    Urine hemosiderin: Present in intravascular hemolysis only

      Urine Hgb: Present in severe intravascular hemolysis;

urine dipstick test is positive for blood but no RBCs seen on microscopic examination

paciente con anemia megaloblástica y ácido metilmalónico y homocisteína plamática elevadas

DX:

Conteo reticulocitario corregido: >2

Frotis periferico: esferocitos

Lab: prueba de antiglobulina directa [+]

Conteo reticulocitario corregido: >2

Frotis periferico: esferocitosis

Lab:prueba de antiglobulina directa [-]

Anemias hemoliticas congenitas asociadas a aparacion de cuerpos de Heinz (granulos de Hb precipitada) en frotis periferico

Def G6PD

B talasemia MAYOR

Drepanocitosis

Cuerpos de Heinz

Anisopoiquilocitolsis

Decriocitos

Punteado basofilo

Eritroblastos

FP: Estomacitos

Enfermedades asociadas

ESTOMACITOSIS CONGENITAS

Sx Rh nulo

Hidrocitosis congenita

xerocitosis congenita

Tx con Isoniazida

Intox por alcohol aguda

Saturnismo (Intox x plomo)

Sx mielodisplasico

Anemia mieloptísica

Mielofibrosis idiopatica/metaplasia mieloide agnogenica

Poiquilocitosis

Dianocitos

Asplenia

Anemias megaloblasticas

Drepanocitosis

(Tambien presenta celulas falciformes [en hoz]

Cuerpos de Heinz

Cuerpos de Howell-Jolly)

Drepanocitosis

celulas falciformes [en hoz]

Cuerpos de Heinz

Cuerpos de Howell-Jolly

Mieloma multiple

Crioaglutininas (0-20%)

Valvulopatías

Hemólisis microangiopatica

• PTT
• CID
• SHU
• HELLP
• *(pueden asociarse a trombocitopenia)
• HT maligna
• Carcinomas diseminados

Conteo reticulocitario corregido: >2

FP: Target cells (Dianocitos) (JohnH)

Talasemias

Hemoglobinopatía

Hepatopatía

Malaria

Babesiosis

Bartonella

Mujer

Hto: 33%

VCM: 70

Fe: 30  mg/dL

Transferrina: 320 mg/dL

Ferritina 10 ng/mL

IST: 10%

Capacidad total de Saturacion de transferrina (TIBC: Total Iron Binding Capacity) = 420 mg/dL

30 Bajo Fe: 50 - 150 mg/dL

320 elevado Transferrina: 170-290 mg/dL

10 BAJO Ferritina 20-300 ng/mL

10 BAJO IST: 20-50%

ELEVADO 420 Capacidad total de Saturacion de transferrina (TIBC: Total Iron Binding Capacity) = 250-400 mg/dL

ANEMIA FERROPENICA

Hombre con hx AR de 20a de evolución con ingesta crónica de Inhibidores COX2

Hb:12

VCM: 60

HCM: 29

Fe: 20 mg/dL

Transferrina: 200 mg/dL

Ferritina: 290 ng/mL

IST: 30 %

Capacidad total de Saturacion de transferrina (TIBC: Total Iron Binding Capacity) = 200 mg/dL

Hct <41% or Hb <13.5 g/dL (men);

20 BAJOFe: 50 - 150 mg/dL

200 NormalTransferrina: 170-290 mg/dL

290 Normal Ferritina 20-300 ng/mL [puede encontrarse normal o elevado]

30 normal IST: 20-50%

200 BAJA Capacidad total de Saturacion de transferrina (TIBC: Total Iron Binding Capacity) = 250-400 mg/dL [DISMINUIDA]

Anemia inflamatoria

•  Dx:

↓ Fe, ↓ TIBC (usually normal or low transferrin sat),

± ↑ ferritin;

usually normochromic, normocytic (~70% of cases) but can be microcytic if prolonged

• Reversible
• (alcohol, lead, isoniazid, chloramphenicol, copper deficiency, hypothermia)

• Iron if
• ferritin <100 or Fe/TIBC <20%.

• Consider ESA if Epo <500.
• erythropoiesis-stimulating agent (ESA, eg, Epo).
• Avoid ESA in cancer if treatment goal is cure (Leuk Res 2012;36:939).

