Hematology & Oncology Flashcards
Polycythemia vera (blood cancer; bone marrow to make too many red blood cells)
- myeloproliferative disorder marked by erthrocytosis
- types:
1. Primary polycythemia (low erythropoietin)
2. Secondary polycythemia ( high erythropoietin)
Manifistation:
- increase blood viscosity (HTN, erythromelalgia, transient visual disturbance)
-increases RBC turnover ( gouty arthritis)
-Aquagenic pruritus
-bleeding
Examination:
- facial plethora (ruddy cyanosis; facial swelling and puffiness.)
- splenomegaly
Laboratroy:
- high Hg
- high leukocytes
- high platelet
- low erythropoietin
- (positive) JAK2 mutation
Complication:
- thrombosis
-myelofibrosis & acute leukemia
Treatment:
- phlebotomy
- hydroxyurea (if, increase risk of thrombus)
Extra finding:
- low ESR
- low iron
Note:
-erythromelalgia: burning cyanosis in hands/feet
- facial plethora: also seen with Cushing syndrome
Chronic myeloid leukemia (CML) vs. leukomoid reaction
CML:
- Caused by: BCR-ABL fusion protein
Feature:
- fatigue + weight loss + nigh sweat + abdominal fullness (splenomegaly)
Laboratory:
- severe leukocytosis (leukocytes > 100,000) + anemia ( low Hg) + high platelet
- low leukocytosis alkaline phosphate score ( low ALP) (neutrophils are cytochemically & functionally abnormal)
- Less mature: myelocytes > metamyelocytes
- presence of absolutes basophilia
Leukemoid reaction:
- caused by: severe infection
Signs:
- leukocyte count > 50, 000
- high Leukocyte alkaline phosphatase (High LAP)
- more mature: metamyelocytes > myelocytes
- absence of absolute basophils
Hemophilia A or B
Inheritance:
- X-linked recessive
Feature:
- delayed/prolonged bleeding after mild trauma
1. Hemarthrosis, intramuscular hematomas
2. GI or genitourinary hematoma
3. Intracranial Hematoma
Laboratory:
1. High activated PTT
2. Normal platelet & Normal PT
3. Absent or low factor 8 (hemophilia A) or factor 9 (hemophilia B)
Treatment:
- factor replacement
-desmopressin for mild hemophilia A
Petechiae ( pinpointed red spots)
- associated with capillary rupture
- seen with platelet disorders ( lead to mucosal bleeding; GI, uterine, oropharyngeal)
Red papule (on trunk & lips)
- represent cutaneous AVM
- seen with hereditary telangiectasia ( autosomal dominant + telangiectasia + epistaxis)
Von Willebrand disease
- heavy menstrual bleeding in women
- abnormality in platelet plug formation —> lead to prolonged mucosal bleeding ( GI, uterine, oropharyngeal)
Graft vs. host disease (GVHD)
- Caused by: activation of the donor T lymphocytes
- after bone marrow transplantation (from matched HLA-siblings)
Target organs of GVHD:
- Skin: maculopapular rash in face, hand, feet
- Intestine: diarrhea + occult blood in stool
- Liver: abnormal LFT + Jaundice
Note:
- activation of host T-lymphocytes = facilitate rejection of the graft = depression of myelopoiesis (production of bone marrow) = low neutrophils for several days + increase risk of infection
Acute myeloid leukemia (AML)
Superior Vena Cava (SVC) syndrome
- caused by: obstruction of SVC, prevent flow of blood from head/neck/ arm to right heart
- obstruction of SVC is due to: malignancy ( small cell lung cancer, non-Hodgkin lymphoma),
Signs:
- SOB + venous congestion + swelling of the head/ neck/ arm
Diagnosis::
- chest X-ray
- follow up with chest CT & histology ( To determine tumor type)
24- hours urinary protein excretion
- assess for nephrotic syndrome
- causes generalized edema
Measurement of albumin
- assess for liver disease
- causes generalized edema
Anemia of chronic diseases
-caused by: long term elevation of inflammatory cytokines ( hepcidin —> destroy iron channel on macrophages —> limits iron availability for erythropoiesis)
- causes Normocytic or slightly Microcytic anemia with low Reticulocyte response
Cancer pain management
Chronic cancer-related pain:
Mild (severity 1-3 out of 10)
Nonopioid:
1. Acetaminophen or NSAID
2. ± adjuvant ( Glucocorticoid, anti-depressant, anti-convulsant)
3. If inadequate relief from these medication move to short-acting opioid
Moderate to severe ( severity 4-10 out of 10)
Short acting opioid:
1. Oxycodone, morphine
2. ±nonopioid ±adjuvant
- multiple daily doses or sleep interruption or if bedtime dosing does not provide relief through out the night :
Long-acting opioid:
- Extended release morphine, fentanyl patch
- ±nonopioid ± adjuvant
+ short acting opioid for breakthrough pain
Upper extremity DVT
- in young + athletic men who lift weight or engage in activities that involves repetitive overhead arm motion (pitching a baseball game)
-sign: acute arm swelling + heaviness + pain + worst with arm elevation/ improved with arm rest
- diagnosis: duplex or doppler U/S
- treatment: thrombolysis &/or 3 months of anti-coagulation
Vitamin B deficiency
- caused by: pernicious anemia (antibody-mediated destruction of intrinsic factor)
- complication: gastric cancer
Signs: - macrocytic anemia (lightheadedness + palpitation)
- glossitis ( smooth tongue)
- lower extremity neurologic finding ( paresthesia + diminished reflexes)
Hemochromatosis
Signs:
- skin hyperpigmentation
- MSK pain
- GI: hepatomegaly ( early), cirrhosis (late), hepatocellular carcinoma ( complication)
-endocrine: DM, hypogonadism, hypothyroidism
- cardiac: restrictive cardiomyopathy
- infection: listeria, Vibrio, Yersinia
Notes:
- hemochromatosis should be considered in patient with abnormal LFT enzymes + diabetes + hyperpigmentation
Long-standing mediastinal lymphadenopathy
- follicular lymphoma ( type of non-hodgkin lymphoma of elderly people)
- present as: non-painful peripheral lymphadenopathy for years in the (cervical, axillary, inguinal region)
- waxing & waning lymphadenopathy
- hilar/mediastinal lymphadenopathy are usually seen
- No B symptoms + No laboratory abnormality
Diagnosis:
- excisional lymph node biopsy
- translocation between chr. 14 & 18 (over-expression of BCL-2; oncogenic that prevent apoptosis)
The distal vs proximal deep vein thrombosis
- distal DVT (calf veins): normally dont lead to PE, & usually resolved
- proximal DVT ( femoral & popliteal veins): usually lead to PE
- PE: (pleuritic chest pain, tachycardia, hypoxemia ..)
