Haematology Flashcards
1
Q
Define anaemia
A
Anaemia is a lower-than-normal concentration of haemoglobin or red blood cells (Hb <130g/L in men, <120 g/L women)
2
Q
What is aplastic anaemia?
A
A form of pancytopenia - deficiency of all three cellular components of the blood including red cells, white cells, and platelets
3
Q
What is haemolytic anaemia?
A
A form of anaemia characterised by an increased breakdown of red blood cells
4
Q
What is microcytic anaemia?
A
A form of anaemia characterised by a reduced mean corpuscular volume (MCV) i.e. the average size of your red blood cells.
MCV = <80 femtolitres [fL]
5
Q
What are some examples of microcytic anaemia?
A
- Iron deficiency
- Lead poisoning
- Anaemia of chronic disease
- Thalassaemia
- Sideroblastic anaemia
6
Q
What is macrocytic anaemia?
A
A form of anaemia characterised by an increased mean corpuscular volume (MCV) i.e. the average size of your red blood cells.
MCV >100 femtolitres [fL]
7
Q
What is macrocytic anaemia?
A
A form of anaemia characterised by an increased mean corpuscular volume (MCV) i.e. the average size of your red blood cells.
MCV >100 femtolitres [fL]
8
Q
What is normocytic anaemia?
A
A form of anaemia with normal MCV of 80-100 femtolitres [fL]
9
Q
What are some examples of normocytic anaemia?
A
- Sickle cell
- Hereditary spherocytosis,
- G6PDH deficiency
- Malaria
- Autoimmune Haemolytic
10
Q
What are some examples of macrocytic anaemia?
A
Megaloblastic:
Folate deficiency: e.g. dietary insufficiency
B12 deficiency: e.g. pernicious anaemia
11
Q
What general symptoms might a patient with anaemia present with?
A
Fatigue, headache, dizziness, dyspnoea (especially on exertion)
12
Q
What general signs might a patient with anaemia present with?
A
Tachycardia, skin pallor, conjunctiva pallor, intermittent claudication
13
Q
What symptoms and signs might a patient with iron deficiency anaemia present with?
A
Symtoms
- Fatigue
- Dyspnoea on exertion
- Pica
- Restless legs syndrome
Signs:
- Nail changes - thinning, flattening, and then spooning of the nails (rare)
14
Q
What is the aetiology of iron deficiency anaemia?
A
- Inadequate dietary iron intake
- Impaired iron absorption (e.g. gastric surgery, or coeliac disease)
- Increased iron loss because of bleeding, usually in the GI tract (e.g. peptic ulcer disease)
15
Q
What are 4 main risk factors of iron deficiency anaemia?
A
Pregnancy
Vegetarian and vegan diet
Menorrhagia (heavy periods)
Hookworm infestation
16
Q
What tests/investigations would you carry out on a patient with suspected iron deficiency anaemia?
A
- Haemoglobin and haematocrit (% of blood occupied by RBCs) (low)
- Platelet count (low, normal or elevated)
- MCV (mean corpuscular volume) - < 80 fL
- MCH (mean corpuscular haemoglobin - average conc of haemoglobin inside one RBC) (low)
17
Q
What is the management/treatment for iron deficiency anaemia?
A
First line: oral iron replacement
Second line: IV iron replacement
18
Q
How is iron deficiency anaemia monitored?
A
Haemoglobin concentration and red cell indices (measures shape, size and quality of RBCs) measured every 3 months for a year, again after one further year, and thereafter when symptomatic
19
Q
Define alpha thalassaemia
A
Thalassaemia is related to a genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin consists of 2 alpha and 2 beta-globin chains.
Deletions in alpha-globin chains leads to alpha thalassaemia
Autosomal recessive
20
Q
What is the epidemiology of alpha thialassaemia?
A
Most likely in people from Mediterranean, South-east Asia, India, Middle East and Sub-Saharan Africa as they are the malarial regions of the world
21
Q
What is the aetiology of alpha thialassaemia?
A
Alpha-thalassaemia is a group of disorders of haemoglobin synthesis, caused by deletions in at least 1 of the 4 alpha-globin genes (on chromosome 16).
The severity of the anaemia depends on the number of genes mutated.
22
Q
What is the pathophysiology of alpha thialassaemia?
A
- Silent carrier - one gene deletion is asymptomatic
- Alpha thalassemia trait - 2 gene deletion > mildly anaemic
- HbH: 3 gene deletions mean patient is unable to form alpha chains, beta chains form tetramers (HbH), which damage erythrocytes causing moderate to severe disease
- Hb Bart’s (alpha thalassemia major) - 4 gene deletions, death in utero as gamma chains form tetramers which cannot carry oxygen efficiently.
23
Q
What signs and symptoms might a patient with alpha-thialassaemia present with?
A
Common:
Anaemia (fatigue, pallor)
Splenomegaly
Uncommon:
Pronounced forehead and malar eminences
24
Q
What investigations/tests would you carry out for a patient with suspected alpha-thialassemia?
A
1) FBC - microcytic anaemia with reticulocytosis as bone marrow increase production of erythrocytes to compensate
2) Haemoglobin electrophoresis (diagnostic)
- Silent carrier: normal electrophoresis
- Alpha thalassaemia trait: near-normal haemoglobin electrophoresis
- HbH: HbH (beta chain tetramers) present on electrophoresis
3) Peripheral smear (blood film) - microcytic, hypochromic erythrocytes (lack of pigment), as well as target cells and nucleated RBCs (Howell-Jolly bodies)
25
What are the differential diagnosis for alpha-thialassemia?