HUS triad = thrombocytopenia + MAHA + renal failure

TTP pentad (all 5 in only ~5%) =

• thrombocytopenia + MAHA (100%)
• ± Δ MS (65%)
• ± renal failure (50%)
• ± fever (25%)

HUS triad = thrombocytopenia + MAHA + renal failure

TTP pentad (all 5 in only ~5%) =

• thrombocytopenia + MAHA (100%)
• ± Δ MS (65%)
• ± renal failure (50%)
• ± fever (25%)

 Dx:

•  unexplained thrombocytopenia (typically <20k) + MAHA → sufficient for dx

• schistocytes (>2–3/hpf)

• [-] Coombs,
• normal PT/PTT & fibrinogen
• ↓↓ ADAMTS13

• ↑↑LDH (tissue ischemia + hemolysis),

• ↑ indirect bili.,

• ↓↓ haptoglobin,

• ↑ Cr (esp. in HUS)

Acquired vWD

Heyde’s syndrome = vWF destruction by severe AS, a/w GI AVMs/bleed

Paciente en tratamiento con warfarina, presenta sangrado, INR:5

¿tx? (Pocket)

Vitk 10 mg IV

+

FFP 2-4 units IV q6-8H

• “catastrophic APS” =
• ≥3 organ systems in <1 wk w/  [+] APLA & tissue microthrombi (Lupus 2003;12:530)
• → 44% mortality (Arth Rheum 2006;54:2568)

•  Postremission therapy options:

consolidation/intensification chemo (~7 mo) followed by maintenance chemo (~2–3y)

• high-dose chemo w/ allo HSCT considered for all Pts in CR1 w/ available donor

•  Ph [+]  t(9;22) → add imatinib or dasatinib, followed by allogeneic HSCT

•  MLL-AF4 t(4;11) or hypodiploidy (<44 chromosomes)→ consider for allogeneic HSCT

•  Flow cytometry:

clonality with

• dim surface Ig (sIg);

• CD5+, CD19+, CD20(dim), CD23+.
• CD38+ or ZAP70+ a/w unmutated Ig variable heavy chain region & worse prognosis.

•  Genetics:

del 11q22-23 & 17p13 unfavorable;

•  Treatment is primarily palliative → early stage disease can be followed w/o Rx

•  Indications for treatment:

Rai stages III/IV,

 Binet stage C,

disease-related sx,

Progressive disease or Richter transformation,  AIHA or ITP refractory to steroids,

recurrent infections

  Bulky lymphadenopathy or organomegaly (JHopkins)

      Constitutional symptoms (weakness, B symptoms)

     Bone marrow failure (anemia or thrombocytopenia) from progressive CLL

Factors a/w worse prognosis include:

unfavorable cytogenetics (eg, 17p-/TP53 mutation)

unmutated (<2% c/w germline) IgVH gene (<8–10 y vs. >20–25 y if mutated)

high (>20–30%) Zap-70 expression (part of T cell receptor; correlated w/ unmutated IgVH)

CD38 >30% or CD49d <30% (correlated with unmutated IgVH)

higher β2-microglobulin levels (correlate with disease stage and tumor burden)

•  BM bx cytogenetics: normal karyotype better than abnl.

• Standard risk =
• hyperdiploidy or t(11;14);

• high risk =
• hypodiploidy,
• del. 17p13 (~10% of Pts),
• t(4;14) &
• t(4;16)

celulas falciformes [en hoz]

Cuerpos de Heinz

Cuerpos de Howell-Jolly

Dx?

paciente con anemia megaloblástica

ácido metilmalónico: N

homocisteína plamática: elevada

Dx:?

• Allo HSCT produces graft-versus-tumor (GVT) effect, in addition to hematopoietic rescue (used for AML, ALL, CML, CLL, MDS, lymphoma)

•  Diagnosis:

↓ Fe, ↑ TIBC, ↓ ferritin (esp. <15), ↓ transferrin sat (Fe/TIBC; esp. <15%),

↑soluble transferrin receptor; ↑ plt;

•  ɑ-thalassemia:

deletions in ɑ-globin gene complex on chr. 16 (nl 4 ɑ genes)

• 3 ɑ → ɑ-thal-2 trait = silent carrier;

 ɑ-thalassemia:

deletions in ɑ-globin gene complex on chr. 16 (nl 4 ɑ genes)

• 3 ɑ → ɑ-thal-2 trait = silent carrier;

