A
  • Factor VIII concentrate for: prophylaxis, on-demand (i.e. to treat a bleed)
  • Anti-fibrinolytic agents (e.g. tranexamic acid)
226
Q

Clinical and laboratory features of ______ identical to hemophilia A (except decreased Factor IX)

A

Hemophilia B

227
Q

Treatment of hemophilia B?

A

Factor IX concentrate (prophylaxis or on-demand), anti-fibrinolytic agents

228
Q

Factor XI Deficiency is more common in?

A

Ashkenazi Jewish population

229
Q

Factor XI level does not correlate with bleeding risk – risk of bleeding correlates with a ____ or _____

A

Previous history

Family history of bleeding

230
Q

Treatment of Factor XI Deficiency?

A

Antifibrinolytic agents, frozen plasma, and Factor XI concentrate

231
Q

Pathophysiology of liver disease

A
  • Deficient synthesis of all factors except VIII (also made in endothelium)
  • Aberrant or diminished synthesis of fibrinogen (factor I)
  • Diminished synthesis of natural anticoagulants and altered regulation of fibrinolysis
232
Q

Investigations of liver disease?

A
  • Peripheral blood film: target cells
  • Primary hemostasis affected. Thrombocytopenia 2o to hypersplenism, nutritional deficiency, direct bone marrow toxicity related to alcohol, diminished production from chronic viral infections (e.g. HCV), and decreased production of thrombopoietin
  • Secondary hemostasis affected: elevated INR (PT), aPTT, TT (thrombin time), low fibrinogen in end-stage liver disease
233
Q

Treatment of liver disease?

A

Supportive, treat liver disease, blood products if active bleeding (frozen plasma, platelets, cryoprecipitate)

234
Q

Etiology of vitamin K deficiency?

A
  • Drugs: vitamin K antagonist (e.g. Warfarin) - diminished production of functional Factors II, VII, IX, X, proteins C and S. Antibiotics eradicating gut flora, altering vitamin K uptake
  • Poor diet (especially in alcoholics) e.g. prolonged fasting or starvation
  • Biliary obstruction
  • Chronic liver disease (decreased stores)
  • Fat malabsorption (e.g. celiac disease, disorders of bile or pancreatic secretion, and intestinal disease, CF)
235
Q

Investigations of vitamin K deficiency?

A
  • INR (PT) is elevated out of proportion to elevation of the aPTT
  • Decreased Factors II, VII, IX, X (vitamin K-dependent)
236
Q

Treatment of vitamin K deficiency?

A
  • Hold anticoagulant if vitamin K antagonist on board
  • Vitamin K PO if no active bleeding
  • If bleeding, give vitamin K 10mg IV (reversal may take up to 12h)
  • If life-threatening bleeding and vitamin K antagonist used, give prothrombin complex concentrate (PCC) or FP if PCC contraindicated
237
Q

Definition of disseminated intravascular coagulation (DIC)?

A
  • Excessive, dysregulated release of plasmin and thrombin leading to intravascular coagulation and depletion of platelets, coagulation factors and fibrinogen
  • Risk of life-threatening hemorrhage or thromboembolism
238
Q

Etiology of disseminated intravascular coagulation (DIC)?

A

Occurs as a complication of many other severe medical, surgical or obstetrical conditions

239
Q

Signs of hemorrhagic diathesis of disseminated intravascular coagulation (DIC)?

A
  • Bleeding from any site in the body (2o to decreased platelets and clotting factors)
  • Neurologic: intracranial bleeding
  • Skin: petechiae, ecchymosis, oozing from puncture sites Renal: hematuria
  • Mucosal: gingival oozing, epistaxis, massive bleeding
240
Q

Investigations + findings of disseminated intravascular coagulation (DIC)?

A
  • Primary hemostasis: decreased platelets
  • Secondary hemostasis: prolonged INR (PT), aPTT, TT, decreased fibrinogen and other factors
  • Fibrinolysis: increased FDPs or D-dimers and short euglobulin lysis time (i.e. accelerated fibrinolysis)
  • Extent of fibrin deposition: urine output and RBC fragmentation
241
Q

Treatment of disseminated intravascular coagulation (DIC)?

