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The FBC and PBF – a general approach to FBC abnormalities and how the PBF can aid diagnosis

Dr Denise Tan Associate consultant SKH Haematology, Dept of General Medicine SGH Dept of Haematology What will be covered:

1) Tools of Haematology: the FBC and the PBF 2) General approach to increased and decreased cell counts 3) Questions – FBC and PBF for some common or important diagnoses

The Full blood count- A general approach

1) Patient ID 2) Date, time 3) Compare to previous FBCs on NEHR • Gives an idea of the chronicity and rate of progression of any abnormalities

4) Assess all 3 cell lines • As a group; how many are affected and • Individually; what are the abnormalities in each?

5) Look out for any remarks! They may contain very useful information • Further description of abnormal cells • Description of the cells in relation to others eg agglutination, roleaux formation • Perhaps even parasites!

The full blood count- Red cell indices

1) Haemoglobin (measured) • The amt of Hb molecule in a volume of blood 2) RBC Count (measured) • The number of RBC in a volume of blood 3) (measured) • Average RBC size 4) Mean corpuscular haemoglobin • Average amt of Hb in each RBC (Hb /RBC) 5) Mean corpuscular haemoglobin concentration • Average concentration of Hb in each RBC (Hb/HCT) • Supports diagnosis of spherocytosis 6) Red cell distribution width • Measures variability in RBC size and shape 7) • The % of whole blood occupied by RBC (MCVxRBC) 8) Immature RBCs • and nucleated RBCs

The full blood count- White cell indices

1) White blood cell count • The number of WBC in a volume of blood

2) Remember to look at the differential count – both percentage and absolute • 5 main groups of WBCs

3) Immature or abnormal WBCs • Band forms, Myelocytes, metamyelocytes, promyelocytes, blasts • “Atypical mononuclear cells” or “atypical lymphocytes”

The full blood count- indices

1) Platelet count • Number of in a volume of blood

2) Mean platelet volume • The average size of platelets in a volume of blood

The peripheral – Looking at cell morphology

• Even if not routinely ordered, it is usually done for abnormal FBC results, especially if there is a significant change from the previous FBC • Cells spread thinly out, able to appreciate individual cell shape, nuclear changes and other cellular contents Keep in mind physiological changes in the FBC

• Keep in mind the clinical context is important when interpreting FBC / PBF for example: • Red cells • Children, males and people living at high altitudes can have higher Hb • In pregnancy, RBC count decreases due to a physiological dilutional effect • Recent blood transfusion can affect the RBC indices

• White cells • Physical activity and stress can increase neutrophil counts

• Platelets • Gestational in 2nd and 3rd trimester of pregnancy • Thrombocytosis can occur with increased physical activity and stress

General causes of anemia and polycythemia Anemia Polycythemia • Nutritional deficiencies (iron, folate, B12) • Polycythemia vera • damage eg infection, drugs • Secondary polycythemia eg chronic • Bone marrow disorders eg hemato hypoxic conditions, smoking malignancies, • Paraneoplastic Epo production • Chronic inflammation and CKD • Dehydration • Pure red cell aplasia • Acute or chronic blood loss • RBC destruction eg hemolytic anemias

Photos from www.slide-share.net Another way to classify anemia: RBC size Microcytic Macrocytic Normocytic + Retic • Iron deficiency RDW ↑ DNA synthesis defects • Acute blood loss response • (vit • Anemia of inflammation B12/Folate deficiency) RDW ↑ Inability to utilize iron • Anemia of chronic renal if trait; • Myelodysplastic syndrome disease • Thalassemia RDW lack retic response normal • • Bone marrow failure • Anemia of inflammation RBC membrane defects • Bone marrow infiltration • Sideroblastic anemia RDW ↑ • Hypothyroidism • Dual pathologies

