Abnormal White Cell Count

White cell count abnormalities -assessment and evaluation

Monocytes- Constitute 3-8 % of the WCC Remain for a relatively short time in the circulation- after which they migrate to tissues and body cavities where they differentiate into macrophages They play a role in the inflammatory process ( members of the mononuclear phagocyte system ) Good evidence exists to suggest that blood monocytes consist of several populations

Monocytosis –Associated with infection and inflammatory process Causes can be  ○ Reactive monoytes Infection- commonest cause Inflammatory conditions as collagen vascular disease chronic neutropenia splenectomy hemolytic anaemia ITTP Haematopoetic and non Haemtopoetic neoplasms  ○ Neoplastic Monocytes several primary hematologic neoplasms harbor neoplastic monocytes including CMML , AMl with monocytic differentiation and myeloproloferative neoplasms as CML

Neutrophilia-Main WCC that respond to bacterial infections Common finding – rarely due to haematological diorder Commonest cause is bacterial infection ○ clinical context ○ raised inflammatory markers as CRP ○ Severe infection -myeloid left shift with toxic granulation on the blood film ( vacuolation and Dohle bodies )

causes-Infection Inflammation Necrosis Steroids Pregnancy Smoking Underlying cancer e.g CML. Red flags -A rapid rise Unwell patient Splenomegaly Cytopenias Abnormal blood film Left shift ( more immature as they are being released earlier ).Consider spurious neutrophilia ( eg due to platelet clumping or cryoglobulinaemia ) If cause unclear ask for CRP , U/E , LFT , Immunoglobulins , Serum free lite assay , Autoimmune screen , PSA ( based on clinical suspicion ) For well people a repeat in 4-6 wks is widely recommended

Refer- Suspected acute leukaemia Suspected Chronic myeloid leukaemia -usually moderate ↑↑ in neutrophil count > 50 x 109 with a left shift and a prominence of myelocytes ( basophilia and eosinophilia may also be present ) Unexplained leucocytosis > 50 x 109 Neutrophilia > 15 x 109 ( persistent and unexplained ) Associated splenomegaly or other FBC abnormalities

Lymphocytes-Main cells of the immune system and include T , B and natural killer cells Responsible for antibody production , direct cell-mediated killing of virus-infected and tumour cells Constitute about 25 % of the WCCs- most rapidly motile cells

Lymphocytosis – Ref flags-Fever of unknown  origin Weight loss Night sweats Lymphadenopathy Hepatosplenomegaly Associated anaemia , thrombocytopenia or neutropenia Suspected acute leukaemia Rapidly rising lymphocyte count or in excess of 20 x 109

Causes- Primary-Lymphoid malignancies ○ CLL ( most common ) ○ Lymphoma ○ Monoclonal B Lymphocytosis. Reactive -Viral ( EBV , CMV, HSV , VZV ) Stress lymphocytosis ○ Drug induced  ○ septic shock ○ acute MI ○ trauma. Chronic -Cig smoking Autoimmune disorder Chronic inflammation Sarcoid ↑↑ BMI/ Metabolic syndrome

Referral-No clear cause – consider repeating in 4-6 wks with blood film + glandular fever/HIV screen  ( if clinical suspicion ). Refer urgently to r/o Neoplastic lymphocytosis Unexplained persistent lymphocytosis > 10 x 109 – refer routinely. Lymphocyte  morphology can help distinguish between reactive and neoplastic causes. If atypical  lymphocytes present consider infectious mononucleosis and  viral serology

Basophils –Make up < 1 % of leukocytes  ( least common ) Contain histamine and share many properties with mast cells Function not fully understood Play a role in immediate hypersenstivity disorders as well as atopy , allergic contact dermatitis and possible autoimmune diseases as SLE Estimated lifespan 60-70 hrs. Basopenia -A low count is difficult to demonstrate Common causes- excess glucocortocoids , acute inflammation , hyperthyroidism. Basophilia -rarely significant clinically myeloproliferative disorders

Eosinophils –Make up 1-6 % of WCC- regarded as inflammatory cells that play an imp role in protection against helminth infection and pathogenesis of inflammation Eosinophila can be caused by a wide variety of conditions which range from allergic , rheumatological , infectious , neoplastic and rare idiopathic disorders Marked eosinohilia ie > 1.5 x 109 should always be investigated further aggressively Eosinophilic infiltration of tissues can cause end organ damage ( can be irreversible and life threatening ) Can be ○ Mild 0.4 -1.5 x 109 ○ Moderate 1.5 to 5 x 109 ○ Severe > 5 x 109 Commonest cause worldwide is parasitic infestation

Assessment –Detailed medical hx Thorough physical examination Check for allergic disorders , skin rashes and cardiorespiratory , GI and constitutional symptoms Detailed travel history ( even in remote past ) Detailed drug history Risk factors for malignancy. Further testing -Blood film Inflammatory markers CRP / ESR Renal , LFT and bone profile LDH Vit B12 CXR Serum IgE Autoantibodies if evidence of autoimmune dis eg ANA , ENA , anti-dsDNA , RhF , ANCA Stool culture for parasites. causes of eosinophilia -Myeloproliferative disorders May also be present with Hodgkin’s lymphoma and T-cell lympoma.Infections -particularly parasites Drugs e.g penicillins , carbamezapine Asthma / atopic dermatitis / acute urticarial Conn tissue disease e.g Rh arthritis, Polyarteritis nodosa, Wegeners granulomatosis ) Solid malignancy ( eg breast , renal and lung cancer ) Hypereosinophilic syndrome- diagnosis of exclusion ( associated with end organ damage , particularly cardiac )

Management –> 1.5 x 109 and severe or potentially severe life threatening clinical manifestations or eosinophil rising rapidly-Discuss with O/C Haematologist ( tel ) to arrange  an urgent assessment. Unclear cause-Repeat FBC Also ask for Us&Es , CRP, auto-immune screen Stool for ova and parasites Consider CXR-Persistent unexplained > 1.5 x 109 for 3 months – Refer Rising without an obvious cause – Refer If travel hx- d/w Infectious dis/ Micro

References

Evaluation of Patients with Leukocytosis Lyrad K Riley MS et al AAFP 2015 https://www.aafp.org/afp/2015/1201/p1004.html
Complete Blood Count in Primary Care BPAC NZ better medicine https://bpac.org.nz/Supplement/2008/May/complete-blood-count.aspx
Leuokopenia Elizabeth Birk-Urowitz Family and Community Medicine – University of Toronto via https://dfcmopen.com/wp-content/uploads/2014/11/Leukopenia.pdf
King’s Health Partners Haematology Institute and Network GP Referral guide Adult Haematology https://www.kingshealthpartners.org/assets/000/002/297/GSTT_-_khp_joint_adult_haematology_original.pdf
Incidental finding of lymphocytosis in an asymptomatic patient BMJ 2009 ; 338: b2119
Lymphocytopenia by Mary Territo MD MSD Manuals professional version
Practical approach to the patient with hypereosinophilia Roufosse, Florence et al. Journal of Allergy and Clinical Immunology, Volume 126, Issue 1, 39 – 44 https://www.jacionline.org/action/showCitFormats?pii=S0091-6749%2810%2900660-3&doi=10.1016%2Fj.jaci.2010.04.011
Haematology in Primary Care Dr Josh Wright Sheffield Teaching Hospitals
UH Bristol Haematology referral guideline for Primary Care May 2016
Monocytes an overview by ScienceDirect
Ask the hematopathologist : Diagnostic Approach to Monocytosis The Hematologist July-August 2016 , Volume 13 , Issue 4

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