A
  • Recognize early and treat underlying disorder- supportive measures: hemodynamic and/or ventilator support, aggressive hydration, and RBC transfusion if severe bleed
  • In hemorrhage: replacement of hemostatic elements with platelet transfusion, frozen plasma, and cryoprecipitate
  • British Hematology Guidelines:
    • Maintain platelets >50 x 109/L, hemoglobin >80 g/L, calcium between 2.2-2.7 mmol/L, and avoid hypothermia
    • 4-5 units of FP if INR >1.5 or aPTT >38
    • 10 units of cryoprecipitate if fibrinogen <1 g/L
    • 1 adult dose of buffy-coat platelets if <10 x 109/L (<20 if febrile, <50 before invasive procedure)
  • In thrombotic phase: UFH or LMWH in critically ill, non-bleeding patients
242
Q

Signs of hemorrhagic diathesis of disseminated intravascular coagulation (DIC)?

A
  • Bleeding from any site in the body (2o to decreased platelets and clotting factors)
  • Neurologic: intracranial bleeding
  • Skin: petechiae, ecchymosis, oozing from puncture sites Renal: hematuria
  • Mucosal: gingival oozing, epistaxis, massive bleeding
243
Q

Definition of leukocytosis?

A

Leukocytosis is an increased white blood cell (WBC) count, with specific cutoffs based on a patient’s age; in adults, leukocytosis is typically defined as WBC count > 11 x 109/L.

244
Q

Leukocytosis in the range of approximately 50,000 to 100,000 per mm3 (50.0 to 100.0 × 109 per L) is sometimes referred to as a _____

A

Leukemoid reaction

245
Q

The most common type of leukocytosis is ?

A

Neutrophilia

246
Q

Definition of leukostasis?

A
  • Leukostasis is an oncologic emergency with risk of life-threatening cerebral infarcts, cerebral hemorrhage, or pulmonary insufficiency.
  • Leukostasis is caused by extreme elevations in WBC count (> 100-400 x 109/L)
247
Q

Definition of neutrophilia?

A

Definition: An absolute neutrophil count (ANC) >7.7 x109/L

248
Q

Etiology of primary neutrophilia?

A
  • Chronic myeloid leukemia (CML)
  • Other myeloproliferative disorders: PV, ET, myelofibrosis
  • Hereditary neutrophilia (autosomal dominant)
  • Chronic idiopathic neutrophilia in otherwise healthy patients
249
Q

Etiology of secondary neutrophilia?

A
  • Stress/exercise/epinephrine: movement of neutrophils from marginated pool into circulating pool
  • Obesity
  • Infection: leukocytosis with left shift
  • Inflammation: rheumatoid arthritis (RA), IBD, chronic hepatitis, MI, PE, and burns
  • Malignancy: hematologic (i.e. marrow invasion by tumour) and non-hematologic (especially large cell lung cancer)
  • Medications: corticosteroids, beta agonists, lithium, epinephrine, colony-stimulating factors
250
Q

Investigations for neutrophilia?

A
  • CBC and differential: mature neutrophils or bands >20% of total WBC suggests infection/inflammation
  • Blood film: Dohle bodies, toxic granulation, and cytoplasmic vacuoles in infection. Cytology
  • May require bone marrow biopsy if MPN suspected
251
Q

Clues to primary MPN

A
  • Clinically well patient with persistent neutrophilia
  • Splenomegaly
  • CBCd – extremely high WBC, myeloid precursors, Increased eosinophils and/or basophils - If you detect any basophilia, be more concerned with CML
  • Blood film: Giant Platelets
252
Q

Definition of lymphocytosis?

A

Lymphocytosis (when lymphocytes make up more than 40% of the WBC count or the absolute count is greater than 4,500 per mm3 [4.5 × 109 per L]

253
Q

Etiology of lymphocytosis?

A
  • Infection (reactive lymphocytosis): Viral infections (majority); particularly mononucleosis. TB, pertussis, brucellosis, toxoplasmosis
  • Smoking
  • Physiologic response to stress (e.g. trauma, status epilepticus)
  • Hypersensitivity (e.g. drugs, serum sickness)
  • Autoimmune (e.g. rheumatoid arthritis)
  • Neoplasm (e.g. CLL,B cell lymphocytosis of undetermined significance)
254
Q

Definition of chronic myeloid leukemia?