RDW ↑ • Liver disease • Early stages of anemia

• Reticulocytosis

Some common RBC abnormalities General causes of leukopenia and leukocytosis

Leukopenia Leukocytosis • Nutritional deficiencies (Fol/B12) • Neutrophils: bacterial infection • Drugs, radiotherapy • Lymphocytes: viral infections, chronic infections eg TB, pertussis • Infections esp viral, also severe • Atypical lymphocytes: viral infections, • Infiltration eg hemato malignancies or lymphoma metastatic cancers • Monocytes: chronic infections eg TB, • Autoimmune destruction inflammatory or autoimmune disorders • Eosinophils: allergic disorders, parasitic infections, various neoplasias, adrenal insufficiency, some autoimmune diseases • Basophils: myeloproliferative neoplasms • Immature cells/blasts: leukaemias, leukemoid reaction Some WBC abnormalities General approach to thrombocytopenia and thrombocytosis

Thrombocytopenia Thrombocytosis • Pseudothrombocytopenia • Reactive states – inflammation, infection • Vitamin deficiencies (folate B12) • Iron deficiency • Bone marrow suppression eg drugs, • Hemato malignancies eg alcohol, viral, Gram negative sepsis myeloproliferative neoplasms • Primary bone marrow disorders eg MDS, aplastic anemia • ITP (primary and secondary) • Non-immune destruction eg TTP, HUS, DIC • Splenic sequestration • Pregnancy-associated syndromes Some platelet abnormalities on PBF Now, on to the fun part! FBC / PBF spot diagnosis questions Question 1: 20 yr old lady

This is…. A. Thalassemia trait B. Transfusion dependent thalassemia C. Iron deficiency anemia D. Megaloblastic anemia Answer: C Key features of Fe deficiency anemia: MCHC anemia with decreased RBC count raised RDW (more anisocytosis) Reticulocytes not increased

Pencil cells, occasional target cells Different degrees of hypochromasia

Pencil cell

Ferritin 1.6 ug/L Question 2:

30 yr old lady, 8 weeks pregnant

Hb 11.0 (12.0 – 16.0 g/dL) TW 4.0 (4.0-10.0 x106/L) Plt 380 (140-440 x106/L) RBC 4.95 (4.2 – 5.4 x1012/L) MCV 70.4 (78-98FL) MCH 24.8 (32-36g/dL) This is…. RDW 13.2 (10.9-15.7%) A. Iron deficiency anemia B. Thalassemia trait C. HbH disease D. Physiological anemia of pregnancy Answer: B Key features of thalassemia trait:

MCHC anemia with Normal RBC count Normal RDW For the same Hb, microcytosis more marked than Fe deficiency anemia

More homogenous looking than Fe deficiency Target cells more numerous Vs. RBCs may have basophilic stippling

Question 3: 64 yr old lady

This is…. A. Thalassemia trait B. Iron deficiency anemia C. Megaloblastic anemia D. Myelodysplastic syndrome Answer: D Key features of Megaloblastic anemia:

Pancytopenia with macrocytic RBC Typically MCV >110

Hypersegmented neutrophils Macro-ovalocytes Some fragmented RBCs and teardrop cells often present

Locally, often due to pernicious anemia rather than dietary lack of folate/B12

Question 4: 61 yr old lady, presented with lethargy and SOBOE

This is…. A. Autoimmune hemolytic anemia B. Iron deficiency anemia C. Myelodysplastic syndrome D. Megaloblastic anemia Answer: A microspherocyte

LDH 1461 U/L Total Bil 37 umol/L Direct bil 9 umol/L <0.10 g/L DCT positive – IgG 4+, C3d 1+ Warm auto-Ab identified

Key features of AIHA:

Raised hemolytic markers, DCT+ Can occur with ITP (Evan’s syndrome) Polychromatic cells Microspherocytes ie reticulocytes Good response / nRBC suggest peripheral destruction

So… why was the MCV raised? Nucleated RBC

Question 5: 76 yr old gentleman presented with malaise and URTI symptoms

This is…. A. Lymphoma B. Viral infection with reactive lymphocytosis C. Infectious mononucleosis D. Acute leukaemia

Answer: D

Key features of Blasts:

Large cells High nuclear: cytoplasmic ratio Open chromatin Nucleoli present

AML diagnosed when BMA ≥20% blasts

Often with anemia and thrombocytopenia May have background dysplasia (if AML transformed from MDS)