- Pulmonary HTN ( acute chest pain + tachycardia + S2)
Fulminant infection in asplenic patient
- pneumococcal pneumonia = fever + tachycardia + hypotension + tachypnea
- patient with asplenia are at high risk for fluminant infection with encapsulated organisms ( due to impaired antibody-facilitated phagocytosis)
- these patients should be immunized with: pneumococcal, meningococcal, & H influenza type B vaccine + take oral antibiotics early in the course of any febrile illness
Hodgkin lymphoma
- young patient
Signs:
- painless hilar/ mediastinal lymphadenopathy in cervical or supraclavicular or mediastinal mass
- B-symptoms ( fever, night sweats, weight loss)
Diagnosis:
- excisional lymph node biopsy
- no evidence of clear peripheral lymphadenopathy of physical examination —> undergo (PET scan with 18-FDG) —> identify area of enhanced metabolic activity (cancer, infection) —> also, will pool in area of high glucose: brain, liver, kidney, urinary collecting system due to radiotracer excretion
Iron study in microcytic anemia
Iron deficiency: (high TIBG)
- low iron
- low MCV
- high TIBG (total iron binding capacity )
- low ferritin
- low transferrin saturation (iron/TIBG)
- in men, it is associated with chronic GI blood loss
Thalassemia ( high iron, ferritin, transferrin)
- high iron
- low low MCV
- low TIBG
- high ferritin
- High high transferrin
Anemia of chronic diseases: ( normal/high ferritin)
- low iron
- normal/low MCV
- low TIBG
- normal/ high ferritin
- normal/low transferrin
Leukemia
( ALL, AML , CLL, CML)
- WBC cancer
- classified by (myeloid or lymphoid)
- types:
1. Acute: - acute lymphocytic leukemia
- acute myeloid leukemia
- Chronic:
- chronic lymphocytic leukemia
- chronic myeloid leukemia
Blood stem cell
- Myeloid stem cell
- RBC
- platelet
- myeloblast —> granulocytes —> basophil, eosinophil, neutrophil - Lymphoid stem cell
- lymphoblast —> B lymphocyte (plasma cell), T lymphocyte, Nk cells
AML vs CML —> involves myeloid stem cell
- AML:
- Involves myeloblast - CML:
- involves Granulocytes —> basophil, predominant neutrophil, eosinophil
Notes:
- mostly in 50-60 years old (middle age)
ALL vs. CLL —> involves lymphoid stem cell
- ALL:
- involves lymphoblast (lymphoid precursor cells in bone marrow)
- seen in children
- most common childhood malignancy - CLL:
- involves predominant B lymphocyte, T lymphocyte, Nk cells
- seen in elderly patients ( >70 years)
- Acute lymphoid leukemia (ALL)
- involves lymphoblast (lymphoid precursor cells in bone marrow)
- seen in children
- most common childhood malignancy
clinical: —> (Anemia, Lumpy, Limping)
1. Hepatomegaly/ splenomegaly
2. Lymphadenopathy
3. Fever
4. Hematologic abnormality —> thrombocytopenia (petechiae, purpura) & anemia ( fatigue, pallor)
5. MSK pain ( limping, can’t bare weight)
diagnosis:
1. CBC with diff: pancytopenia —> anemia (low Hg), thrombocytopenia ( low platelet), WBC derangement ( low, normal or high WBC count)
- Bone marrow Biopsy —> more than 20% lymphoblast
Treatment:
- Chemo ( highly responsive to chemo)
- CNS preventative therapy (Intrathecal Methotrexate) —> (because ALL can hide in CNS & lead to leukemic meningitis)
- Acute Myeloid leukemia (AML)
- most common type of acute leukemia in adults
- subtypes:
1. Acute pro-myelocytic leukemia (APL) ( m3 variant) - myeloperoxidase positive stain
- Auer rods ( rod stick out of cytoplasm)
- Vitamin A ( All trans-retinoic acid) ( in addition to chemo treatment)
Clinical:
1. Fatigue ( proceed disease by # of months)
2. Pallor/ weakness ( related to anemia)
3. Infection ( related to neutropenia)
Diagnosis:
1. CBC with diff: pancytopenia ( anemia, thrombocytopenia, neutropenia)
- Bone marrow biopsy —> more than 20% myeloblast
Treatment:
1. Chemo
2. Add vitamin A to chemo regimen if APL subtypes
Chronic lymphocytic leukemia ( CLL)
- mature B-cell neoplasm involving a progressive accumulation of monoclonal B lymphocytes
- older adults ( median age of diagnosis is 70)
Clinical: ( Lumpy)
- Asymptomatic
- Fatigue
- Lymphadenopathy
- Splenomegaly/ hepatomegaly
Diagnosis:
1. CBC with peripheral smear: (absolute lymphocytosis > 5000)
- Smudge cells (crushed little lymphocytes)
Treatment:
1. Asymptomatic —> observe only
2. Symptomatic —> chemo or stem-cell transplant
Chronic myeloid leukemia (CML)
- Seen in middle age patients (50-60)
- myeloproliferative neoplasm with uninhibited proliferation granulocytes
Patho:
- Associated with a reciprocal translocation between Chr. 9 & 22 that give rise to an abnormal chromosome called —> Philadelphia chromosome
Clinical:
- asymptomatic
- splenomegaly
- fatigue
- weight loss
- fever
Diagnosis:
- CBC: leukocytosis with neutrophil predominance ( neutrophilia)
Treatment:
- tyrosine-kinase inhibitor (Imatinib) (target over-expression of Tyrosine-kinase in CML)
Tyrosine kinase inhibitor (Imatinib)
- for treatment of CML
CNS prophylaxis ( Intrathecal Methotrexate)
- used in ALL
Smudge cell seen in
- CLL
Philadelphia chromosome (9 & 22 reciprocal translocation)
- seen in CML
Auer rod, & positive stained myeloperoxidase seen in. ?
