Hematology & Oncology - Anemias

hezikry's version from 2015-09-01 19:58

Anemias - broad categorizations

Question Answer
Iron deficiencyMicrocytic
ACDMicrocytic (may first present as normocytic)
Lead poisoningMicro
Sideroblastic anemiaMicrocytic
ACDNonhemolytic normocytic
Aplastic anemiaNonhemolytic normocytic
Chronic kidney diseaseNonhemolytic normocytic
RBC membrane defect: hereditary spherocytosisIntrinsic, hemolytic normocytic
RBC enzyme deficiency: G6PD, PKIntrinsic, intravascular/extravascular hemolytic normocytic
HbCIntrinsic, hemolytic normocytic
Sickle cell anemiaIntrinsic, hemolytic normocytic
Paroxysmal nocturnal hemoglobinuriaIntrinsic, intravascular, hemolytic normocytic
AutoimmuneExtrinsic, hemolytic normocytic
MicroangiopathicExtrinsic, hemolytic normocytic
MacroangiopathicExtrinsic, hemolytic normocytic
InfectionsExtrinsic, hemolytic normocytic
Folate deficiencyMegaloblastic macrocytic
B12 deficiencyMegaloblastic macrocytic
Orotic aciduriaMegaloblastic macrocytic
Liver diseasenonmegaloblastic macrocytic
Alcoholismnonmegaloblastic macrocytic
Reticulocytosisnonmegaloblastic macrocytic
Microcytic anemiasIron def
Lead poisoning
Sideroblastic anemia
Nonhemolytic normocytic anemiasACD
Aplastic anemia
Chronic kidney disease
Intrinsic, hemolytic normocytic anemiasRBC membrane defect: hereditary spherocytosis
RBC enzyme deficiency
Sickle cell anemia
Paroxysmal nocturnal hemoglobinuria
Extrinsic, hemolytic anemiasAutoimmune
Megaloblastic macrocytic anemiasFolate deficiency
B12 deficiency
Orotic aciduria
Nonmegaloblastic macrocytic anemiasLiver disease
Hypochromic anemiasIron deficiency
Lead poisoning
Sideroblastic anemia

Microcytic, hypochromic anemia (MCV <80 fL)


Name of AnemiaDescription
Iron deficiencyChronic bleeding
increased demand (pregnancy)
→ final step in heme synthesis
α-thalassemiaDefect: α-globin gene mutatoins → ↓ α-globin synthesis
Asains: cis deletion
Africans: trans deletions
β-thalassemiaPoint mutations in splice sites and promoter sequences → ↓ β-globin synthesis
Mediterranean populations
Lead poisoningInhibits ferrochelatase and ALA dehydratase → ↓ heme synthesis
Inhibits rRNA degradations → RBCs retain aggregates of rRNA (basophilic stippling)
Sideroblastic anemiaDefect in heme synthesis
Hereditary: X-linked defect in δ-ALA synthase gene
Reversible causes: alcohol, lead, isoniazid (pyridoxine deficiency)


Question Answer
cis deletion in alpha thalasian populations
trans deletion in alpha thalafrican populations
4 allele deletionHb barts. incompatible with life.
3 allele deletionHbH disease.
1 deletionalpha thal trait
point mutations in splice sites and promoter sequencesdecreased beta globin synthesis
B thal minor diagnosisincreased HbA2 on gel
B thal majormarrow expansion
B thal major increased risk of what infectionparvovirus B19 induced aplastic crisis.
lead poisoning treatment in kidssuccimer
leading poisoning treatment in adultspenicillamine
lead inhibitsferrochetalase and ALA dehydratase

Macrocytic anemias (MCV > 100 fL)


Question Answer
Folate deficiencyEtiologies:
Malnutrition (alcoholics)
antifolates (e.g. methotrexate, trimethoprim, phenytoin)
↑ requirement (e.g. pregnancy, hemolytic anemia)
B12 deficiencyEtiologies:
Insufficient intake (strict vegans)
malabsorption (Crohn's disease)
Pernicious anemia
Diphyllobothrium latum (fish tapeworm)
Orotic aciduriaGenetic mutations in enzyme that synthesizes uridine from orotic acid
Children w megaloblastic anemia that cannot be cured by folate or B12
Nonmegaloblastic macrocytic anemiasDNA synthesis is unimpaired
Liver disease
reticulocytosis → ↑ MCV
drugs (5-FU, AZT, hydroxyurea)