•  2 ɑ → ɑ-thal-1 trait or ɑ-thal minor = mild anemia

• 1 ɑ → HbH (β4) disease =severe anemia, hemolysis and splenomegaly

• 0 ɑ genes → Hb Barts (γ4) = intrauterine hypoxia and hydrops fetalis

• Hb electrophoresis:
• ↑HbA2 (ɑ2δ2) in β-thal;
• normal pattern in ɑ-thal trait

•  Diagnosis:

MCV <70, normal Fe,

• MCV/RBC count<13 [Mentzer Index, 60% Se, 98% Sp; (Ann Hem 2007;86:486)],

• ± ↑ retics, basophilic stippling;

• idiosyncratic med rxn
• (eg, chloramphenicol, NSAIDs, sulfa drugs, gold, carbamazepine, antithyroid)

• Fanconi’s anemia
• congenital disorder w/ pancytopenia,
• macrocytic anemia,
• ↑ risk of MDS, AML, & SCC of head & neck, and
• multiple physical anomalies

• TPO mimetics (eg, eltrombopag) may be option in refractory disease (NEJM 2012;367:11)

•  Dx:

flow cytometry (↓ CD55 & CD59) on RBCs and granulocytes;

urine hemosiderosis

•  Treatment:

supportive care (iron, folate, transfusions);

consider anti-coagulation

• allogeneic HSCT for hypoplasia or severe thrombosis

• eculizumab (Ab inactivates terminal complement C5s):
• ↓ hemolysis, improves QoL & stabilizes Hb levels (NEJM 2004;350:552 & 2006;355:1233; Lancet 2009;373:759);

• must have meningococcal vaccination

•  Intravascular:

↑↑ LDH, ↓↓ haptoglobin;

hemoglobinemia, hemoglobinuria, hemosiderinuria

• MDS with isolated 5q
• <5% blasts, del (5q)

• Low/intermediate risk →
• Epo (esp. if Epo level <500);
• lenalidomide (esp. for 5q syndrome; NEJM 2005;352:549);
• DNA hypomethylating agents (azacitidine or decitabine)

• Intermediate/high risk →
• DNA hypomethylating agents (survival advantage w/azacytidine; Lancet Oncol 2009;10:223),
• combination chemo (akin to AML Rx) or
• allogeneic HSCT if age <55 (consider reduced-intensity transplant for ages 55–75)

•  Phlebotomy to moderate degree of Fe defic., goal Hct <45% (NEJM 2013;368:22),

consider <42% in

•  Low-dose ASA in all Pts (NEJM 2004;350:114)

•  Hydroxyurea if

• high risk of thrombosis (age ≥60, prior thrombosis) or
• sx thrombocytosis (plt >1.5 × 106/µL)

• PEG IFNa-2a yields high response rate w/ limited toxicity (Blood 2008;112:3065)

•  Supportive:

allopurinol (gout), H2-blockers/antihistamines (pruritus)

Diagnostic evaluation

•  Peripheral smear:

large hypogranular platelets

•  BM bx:

megakaryocytic hyperplasia;

absence of Philadelphia chromosome and lack of collagen fibrosis; normal iron stores

•  JAK2 V617F present in ~50% of ET

• Patients should not meet WHO criteria for diagnosis of CML, PV, PMF or MDS

Treatment (Blood 2011;117:3494)

•  In absence of adverse prognostic factors (eg, anemia or sx) → no treatment

•  Allogeneic HSCT only potential cure → consider in young Pts with poor prognosis

•  Supportive care:

transfusions;

inconsistent benefit from androgens or Epo;

Splenectomy for blood counts refractory to transfusion or painful splenomegaly

•  Hydroxyurea for significant leukocytosis or thrombocytosis

•  Ruxolitinib (JAK1/JAK2 inhibitor)

↓ sx, ↓ splenomegaly, ↑ survival (NEJM 2012;366:787 & 799)

•  Thalidomide and lenalidomide (improve red cell count)

•  Acquired hematopoietic diseases:

MDS, MPN (esp. CML), aplastic anemia, PNH

•  Inherited:

• Down’s & Klinefelter’s,
• Fanconi’s anemia,
• Bloom syndrome,
• ataxia telangiectasia

•  Presence of certain cytogenetic anomalies, eg, t(15;17), t(8;21), inv(16) or t(16;16), are sufficient for dx of AML regardless of the blast count