- seen with APL ( M3 variant) subtype of AML
Thrombocytopenia ( ITP, TTP, HUS, DIC, HIT)
Sickle cell disease
- In sickle cell disease, the hemoglobin is abnormal, causing the red blood cells to be rigid and shaped like a “C” or sickle, the shape from which the disease takes its name. Sickle cells can get stuck and block blood flow, causing pain and infections.
- The worst complications include stroke, acute chest syndrome (a condition that lowers the level of oxygen in the blood), organ damage, other disabilities, and in some cases premature death.
Hereditary spherocytosis (HS)
- autosomal dominant
- northern European descent
Clinical:
- hemolytic anemia
- jaundice
- splenomegaly
Findings:
1. increase MCHC
2. negative coombs test
3. spherocytes on peripheral smear ( small round RBC without central pallor)
4. increase osmotic fragility on acidified glycerol lysis test
5. abnormal eosin-5-maleimide binding test
Complication:
- pigment gallstone
Treatment:
1. Folic acid supplement
2. Blood transfusion
3. Splenectomy
Hemoglobin A2 level
- in patient with beta thalassemia trait
Hemoglobin F seen with
- Sickle cell anemia
- Beta thalassemia
- Congenital aplastic anemia
- Hereditary persistence of fetal hemoglobin
** no spherocytosis seen with these conditions
G6PD
-Caused by: infection, sulfa drugs, fava bean, dapsone, primaquine
Clinical:
- pallor/fatigue
- dark urine, jaundice, icterus
- abdominal pain/ back pain
Laboratory:
1. Hemolysis: low Hg, low haptoglobin, high bilirubin, high LDH, high reticulocytes
- Peripheral smear: bite cells & heinz bodies
- Negative coombs test
- Low G6PD activity level
Management:
1. Remove or treat responsible agent/ condition
- Provide supportive care
low Hg, low haptoglobin, high bilirubin, high LDH, high reticulocytes
Indicates hemolysis
Hereditary hemorrhagic telangiectasia (HHT)
(Osler-Weber- Rendu Syndrome)
- autosomal dominant
- lead to diffused telangiectasia ( ruby-colored papules that blanch with pressure)
- composed of dilated capillaries and veins in the skin, mouth, respiratory system, GI system and urinary tract. Sometimes these can rupture, causing nosebleeds, GI bleeding or hematuria
Clinical:
1. Recurrent nose bleed
2. Oral lesions
3. Widespread AVM ( mucous membrane, skin, GI tract, liver, brain , lung)
—> AVM in the lung shunt blood from the right to the left side of the heart —> causing chronic hypoxemia + digital clubbing + reactive polycythemia
- High hematocrit
Polycythemia Vera
- myeloproliferative disorders
Clinical:
- increase production of all 3 blood cell lines
- splenomegaly
- median age is 60
Pulmonary HTN & polycythemia commonly co-exist
- polycythemia lead to pulmonary HTN —> increasing blood viscosity within pulmonary vasculature —> lead to chronic hypoxemia
Vitamin C or Vitamin K
- lead to bleeding
Hereditary hemorrhagic telangiectasia
- lead to pulmonary AVM associated with hemoptysis & right-to-left shunt
- patient have recurrent nose bleed & oral lesion
Folate deficiency
- seen with alcohol use disorder
- result in folate deficiency within 5-10 weeks
- develop megaloblastic anemia with macrocytosis ( increase MCV > 110) + mild thrombocytopenia + mild leukcytopenia
Alcohol use disorder
- lead to megaloblastic anemia
- lead to folate deficiency more common than vitamin B12 deficiency —> due to little body stores of folate
- related to vitamin B 12 deficiency in older patient with disorder of the stomach ( pernicious anemia, atrophic gastritis) or small intestine that impair absorption
Obstructive sleep apnea (OSA)
Risk factor:
- obesity (> 35)
- respiratory symptoms ( snoring, gasping for air)
- erectile dysfunction, arterial HTN
Patho:
- Transient airway obstruction —> short period ( 20-40 sec) of apnea/hypoxia —> reduction in blood oxygen —> kidney response to hypoxemia by increasing EPO —> Stimulates bone marrow to release more RBC —> Lead to elevated hematocrit
Notes:
Hypoxemia —> elevated EPO —> elevated hematocrit
Polycythemia
-polycythemia —> increase RBC + increase hematocrit
- Absolute polycythemia (erythrocytosis)
- due to increase RBC mass
- seen with:
- primary ( polycythemia vera) —> low EPO
- secondary (due to chronic hypoxia or EPO- producing tumor/ renal cell carcinoma, chronic CO toxicity) —> high EPO
—> chronic hypoxia lead to kidney producing more EPO —> Stimulates bone marrow to produce more RBC —> Elevated hematocit
- Relative polycythemia
- due to reduced plasma volume ( abnormal BUN/Cr)
Testosterone excess —> lead to erythrocytosis ( absolute polycythemia = increase RBC mass)
- treat with positive airway pressure to improve sexual function
Hemolytic anemia —> caused by G6PD
Finding
- increase reticulocyte
- increase bilirubin
- increase LDH
- Decrease Hg
- Decrease heptiglubin
Can develop after patient taking (Dapsone/primaquine/ TM-SMX/nitrofurantoin) due to G6PD deficiency —> lead to oxidative injury to RBC
Mechanism:
- lysed erythrocytes —> release heme into circulation
1. Hyperbilirubinemia: heme —> bilirubin —> jaundice + scleral icterus
- Hemoglobinuria: heme excreted in urine —> dark urine + false-positive urine dipstick for blood
Immune complex deposition causes membranous glomerulonephritis
Lead to:
1. hematuria + dysmorphic RBC on urinalysis
