HAEMATOLOGY OF CHRONIC DISORDERS (1) copy.pptx

HAEMATOLOGY OF CHRONIC DISORDERS
GROUP 1

Group Members
● Akagha Akunna Angelica
● Akinsanya Oyinkansola Christine
● Akogwu Mercy Igbe
● Alomooluwa Oluwamayowa Hephzibah
● Aregbesola Diekolayomi Sarah
● Azubuike Victory Onyebuchi
● Dike-Israel Vanessa Chinonyelum
● Ebiowe Samuel Miracle
● Enaohwo Evelyn Ogheneruona
● Idowu Moyinoluwa Joan
● Ifeanyichukwu Ogeoma Chidinma
● Musa Tekomi Testimony
● Nwa Edidiong Hanson
● Nwajei Christopher-Lawrence Chidera
● Nwogoh Martin Ikechukwu
● Okafor Obinna Kingsley
● Okereke Princess Deborah
● Okorie Adaeze Alexandria
● Olatunji Jochebed Oluwaferanmi
● Onugha Jessica Chiamaka
● Oseni Oluwabusayo Esther
● Otis-Ehiemuan Osemudiamen Anthony
● Owolabi Hamida Adedolapo
● Oyelakin Oluwatosin Olaoluwa
● Oyewolu Oluwademilade Opemipo

Congestive Heart Failure
● A syndrome that can be caused by a variety of abnormalities,
including pressure and volume overload, loss of muscle, primary
muscle disease or excessive peripheral demands such as high output
failure in both ventricles.
● The current worldwide prevalence of CHF is 63.34 million cases
according to the Global Health Data Exchange registry.
● The registry also notes a predilection for race with a 25% higher
prevalence of HF in patients of African-American descent than
Caucasians.

Aetiology
1. Coronary artery disease
2. Myocardial infarction.
3. Diabetes mellitus
4. Hypertension
5. Valvular heart disease
6. Uncontrolled arrhythmias

Pathophysiology
● Several compensatory mechanisms kick in to
maintain CO and meet systemic demand.
● These mechanisms may restore CO to near-normal.
● Their excessive response over the long-term
become deleterious and cause worsening heart
failure!

Haematological findings
There is anemia is present in 30–50%
of patients with CHF which is
secondary to chronic kidney disease,
diabetes and release of cytokines
increasing hepcidin synthesis
(reducing iron absorption and
recycling of iron from macrophages)
and reducing erythropoietin
secretion.
Peripheral blood film slide from a patient with CHF 20 to
CKD

Treatment
Oral or intravenous iron may improve left ventricular ejection
fraction, lower CRP and brain natriutetic peptide (BNP) levels,
reduce fatigue, and increase exercise capacity and quality of
life, even in those without iron deficiency.

Crohn’s Disease
● Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal
tract characterized by local deposition of histiocytes and the development
of non-caseating granulomas
● Crohn’s disease is more common North America and Europe, where it
20-30% of all diagnoses are made before age 20 years- however, a greater
proportion its diagnoses have been made in the older population.
● It has little incidence among Africans

Pathophysiology
● It is implicated by the chronic inflammation from T-cell
activation leading to tissue injury.
● There is then an unrestrained response of type 1 helper cells
after activation by an antigen, stimulating the inflammatory
response and resulting in direct injury to the intestine.
● Extensive inflammation may result in hypertrophy of the
muscularis mucosae, fibrosis, and stricture formation,
which can lead to bowel obstruction.

● Thrombocytosis and anaemia, resulting from functional or absolute iron
deficiency, are common secondary changes in the disease.
● There could be an increased platelet function, fibrinolytic abnormalities,
hypercoagulation, recognised to be caused by inflammation, may lead to
thromboembolic events.
● Reduced FXIII (Fibrin-stabilizing factors) levels have been observed in Crohn’s
disease.

