Aplastic anemia

- BM failure that arises from injury to or abnormal

expression of the stem cell (hypoplastic BM/ pancytopenia)
- Causes: - congenital
- idiopathic (?autoimmune)
- SLE
- chemotherapy/radiotherapy
- toxins: benzenes, tolune, insecticides
- drugs: CAF, phenylbutazone, Au, sulfa
- post- hepatitis
- pregnancy
- PNH
Clinical features
• Anemia (severe: neutrophil <500/mcL
platelets <20,000
BM cellularity <20%
retic count <1%
• vulnerability to bacterial infection
• mucosal/skin bleeding
• pallor, purpura, petechie
Pancytopenia, causes
 BM disorder
 Aplastic anemia
 MDS
 acute leukemia
 MF
 infiltrative diseases
(lymphoma, myeloma, Ca)
 megaloblastic anemia
 nonmarrow disorders
 hypersplenism
 SLE
 infections (TB, AIDS, leishmaniasis, brucellosis)
Treatment
supportive (most)
• transfusion (RBC, platelets)
• antibiotics
in severe cases + young <50: allogenic BMT
(HLA-matched)
elderly (>50): - immunosuppressive + anti-thymocyte
globulin (ATG) + cyclosporin (or tacrolimus)
high dose immunosuppressive with
cyclophosphamide, 200mg/kg
androgens (oxymetholone) 2-3mg/d
Course & prognosis
rapidly fatal if not treated
ABMT: durable complete response 80%
ATG Rx: partial response 60%
long-term responders: good prognosis
Pure red cell aplasia
-Rare
- autoimmune disease against erythroid precursors
- idiopathic
- SLE, CLL, lymphoma, thymoma
- drugs: phenytoin, CAF)
- in response to viral infection- papovirus
- anemia: often severe, NCNC
- low/absent reticulocytes
- RBC morphology : N
- myeloid & platelet lines not affected
- BM: normocellular, erythroid precursors are markedly reduced or absent
- treatment:
stop offending drug
resection of the tumor( eg, thymoma)
high –dose iv Ig (eg, papovirus – related)
immunosuppressive therapy: ATG+ cyclosporine (tacrolimus)
anti-CD20 monoclonal antibody (rituximab)
 Myeloproliferative Disorders
-Due to acquired clonal abnormality of the
hematopoeitic stem cells
Classification:
- myeloproliferative syndromes
• PV
• MF
• ET
• CML
- MDS
- AML
 PV
• overproduction of all the 3 hematopoeitic cells lines (most RBC)
• autonomous production of erythroid cell in the BM
• independent of EPO
• mutation in JAK2 gene, 95%
Clinical
- Sxs related to expanded plasma volume & increased blood
viscosity
- headache, dizziness, tinnitus, blurred vision, fatigue
- generalized pruritus
- epistaxis
- male predominance (60%)
- median age: 60yrs
- plethora & engorged retinal vessels,
- spleen always enlarged (75% palpable)
- thrombosis is the commonest complication
- high incidence of PUD
Lab
- Hct >60%
- WBC 10,000-20,000/mcL
- platelets > 1,000,000/mcL
- basophilia + eosinophilia
- BM: hypercellular
panhyperplasia
absent Fe store
- Vit B12
- hyperurecemia
Treatment
- Phlebotomy
- 1 unit/week
- target : Hct <45%
- myelosuppressive therapy
- indication: - high phlebotomy requirement
- thrombocytopenia
- intractable pruritus
- HU 500-1500mg/d
- anaglinide
- aspirin (75-81mg)
- allopurinol
- antihistamines
- prognosis
- survival : 11-15 years
- may arrest MF/CML
- AML (5%)
 ET
- Uncommon
- unknown cause
- marked proliferation of megakaryocytes in BM
leading to elevation of the platelet count
- mutation of JAK2 (50%)
Clinical
-Median age of presentation: 50-60 yrs
- increased platelet count
- thrombosis most common
- erythromelalgia
- splenomegaly 25%
Lab
- Platelet 2,000,000/mcL
- WBC <30,000/mcL + immature myeloid forms
- Hct: N
- BF: large platelets
- BM: megacaryocytes
Treatment
-HU 0.5-2g/d
- anaglide 1-2mg/d
- aspirin
- plateletphresis
Course & prognosis
- Indolent
- average survival: >15yrs
- late course fibrotic BM + massive splenomegaly
- 10-15% risk of progression to MF after 15 yrs, 1-5% to AML over
20 yrs
ET- BM
 MF
- In adults >50
- usually insidious in onset
- present with fatigue (anemia), abdominal fullness
(splenomegally)
- unusual: bleeding, bone pain
- splenomegally invariable & massive
- heptomegaly 50%
- anemia + progressive thrombocytopenia
bleeding
- hematopoeisis in the liver portal hypertension,
ascites, esophageal varices
Lab
- Anemia
- WBC variable
- platelet variable
- peripheral blood
- significant poikilocytosis
- tear drop forms
- nucleated RBC
- myeloid features shifted to immature forms
- platelet morphology bizzare (giant degranulated form)
- megakaryocyte fragments
- BM: - dry tap
- fibrosis, reticulum fibers
collagen
- No specific chromosomal
abnormality
Treatment
-Mild form: no Rx
- transfusion
- thalidomide / lenalidomide
- allogenic BMT
- EPO
- splenectomy
Course & prognosis
-Median survival from the time of Dx: 5yrs
- end-stage MF
-Generalized debility
- liver failure
- bleeding (thrombocytosis)
- some terminate with AML
 MDS
- A group of acquired clinical disorders of
hematopoeitic stem cells
- xed by cytopenias, hypercellular BM, a number of
morphologic & cytogenic abnormalities
- usually idiopathic
- may be after cytotoxic chemotherapy
- no specific chromosomal abnormality
- contains heterogenous syndromes
 without excess BM blasts = refractory anemia with or
without ringed sideroblasts
 with excess blasts (RAEB 5-19% blasts)
 with proliferative syndrome = CMML (monocytosis)
>1000/mcL
Clinical
-Usually > 60 yrs
- 1st diagnosed because of abnormal counts
- fatigue, infection, bleeding
- course indolent
- wasting illness (fever, wt, loss, general debility)
- splenomegally may be present
Lab
- Marked anemia
- MCV: N / increased
- macro-ovalocytes
- WBC: N/ decresed
- neutropenia common
- deficient granules or bilobed nucleus (Pelger-Huet)
- myeloid series: left shifted
- platelet : N/decreased; hypogranular platelet
-BM: - xically hypercellular
- erythroid hyperplasia
- sign of abnormal erythropoisis
- megaloblastic features
- nuclear budding
- multinucleated erythroid precursors
- ringed siderblasts
- dwarf megakaryocyte with a unilobed nucleus
- variety of cytogenic abnormality (5q- syndrome, monosomy 7)

- treatment
- blood transfusions
- EPO, 30,000 U ,sc
- myeloid granulocyte factors (G-CSF) + EPO
- lenalidomide, 10mg/d
- azacidine
- decitabine
- immunosuppressive (anti-thymocyte globulin)
- allogenic stem cell transfusion - curative
Course & prognosis
- Ultimately fatal
- cure rate: 30-60%
- most die of infection/ bleeding
- pts with refractory anemia may survive many yrs
(risk of leukemia: <10%)
- Those with excess blasts or CMML: short survival
(<2 yrs) & higher (20-50%) risk of developing
acute lekemia
- full deletion of C5 and C7: poor prognosis