Caused by:
1. Chronic infection: hepatitis B or C
2. Rheumatic disease ( SLE)
3. Monoclonal gammopathy ( Multiple myeloma)
Sideroblastic anemia
- defective heme synthesis
- lead to: pyridoxine- dependent impairment in the early steps of proto-porphyrin synthesis within mitochondria
- types: congenital or acquired
- acquired form is caused by: alcohol, nutrition, medication ( isoniazid/ INH in treatment of TB—> vitamin B6/pyridoxine antagonist)
Finding:
1. Increase iron + Decrease TIBG
2. Microcytic anemia
3. Low MCHC (hypochromic)
4. High ESR
Diagnosis:
- bone marrow biopsy: shows ring sideroblast ( iron deposits in the periphery of mitochondria)
Treatment:
- vitamin B6/pyridoxine administration
Sickle cell disease
Treat with:
1. Hydroxyurea (for patient with recurrent vaso-occlusion crises)
2. Vaccination
3. Penicillin ( until age 5)
4. Folic acid supplement
5. Acute pain crises: hydration + analgesia (NSAIDS/opioids) + transfusion
Note:
1. Hydroxyurea —> 1st line treatment if history of acute chest syndrome + severe anemia occur —> this drug increases fetal hemoglobin + decrease risk of acute chest syndrome/ requiring RBC transfusion —> drug side effect : dose-limiting effect of myelosuppression ( neutropenia, anemia, thrombocytopenia)
Alcohol use disorder + vegan diet
- lead to megaloblastic anemia:
- Vitamin B 12 deficiency:
- Anemia
- neurologic symptoms: with loss of proprioception & vibration sense in the lower extremity ( defect of myelin formation in the dorsal column) + memory defect + irritability + dementia - Folic acid deficiency:
- anemia
- no neurologic symptoms
Management:
1. Folic acid supplement will resolve anemia within 1-2 months —> will not resolve neurologic symptoms caused by vitamin B 12 def.,
Delayed hemolytic transfusion reaction ( DHTR)
- occurs in patient who have previously exposed to a foreign RBC antigen ( prior transfusion, pregnancy)
- antigen is a minor: non-ABO
- Causes a low & undetectable antibody response after initial exposure —> however, on subsequent exposure via repeat transfusion —> an anamnestic antibody response occurs in which memory B cells rapidly produce more antibodies —> these antibody binds to donor RBC & causes extravascular hemolysis
Delayed hemolytic transfusion reaction ( DHTR)
- onset > 24 hours up to a month after transfusion
Clinical:
1. Fatigue, dyspnea, tachycardia
2. Jaundice
3. Fever
Laboratory:
1. Decrease hemoglobin & haptoglobin
2. Increase LDH, Bilirubin, reticulocyte count
Diagnosis:
3. Newly Positive Coombs test
Management:
- supportive ( fluid)
Prevention:
1. Review transfusion history & antibody screen
2. Transfuse when necessary with extended- antigen cross-matched blood
Note:
1. Frequently seen with sickle cell disease
Paroxysmal nocturnal hemoglobinuria (PNH)
Clinical:
1. Hemolysis (hemoglobinuria)
2. Cytopenia (fatigue, dyspnea from anemia)
3. Hypercoagulable state: Venous thrombosis ( intraabdominal/portal/hepatic, cerebral veins)
Laboratory:
1. CBC: anemia, thrombocytopenia, leukopenia
2. High LDH + high bilirubin
3. low hemoglobin + low haptoglobin
4. Hemoglobinuria ( urinalysis)
5. Low/absent CD55 & CD 50 ( flow cytometry) —> diagnostic
Treatment:
1. Iron & folic acid supplement
2. Eculizumab ( monoclonal antibody that inhibits complement activation)
Note:
1. PNH: clonal stem cell disorder —> lead to intravascular & extravascular hemolysis + hemoglobinuria
2. Is an acquired genetic disorder that lead to defective CD55 & CD59 responsible for inhibiting the activation of complement proteins
Cytopenia
-Anaemia - reduced red blood cells.
-Neutropenia - reduced white blood cells.
-Thrombocytopenia - reduced numbers of platelets.
-Pancytopenia - deficiency in all types of blood parts.
Pica
- appetite for items other than food ( paper, ice, clay)
- developed due to iron-deficiency anemia —> due to chronic bleeding ( chronic GI bleeding from ulcer)
Budd-chiari syndrome (BCS)
- hepatic outflow obstruction
- due to:
1. Myeloproliferative disorders ( polycythemia vara)
2. Malignancy ( hepatocellular carcinoma)
3. Oral contraception use/pregnancy
Clinical:
1. Acute:
- jaundice + hepatic encephalopathy + variceal bleeding
- prolonged INR/PTT + high ALT/AST
- Subacute/chronic:
- vague, progressive abdominal pain
- hepatomegaly/splenomegaly + ascites
- mild/moderate elevation in bilirubin, AST, ALT
Diagnosis:
1. Abdominal doppler U/S —> decrease hepatic vein flow
- Investigation for underlying disorder ( JAK2 - V617F mutation testing for polycythemia vera)
Note:
1. PV symptoms: aquagenic pruritus + burning in feet/hand + vision disturbance+ facial plethora + elevated hematocrit —> increase RBC mass
2. Use of aspirin reduce pruritus & burning sensation in Polycythemia Vera
Autoimmune hemolytic anemia (AHA)
- autoantibodies to RBCs
- negative family history + positive coombs test
- lead to extravascular hemolysis
- peripheral blood smear = shows spherocytosis without central pallor
Intravascular hemolysis
- RBC structural damage within intravascular space
- examples:
1. DIC
2. PNH
Note:
1. hemoglobin released from hemolyzed RBC binds to haptoglobin —> hemoglobin-haptoglobin complex is cleared by the liver —> lead to low serum haptoglobin.