Question Answer
neurologic symptoms of B12 deficiencydegeneration of spinocerebellar tract, lateral corticospinal tract and dorsal column dysfunction
inability to convert orotic acid to UMPorotic aciduria
orotic acid in urineorotic aciduria or OTC deficiency
no hyperammonemiaorotic aciduria. inability to convert orotic acid to UMP because of defect in UMP synthase
treatment for orotic aciduriauridine monophosphate to bypass mutated enzyme

Nonhemolytic, normocytic anemias


Question Answer
Anemia of chronic diseaseMC anemia in hospitalized pts, malignancy, and alcohol excess
Inflammation → ↑ hepcidin - released by liver, binds ferroportin on intestinal mucosal cells and macrophages inhibiting iron transport
→→ ↓ release of iron from macrophages
Aplastic anemiaFailure or destruction of myeloid stem cells d/t:
- Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
- Viral agents (parvovirus B19, EBV, HIV, HCV)
- Fanconi's anemia (DNA repair defect)
- Idiopathic (immune mediated, 1° stem cell defect) - may follow acute hepatitis
Chronic kidney disease↓ erythropoietin → ↓ hematopoiesis


Question Answer
Anemia of chronic disease↓ iron
↑ ferritin
Can become microcytic, hypochromic
Aplastic anemiaPancytopenia: severe anemia, leukopenia, thrombocytopenia
Normal cells, but much fewer cells in BM (dry BM tap)
Sxs: fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection
Tx:Withdraw from antithymocyte globulin or cyclosporin; allogeneic BM transplant;RBC and platelet transfusion;G-CSF or GM-CSF
Chronic kidney disease↓ erythropoietin → ↓ hematopoiesis

Intrinsic hemolytic normocytic anemias


Question Answer
Hereditary spherocytosisDefective RBC membrane → small/round RBCs with no central pallor → Premature removal by spleen
G6PD deficiencyX-linked
Defect in G6PD → ↓ glutathione → ↑ RBC susceptibility to oxidant stress
Hemolytic anemia following sulfa drungs, infxns, fava beans
RBCs destroyed extravascularly
Pyruvate kinase deficiencyAutosomal recessive
Defect in PK → ↓ ATP → rigid RBCs
HbC defectGlutamic acid-to-lysine mutation at residue 6 in β-globin
Paroxysmal nocturnal hemoglobinuria↑ complement-mediated RBC lysis
Acquired mutation in a hematopoietic stem cell
Sickle cell anemiaGlutamic acid is replaced by valine at position 6 of β chain of HbS
Precipitated by low O2 or dehydration
Newborns - asymptomatic d/t ↑ HbF and ↓ HbS
Heterozygotes have resistance to malaria
8% of AAs carry the HbS trait


Question Answer
increased MCHChereditary spherocytosis
decreased glutathionedefect in G6PD
heinz bodies and bite cellsG6PD deficiency
glutamic acid to lysine mutationHbC defect
PNHincreased complement mediated RBC lysis
treatment for PNHeculizumab
black urine occurring at nightPNH
substitution of glutamic acid with valinesickle cell anemia

Extrinsic hemolytic normocytic anemias

AnemiaDescription & Findings
Autoimmune hemolytic anemiaWarm agglutinin - IgG
chronic anemia seen in SLE, CLL, or drugs (α-methyldopa)
warm weather is GGGGreat!
Cold agglutinin - IgM - acute anemia triggered by cold
Seen in CLL, Mycoplasma pneumonia infxns, or mono
cold ice cream - yuMMM
Microangiopathic anemiaRBCs are damaged when passing through obstructed/narrowed vessels
Seen in DIC, TTP-HUS, SLE, malignant hypertension
Schistocytes (helmet cells)
Macroangiopathic anemiaMechanical destruction by prosthetic heart valves and aortic stenosis
Schistocytes (helmet cells)
Infections↑ destruction of RBCs
malaria, Babesia
Coomb's positive anemiaAutoimmune hemolytic anemia
Direct Coombs test - anti-Ig antibody added to pt's serum. RBCs agglutinate if RBCs are coated with Ig
Indirect Coombs' test - normal RBCs added to pt's serum agglutinate if serum has anti-RBC surface Ig

