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7/30/2019 Hematology - Blood Films
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Hematology
FBC
Hb 13-15
WBC 4-10
Platelets 150-400 MCV 85-95
Case 2
60yo female: Hb 7.2, WBC 12, Platelets 470, MCV 71
What are the causes of hypochromic, microcytic red cells?
- Iron deficiency 98%
- Thalassemia intermedia coz of age
- Lead poisoning, sideroblastic anemia, anemia of chronic dz (rare)
Blood film
- pale centre in the middle- Pale area should not exceed >1/3 area of RBC
Causes of Fe deficiency(a) Females
Young – menorrhagia
GI bleed
Tests used for Ix of Fe deficiency
- Colonoscopy + OGD to find blding source esp in post menopausal
- don’t waste time on fobt
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low MCV, MCH w anemia
Case: Thalassemia
PBF: poikilocytosis and anisocytosis , target cell circle w dot in middle
Tests used for Ix of Thal Intermedia
- Thalassemia screen - electrophoresis- Fe panel (to ensure GI pathology not missed out) check serum ferritin lvls. should be
high in thalassemia
60yo female, pale and jaundiced: Hb 5.0, WBC 12, platelets 480, MCV 99
MCV and MCH raised
DDx: haemolytic anemia, liver pathology
MCV and MCH raised bcoz of reticulocytes, larger cell size
Haemolytic anemia bcoz of jaundice n significant anemia
PBF: loss of central pallor (spherocytes) no longer biconcave
Spherocytes indicate loss of membrane (reduced diameter, decreased surface areabut normal volume)
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Spherocytosis
- Hereditary (1%) coombs test negative, born with spherocytes
- Acquired (99%)
Develop antibodies against the RBC membrane (autoimmune haemolytic anemia)
What are the necessary lab tests: direct coombs test! dist acquired fm non acquired Positive direct Coomb’s test for acquired form
Coomb’s test looks for antibodies – direct looks for presence of antibodies onsurface of RBCs; indirect looks for freely floating antibodies in patient’s
plasma
E.g. direct coomb’s test of baby’s blood, indirect of mother’s blood
Causes of acquired autoimmune haemolytic anemia
Infective Mycoplasma
Inflammatory SLE
Sjogren’s disease
Neoplastic Lymphoma
leukemia
Drugs PENICILLIN
Methyldopa
Mefenamic acid
Idiopathic (50%)
AIHA is most often caused in great part due to the inability of corrupted IgM
produced by CLL cells to control the IgG produced by normal B-cells. IgG can and
does attack "self antigens", if it is not controlled by proper functioning of IgM.
One way of handling this is to use intravenous injections of Ig obtained from healthy
blood donors, which contain the good and effective variety of Ig. Viral or bacterial infections that cause danger signals to be sent out can get the
immune system go into over-drive. Lactate dehydrogenase is one of these danger
signals, and any viral infection that causes increase in LDH will activate
macrophages, which may exacerbate AIHA
AIHA treatment
A tried-and-true approach to treating AIHA is corticosteroid drugs such as
prednisone. These drugs control AIHA by immune suppression, reducing the level of
inflammation, reducing the level of T-cell and macrophage activation. But steroiddrugs by their very nature also expose patients to increased risk of infections and even
secondary cancers.
Since the bulk of the red blood cells are killed by activated macrophages from the
spleen, one drastic way of controlling AIHA is to remove the spleen surgically. Or,
one can look to recent studies where low-toxicity liposomal drugs such as clodronate
have been effective in targeting splenic macrophages (in mice studies).
the viral or bacterial infection may well do the job of reducing the LDH, reduce
macrophage activation, reduce the killing of red blood cells.
case 5; Chronic haemolytic anaemia: Hereditary spherocytosis
Epidemiology
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Most common cause of hereditary haemolytic anaemia in people of Northern Europeanheritage
Rare locally Pathogenesis
AD inheritance in 75% Affects membrane protein spectrin RBC loses part of membrane as it passes through the spleen spherocytes (SA:V ratio)
Clinical Features Asymptomatic Cardinal features of
o Anaemia (mild: 9-11g/dL)o Jaundiceo Splenomegaly (mild to moderate)
Aplastic crisiso Clinical course may be punctuated by aplastic crises: transient cessation of RBC
productiono Triggered by parvovirus infectionso Because of the shortened lifespan of the RBCs, even a short period of failure of
erythropoiesis results in rapid worsening of anaemiao Self-limited in most caseso May require blood transfusions
Gallstone disease
Investigations FBC: anaemia PBF: spherocytes Pseudohyperkalaemia: K
+leakage as blood is cooled
osmotic fragility
Management No treatment available
When they present, we need to prevent complications of haemoglobinuria by hydratingpatient and encouraging diuresis.