2. RBC hemolysis —> lead to high bilirubin & LDH
Extravascular hemolysis
- RBC is destroyed by phagocytosis in reticuloendothelial system (lymph node, spleen)
- lead to less Hg released ( compared to intravascular hemolysis)
- lab shows: normal/low haptoglobin, high LDH, high indirect bilirubin
- examples:
1. Antibody-mediated RBC destruction ( AIHA) —> negative family history & positive coomb test
2. G6PD
3. Hereditary spherocytosis —> positive family history & negative coombs test
4. SCD
5. Thalassemia
Autoimmune hemolytic anemia (AIHA)
- Warm agglutinin AIHA
- Cold agglutinin AIHA
Hypertensive emergency (headache + Nausea + HTN + retinal hemorrhage) in CKD
- can develop from:
- Erythropoiesis- stimulating agent ( ESA) —> Epoetin or darbepoetin
- ESA for CKD- induced anemia develop a new onset of HTN —> 2-8 weeks after initiation of treatment
Low hemoglobin + low MCV + low iron
- Iron deficiency anemia
- Anemia of chronic disease
Low hemoglobin + low MCV + Increase iron
- Thalassemia
- Sideroblastic anemia
Low hg+ Normal MCV
- low reticulocyte count
1. Leukemia
2. Aplastic anemia
3. Anemia of chronic disease - high reticulocyte count
1. Hemorrhage
2. Hemolysis - hereditary spherocytosis
- G6PD
- AIHA
- microangiopathic (MAHA) ( DIC, hemolytic-uremic syndrome, Thrombotic thrombocytopenia purpura)
Low hemoglobin + high MCV
- Folate deficiency
- Vitamin B12 deficiency
microangiopathic hemolytic anemia (MAHA)
( DIC, hemolytic-uremic syndrome, Thrombotic thrombocytopenia purpura) & prosthetic cardiac valves
- Lead to schistocytes (Helmet cells)—> fragmented erythrocytes
- hemolytic anemia = low haptoglobin, high LDH, High bilirubin
Anemia of chronic diseases
Cytokine- mediated iron dysregulation
Heridetary spherocytosis
- Present with anemia, jaundice, splenomegaly
- Autosomal dominant with high reticulocyte count and normal MCV
- Complication: acute cholecystitis due to pigmented gallstone
High reticulocyte count
- suggest there is adequate Iron, Vitamin B 12 & folate to generate new erythrocytes
Warm agglutinin disease (extravascular hemolysis)
Etiology:
1. Drugs ( penicillin)
2. Viral infection
3. Autoimmune (SLE)
4. Immunodeficiency —> lymphoproliferative (CLL)
Clinical:
1. Asymptomatic to life threatening anemia
2. Direct coomb positive with anti-IgG, anti-C3 or both
Treatment:
1. Corticosteroid
2. Splenectomy for refractory disease
Complication:
1. Venous thromboembolism
2. Lymphproliferative disorders
Cold agglutinin AIHA ( intravascular hemolysis)
Etiology:
1. Infection: mycoplasma pneumonia, infectious mononucleosis
2. Lymphoproliferative disease
Clinical:
1. Symptoms of anemia
2. Livedo reticularis & acral cyonosis with cold exposure that disappear with warming
3. Direct Coombs positive with anti- IgM, and Anti- C3
Treatment:
1. Avoid cold weather
2. Rituximab ± fludarabine
Complication:
1. Ischemia & peripheral gangrene
2. Lymphoproliferative disorder
Different between Iron deficiency, alpha thalassemia & beta thalassemia
Iron deficiency:
1. Low iron & low ferritin & high TIBG
2. Increase Hemoglobin after iron supplement
3. High RDW, low RBC, low MCV, low MCHC
4. Target cells & hypochromia
Alpha- thalassemia:
1. Increase Iron & increase ferritin
2. No improvement with iron supplement
3. Normal RDW, Normal RBC, low MCV, low MCHC
4. Target cells & hypochromia
Beta-thalassemia:
1. Increase iron & ferritin
2. No improvement with iron supplement
3. Normal RDW, normal RBC, low MCV , low MCHC
4. Increase hemoglobin A2 with hemoglobin electrophoresis
5. Target cells & hypochromia
Hemoglobin variants
- Hemoglobin A ( alpha 2, beta 2) —> Normal adult
- Hemoglobin A2 ( alpha2, delta2) —> beta thalassemia
- Hemoglobin F (alpha2, gamma2) —>
- Hemoglobin H ( beta 4) —>
- Hemoglobin Bart’s ( gamma 4) —> alpha thalassemia ( 4 gene mutation)
Alpha thalassemia
1 deletion: minima
- ( alpha, alpha) ( alpha, -) —> carrier
- normal electrophoresis
- asymptomatic
2 deletion: minor
- ( alpha, -) ( alpha, -) or ( -, -) ( alpha, alpha) —> trait
- normal electrophoresis
- mild symptoms of anemia
3 deletion: major
-( alpha, -), ( -,-) —> Hb H disease
- electrophoresis: Hb H (adults)
- chronic hemolysis
4 deletion:
- major ( fetal hydrops) —> (-,-) (-,-)
- electrophoresis: Hb barts, Hb portland & Hb H present —> absent of Hb A, Hb A2, Hb F
- Fetal in uterus
Beta thalassemia
Trait ( beta, beta null)
- increase (Hb A2) in electrophoresis
- Mild anemia
Intermediate ( positive beta, positive beta)
- increase (Hb F) in electrophoresis
- moderate anemia