Heme synthesis, porphyrias, lead poisoning

Question Answer
Affected enzyme in lead poisoningFerrochelatase and ALA dehydratase
Accumulated substrate in lead poisoningProtoporphyrin, δ-ALA
Sxs of lead poisoningMicrocytic anemia, GI & kidney disease
Kids: Mental deterioation
Adults: environmental exposure (Batteries, ammunition, radiator factory) → HA, memory loss, demyelination
Affected enzyme in Acute intermittent porphyriaPorphobilinogen deaminase
Accumulated substrate in Acute intermittent porphyriaPorphobilinogen, &dealt;-ALA, uroporphyrin (urine)
Sxs of Acute intermittent porphyria5P's:
Painful abdomen
Port wine colored urine
Psychological disturbances
Precipitated by drugs
Tx: glucose + heme (inhibits ALA synthase)
Affected enzyme in porphyria cutanea tardaUroporphyrinogen decarboxylase
Accumulated substrate in porphyria cutanea tardauroporphyrin (tea-colored urine)
Sxs of porphyria cutanea tardaBlistering cutaneous photosensitivity
Most common porphyria

Clotting/platelet disorders

Question Answer
Bernard-Soulier syndrome↓ Platelet Count; ↑ Bleeding time
Defect in platelet plug flormation
↓ GpIb → defect in platelet-to-vWF adhesion
Glazmann's thrombasthenia↑ BT
Defect in platelet plug formation
↓ GpIIb/IIIa → defect in platelet-to-platelet aggregation
Labs show no platelet clumping
Idiopathic thrombocytopenic purpura (ITP)↓ PC; ↑ BT
anti-GpIIb/IIIa antibodies → splenic macrophage consumption of platelet/antibody complex
↓ platelet survival
Labs: ↑ megakaryocytes
Thrombotic thrombocytopenic purpura (TTP)↓ PC; ↑ BT
Defect of ADAMTS13 (vWF metalloprotease) → ↓ degradation of vWF multimers → ↑ large vWF multimers → ↑ platelet aggregation and thrombosis
↓ platelet survival
Labs: schistocytes, ↑ LDH
Sxs: Neuro/renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia
von Willebrand's disease↑ BT; normal/↑ PTT
Intrinsic coag defect: ↓↓ vWF → ↑ PTT (vWF carries/protects factor 8)
Defect in platelet plug
Very common and mostly mild - Autosomal dominant
Dx: ristocetin cofactor assay
Tx: DDAVP (desmopressin) - releases vWF stored in endothelium
DIC↓ PC, ↑ BT, ↑ PT, ↑ PTT
Widespread activation of clotting → deficiency in clotting factors → bleeding state
Causes: STOP Making New Thrombi
Sepsis (gram-neg)
OB complications
acute Pancreatitis
Nephrotic syndrome
Labs: schistocytes, ↑ fibrin split products (d-dimers), ↓ fibrinogen, ↓ factors 5 and 8
Factor V LeidenInherited hypercoagulability disorder
Mutant factor 5 - resistant to degradation by activated Protein C
MCC of inherited hypercoagulability in whites
Prothrombin gene mutationHyper coagulability disorder
Mutation in 3' untranslated region → ↑ production of prothrombin → ↑ plasma levels and venous clots
Antithrombin deficiencyInherited deficiency of antithrombin (thrombosis syndrome)
↑ in PTT is blunted after heparin administration
Protein C or S deficiencyHypercoagulability disorder
↓ ability to inactivate factors 5 and 8
↑ risk of thrombotic skin necrosis with hemorrhage following administration of warfarin
When to give packed RBCsAcute blood loss, severe anemia
Increases Hb and O2 carrying capacity
When to give plateletsTo stop significant bleeding in thrombocytopenia or qualitative platelet defects
When to give fresh frozen plasmaDIC, cirrhosis, warfarin overdose
↑ coagulation factor levels
When to give cryoprecipitateCoagulation factor deficiencies involving fibrinogen and factor 8
Contains: fibrinogen, factor 8, factor 13, vWF, and fibronectin