Give folate supplements. Cholecystectomy may be needed in patients with gallstone disease. If patient requires cholecystectomy, perform splenectomy at same sitting for convenience. Splenectomy is beneficial because the major site of destruction is removed.
Administer vaccination against meningococcus, pneumococcus and Hib and possible
case 6 post Splenectomy changes
PBF:
- Cell membrane abnormalities- target cells seen morphology on film
- Howell-jolly bodies (purplish blue inclusion seen in RBC)
Remnants of DNA in circular erythrocytes
- Basophilic stippling (RNA)
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basophilic stripping
HJ body
Causes
- Surgical splenectomy
- Splenic atrophy
Sickle cell disease (autosplenectomy)
IBD (celiac disease, ulcerative colitis) – can p/w hyposplenism
Case
60yo female with SOB, diarrhea: Hb 3, WBC 3.2, platelets 70, MCV 110
DDx for pancytopenia and raised MCV
- Bone marrow failure e.g. primary (aplastic anemia, myelodysplastic syndrome),
secondary: replaced by malignant cells (leukemia)
- SLE and other autoimmune dz. Abx against BM cells
- Hypersplenism fm liver dz
- Vit B12/folate deficiency
Vit B12 is normally involved in the metabolism of every cell of the human body,
especially affecting DNA synthesis and regulation, but also fatty acid synthesis
and energy production. cells cant divide hence larger
PBF of megaloblastic anemia- Hypersegmented neutrophils. oval n huge rbc
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More often seen in renal failure hence it’s a d/d
B12 def in vegan. folate def in those who nvr eat veg
more impt in those w gastrectomy ( parietal cells that produces IF removed) or ileum ( IC of
absorption of b12) removed!
Malaria PBF
- Vivax usu BENIGN: ring forms (early trophozoites), amoeboid forms (growing
trophozoites, diving forms (schizonts), gametocytes all types of cells seen
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- Falciparum: ring forms (early trophozoites), gametocytes
Determine severity of parasitemia
- 20% medical emergency
- 40% fatal
Determine resistance to medication
complications
Manifestation Features
Initial World Health Organization criteria from 1990 [3]
1. Cerebral malaria: Unarousable coma not attributable to any other cause, with a
Glasgow Coma Scale score ≤9; Coma should persist for at least 30min after a generalized convulsion
2. Severe anemia Hematocrit <15% or hemoglobin < 50 g/l in the presence of parasite count >10000/µl
3. Renal failure Urine output <400 ml/24 hours in adults (<12 ml/kg/24 hours inchildren) and a serum creatinine >265 µmol/l (> 3.0 mg/dl)
despite adequate volume repletion
4. Metabolic (Lactic)
Acidosis/acidosis Metabolic acidosis is defined by an arterial blood pH of <7.35 with
a plasma bicarbonate concentration of <22 mmol/L;hyperlactatemia is defined as a plasma lactate concentration of 2-5 mmol/L and lactic acidosis is characterized by a pH <7.25 and a
plasma lactate >5 mmol/L. 5. Pulmonary edemaor acute respiratorydistress syndrome(ARDS)
Breathlessness, bilateral crackles, and other features of pulmonaryoedema. The acute lung injury score is calculated on the basis of radiographic densities, severity of hypoxemia, and positive end-expiratory pressure
6. Hypoglycemia Whole blood glucose concentration of less than 2.2 mmol/l (less
than 40 mg/dl).
7. Hypotension andshock (algid malaria)
Systolic blood pressure <50 mmHg in children 1-5 years or <70mm Hg in patients ≥5 years; cold and clammy skin or a core -skin
temperature difference >100C
8. Abnormal bleeding
and/or disseminatedintavascular
Spontaneous bleeding from the gums, nose, gastrointestinal tract,
retinal haemorrhages and/or laboratory evidence of disseminatedintravascular coagulation.