Major ( beta null, beta null)
- absent HbA, only (Hb A2 & HbF) present in electrophoresis
- severe anemia
Thalassemia minor
- 1 or 2 deletion in alpha thalassemia (minima, or minor)
- 1 deletion in beta thalassemia
- is associated with mild to moderate reduction in hematocrit ( < 28%) & low MCV ( 55-75)
Carbon monoxide poisoning
- in the setting of underground garage with less ventilation ( automobile exhaust)
- defective heating system
- smoke inhalation
- headache + dizziness + nausea +polycythemia (elevated hematocrit)
- ABG: Carboxy-hemoglobin level
- ECG ± cardiac enzymes
- treat with:
1. High flow 100% oxygen
2. Intubation/ hyperbaric oxygen ( severe) - HBOT = breathing pure oxygen in a room enclosed with high pressure ( used in serious infection, decompression sickness, wound not healing as result of diabetes or radiation injury)
Note:
- carboxyhemoglobin shifts oxygen dissociation curve to the left —> impair the ability of Hemoglobin to unload oxygen —> lead to tissue hypoxia —> the kidney response to tissue hypoxia by producing more EPO —> EPO stimulates bone marrow to differentiate more & produce more RBC—> chronic CO toxicity lead to secondary polycythemia
Polycythemia vera
Signs of:
- increase blood viscosity ( transient neurologic symptoms, thrombosis) + aquagenic pruritus + gout + increase all 3 cell line ( RBC, WBC, platelet)
Clinical:
1. Increase blood viscosity
- HTN
- erythromelalgia: burning cyanosis in hand/feet
- transient visual disturbance
2. Increase RBC turnover ( gouty arthritis)
3. Aquagenic pruritus
4. Bleeding
Examination:
1. Facial plethora ( ruddy cyanosis)
2. Splenomegaly
Lab:
1. High hemoglobin, high platelet, high leukocytes
2. Low EPO level
3. JAK 2 mutation
Complication:
1. Thrombosis
2. Myelofibrosis & acute leukemia
Treatment:
1. Phlebotomy
2. Hydroxyurea ( if increase risk of thrombus)
Jaundice splenomegaly anemia young patient
Investigation for hemolytic anemia
- bone marrow biopsy—> for leukemia
- ANA antibody —> for SLE
- LFT —> for viral hepatitis
- hemoglobin electrophoresis —> for SCD or thalassemia
- splenectomy —> improve platelet count in idiopathic immune thrombocytopenia (ITP)
- Drug- stopping —> for drug-induced hemolytic anemia caused by penicillin (ex: amoxicillin) & cephalosporin —> example: diagnosed with otitis media & prescribed amoxicillin
During pregnancy
- physiologic anemia occur
- due to hemedilution ( increased plasma volume)
- MCV does not change during pregnancy
Investigation of anemia in pregnancy
- normocytic ( mcv 80-100), mild anemia pregnant women do not require further investigation
- Microcytic ( MCV < 80), anemic pregnant women + normal iron studies—> require further investigation for hemoglobinupathy with hemoglobin electrophoresis
Microcytic anemia investigation (MCV < 80)
- Iron deficiency anemia
- low iron, low ferritin, high TIBG - Anemia of chronic disease
- high ferritin - Sideroblastic anemia
- caused by lead toxicity
- high iron, high ferritin - Thalassemia
- high iron, low MCV, low MCHC, abnormal hemoglobin in hemoglobin electrophoresis
Scleroderma renal crisis ( SRC)
- presence of HTN + mild proteinuria + AKI in the setting of sclerosis (scleroderma)
—> malignant HTN ( headache, blurry vision, nausea)
—> sudden onset of AKI
—> microangiopathic hemolytic anemia ( as seen with DIC, TTP, HUS) —> shows schistocytes + thrombocytopenia
—> mild proteinuria - usually occur within the first 5 years of diagnosis of “diffuse cutaneous systemic sclerosis (SSc)
Patho:
1. Increase vascular permeability
2. Activation of coagulation cascade
3. Increase renin secretion
Burr cells (echinocytes)
- seem with liver disease & ESRD
- spiculated appearing RBCs with serrated edge
Howell-Jolly (HJ) body
- seen in patient with history of splenectomy or functional asplania
- basophilic remanent of nucleus that appear as small, black pellet in RBC
NOTE:
- Normal spleen removes them
Spur cells (acanthocytes)
- seen in liver disease
- RBC with irregularly sized & spaced projection
Target cell
- seen with (hemoglobinopathy) thalassemia, iron deficiency, obstructive liver disease
- RBC with central density surrounded by pallor ( Bull’d eye appearance)
Splenectomy
Useful in many antibody-mediated hematologic disorder ( AIHA, ITP)
Prednisone
- suppress immune activation
- useful in AIHA
Plasma exchange
-remove toxic substances from plasma
- useful in TTP & HUS
Anticoagulation
- useful in thromboembolism disorder & antiphospholipid antibody syndrome
Exposure to radiation increase risk for