Peripheral blood film slide showing microcytic anaemia, a complication
of Crohn’s disease

Management
● Iron supplementation as soon as a patient is found to have iron
deficiency anaemia and in the form of oral iron, parenteral iron, or
erythropoietin.
● Aspirin when platelet counts exceed 1,000,000/μL
● Fresh frozen plasma or cryoprecipitate to treat bleeding
● Pain relief

Renal failure
● Renal failure or chronic renal failure of chronic kidney disease is the
inability of the kidneys to perform excretory function leading to
retention of nitrogenous waste products from the blood.
● CKD is a progressive condition that affects >10% of the general
population worldwide, amounting to >800 million individuals.
● It is more prevalent in older individuals, women, racial minorities,
and in people experiencing diabetes mellitus and hypertension.

Aetiology
● Diabetes
● Hypertension
● Polycystic kidney disease
● Glomerular disease

● Anemia is a common finding in CKD. It is majorly due to insufficient
erythropoietin. Anaemia could also result from chronic blood loss,
hemolysis and bone marrow suppression by retained uremic factors.
● Reduced Hb levels
● Reduced platelet count
● Prolonged bleeding
● Increased WBC count

Management
Investigations
● Urinalysis
● Dipstick for blood and protein;
● Microscopy for cells, casts, and crystals
● Renal ultrasound sonography (USS)
● Radionucleotide renal scan, CT scan,
and/or MRI
● Kidney biopsy
Treatment
Dependent on the cause of failure.
Treatment is made by replacing renal
function through:
● Dialysis
● Kidney transplant

Systemic Lupus Erythematosus
● Systemic lupus erythematosus is a systemic autoimmune disease with
a worldwide distribution.
● Although both men and women of all age groups can be affected,
women outnumber men almost 10-fold and the typical lupus patient is
a young woman during her reproductive years.

Pathophysiology
SLE occurs through the production of
auto-antibodies that attacks a person’s
own cells thus contributing to the
inflammation of various parts of the body,
and may cause damage to organs and
tissues.

Haematological Findings
Haematological abnormalities in SLE can be caused by its pathophysiology
or can be due to certain treatment options like immunosuppressive therapy.
● Anaemia resulting from renal impairment, drug-induced GI blood loss, or
autoimmune haemolysis (typically with IgG and the C3 component of
complement on the surface of the RBC).
● Leukopenia with reduced neutrophil and lymphocyte counts.
● Arterial and venous thrombosis.

Management
Investigations
● Erythrocyte sedimentation rate
● Blood counts and differential blood
counts
● Urinalysis
● Antinuclear antibodies (ANA) (Hep-2
cell test with fluorescence pattern)
Treatment
● Topical glucocorticoids for skin lesions
● Antimalarials unless there are
contraindications.
● Immunosuppression
● Adjunct treatment which is determined by
the comorbidities such as infections,
HTN, arteriosclerosis, diabetes,
osteoporosis

Rheumatoid Arthritis
● Rheumatoid arthritis is a chronic inflammatory disease that results in
joint destruction.
● It is characterised by severe pain, swelling, stiffness and loss of
function of the joint. Its hallmark feature is polyarthritis (synovitis)
affecting the hands and feet.
● The precise cause is not known but genetics, hormones, and
environment are contributing factors.
● RA has a population prevalence of 0.5-1% annually depending on
gender, race and calendar year.

Pathophysiology
● RA is an autoimmune disease characterised by dysregulation of the
immune system resulting in chronic activation of T-cell responses
and overproduction of proinflammatory cytokines (TNF and IL-1).
● The synovium becomes infiltrated with lymphocytes especially
helper T cells, plasma cells, and macrophages.
● Inflammatory granulation tissue (pannus) spreads over and under the
articular cartilage which is irreversibly eroded and destroyed.

● Mild anaemia characterised by low concentration of serum iron and
low serum iron binding capacity.
● Chronic anaemia in true iron deficiency secondary to gastrointestinal
blood loss from those treated with NSAIDs
● White blood cells may be within normal range - slightly elevated or
markedly elevated due to left-shift.