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coagulation
9. Repeated
generalisedconvulsions
≥3 generalized seizures within 24 hours
10. Haemoglobinuria Macroscopic black, brown or red urine; not associated with effects
of oxidant drugs or enzyme defects (like G6PD deficiency) Added World Health Organization criteria from 2000 [4]
11. Impairedconsciousness
Various levels of impairment may indicate severe infectionalthough not falling into the definition of cerebral malaria. Thesepatients are generally arousable
12. Prostration Extreme weakness, needs support
13. Hyperparasitemia 5% parasitized erythrocytes or > 250 000 parasites/µl (in
nonimmune individuals)
14. Hyperpyrexia Core body temperature above 400C
15. Jaundice
(Hyperbilirubinemia)
Serum bilirubin of more than 43m mol/l (2.5 mg/dl).
Other
16. Fluid andelectrolyte
disturbances [5]
Dehydration, postural hypotension, clinical evidence of hypovolemia
17. Vomiting of oraldrugs
Patients with persistent vomiting may have to be admitted forparenteral therapy.
18. Complicating orassociated infections
Aspiration bronchopneumonia, septicemia, urinary tract infectionetc.
19. Other indicatorsof poor prognosis [5]
Leukocyte count >12,000/cumm; high CSF lactate (>6mmol/l)and low CSF glucose; more than 3-fold elevation of serum
enzymes (aminotransferases); increased plasma 5'-nucleotidase;low antithrombin III levels; peripheral schizontemia;
papilloedema/retinal oedema
20. MalarialRetinopathy
A large, prospective autopsy study of children dying with cerebralmalaria in Malawi found malarial retinopathy to be a betterindicator of malarial coma. Similar retinopathy in an adult has alsobeen reported.
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Leukemia
- Acute: short hx, higher % of blast cells
If the cells do not mature past the blast stage
Early cells – nucleus takes up whole cell. nucleus size decreases as it matures.
To differentiate AML vs ALL – flow cytometry
Use antibodies against myeloid and lymphoid antigens, see which is taken up
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- Chronic: longer hx
myeloproliferative ( abnormal quantity) vs myelodysplastic dz ( abnormal quality/
morphology hence undergoes apoptosis)
ALL most common in childn
ALL is most common in childhood with a peak incidence at 2 – 5 years of age, and another
peak in old age.
See that compared to AML – there is RAISED WBC level bcoz lymphocytes = wbc form
The FAB classification
Subtyping of the various forms of ALL used to be done according to the French-American-
British (FAB) classification,[18]
which was used for all acute leukemias (including acutemyelogenous leukemia, AML).
ALL-L1: small uniform cells
ALL-L2: large varied cells
ALL-L3: large varied cells with vacuoles (bubble-like features)
Each subtype is then further classified by determining the surface markers of the abnormal
lymphocytes, called immunophenotyping. There are 2 main immunologic types: pre-B cell
and pre-T cell. The mature B-cell ALL (L3) is now classified as Burkitt's
lymphoma / leukemia. Subtyping helps determine the prognosis and most appropriate
treatment in treating ALL.
Case
Hb 21 10 15 9
WBC 17 240 18 17
Platelets 500 500 1800 680
Cause Polycythemia CML Essential
thrombocytosis
Thrombocytes –
platelets
Myelofibrosis
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Essential –
primary and not
due to causes ie
surgery
60yo female headache, CVA: Hb 21, WBC 17, Platelet 600 Myeloproliferative disease, predominantly high Hb (polycythemia)
Ix
- O2 saturation
- Erythropoietin levels
- Jak2
mx- hydrate
- venesection
- aspirin cox worried about stroke
- myelosupprsssion
Hb 10, WBC 240, platelets 600
Check Differential count – increased nos of most mature cells and blasts hence chronic
CML- increased and unregulated growth of predominantly myeloid cells in the bone marrow
and the accumulation of these cells in the blood. CML is a clonal bone marrow stem
cell disorder in which proliferation of mature granulocytes (neutrophils, eosinophils
and basophils) and their precursors is the main finding.