A

Myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate

255
Q

Clinical features of chronic myeloid leukemia

A
  • Nonspecific symptoms: fatigue, weight loss, malaise, excessive sweating, fever
  • Secondary to splenic involvement:
  • Early satiety, LUQ pain/fullness, shoulder tip pain (referred)
  • Splenomegaly (most common physical finding)
  • Anemia
  • Bleeding: secondary to platelet dysfunction
  • Pruritus, PUD: secondary to increased blood histamine
  • Leukostasis, priapism, encephalopathy (rare): secondary to very elevated WBC (rare)
256
Q

Investigations + findings for chronic myeloid leukemia

A
  • Elevated WBC, decreased/normal RBC, increased/decreased platelets, increased basophils
  • WBC differential shows a bimodal distribution, with predominance of myelocytes and neutrophils
  • Peripheral blood film + cytology: Blood smear shows mature lymphocytes and smudge cells
  • Presence of different mid-stage progenitor cells differentiates it from AML
  • Bone marrow: Myeloid hyperplasia with left shift, increased megakaryocytes, mild fibrosis
  • Molecular and cytogenetic studies of bone marrow or peripheral blood for Philadelphia chromosome
257
Q

Treatment of chronic myeloid leukemia

A
  • Prophylactic: allopurinol
  • Chronic phase: tyrosine kinase inhibitors
  • Stem cell transplantation may be curative: to be considered in young patients who do not meet therapeutic milestones
258
Q

Definition of neutropenia?

A
  • Neutropenia (<1.5 x 109) is defined as a count less than 1.5 x 109
  • > 1 x 109 = no significant increased risk of infections
  • 0.5-1 x 109 = mild increased risk
  • <0.5 = HUGE RISK, especially if <0.2.
259
Q

Etiology of neutropenia?

A
  1. Decreased Production:
    - Infection: Viral hepatitis, Epstein-Barr virus, HIV, TB, typhoid, malaria
    - Hematological Diseases: Idiopathic, aplastic anemia, myelofibrosis, BM infiltration, cyclic, PNH, MDS, immune-mediated
    - Drug-Induced: Alkylating agents, antimetabolites, anticonvulsants, antipsychotics, anti-inflammatory agents, anti-thyroid drugs
    - Toxins/Chemicals: High dose radiation, benzene, dichlorodiphenyl trichloroethane (DDT)
    - Nutritional Deficiency: B12, folate
    - Idiopathic: Constitutional neutropenia, benign cyclic neutropenia
  2. Peripheral Destruction/Sequestration
    - Anti-neutrophil antibodies
    - Spleen or lung trapping
    - Autoimmune disorders: rheumatoid arthritis (Felty’s syndrome), SLE
    - Granulomatosis with polyangiitis (formerly Wegener’s)
    - Drugs: haptens (e.g. α-methyldopa)
260
Q

The most common cause of neutropenia in the outpatient setting is usually ___

A

Viral

261
Q

Clinical features of neutropenia?

A
  • Fever, chills (only if infection present)
  • Infection by endogenous bacteria (e.g. S.aureus, Gram negatives from GI and GU tract)
  • Painful ulceration on skin, anus, mouth, and throat following colonization by opportunistic organisms
  • Avoid digital rectal exam
262
Q

Investigations of neutropenia?

A

1st repeat the CBC + diff as it will normalize, if not investigate further: blood film, thorough review of drugs (chemo/immunosuppression/new med?), HIV serology, vitamin B12 level and serology for autoimmune disease

263
Q

Treatment of neutropenia?

A
  • Regular dental care: chronic gingivitis and recurrent stomatitis are major sources of morbidity
  • Treatment of febrile neutropenia
  • In severe immune-mediated neutropenia, G-CSF may increase neutrophil counts: If no response to G-CSF, consider immunosuppression (e.g. steroids, cyclosporine, and methotrexate)
264
Q

Management of chemotherapy-related cytopenias?

A
  • Assess/treat life-threatening complication: Do they meet criteria for febrile neutropenia? If yes: panculture and institute empiric antimicrobial therapy. Consider G-CSF
  • Treat the underlying cause of neutropenia: viral (supportive), severe sepsis (treat the infection), drug-related (stop drug), autoimmune disease (manage disease, surveillance), bone marrow disease
265
Q

Indications for G-CSF (granulocyte-colony stimulating factor)?

