FUNNY HAEMATOLOGY

Nicolas Novitzky

Leukocytosis

Leukocytosis: Elevation of leukocyte count above normal for

age Laboratories validate reference ranges in these

populations Neonates: 30 x 109/L Adult 10 x109/L

Spurious elevation Normoblasts in severe anaemias Platelet clumps

Examination of blood smear Slide review mandatory in unexplained leukocytosis

Lymphoid Leukocytosis

Reactive lymphocytosis

Not a haematological disorder

Infective mononucleosis syndrome

Range from small to reactive immunoblastas, plasmacytoid and granular lymphocytes

Epstein-Barr virus

Cytomegalovirus infection

HIV primoinfection

Bordetella pertussis Small immature lymphocytes

Large granular lymphocytes

Toxoplasmosis

Hepatitis B, C

Drug reaction (phenytoin)

Precursors B-cells (haematogones)

Reactive B-cell lymphocytosis

Lymphoid Leukocytosis

Mononucleosis syndrome

Protracted pyrexia

Weakness

Cervical and generalised adenopathy

Mouth ulcers

CMV colitis, hepatitis

Gillain Barre’ syndrome

Laboratory Leukocytosis

Atypical lymphocytes

Absolute lymphocytosis

Positive antibodies (ELISA), PCR, VL

EBV 79%

CMV 21%

Cold agglutinins

ANA, RhF

Anaemia, thrombocytopenia

Malignant Lymphocytosis

Acute lymphoblastic leukaemia T, B phenotypes

Chronic lymphocytic leukaemia

Lymphoma with spill Follicular lymphoma 30%

Mantle cell lymphoma

T-cell lymphoma

Prolymphocytic leukaemia

Sezary syndrome

Lymphadenopathy

Hepato-splenomegaly

Mediastinal adenopathy

Abdominal masses

Laboratory findings Pancytopenia

Quite typical morphology

Monomorphic populations

Monoclonal lymphocytes

Biochemical abnormalities

Malignant Lymphocytosis

Abnormal karyotype

Clonal rearrangement of IgH

Single light chain Chronic lymphocytic

leukaemia

Lymphoma with blood spill

Acute lymphoblastic leukaemia

Malignant Lymphocytosis

History Physical exam

Adenopathy common Splenomegaly in

children Blood cytopenias

Blood tests Absolute increase in

mature cells Increase in LGLs Increase in activated

lymphocytes

Neutrophilic Leukocytosis

Neutrophilic leukaemoid reaction

> 35 or 50 x 109/L Left shift

Infections Chlostridium difficile,

Pneumonia, Tuberculosis Tissue ischaemia Haemolytic anaemia Obstetric cases Epithelial malignancies

GM-CSF, G-CSF Haematological

malignancies AML CML MDS / MPS

Leukoerythroblastic reaction

Older age, median 75 years

Positive blood cultures Longer than 1 day LR No correlation

between height of WCC and survival

Hospital mortality 38% Age > 60 years Sepsis

Neutrophilia

Investigate inflammatory process

Treat infection

Investigate malignancy Paraneoplastic Frequently implies

disseminated disease Treatment of malignancy

Bone marrow biopsy Specific treatment

Implies bone marrow involvement

Bone marrow biopsy may be diagnostic

Granulomata TB, others…

Metastatic marrow infiltration

Haematological malignancy

Leukaemoid reactionLeukoerythroblastic picture

Hyperleukocytosis

Haematological malignancy > 100 x 109/L Increased mortality

May have lineage implications

T, B cell, monocytic Increased morbidity

Tumour lysis syndrome Disseminated intravascular

coagulation Hypercalcaemia, hypo

phosphataemia Respiratory failure

Hyperleukocytosis

Leukostasis Mainly affects

CNS Confusion Focal deficit Stupor, coma

Lungs Hypoxia

Diseases Monocytic leukaemia T, B ALL CML

Mechanism Increased blood viscosity Deformability, volume Endothelial adhesion

Management Medical emergency

Hydrate properly

Oxygen

Leukapheresis 2 blood volumes (removes 87%) Do not use HES

Ca++ supplementation

Repeat if symptomatic

Start chemotherapy Doxorubicin, cytarabine

Hydrea

Thrombocytosis

Platelet count > 450 x109/L Reactive causes most common

(90%). Extreme 3-5%

Spurious Cryoglobulins Bacteria Red cell vesicles in burn injury

Reactive Infection Chronic inflammation, tissue

damage Malignancy Haemolysis Fe deficiency anaemia Splenectomy

CRP, ESR IL-1, IL-6, TPO

Ferritin low High Epo

Reactive Laboratory markers

• Self limiting• Low risk of thrombosis (1.6-4%)

