Hematology - Anemia Flashcards
Discuss the causes of decreased RBC production
- usually low reticulocyte count <2 Hormone Stimulation - decreased EPO from renal failure - hypothyroidism Bone Marrow Suppression - medication - chemotherapy - Radiation Bone Marrow Disorder - aplastic anemia - RBC dysplasia - marrow infiltration Lack of Nutrients - iron deficiency - vit B12 or folate deficiency Ineffective RBC erythropoiesis - megaloblastic anemia - alpha and beta thalassemia - myelodysplastic syndrome - sideroblastic anemia
Discuss the causes of increased RBC desctruction
- high reticulocyte count, LDH, bilirubin (jaundice) and low haptoglobin
Intravascular Hemolysis
- migroangiopathic hemolytic anemia: TTP, aortic stenosis, prosthetic valve
- transfusion reaction
- infection: malaria
- paroxysmal cold hemoglobinuria
Extravascular RBC Defects
- intrinsic RBC defects
- enzyme deficiency: G6PD, pyruvate kinase deficiency
- hemoglobinopathies: sickle cell anemia, thalassemia
- membrane defect: spherocytosis
- extrinsic RBC defect
- liver disease
- hypersplenism
- infection: malaria
- toxin: lead, copper
- autoimmune hemolytic anemia
Blood lossDiscuss the presentation and investigation for anemia
Presentation
- fatigue
- headache, syncope
- palpitation
- shortness of breath on exertion
- skin pallor
Investigations
- CBC for Hgb, MCV
- Reticulocyte count
- blood film
- iron: total iron binding capacity, transferrin, ferritin
- LDH, bilirubin, haptoglobin, Coomb's test (direct)
- anemia with reticulocytosis
- pancytopenia or blast cells require bone marrow biopsyDiscuss the differential for microcytic anemai
- MCV <80 TAILS - Thalassemia - Anemia of chronic disease - Iron deficiency - Lead poisoning - Sideroblastic anemia
Discuss the differential for macrocytic anemia
- MCV >100 BALDRAT - B12 and folate deficiency - Alcohol - Liver disease - Drugs (anti-metabolites) - Reticulocytosis - Aplastic anemia (AML, myelodysplastic) - Hypothyroid
List the differential for normocytic anemia
Low Reticulocyte Count
- anemia of chronic disease
- bone marrow failure
High Reticulocyte Count
- hemolytic anemia, inherited
- hemoglobinopathy: sickle cell, thalassemia
- membrane: spherocytosis
- metabolic: HMP shunt, glycolytic pathway
- hemolytic anemia, acquired
- immune: Coombs positive, drug related
- infection: malaria
- microangiopathic hemolytic anemia: DIC, TTP, HUS, HELLP
- drug related
- acute hemorrhage
- chronic renal failure
- endocrine dysfunction: hypothyroid, hypopituitarism
Discuss the presentation, investigations, diagnosis and management of multiple myeloma
- neoplastic proliferation of plasma cells which produce monoclonal antibodies
Presentation - CRAB
- Hypercalcemia: n/v, confusion, constipation, polyuria
- Renal failure
- Anemia: weakness, fatigue
- Bone lesions: pain, pathologic fracture
- lytic lesions present in skull, spine, ribs, proximal long bones - bleeding due to thrombocytopenia
- hyperviscosity leading to headache, stroke, angina
Investigation - CBC: normocytic anemia, thrombocytopenia, leukopenia
- Rouleax formation on blood film
- high creatinine
- high beta2-microglobulin
- serum protein electrophoresis: Monoclonal protein
- urine protein electrophoresis: light chains
- Bone marrow aspirate: >10% plasma cells
- Skeletal x-ray: lytic lesions
Diagnosis - all of the following
- serum or urinary monoclonal protein
- clonal plasma cells in bone marrow or plasmacytoma
- end organ damage by >=1 of CRAB
Management - <65 then autologous stem cell transplant
- > 65 chemotherapy with Melphalan, Prednisone, Bortezomib
- bisphosphonate for hypercalcemia and osteopenia
- local radiotherapy for bone pain or spinal cord compression
- EPO
Discuss the average lifespan of each of the cells lines and a work up for a deficiency
Lifespan
- RBC: 90-120d
- Neutrophils: 1d
- Platelets: 7-10d
Work Up
- All cells lines then pancytopenia from decreased production, sequestrations, or hemodilution
- Deficit in platelets and RBC: non-immune microangiopathic hemolytic anemia/thrombotic microangiopathy
- Deficit in platelets: Immune mediated process
Discuss the pathophysiology, presentation and management of iron deficiency anemia
Pathophysiology - Increased demand (pregnancy) - Decreased supply (dietary deficiency) - Increased loss (hemorrhage, hemolysis) Presentation - fatigue, lightheadedness - decreased exercise tolerance, dyspnea - menorrhagia - pallor, angular cheilitis - jaundice Investigation - microcytic anemia - low ferritin, increased total iron binding capacity, low serum Fe, low saturation Management - Supplementation: ferrous sulphate, ferrous gluconate, ferrous fumarate with citrus juice - IV iron - reticulocyte should increase 1 weeks following supplementation
Discuss the pathophysiology, presentation and management of anemia of chronic inflammation
Pathophysiology - impaired iron utilization as hepcidin production is increased trapping iron in enterocytes - reduced plasma iron level - marrow unresponsive to EPO Investigtions - elevated ESR, CRP - serum iron and total iron binding capacity low or normal with low % saturation - ferritin normal or increased Management - treat underlying cause
Discuss the laboratory findings of hemolytic anemia
- Increased reticulocytes
- decreased haptoglobin