Peripheral blood film showing rheumatoid arthritis

Management
Investigations
● C-reactive protein level
● Rheumatoid factor assay
● Antinuclear antibody assay
● Anti-cyclic citrullinated peptide
and anti-mutated citrullinated
vimentin assays
● Radiography of the joints
● MRI scans or primarily the
cervical spine.
● Ultrasonography of joints, tendon
sheaths.
● Joint aspiration and analysis of
synovial fluid may be considered.

Treatment
Non-pharmacological
● Exercise
● Diet
● Massage
● Counselling
● Stress reduction
● Physical therapy
● Surgery
Pharmacological
● NSAIDs
● Immunosuppressants
● Non-biologic and biologic
disease-modifying antirheumatic
drugs (DMARDs)

Asthma
● Asthma is a major noncommunicable disease (NCD), affecting both
children and adults, and is the most common chronic disease
among children.
● Inflammation and narrowing of the small airways in the lungs
cause asthma symptoms, which can be any combination of cough,
wheeze, shortness of breath and chest tightness.
● Asthma affected an estimated 262 million people in 2019 (1) and
caused 455 000 deaths.

Pathophysiology
In the pathophysiology of Asthma, Airflow limitation in asthma is recurrent and caused by a
variety of changes in the airway. These include:
● Bronchoconstriction.: In asthma, the dominant physiological event leading to clinical
symptoms is airway narrowing and a subsequent interference with airflow. In acute
exacerbations of asthma, bronchoconstriction occurs quickly to narrow the airways in response
to exposure to a variety of stimuli including allergens or irritants. Allergen-induced acute
bronchoconstriction results from an IgE-dependent release of mediators from mast cells that
includes histamine, tryptase, leukotrienes, and prostaglandins that directly contract airway
smooth muscle.
● Airway oedema: As the disease becomes more persistent and inflammation more progressive,
other factors further limit airflow. These include oedema, inflammation, mucus hypersecretion
and the formation of inspissated mucus plugs, as well as structural changes including
hypertrophy and hyperplasia of the airway smooth muscle.

Pathophysiology continued
● Airway hyperresponsiveness: Airway hyperresponsiveness—an exaggerated
bronchoconstrictor response to a wide variety of stimuli—is a major, but not
necessarily unique, feature of asthma. The degree to which airway
hyperresponsiveness can be defined by contractile responses to challenges with
methacholine correlates with the clinical severity of asthma.
● Airway remodelling. Airway remodelling involves an activation of many of the
structural cells, with consequent permanent changes in the airway that increase
airflow obstruction and airway responsiveness and render the patient less responsive
to therapy. These structural changes can include thickening of the sub-basement
membrane, subepithelial fibrosis, airway smooth muscle hypertrophy and hyperplasia,
blood vessel proliferation and dilation, and mucous gland hyperplasia and
hypersecretion.

Common hematological abnormalities encountered during
asthma include:
● Increased eosinophil count (Eosinophilia)
● Increased neutrophil count (Neutrophilia)
● Leukocytosis
● Increased erythrocyte sedimentation rate

Management
Management of persistent asthma requires:
● Avoidance of aggravating environmental factors
● Use of short-acting β2-agonists for rapid relief of symptoms
● Daily use of inhaled corticosteroids.
● Other controller medications, such as long-acting bronchodilators
and biologics, may be required in moderate and severe asthma.
● Patients with severe asthma generally benefit from consultation
with an asthma specialist for consideration of additional treatment,
including injectable biologic agents.

Chronic anaemia
● Anaemia is a condition in which the blood doesn’t have enough
healthy red blood cells.
● Chronic anaemia or anaemia of chronic diseases occurs when an
autoimmune disease or other illness lasts longer than 3 months and
causes inflammation as well.
● This pathology affects the body’s ability to use iron needed to make
enough RBCs.
● Chronic anaemia is the second most common form of anaemia
worldwide.