• Venous• Post operative

Clonal Thrombocytosis

Chronic myelogenous leukaemia Ph – t(9;21), BCR/ABL

Essential thrombocythaemia JAK-2, MPL

Polycythaemia Vera JAK-2, exon 12,

calreticulin Myelofibrosis

JAK-2, MPL

Microvascular thrombosis Vasomotor symptoms Headaches, syncope, visual Erythromelalgia

Elevated thrombexane

Macrovascular disease Arterial, venous thrombosis

Splacnic vessels Mesenteric, portal (25% MPS)

Cerebral sinuses

Accumulative risk: 10yr:42% 20yr:52%

Risk factors: Previous thrombosis Age >65 years

Both: 10% per year Leukocytosis Erythrocytosis

Viscosity

Thrombosis major problem

Thrombocytosis: Management

Treat primary condition Fe supplementation Specific immune

therapy Dispirin

Depending on risk factors Dispirin

Hydroxyurea

Plateletpheresis

Awareness off bleeding tendency Acquired vWD

Reactive Clonal

Myelodysplastic Syndromes

Nicolas Novitzky

Myelodysplastic Syndromes (MDS)

Clonal hematopoietic Stem Cell Disease Dysplasia Ineffective

Hematopoiesis (1 or more lines)

Myeloblasts < 20% of all marrow cells

Synonyms: Dysmyelopoietic

syndromes Preleukemic syndromes Oligoblastic leukemia

Older adults

median age: 70 years

Primary vs. Secondary MDS (S/P chemotherapy)

Incidence: 3/100,000 non-age corrected

20/100,000 over age 70

MDS: Clinical

Symptoms of Cytopenia

Anemia > Neutropenia +/- Thrombocytopenia

Organomegaly (infrequent) Hepatomegaly

Splenomegaly

Classified according to: Marrow and blood %

blasts Type and degree of

dysplasia +/- ringed sideroblasts Cytogenetic

abnormalities del (5q) 500 cell diff in marrow 200 cell diff in PB

MDS:

Primary

No known history of toxic exposure

Possible etiologies: Virus, Benzene, cigarette (2 fold risk), Fanconi anemia.

Therapy-related

Chemotherapy (alkylating agents)

Radiation Therapy

B12/folate deficiency

Heavy metals (Arsenic)

Congenital dyserythropoietic anemia

Parvovirus B19

GCSF therapy (increased blasts)

Differential DiagnosisEtiology

Myelodysplastic Syndromes

RA RARS RAEB RAEB-T

CMML

Myelodysplastic Syndromes

RA

RARS

RCMD & RCMD-RS

RAEB-1 & RAEB-2

MDS Unclassified

MDS del(5q)

Myelodysplastic/Myeloproliferative Diseases

CMML

Atypical CML

Juvenile CMML

MDS/MPD, unclassified

FAB Classification WHO classification

MDS: Genetics

5q- syndrome (women, megakaryocyte anomalies

Del 17p (pseudo Pelger-Huet anomaly, therapy related)

Complex cytogenetic (chromosomes 5 & 7) unfavorable prognosis

Del(20q) (erythroid and megakaryocytes) Abnormal Ch 3 (abnormal megas)

MDS: Prognosis

RA, RC and RARS Normal cytogenetics,

del(5q), del(20q) and -Y

RAEB and RCMD Complex

abnormalities Monosomal

karyotype 1, 3, 5, 7, 17

Abnormal Chromosome 7

Low Risk group High Risk

Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) Clonal hematopoietic

neoplasms No history of underlying

CMPD or MDS,

toxins,

Ph’, no del (5q), no t(3;3)(q21;q26), no inv (3)(q21q26)

+ finding c/w chronic myeloproliferative diseases, No Ph’ chromosome

No JAK-2

Spleno & hepatomegaly

Prominent myeloproliferative features Hypercellular marrow,

Lab and Morphologic features of MDS

AND

Dysplasia

Blasts <20%

Mixed MPD and MDS cannot be assigned any other category

MDS: Management

Supportive care Transfusions of blood

products Iron overload Infections

Specific therapy Low risk

Growth factors High risk

Demethylating agents Stem cell

transplantation

Supportive care Transfusions of blood

products Iron overload Infections

Specific therapy Hyroxyurea azacytidine

MDS MPS

Conclusion

Medical emergency Represents serious

systemic disorder Requires urgent

investigation Therapy

Antibiotics Cytotoxics Apheresis Treatment of the

specific problem

Clonal bone marrow failure

Proper management associated with extended survival

Supportive care Demethylating agents

Hyperleukocytosis Myelodysplasia