•  Poor prognostic factors:

age >60,

unfavorable cytogenetics (see above),

FLT3-ITD  ,

poor performance score,

antecedent MDS/MPN,

therapy-related AML;

genetic profiling

(NEJM 2012;366:1079)

•  Induction regimen:

anthracycline + ATRA ± cytarabine → CR in ~90%; or ATRA + ATO alone (ASH 2012; JCO 2009;27:504)

•  Cytochemistry:  

terminal deoxynucleotidyl transferase (TdT) in 95% of ALL

CALLA (Common Acute Lymphocitic Leukemia Antigen) [Perlas]

•  Cytogenetics (Blood 2010;115:206):

t(9;22) = Philadelphia chrom (Ph) ~25% of adultsw/ ALL

•  CNS prophylaxis:

intrathecal MTX/cytarabine ± cranial irradiation or systemic MTX

•  Good prognostic factors:

younger age,

WBC <30,000/µL,

T-cell immunophenotype,

absence of Ph chromosome or t(4;11),

early attainment of CR

•  Peripheral smear:

leukocytosis (often >100,000/µL),

left-shifted with all stages of myeloid maturation;

anemia, thrombocytosis, basophilia

•  Bone marrow:

hypercellular, ↑ myeloid to erythroid ratio, ↓ leuk alkaline phosphatase (dato diferencial de reaccion leucemoide, donde se encuentran elevados)

Paciente con dx leucemia cronica, t(9;22) [+]

recibio tx con imatinib sin obtener respuesta, cuales son sus opciones terapeuticas (Pocket)

LMC

Resistance = recurrent dis. on TKI, often result of BCR-ABL mutation or amplification.

• Nilotinib, dasatinib, bosutinib, & ponatinib approved for resistant disease,

•  w/ only ponatinib effective on T315I resistance mutation (NEJM 2012;367:2075).

Paciente con dx leucemia cronica, t(9;22) [+], con mut T315l

recibio tx con imatinib sin obtener respuesta, cuales son sus opciones terapeuticas (Pocket)

LMC

Resistance = recurrent dis. on TKI, often result of BCR-ABL mutation or amplification.

• Nilotinib, dasatinib, bosutinib, & ponatinib approved for resistant disease,

•  w/ only ponatinib effective on T315I resistance mutation (NEJM 2012;367:2075).

LMC

MO:

•  Blastic:

>20% blasts (2⁄3 myeloid, 1⁄3 lymphoid),

may see extramedullary leukemia

Tx:

•  Blastic phase:

TKI + HSCT vs. ALL or AML induction (based on cell type) + HSCT

• Allogeneic HSCT:

 consider for Pts w/ available donor who present in accelerated or blastic phase;

reasonable option for Pts with relapsed/refractory disease to TKIs

LLC

~5% develop Richter’s syndrome =

 transformation into high-grade lymphoma (usually DLBCL) and sudden clinical deterioration

paciente con LLC con del17p[-17p] que recibio tx con esquema CHOP + Alemtuzumab (CD52)

que no obtuvo respuesta

tx?

•  Novel Rx refractory dis.:

 ofatumumab (ɑ-CD20),

ibrutinib (BTK inhib),

CAL101 (PI3Kinhib)

•  Consider allo-HSCT in

p53 mut or refractory CLL (BBMT 2009;15:53; BJH 2012;158:174)

Mujer 19a, presenta adenopatía cervical >3cm, dura, adherida a planos profundos, resección (DxAP: LH), en estudios de extensión se encuentran adenopatías mediastinales (AH II)

Cual es la variante AP mas probable para este caso?

Esclerosis nodular 60-80%

afecta pac jocenes, predominancia en mujeres, estadio I-II al dx

Consider CNS prophylaxis w/ intrathecal or systemic high-dose methotrexate if

paranasal sinus, testicular, breast, periorbital, paravertebral or bone marrow involved;

≥2 extranodal site + ↑ LDH may also warrant

WALDENSTRÖM’S MACROGLOBULINEMIA (WM)

•  B-cell neoplasm (lymphoplasmacytic lymphoma) that secretes monoclonal IgM

•  MYD88 (NF-кB pathway) L265P somatic mutation found in 91% of Pts w/ WM and could

be used to distinguish WM from MM (NEJM 2012;367:826)

Ag mieloides

([+] en LMA)