- breast & lung malignancy
- arise > 5 years after treatment
Exposure to chemotherapy increase risk for
- hematologic malignancy
- arise > 5 years after treatment
Patient treated with combination of chemo & radiation for Hodgkin Lymphoma (HL)
Are at increased risk for developing: (after curing from HL)
1. solid organ malignancy
2. cardiovascular disease
3. Pulmonary disease ( fibrosis, bronchiectasis )
4. Hypothyroidism
Pancytopenia (low reticulocyte count & hypo-cellular bone marrow from biopsy)
Clinical:
1. Anemia (fatigue, dyspnea, pallor)
2. Leukopenia ( infection such as pneumonia)
3. Thrombocytopenia (bleeding or bruising)
Types:
- Damage to hematopoietic stem cell
- Aplastic anemia ( drug/toxin/radiation, parvovirus B19, SLE, Eosinophilic fasciitis) —> no splenomegaly
- Parvovirus, HIV, viral Hepatitis
- vitamin B 12/ folate deficiency
- hydroxyurea
- Infiltration of the bone marrow with atypical cells
- hematologic, metastatic cancer
- myelofibrosis (collagen deposits in bone marrow) —> hepatosplenomegaly
- infection (TB, Fungal)
- Peripheral destruction of mature blood cells
- intravascular (DIC, TTP)
- Extravascular ( hypersplenism)
Multiple myeloma
- replacement of bone marrow with plasma cells
- Present with: anemia + high Ca + renal disease ( high creatinine) + lytic bone lesion (Back pain)
Difference between:
CLL vs HCL
- chronic lymphocytic leukemia
- Anemia, bleeding, fever, splenomegaly
- Smudge cell on biopsy
- hairy cell leukemia
- Anemia, bleeding, fever, splenomegaly
- Hairy cell on biopsy
CLL
Clinical:
- asymptomatic
- fatigue + lymphadenopathy + hepatosplenomegaly
- mild anemia + mild throombocytopenia
- dramatic leukocytosis with lymphocytes
Diagnosis:
- with flow cytometry ( shows clonality of mature B cells)
- lymph node & bone marrow biopsy are not needed
Complication:
- infection ( infection —> increase leukocytosis —> increase neutrophils)
- AIHA
- Secondary malignancy ( Richter syndrome)
Bacterial pneumonia
- fever + productive cough + right lower lobe infiltrate
- most bacterial infection causes mild-to-moderate leukocytosis with predominance of neutrophil
Non-hodgkin lymphoma (NHL) due to reactivation of EBV in B Lymphocytes
- 10% of patient with AIDS develops NHL —> due to reactivation of EBV
CLINICAL:
- LAD (epitrochlear, supraclavicular, & mediastinal/enlarged cardiac silhouette)
- B symptoms ( fever, night sweat, weight loss)
- Diagnosis= excisional lymph node biopsy
Patient with HIV at increased risk for
- immune dysregulation & reactivation of oncogenic viruses
- Non-Hodgkin lymphoma (EBV)
- Invasive cervical carcinoma ( HPV)
- Kaposi sarcoma ( HHV8)
- CNS system lymphoma ( EBV)
CML vs CLL vs Hodgkin Lymphoma vs Infectious mononucleosis: vs Hairy cell leukemia
CML
- massive leukocytosis with a variety of neutrophils precursor cells ( promyelocytes, myelocytes)
CLL
- massive leukocytosis with predominant lymphocytes & smudge cells
Hodgkin Lymphoma :
- painless LAD + B symptoms ( fever, weight loss, night sweat) + itching + mediastinal mass
Infectious mononucleosis:
- young patient + fever + splenomegaly + pharyngitis + WBC ( 12,000-18,000) + tender LAD
Hairy cell leukemia
- splenomegaly + pancytopenia
Comparison of leukomoid reaction vs CML
Leukomoid reaction
1. Leukocytes count > 50,000
2. Occurs in response to Severe infection
3. High LAP (leukocyte alkaline phosphatase) score
4. More mature neutrophil precursors ( metamyelocytes > myelocytes)
5. Absolute basophilia not present
CML
1. Leukocyte count > 100,000
2. Occurs in response to BCR-ABL fusion
3. Low ALP score
4. Less mature neutrophil precursor (myelocytes> metamyelocytes)
5. Absolute basophilia present
Hodgkin lymphoma (HL)
Epidemiology:
- bimodal peak incident ( 15-35) & (> 60)
- associated with EBV in the immunosuppressed
Clinical:
- painless LAD ( cervical & supraclavicular chains)
- B-symptoms ( fever, night sweat, weight loss)
- pruritus
- mediastinal mass (cough, SOB, retrosternal chest pain) —> high LDH & high eosinophilia
Diagnosis:
- lymph node biopsy
- Reed Sternberg cells on histology
Supraclavicular LAD suggest
-malignancy
SLE
Diagnosis:
- Antinuclear antibody
- fatigue + fever + peripheral LAD in the cervical, axillary, or inguinal chain + malar rash + arthralgia + serositis
MD SOAP N HAIR
1. Malar rash
2. Discoid rash
3. Serositis
4. Oral ulcer
5. Arthritis
6. Photosensitivity
7. Neurologic abnormality
8. Hematologic abnormalities (anemia, thrombocytopenia)
9. ANA (+)
10. Immunologic abnormalities
11.
