funny haematology nicolas novitzky. leukocytosis leukocytosis: elevation of leukocyte count above...
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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