Pathophysiology
The pathophysiology of ACD is related to a reduction in the release of
iron from the macrophages to the plasma because of raised serum
hepcidin levels, reduced red blood cell span and inadequate
erythropoietin response to the anaemia caused by the effects of
cytokines such as IL-1 and TNF on erythropoietin.

● Normochromic, normocytic or mildly hypertonic (MCV rarely
<75Fl)
● Both serum iron and total iron-binding capacity are reduced.
● Serum ferritin is normal or raised.
● Bone marrow storage of iron is normal but erythroblast iron is
reduced

Peripheral blood film showing ACD- basophilic stippling

Management
Investigations
● Bone marrow biopsy to test for
iron stores and serum iron levels
● Complete blood count
● Reticulocyte count
● C-reactive protein
Treatment
● Successful treatment of
underlying disease
● Erythropoietin injections improve
the anaemia.
● Do not administer iron!

Haemophilia
● Haemophilia is an inherited bleeding disorder characterized by the
inability of the blood to clot properly. There are three types of
haemophilia: Haemophilia A, B and C.
● Haemophilia A: is a recessive X-linked genetic disorder involving a
lack of clotting factor VIII. It is the most common type of
haemophilia, representing about 80% of all haemophilia cases.
● Haemophilia B: is a recessive X-linked disorder involving a lack of
clotting factor IX. Represent about 20% of all haemophilia cases.
● Haemophilia C: is an autosomal disorder involving a lack of clotting
factor XI. It is the rarest form of haemophilia.

Epidemiology
● Haemophilia A affects about 1 in 5,000-10,000.
● Haemophilia B affects about 1 in 40,000 males.
● Haemophilia C affects about 1 in 100,000 and is common in
Ashkenazi and Iraqi jews.
● In Nigeria, there is an estimated 9,000-12,000 people living with
haemophilia according to World federation of Haemophilia (WFH).
● Haemophilia is more common in males than in females because the
affected genes are located on the X chromosome. Females are
usually carriers, but can be affected in rare cases where both X
chromosomes are affected.

Pathophysiology
● Haemophilia is caused by a mutation or change in one of the genes
that provides instructions for synthesis of the clotting factor proteins
needed to form a blood clot.
● These genes are located on the X chromosome.
● This change or mutation can cause abnormal or deficient function of
the clotting proteins or an overall deficiency of the clotting proteins
themselves.

Pathophysiology continued
● In haemophilia A, the factor VIII gene is affected, in haemophilia B,
there is a decrease in the clotting activity of factor IX, while in
haemophilia C, the factor XI gene is affected.
● When any of these factors are deficient of dysfunctional, the
intrinsic pathway of the coagulation cascade cannot be appropriately
activated, thus making the process of clot formation deficient,
resulting in prolonged bleeding.

Clinical Manifestations
● Unexplained or excessive haemorrhage from injuries.
● Cephalohematomas in new-borns during delivery.
● Haematuria and bloody stool.
● Hemarthrosis
● Excessive formation of subcutaneous hematomas.
● Muscle haemorrhages and hematomas
● Idiopathic epistaxis
● Prolonged haemorrhage after surgical or dental procedures.
● Prolonged post circumcision haemorrhage.

HAEMOPHILI
AS
CLOTTING FACTORS BLEEDING
TIME
PROTHRO
MBIN
TIME
APTT FIBRINOG
EN
PLATELE
T COUNT
FACTOR
VIII
FACTO
R IX
FACTOR
XI
A Low Normal Normal Normal Normal Prolonged Normal Normal
B Normal Low Normal Normal Normal Prolonged Normal Normal
C Normal Normal Low Normal Normal Prolonged Normal Normal