Infectious mononucleosis
Diagnosis:
- Heterophiles antibody testing
- Fatigue + fever + tender peripheral LAD ( in the cervical chain) + sore throat (pharyngitis) + splenomegaly
Syphilis
Diagnosis:
- Rapid plasma reagin (RPR) testing
- Primary syphilis causes chancre ( at the infected area oral, penis, vaginal)
- Secondary syphilis causes painless peripheral LAD + Diffused, symmetric maculopapular rash that includes palm & soles
Causes of anemia
- Increase RBC destruction ( hemolysis)
- Decrease production of RBC ( myeloproliferative disorders —> lymphoma —> cancerous cell deposits in bone marrow)
- Blood loss
Hairy cell leukemia (HCL)
Epidemiology:
1. Clonal B-cell neoplasm
2. Middle age & older adults
3. BRAF mutation
Clinical:
1. Pancytopenia ( due to bone marrow fibrosis)
- anemia ( fatigue, dyspnea, pallor)
- thrombocytopenia ( bleeding, bruising)
- Granulocytopenia (infection)
2. Splenomegaly ( early satiety)
3. Rarely (hepatomegaly or LAD)
Diagnosis:
1. Peripheral smear shows hairy cell leukocytes
2. Bone marrow biopsy with flow cytometry
Treatment:
1. Chemotherapy for moderate/severe
2. Normal life expectancy
Acute myeloid leukemia
Epidemiology:
1. Middle age (65)
Clinical:
1. Fatigue
2. Cytopenia
3. Rarely hepatosplenomegaly/ LAD
4. DIC ( if APML)
Laboratory:
1. Leukocytes ( low, high, or normal)
2. High LDH
3. Myeloblast with auer rods
Diagnosis:
1. Bone marrow biopsy (hypercellular with myeloid blasts)
Diphenhydramine
- to treat pruritus
Thrombotic thrombocytopenic purpura (TTP)
- Decrease ADAMTS13 level —> uncleaved vWF multimer —> increase palatelet trapping
Symptoms:
1. Hemolytic anemia ( low Hg, low heptoglobin, high LDH, high creatinine, high reticulocyte count)
- Thrombocytopenia ( high bleeding time, normal PT/PTT)
- Renal failure + neurologic dysfunction + fever
Diagnosis:
1. Peripheral blood smear ( shows signs of intravascular hemolysis= schistocytes)
Management:
1. Plasma exchange
2. Glucocorticoid
3. Rituximab
Immune thrombocytopenia (ITP)
- autoimmune disorder
- associated with isolated thrombocytopenia
- can be primary or associated with (HIV, HCV)
- testing required:
1. HIV & HCV
2. SLE ( anti-nuclear antibody) - isolated thrombocytopenia ( low platelet of 30,000)
- treat with: corticosteroid, IVIG, or splenectomy if refractory
- usually bone marrow aspiration shows Megakaryocytes
Pseudothrompocytopenia
- laboratory error (platelets aggregation in vitro)
- confirmed when peripheral blood smears shows clumps of platelets
Anti-phospholipid syndrome
- found in patient having SLE
- lead to venous/arterial thromboembolism + miscarriage
- diagnostic:
1. Lupus anticoagulant ( have increased PTT) —> DOES NOT IMPROVE WITH (1:1) DILUTION WITH NORMAL SERUM
- Anti-cardiolipin
- Beta2-glycoprotein-1 antibody
Deep venous thrombosis
- Initially, with compression ultrasound
- Then, D-dimer ( elevated level is not sufficient to establish diagnosis)
Chronic DIC
- associated with cancer ( pancreatic cancer)
- lead to venous/arterial thromboembolism + mucucutaneuous bleeding
Warfarin (anticoagulation drug)
- need monitor (INR: 2-3)
- inhibits synthesis of vitamin K-dependant factors 2,7,9,10 & protein S & protein C
Multiple myeloma
(Caused by impaired effective antibody production)
Caused by:
1. Monoclonal Plasma cell neoplasm infiltrates bone marrow
Symptoms:
1. Bone pain + fracture
2. Constitutional symptoms ( fatigue, fever, weight loss)
3. Recurrent infection ( due to plasma cell neoplasm infiltration of bone marrow, which alter the normal leukocyte population & causes hypogammaglobinemia
Laboratory:
1. Normocytic anemia ( low hg, MCV 80-100)
2. Renal insufficiency ( high creatinine)
3. Hypercalcemia (constipation, muscle weakness)
4. Monoclonal paraproteinemia ( M-spike)
5. Coin-stalking RBC on smear
6. Elevated protein gap (> 4) (between total protein &albumin)
Diagnosis:
1. Screening: serum protein electrophoresis, urine protein electrophoresis, free light chain analysis
2. Confirmed with: bone marrow biopsy
Imaging
1. Osteolytic lesion/osteopenia (osteoclast activation) (moth-eaten appearance)
Prevent tumor lysis syndrome
- release of tumor content into circulation when under chemotherapy
- this lead to electrolyte disturbance & AKI due to precipitation of uric acid & calcium-phosphate
Laboratory:
1. Low calcium
2. High phosphate & phosphorus
3. High K, uric acid
- Prevent AKI via:
1. Normal saline —> flush kidney
2. Xanthine oxidase inhibitor—> allopurinol & febuxostat
Chemotherapy induced vomiting/nausea
- prevented with: Serotonin 5H antagonist (ondasteron)
Prevent hypercalcemia caused by malignancy ( high PTHrP, low PTH)
- Via bisphosphonate
Prostate cancer
Presentation:
1. Slowly progressive lower back pain
2. Functional impairment ( motor weakness, incontinence )
3. Osteoblastic bone lesion (sclerosis) —> elevated ALP, normal/low Ca, elevated PO4
4. X-RAY: focal, sclerotic lesion
The adrenal gland is the most common site for metastatic cancer
—> lead to autoimmune adrenalitis (Primary adrenal insufficiency)
- Hyponatremia + hyperkalemia + hypotension/orthostatic + hypoglycemia
- Diagnosis via cosytropin (ACTH) stimulating test
Waldenstrom macroglobinemia
- Hyper-viscosity syndrome + neuropathy + cryoglubinemia (bleeding + hepatosplenomegaly + lymphadenopathy)
- Serum protein electrophoresis shows —> IgM spike
- Peripheral smear —> Rouleaux
- Bone marrow biopsy—> >10% clonal B-cell
Multiple myeloma
- Osteolytic lesion/fracture + anemia+ hypercalcemia + renal insufficiency + recurrent infection
- Serum protein electrophoresis —> IgG, IgA, light chain
- Peripheral smear —> rouleaux
- Bone marrow biopsy —> > 10% clonal Plasma cells
More than 1 unit of blood transfusion per 24 hrs can lead to
- citrate chelates Ca & Mg —> reduce their plasma concentration —> lead to paresthesias
Transfusion reaction timeline
0-sec/min—> anaphylactic
- shock, angioedema/urticaria, respiratory distress
Sec/min-1 hour —> acute hemolytic
- fever, flank pain, hemoglubenuria, DIC
1-6 hours —> febrile non-hemolytic, TACO, TRALI, TTBI, urticarial
- TRALI: Respiratory distress, noncadio pulmonary edema, bilateral lung infiltrates
TTBI: fever, chill, septic shock, DIC
6 hr-10 days —> delayed hemolytic
Leukoreduction of donor blood
- reduces febrile non-hemolytic transfusion reaction (1-6 hrs)