- increased unconjugated, indirect bilirubin
- increased urobilirubin
- increased LDH
Discuss the pathophysiology, presentation and management of B-thalassemia Minor
- Defect in single beta gene (heteroxygous for one normal B globin allele and one B globin thalassemic allele) Presentation - Asymptomatic Investigation - Microcytic anemia - Hb electrophoresis: HbA2 3.5-5% and slight increase in HbF Management - Genetic counselling
Discuss the pathophysiology, presentation and management of B-Thalassemia Major
- Defect in both B gene, autosomal recessive
Pathophysiology - ineffective chain synthesis leading to ineffective erythropoisis, hemolysis and increase in HbF
Presentation - present between age 6-12 months when HbA replaces HbF
- result in severe anemia and jaundice - Iron overload leading to hemachromatosis
- Stunted growth
- Hepatosplenomegaly
Investigation - severe microcytic anemia
- Hb electrophoresis: 0 HbA, >2.5% HbA2 HbF >90%
Management - Regular transfusions to suppress endogenous erythropoiesis
- Iron chelation
- Allogenic bone marrow transplant
Discuss the pathophysiology, presentation and management of B-thalassemia intermedia
- inbetween B-thalassemia major and minor based on clinic characteristics
- usually both B-globin chains affected
Pathophysiology - subnormal B-chain synthesis
- Increased number of gamma chains
- coinheritance of a-thalassemia
Discuss the pathophysiology, presentation and management of a-Thalassemia
- Defect in alpha genes
Presentation - defective alpha gene: silent
- 2 defected alpha gene (aa/– or a-/a-): decreased MCV but normal Hgb
- 3 defective genes: HbH disease present in adults with decreased MCV, Hgb, and splenomegaly
- 4 defective genes: Hb Barts (gamma4) with hydrops fetalis and incompatible with life
Investigation - Screen for HbH inclusion bodies and electrophoresis
Discuss the pathophysiology, presentation of sickle cell disease
- autosomal recessive from mutant B-globin chain by Glu -> Val substitution on position 6 on chromosome 11
- results in HbS variant
- Occurs when have two HbS genes or HbS and compound with another B-globin variant (B-thal)
Pathophysiology - low pO2 deoxy HbS polymerize to form rigid crystal-like rod which distorts membrane
- Fragile cell hemolyze or cause occlusion of small vessels
- Increased sickling with acidemia, high CO2, increased 2,3-DPG, fever, and osmolality
Presentation - chronic hemolytic anemia
- jaundice in first year of life
- retarded growth
- splenomegaly in childhood and then atrophy
Acute Pain Episode - aplastic crisis from toxins or infection (parvovirus)
- splenic sequestration
- vaso-occlusive crisis: ischemia-reperfusion injury
- acute chest syndrome
Discuss the investigations and management of sickle cell disease
Investigation
- no HbA, only HbS and HbF on electrophoresis
- Sickle cell prep
Management
- Folic acid
- Hydroxyurea to enhance production of HbF
- Vaso-occlusive: oxygen, hydration, opiates
- prevention: avoid conditions, vaccination
Differentiate cold and warm hemolytic anemia in terms of antibody allotype, agglunation temperature, Direct Coombs test, blood film and management
Antibody Allotype - IgG in Warm - IgM in cold Temperature - 37 in warm - 4-37 in cold Direct Coombs Test - Positive for IgG and complement in warm - Positive for complement in cold Blood film - spherocytes in wamr - aggglutination in cold MAnagement - steroids, immunosuppresion, splenectomy for warm - warm patient, rituximab, plasma exhance, folic acid for cold
Differentiate the etiologies for warm and cold autoimmune hemolytic anemia
Warm - Idiopathic - Lymphoproliferative disorder (CLL, Hodgkin's) - Autoimmune (SLE) - Drug induced Cold - Idiopathic - Infectious (mycoplasma pneumonia, EBV) - Lymphoproliferative (macroglobulinemia, CLL)
Discuss the pathophysiology, presentation and management of hereditary spherocytosis
Pathophysiology
- abnormality in RBC membrane protein spectrin
- Spleen makes defective RBCs more spherocytotic by membrane removal
- Autosomal dominant
Investigations
- Spherocytes
- Osmotic fragility
Management
- Splenectomy and vaccination against pneumococcus, meningococcus, H influenza type B
Discuss the pathophysiology, presentation and management of Glucose-6-phosphate deficiency
Pathophysiology - X-linked recessive - increased RBC sensitivity to oxidative stress from reduced glutathione Presentation - episodic hemolysis due to oxidative stress, drugs, infection Investigation - neonatal screening - G6PD assay - Heinz body Managmenet - Folic acid
Discuss the pathophysiology, presentation and management of Vitamin B12 deficiency
- binds to instrinsic factor secreted by gastric parietal cells
- Absorbed in terminal ileum
Pathophysiology of pernicious anemia - auto-antibodies produced against gastric parietal cells leading to achlorhydria and lack of instrinsic factor production
Presentation - Peripheral neuropathy
- confusion, delirium, dementia
- irreversible spinal cord damage
Investigations - macrocytic anemia
- Megaloblasts (neutrophils with many nuclei)
- low reticulocyte
- low Serum B12
- elevated urine methylamlonate and homocysteine
- Schilling test (normal than pernicious anemia)
- When severe can have hemolysis and pancytopenia
Management - Vitamin B12 1000microgram IM