Management
Investigations
● Full/Complete Blood Count
(including platelet count)
● Activated Partial Prothrombin Time
● Bleeding time
● Prothrombin time
● Fibrinogen test
Coagulation Factor Assays
● Factor VIII: Low in A but normal in B
and C.
● Factor IX: Low in B but normal in A
and C.
● Factor XI: Low in C but normal in A
and B.
Treatment
The main treatment for severe haemophilia
involves replacing the clotting factors needed
via IV infusion of donated blood or free
recombinant clotting factors. Other treatments
include:
● Desmopressin
● Antifibrinolytic drugs
● Fibrin sealants
● Emicizumab (Hemlibra)
● Clot-preserving medications
● Physical therapy
● First aid for minor cuts and bruises

Chronic lymphocytic leukaemia
● Chronic lymphoid leukemias include several disorders characterized
by accumulation of mature lymphocytes, of either B cell or T cell
type, in the blood.
● Of all the chronic lymphoid leukemias chronic lymphocytic
leukemia is the most common with its peak incidence being between
60-80 years of age. It is a chronic lymphoproliferative disorder
characterized by monoclonal B cell proliferation.
● Aetiology has been traced to genetic predisposition.

Pathophysiology
● The CLL tumor cell is a mature B cell with weak surface expression
of immunoglobulin (IgM or IgD). CLL cells typically exhibit
impaired apoptosis and a prolonged lifespan, and this is reflected in
their accumulation in the blood, bone marrow, liver, spleen and
lymph nodes.

● Lymphocytosis
● Normochromic normocytic anaemia in later stages as a result of
marrow infiltration or hypersplenism.
● Autoimmune haemolysis may occur.
● Thrombocytopenia
● Bone marrow aspiration shows up to 95% lymphocytic replacement of
normal marrow elements. Trephine biopsy reveals nodular, diffuse or
interstitial involvement by lymphocytes.
● Reduced serum immunoglobulin

Trephine biopsy showing nodular pattern of lymphocyte accumulation (left)
Trephine biopsy showing diffuse increase in marrow lymphocytes- closely packed
cells with small nuclei (right)

Management
Investigations
● Complete blood count: to elicit
lymphocytosis
● Bone marrow biopsy: to elicit
malignancies
● Lymph node biopsy
● Genetic testing: to elicit
abnormal genes
Treatment
● Chemotherapy
● Targeted therapy:
● Radiotherapy
● Immunotherapy:
immunomodulating agents, car-t
cell therapy
● Stem cell transplantation

Chronic Myeloid Leukaemia
● This is a clonal disorder of a pluripotent stem cell known as the
myeloid cells.
● The disease accounts for approximately 15% of leukaemia's and it
occurs more in males than females (1.4:1) and frequently between
the ages of 40-60 in either sex. However, it may occur in any age
group.

Pathophysiology
● The condition results from the translocation between chromosomes 9
and 22, causing part of the oncogene ABL1 on chromosome 9 to
move to the BCR (Breakpoint cluster region) gene on chromosome 22
and part of chromosome 22 moves to chromosome 9.
● The abnormal chromosome 22 is known as Philadelphia (Ph)
chromosome. The resulting chimeric BCR-ABL1 gene codes for a
fusion protein which has constitutively active tyrosine kinase activity
in excess of the normal ABL1 product, resulting in uncontrolled
proliferation.

● Leucocytosis -The levels of neutrophils and myelocytes exceed those
of blast cells and promyelocytes.
● Increased circulating basophils
● Normochromic normocytic Anaemia
● Platelet count may be increased (most frequently), normal or
decreased
● Bone marrow is hypercellular with granulocytic predominance
● Elevated serum uric acid

Management
Investigations
● Peripheral blood film
● BCR-ABL genetic test
● Cytogenic testing- for Ph
chromosome
Treatment
● Tyrosine kinase inhibitors
● Chemotherapy
● Stem cell transplant

Human Immunodeficiency Virus (HIV)
● Human immunodeficiency Virus is an RNA and a retrovirus. It attacks the body’s
immune system.
● Globally, 38.4 million [33.9–43.8 million] people were living with HIV at the
end of 2021. An estimated 0.7% of adults aged 15–49 years worldwide are living
with HIV, although the burden of the epidemic continues to vary considerably
between countries and regions.
● In 2021, 1.9 million people in Nigeria were living with HIV. Women were the
most affected group, counting 1.1 million, while men counted 630,000. Also,
children up to age 14 who were HIV positive equaled 170,000.