- a/w characteristic chromosomal translocation (Philadelphia chromosome)
60yo female TIA: Hb 15, WBC 18, platelet 1800 MPD - Essential thrombocytosis
- Vs reactive thrombocytosis or secondary form; here, essentially a bone marrow
problem
- Overproduction of platelets by megakaryocytes in the bone marrow in the absence of
an alternative cause
- Platelets derived from the abnormal megakaryocytes do not function properly, which
contributes to the clinical features of bleeding and thrombosis
Physical signs: TIA, stroke related stuff, decreased cerebral bld flow, ischemia
symptoms : erythromelalgia - a rare neurovascular peripheral pain disorder in which
blood vessels, usually in the lower extremities (or hands), are episodically blocked(frequently on and off daily), then become hyperemic and inflamed. There is severe
burning pain (in the small fiber sensory nerves) and skin redness. The attacks are
periodic and are commonly triggered by heat, pressure, mild activity, exertion,
insomnia or stress. Erythromelalgia may occur either as a primary or secondary
disorder (i.e. a disorder in and of itself or a symptom of another condition). Secondary
erythromelalgia can result from small fiber peripheral neuropathy of any cause,
essential thrombocytosis, hypercholesterolemia, mushroom or mercury poisoning, and
some autoimmune disorders
60yo female splenomegaly: Hb 9, WBC 6.8, platelet 364
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MPD - Myelofibrosis Myelofibrosis (MF) is a chronic bone marrow disorder in which excessive scar
tissue forms in the bone marrow and impairs its ability to produce normal blood cells. MF is thought to becaused by abnormal blood stem cells in the bone marrow. The abnormal stem cells produce more maturecells that grow quickly and take over the bone marrow, causing both fibrosis (scar tissue formation) andchronic inflammation. As a result, the bone marrow becomes less able to create normal blood cells andblood cell production may move to the spleen, causing enlargement, or to other areas of the body.
- Production of cytokines which causes fibrosis of marrow- Proliferation of an abnormal type of bone marrow stem cell results in fibrosis, or
replacement of the marrow with collagenous connective tissue fibers
PBF: tear-drop cells
Case:
60yo female, backache: Hb 9, WBC 7, platelets 150, MCV 99
Bone scan normal (looks for osteoblast activity; MM has increased osteoclast activity)
PBF:
- Rouleaux formation of RBCs – due to clumping together like stack of coins
Occur when the plasma protein (globulins) concentration is high
positively charged proteins link negatively charged rbc tgt The presence of acute phase proteins, particularly fibrinogen, interacts with sialic
acid on the surface of RBC and allows the formation of rouleau. Anemia, by
altering the ratio of RBC to plasma, increases rouleaux formation and accelerates
sedimentation. Rouleaux formation is retarded by albumin proteins.
Causes an increased ESR
Causes:
Infx, multiple myeloma, inflammatory and connective tissue disorders,
cancers
to diff cause - Check protein electrophoresis
Polyclonal band – many types of proteins – inflammation/ chronic
infx/autoimmune disease . maybe TB
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Monoclonal pattern (all from 1 type, 1 malignant cell producing protein) –
multiple myeloma
Check bone marrow for evidence of multiple myeloma – many plasma
cells (basophilic – stained v blue bcoz of RNA, eccentric- peripheral and
round nucleus)
plasma cells produce a lot of proteins, RNA, ribosome hence v blue
Multiple myeloma
- Cancer of plasma cells (WBC responsible for pdtion of antibodies). Collections of abn
cells accumulation in bones where they cause bone lesions (abnormal areas of tissue),
and in the bone marrow where they interfere with the production of normal blood cells.
- Most cases of myeloma also feature the production of a paraprotein, an abnormal
antibody that can cause kidney problems and interferes with the production of normal
antibodies leading to immunodeficiency. Hypercalcemia (high calcium levels) is often
encountered.
DIFFERENTIALS for Very HUGE SPLEEN
myelofibrosis which is essentially a myeloproliferative dz. fibrosis in marrow due to
cytokine production
CML
lymphoma
hypersplenism
Elliptocytes, also known as ovalocytes are abnormally shaped red blood cells that appear
oval or elongated.
These abnormal red blood cells are seen in blood films of patients with:
Hereditary elliptocytosis
Thalassemia
Iron deficiency
Myelophthisic anemias
Megaloblastic anemias