Leukocytosis - Some Learning Points

Koh Liang Piu Department of - National University Institute National University Health System Objectives of this talk:

1. To provide some useful practical diagnostic algorithms when confronted with abnormal FBC.

2. To help the non-haematologist to decide when you can circumvent yourself and when haematology consult is necessary.

Simple Approach to Abnormal FBC results

High White Blood Counts

Causes: 1. Central: • Myeloproliferative/lymphoproliferative disease • Leukaemia 2. Peripheral: • ‘Stress’’ , • Infection, inflammation, • Malignancy, splenectomy Simple Approach to Abnormal FBC results

High White Blood Counts

Important Clues to look for 1. History 2. Physical Exam: Liver/Spleen, , Lymphadenopathy etc 3. Peripheral Blood Film (Most Important) 4. WBC: Differentials 5. Biochemisry: ESR/CRP, LDH 6. PT/PTT/DIC screen. 7. Septic/ Malignancy screen Important Questions for Leucocytosis :

• Is this Reactive ? • Is this Neoplastic (Clonal) ? • Which subset of WBC is elevated ? Reactive Neoplastic ? ++ + ? ++ + ? ++ + ? ++ + Basophil ? + Blast ? - +++

Important Questions for Leucocytosis :

• Is this affecting the other 2 cell lines (lineages), i.e. RBC/Hb and platelet count ?

- If yes, this is probably neoplastic (although not absolute)

42 Male Abnormal FBC during health screen 42 Male Abnormal FBC during health screen

1. Take good history 2. Look for Hepatosplenomegaly 3. Look at PBF

MPD ?? Leukemoid Reaction PBF of a patient with severe postoperative sepsis due to a Gram- negative organism.

WBC 92 x 109/L - Neutrophil count of 74 × 109/l (80%) - count of 16 × 109/l (17%) Hb 12g/dL PBF shows a band form, a Platelet 100 x 109/L macropolycyte and monocytes with increased cytoplasmic . • Reactive (Leukemoid Reaction) • Infection • Inflammation • Malignancy • Drugs - Steroids, GCSF, Psychiatric Medications

• Myeloid Malignancy • CML • MPD • Chronic Neutrophilic (rare) Reactive Neutrophilia

band forms showing vacuolation and marked toxic granulation 45 / Chinese/ female

Presenting Complaints: -Vague epigastric discomfort x few months.

Clinical Examinations: - Massive splenomegaly 45 / Chinese/ female

Presenting Complaints: -Vague epigastric discomfort x few months.

Clinical Examinations: - Massive splenomegaly 45 / Chinese/ female

Presenting Complaints: -Vague epigastric discomfort x few months.

Clinical Examinations: - Massive splenomegaly Chronic Myeloid Leukaemia

Peripheral Blood Film

Marrow Aspirate Normal Hematopoiesis In CML and being the most frequent cells.

CML FBC of a patient with Acute Leukemia Peripheral Blood Film

AML CML Differentiating acute versus chronic myeloid leukemia based on FBC

AML CML • Leucocytosis. • . • Predominant population • Mixture of blasts amd of blasts. immature cells. • and • Anemia usually mild. Plts thrombocytopenia more may be mildly low, normal sig. or even high. • Eosinophilia/ basophilia • Eosinophilia and basophilia unusual. common. A 56 year old man with epistaxis.

Clinically: Small cervical Lymphadenopathy Massive splenomegaly Reactive causes present (infection, postsplenectomy) PBF and Flow Cytometry

Clonal disorder No Clonal disorder present (Reactive Lymphocytosis)

Exclude Infectious etiologies

• Viral (HIV, EBV, Hepatitis). • Other Infections (TB, Toxoplasmosis) CLL Mantle Cell Cell Surface Markers of Lymphocytes in B/T LPD 34 / Male

Presenting Complaints: -LHC fullness for many months, a/w LOW

Clinical Examination: - Massive splenomegaly 34 / Male

Presenting Complaints: -LHC fullness for many months, a/w LOW

Clinical Examination: - Massive splenomegaly Monocytosis • “Reactive” • Chronic Infectious/ Inflammatory/ Granulomatous • Metastatic Cancer • Lymphoma • Follow AMI

• “Relative” • Recovery from Chemotherapy or drug- induced neutropenia

• Neoplastic • Marker of MPD (eg: Chronic Myelomonocytic Leukemia, CMMoL)

Eosinophilia

• “Primary” • Clonal • Hypereosinophilic Syndrome (HES) • • “Secondary” • Parasite • Drugs • Allergic conditions • Vasculitides • Lymphoma (T-NHL, Hodgkin) • Metastatic Cancer Eosinophilia

1. Obtaining a good patient history 2. Stool test for ova and parasites

In patients with “primary eosinophilia” - biopsy recommended - distinguish between clonal eosinophilia and HES

In patients with suspected HES - Cytogenetic studies, - FISH for FIP1L1-PDGFRA mutation, - Immunohistochemical stains for tryptase - Mast cell immunophenotyping. Basophilia

• Rare • Seen in CML and Chronic Basophilic Leukemia (extremely rare)

• Refer Hematology • Bone Marrow Biopsy 59 / Chinese/ Male

Presenting Complaints: -LHC fullness for many months, a/w LOW

Clinical Examination: - Massive splenomegaly

Tear Drop Cells Leukoerythroblastic Reaction

Bone Marrow Infiltration (the ‘M’s)

Malignancy Metastasis Myelofibrosis Marble Bone Disease (metabolic disease) Mycobacterial (infection)

Peripheral Stress/ Destruction/ Loss Infection Hemolysis Hemorrhage Conclusions Simple Approach to Leukocytosis

High White Blood Cells: Which subtype

Important Clues to look for 1. Obtain good history 2. Physical Exam: Liver/Spleen, , Lymphadenopathy etc 3. Peripheral Blood Film (Most Important) 4. WBC: Differentials 5. Biochemisry: ESR/CRP, LDH 6. PT/PTT/DIC screen. 7. Septic/ Malignancy screen Any doubt, ask a haematologist Thank you for your attention

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