The haematological changes associated with HIV are wide ranged and tend to be
worse in advanced forms of the disease- due to marrow defect and immune
cytopenia, infection from an opportunistic infection, lymphoma and side effects of
drug treatments.
● Anaemia
● Thrombocytopenia and neutropenia
● Increased plasma cells in the marrow and polyclonal increase in
immunoglobulins
● Non-Hodgkin lymphoma

Management
Investigations
● X-ray
● CT scan
● PET scan
● Lymph node biopsy
Treatment
● Blood transfusions or recombinant
erythropoietin injections
● Corticosteroids
● High-dose gamma globulin infusions
● Antiretroviral therapy
● Chemotherapy and immunotherapy

Malaria
● Malaria is an acute illness caused be infestation of the plasmodium parasite. It is a
febrile illness that is spread through the bite of the female anopheles mosquito.
There’s are five species of plasmodium that cause malaria in humans, P. vivax,
falciparum, ovale, knowlesi, and malariae. P. Falciparum is the deadliest and the
most prevalent in sub-Saharan Africa.
● Africa alone bears 95% of all malaria deaths worldwide, and 80% of all the deaths
are of children under the age of 5. Of all the nations of the world, four of them
bear the highest death rates, the nations being Nigeria, Democratic republic of
Congo, Tanzania and Mozambique.

Pathophysiology
● The classical manifestations of malaria occur as a result of infection
the red blood cells by asexual forms of the parasite. The parasite
causes adherence of the red blood cells to the vascular endothelium.
● This causes sequestration of parasitized red blood cells in the
capillaries and post capillary venues, causing micro-obstruction and
tissue hypoxia.
● Due to the fact that the early developmental stages of the mosquito
take place in stagnant water bodies, living near bodies of water such
and lake and swamps predisposes an individual to a higher risk of
malaria.

● Haematologically, the main manifestation of malaria is severe anaemia, which
happens as a result of rupture of the red cells after multiplication of the parasite.
This drops the haematocrit value and depending of the severity can go as low as
15%. The trophozoites can be seen arranged in a ring inside the infected red
cells. They then rupture the cell and the daughter plasmodia infect ,ore cells.
● Oxidative stress also plays a roll in the death of red cells. Formation of
haemoglobin metabolism derivatives which build up and can activate the
coagulation pathway and trigger phagocytosis of infected red blood cells.
● In severe malaria, thrombocytopenia is usually in about 50-80% of cases. The
presence of high molecular weight Von-Willebrand factor is a sign that there is
associated vascular damage and platelet consumption. Leukopenia is a rather
rare finding in blood films, only 8.8% of cases have such.

Microgram of the peripheral blood film of a malaria patient showing infected
erythrocytes with the trophozoite stage of the Plasmodium falciparum
parasite.

Management
Investigations
● The important investigations in the
diagnosis of malaria are a full blood
count, with a microscopy test for the
plasmodium that is suspected. FBC is
usually low, with some form of
leucocytosis occasionally.
● Microscopy will reveal trophozoites of
P. falciparum present.
Treatment
● Modern day management of malaria is
via the use of ACT- Artemisinin
combined therapy, using artemisinin
analogues and other anti-microbial
agents to clear the parasite and prevent
resistance.
● Rehydration, rest and proper nutrition
do go a long way in managing malaria.
● Blood transfusions can also be
indicated in severe malaria where the
PCV of the individual is dangerously
low.

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