Chronic myeloid leukaemia

Leukocytosis, with blasts present; but whole range of maturation seen, and predominantly mature neutrophils

Anemia, thrombocytosis Basophilia Usually with hepatosplenomegaly

High WBC count well tolerated (vs Acute leukaemia where TW mainly blasts, if TW >100, high risk of leukostasis)

Question 6: 16 yr old gentleman Fever, malaise and cervical lymphadenopathy x 1 wks

Hb 15.0 (12.0 – 16.0 g/dL) TW 28.1 (4.0-10.0 x106/L) Plt 400 (140-440 x106/L) Neut 19.1% 5.4 (2.0 – 7.5 x106/L) https://oncohemakey.com Lymp 31.3% 8.8 (1.0 – 3.0 x106/L) Mono 3.6% This is…. 1.0 (0.2-0.8 x106/L) Eos 0.7% A. Lymphoma 0.2 (0.0 – 0.4 x106/L) B. Infectious mononucleosis Bas 1.3% C. T-large granular leukaemia 0.4 (0.0 – 0.1 x106/L) D. Acute leukaemia Atypical mononuclear cells 40% 11.24 x106/L Answer: B

“Atypical mononuclear cells”

Can be anything from… Reactive lymphocytes, indolent lymphoma, aggressive lymphoma (Burkitt’s), blasts!

Normal • Blood film is crucial lymphocyte • Look at the rest of the FBC – cytopenias suggest marrow infiltration or secondary autoimmune phenomena (AIHA/ITP)

• Always put it into clinical context as well – age, tempo etc Lymphoblasts

Question 6: 50 yr old gentleman, admitted overnight for epistaxis

What to do next? A. Review medications, do baseline bloods to assess renal and liver function, including folate/B12 levels B. Call haematologist on call C. Call ENT on call for nasal packing D. Transfuse platelets and wait till the day time to refer – since Hb is still stable and epistaxis can be easily controlled Key learning point: Always look at the differential counts!

Answer: B

Key features of Acute promyelocytic anemia

Can present with leukocytosis but also with pancytopenia! - Look out for promyelocytes on the differential count - Look out for concomitant DIC (plt/PT/aPTT/)

Abnormal promyelocytes are hypergranular or bilobed (or both) Large cells with nucleoli Hypergranular with Auer rods : “Faggot cells”

A medical emergency! Need to start treatment with ATRA overnight

Question 7: 52 yr old female, presented with fever, mild renal impairment

https://teamhaem.com Hemolytic markers are elevated

This is…. % A. Drug induced hemolysis B. Disseminated intravascular C. Thrombotic thrombocytopenia purpura D. Autoimmune hemolytic anemia Answer: C

Key features of TTP:

MAHA features: • RBC fragments especially schistocytes • Anemia in TTP usually not severe (6-8) • Direct coombs tests negative Consumptive thrombocytopenia

A medical emergency – by the time the full “pentad” is present, it’s too late!

Microangiopathic hemolytic anemia + thrombocytopenia = TTP until proven otherwise

Requires urgent plasma exchange Question 8:

40 yr old lady, pre-op assessment for elective cholecystectomy

Hb 13.0 normocytic normochromic TW 5.0 x109/L, differential normal Plt 50 x109/L

What is your next step of action? A. Review medication list B. Work up for acute thrombocytopenia C. Repeat FBC stat D. Send blood for platelet count in citrate tube

Answer: D

Always rule out Pathophysiology of platelet clumping: pseudothrombocytopenia! • In vitro agglutination of platelets

• Occurs in ~0.1% of normal individuals Especially if there is no clear reason for the patient to be thrombocytopenic. Usually platelet • Platelet surface GPIIb/IIIa epitopes clumping is reported under “FBC Comments” exposed by EDTA-induced conformational changes

• “Naturally-occurring” autoAb directed against a concealed epitope on GPIIb/IIIa binds and causes platelet agglutination

• Can be resolved by checking platelet count using citrate (20% also clump with citrate) or heparin tube

Questions?

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