A
  1. Prior episode of febrile neutropenia who are about to undergo chemotherapy (secondary prophylaxis)
  2. Settings of neutropenia with severe infection neutropenic on chemo
  3. As primary prophylaxis in certain chemotherapy regimens with high risk of infectious death
  4. Current symptomatic neutropenia
  5. Congenital neutropenia
266
Q

Factors that compromise the immune system

A
  • General: age (very young or elderly), malnutrition
  • Immune disease: HIV, malignancies, asplenia (functional or anatomic), hypogammaglobulinemia, neutropenia
  • DM
  • Iatrogenic: corticosteroids, chemotherapy, radiation treatment, anti-TNF therapy, other immunosuppressive drugs (e.g. in transplant patients)
267
Q

Types of Immunodeficiency

A
  • Cell mediated immunity
  • Humoral Immunity
  • Neutrophil Function
268
Q

Etiology of cell-mediated immunity?

A

HIV, Hodgkin, hairy cell leukemia, cytotoxic drugs, SCID, DiGeorge syndrome

269
Q

Etiology of humoral Immunity?

A

CLL, lymphosarcoma, multiple myeloma, nephrotic syndrome, protein-losing enteropathy, burns, sickle cell anemia, asplenia, splenectomy, selective Ig deficiencies, Wiskott-Aldrich syndrome

270
Q

Etiology of neutrophil function?

A

Chemotherapy, myelodysplasia, paroxysmal nocturnal hemoglobinuria, radiation, cytotoxic drug therapy, C3 or C5 deficiencies, chronic granulomatous disease

271
Q

Common organisms that cause infection/fever in cell-mediated immunity disorders

A
  • Bacteria (L. monocytogenes, Salmonella spp., Legionella spp., and mycobacterial spp.)
  • Fungal (C. neoformans, Can- dida spp., P. jirovecii/carinii)
  • Parasitic (T. gondii)
  • Viral (varicella-zoster, HSV)
272
Q

Common organisms that cause infection/fever in humoral immunity disorders

A

Encapsulated organisms (S. pneumoniae, H. influenzae, N. meningitidis, Salmonella typhi, GBS)

273
Q

Common organisms that cause infection/fever in neutrophil function disorders

A

Catalase-producing organisms (Staphylococcus, Serratia, Nocardia, Aspergillus)

274
Q

Definition of febrile neutropenia?

A

Fever (≥38.3°C/101°F or ≥38.0°C/100.4°F for ≥ 1h) and one of:

  • ANC <0.5 OR
  • ANC <1.0 but trending down to 0.5
275
Q

Pathophysiology decreased neutrophil production

A
  • Marrow: infection, aplastic/myelophthisic anemia, leukemia, lymphoma, myelodysplastic syndromes
  • Iatrogenic: cancer chemotherapy, radiation, drugs
  • Deficiencies: vitamin B12, folate
276
Q

Pathophysiology increased peripheral neutrophil destruction

A
  • Autoimmune: Felty’s syndrome, SLE, antineutrophil antibodies
  • Splenic sequestration
277
Q

Investigations of febrile neutropenia?

A
  • Examine for potential sites of infection: mucositis and line infections are most common
  • Do NOT perform DRE; examine perianal region for perianal abscess
  • Blood C&S (x2sets), urine C&S, culture all indwelling catheter ports, ¬ ± sputum C&S and nasopharyngeal swab for respiratory viruses
  • CBC and differential, Cr, urea, electrolytes, AST/ALT, total bilirubin, CXR (depending on stage of disease)
278
Q

Treatment of febrile neutropenia?

A
  • Broad-spectrum antibacterials should be given should be initiated immediately after blood cultures have been obtained and before any other investigations have been completed. Antimicrobial therapy should be administered within 60 minutes of presentation.
  • Initiation of monotherapy with an antipseudomonal beta-lactam agent, such as cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam.
  • Augmentin
  • Consider empiric antifungal therapy after four to seven days if cause not yet identified
279
Q

Common infections >1 mo post-transplant

A
  • viral (especially CMV, EBV, VZV)
  • fungal (especially Aspergillus, Cryptococcus, P. jiroveci)
  • protozoan (especially Toxoplasma)
  • unusual bacterial/mycobacterial infections (especially TB, Nocardia, Listeria)
280
Q

Which prophylactic vaccinations are given before solid-organ transplant

A
  • To all transplant patients: DTaP, pneumococcal, influenza, hepatitis A and B vaccines
  • If low titre or poor documentation: MMR, polio, varicella vaccination (with booster 4-8 wk later)

LMCC (anglais) (23 decks)

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