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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) Mean corpuscular volume (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) Hematocrit • The % of whole blood occupied by RBC (MCVxRBC)
8) Immature RBCs • Reticulocytes 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- Platelet indices
1) Platelet count • Number of platelets in a volume of blood
2) Mean platelet volume • The average size of platelets in a volume of
blood
The peripheral blood film – 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 thrombocytopenia in 2nd and 3rd trimester of pregnancy • Thrombocytosis can occur with increased physical activity and stress
General causes of anemia and polycythemia Anemia • Nutritional deficiencies (iron, folate, B12)
• Bone marrow damage eg infection, drugs
• Bone marrow disorders eg hemato malignancies, aplastic anemia
• Chronic inflammation and CKD
• Pure red cell aplasia
• Acute or chronic blood loss
• RBC destruction eg hemolytic anemias
Polycythemia • Polycythemia vera
• Secondary polycythemia eg chronic hypoxic conditions, smoking
• Paraneoplastic Epo production
• Dehydration
Another way to classify anemia: RBC size Macrocytic DNA synthesis defects
• Megaloblastic anemia (vit B12/Folate deficiency)
• Myelodysplastic syndrome
• Chemotherapy
RBC membrane defects
• Hypothyroidism
• Liver disease
• Reticulocytosis
Normocytic • Acute blood loss
• Anemia of inflammation
• Anemia of chronic renal disease
• Bone marrow failure
• Bone marrow infiltration
• Dual pathologies
• Early stages of anemia
Microcytic • Iron deficiency
Inability to utilize iron
• Thalassemia
• Anemia of inflammation
• Sideroblastic anemia
Photos from www.slide-share.net
+ Retic response
lack retic response
RDW ↑
RDW ↑
if trait; RDW normal
RDW ↑
RDW ↑
Some common RBC abnormalities
General causes of leukopenia and leukocytosis
Leukopenia • Nutritional deficiencies (Fol/B12)
• Drugs, radiotherapy
• Infections esp viral, also severe sepsis
• Infiltration eg hemato malignancies or metastatic cancers
• Autoimmune destruction
Leukocytosis • Neutrophils: bacterial infection
• Lymphocytes: viral infections, chronic infections eg TB, pertussis
• Atypical lymphocytes: viral infections, lymphoma
• Monocytes: chronic infections eg TB, 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 • Pseudothrombocytopenia
• Vitamin deficiencies (folate B12)
• Bone marrow suppression eg drugs, alcohol, viral, Gram negative sepsis
• Primary bone marrow disorders eg MDS, aplastic anemia
• ITP (primary and secondary)
• Non-immune destruction eg TTP, HUS, DIC
• Splenic sequestration
• Pregnancy-associated syndromes
Thrombocytosis • Reactive states – inflammation, infection
• Iron deficiency
• Hemato malignancies eg myeloproliferative neoplasms
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
Ferritin 1.6 ug/L
Pencil cell
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
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)
RDW 13.2 (10.9-15.7%) This is…. 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 RBCs may have basophilic stippling
Vs.
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
Key features of AIHA: Raised hemolytic markers, DCT+ Can occur with ITP (Evan’s syndrome) Microspherocytes Good reticulocyte response / nRBC suggest peripheral destruction So… why was the MCV raised?
microspherocyte
Polychromatic cells ie reticulocytes
Nucleated RBC
LDH 1461 U/L Total Bil 37 umol/L Direct bil 9 umol/L Haptoglobin <0.10 g/L DCT positive – IgG 4+, C3d 1+ Warm auto-Ab identified
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
This is…. A. Lymphoma B. Infectious mononucleosis C. T-large granular leukaemia D. Acute leukaemia
https://oncohemakey.com
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) Lymp 31.3% 8.8 (1.0 – 3.0 x106/L) Mono 3.6% 1.0 (0.2-0.8 x106/L) Eos 0.7% 0.2 (0.0 – 0.4 x106/L) Bas 1.3% 0.4 (0.0 – 0.1 x106/L) 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! • Blood film is crucial
• 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
Normal lymphocyte
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/fibrinogen)
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
Hemolytic markers are elevated This is…. A. Drug induced hemolysis B. Disseminated intravascular coagulation C. Thrombotic thrombocytopenia purpura D. Autoimmune hemolytic anemia
https://teamhaem.com
%
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 pseudothrombocytopenia! Especially if there is no clear reason for the patient to be thrombocytopenic. Usually platelet clumping is reported under “FBC Comments”
Pathophysiology of platelet clumping:
• In vitro agglutination of platelets
• Occurs in ~0.1% of normal individuals
• Platelet surface GPIIb/IIIa epitopes 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