- Iron deficiency anaemia
- Beta-thalassaemia
26
What is the treatment/management for alpha-thialassaemia?
- Alpha thialassaemia trait - mild anaemia no treatment needed
HbH:
- Monitoring the full blood count
- Monitoring for complications
- Regular blood transfusions if symptomatic or Hb < 70g/L
- Iron chelation- to treat iron overload
- Splenectomy
- Bone marrow transplant can be curative
27
Define beta-thialassemia
Normal haemoglobin consists of 2 alpha and 2 beta-globin chains.
Beta thalassaemia occurs due to impaired synthesis of β-globin. 2 alleles (on chromosome 11) are responsible for chain synthesis. Mutations (not deletions like in alpha thalassaemia) can cause reduced or absent beta chain synthesis, resulting in 3 possible phenotypes, with thalassaemia major being the most severe
Autosomal recessive
28
What is the epidemiology of beta-thialassemia?
Most likely in people from Mediterranean, South-east Asia, India, Middle East and Sub-Saharan Africa as they are the malarial regions of the world
29
What is the aetiology of beta-thialassemia?
Beta-thalassaemia is an inherited microcytic anaemia caused by mutation(s) of the beta-globin gene, 2 alleles on chromosome 11 > decreased or absent synthesis of beta-globin, resulting in ineffective erythropoiesis (RBC production)
Range from beta-thialassaemia trait (asymptomatic), beta-thialassaemia intermedia and beta-thialassaemia major (severe anaemia and skeletal changes).
30
What are the risk factors for beta-thialassaemia and alpha-thiassaemia?
- Mediterranean, South-east Asia, India, Middle East and Sub-Saharan Africa background
- Positive family history
31
What are the three different types of beta-thialassemia?
- Beta-thalassaemia trait (minor) = B/B+
- Beta-thalassaemia intermedia = B+/B+ or B+/B0
- Beta-thalassaemia major = B0/B0
B = normal beta-chain
B+ = reduced beta-chain
B0 = absent beta-chain
32
Describe beta-thlassaemia minor
- Patients with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal allele (B/B+)
- Thalassaemia minor causes a mild microcytic anaemia and present with anaemia symptoms such as fatigue.
- Usually only require monitoring and no active treatment.
33
Describe beta-thialassaemia intermedia
Patients have two abnormal copies of the beta-globin gene - defective gene and/or beta-zero mutation gene (resulting in absent beta-chain)
- Either two defective genes (B+/B+) or
- One defective gene and B0 gene (B+/B0)
- Causes more significant microcytic anaemia
- Require monitoring and occasional blood transfusions.
- If patients need more transfusions they may require iron chelation to prevent iron overload.
34
Describe beta-thialassaemia major
Patients are homozygous for the beta-zero mutation in the beta-globin genes (B0/B0)
- No functioning beta-globin genes = absent beta chain production
- Most severe form and usually presents in children < 2 with:
- Severe microcytic anaemia
- Failure to thrive
- Splenomegaly
- Bone deformities
35
What are the tests/investigations you would carry out for a patient with suspected beta-thialassaemia?
1) FBC (microcytic anaemia)
2) Peripheral smear (microcytic red cells, tear drops, target cells, nucleated RBCs)
3) Reticulocyte count (elevated)
4) Haemoglobin electrophoresis (diagnostic) - reduced HbA (normal Hb unit 2 alpha and 2 beta chains)
5) DNA testing can be used to look for the genetic abnormality
36
What are some DDx for beta-thialassaemia?
- Congenital dyserythropoietic anaemia (CDA)
- Pyruvate kinase (PK) deficiency
- Mild iron deficiency anaemia
37
What is the treatment/management for beta-thialassaemia?
1) Minor- genetic counselling and iron advice
2) Intermedia: non-transfusion-dependent
- 1st line – transfusions at times of symptomatic anaemia or if Hb < 70 g/L
- Consider iron monitoring + chelation therapy to prevent iron overload
3) Intermedia: transfusion-dependent & Major
1st line –
- Regular transfusion
- Iron monitoring + chelation
- Genetic counselling
Consider
- Splenectomy
- Stem cell/bone marrow transplantation might be curative
38
Name one complication of beta-thialassaemia
Iron overload
It causes effects similar to haemochromatosis:
Fatigue
Liver cirrhosis
Infertility and impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
39
What is iron overload?
Occurs in thalassaemia as a result of faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in response to the anaemia.
40
How is iron overload managed?
Management involves montioring serum ferritin levels for iron overload, limiting transfusions and iron chelation.
41
What follow-up monitoring is carried for patients with beta-thialassaemia?
- Iron load
- Cardiovascular function
- Hepatobiliary function
- Renal function
- Endocrine function
42
Define normocytic anaemia
Anaemia with normal MVC ( 80-100 femtolitres [fL]) but low number of RBCs
E.g. haemolytic anaemia
43
What is haemolytic anaemia?
Haemolytic anaemia is where there is destruction of red blood cells (haemolysis) leading to anaemia
44
What are some causes of haemolytic anaemia?
- Sickle cell
- Thialassaemia
- Autoimmune haemolytic anaemia
- Sepsis / disseminated intravascular
coagulopathy (DIC)
45
Define sickle cell anaemia
Sickle cell anaemia is an autosomal recessive mutation in the beta chain of haemoglobin, resulting in sickling of red blood cells (RBCs) and haemolysis.
The point mutation results in a hydrophilic glutamic acid amino acid being substituted for a hydrophobic valine, changing the structure of the beta chain.
If only one gene is mutated, this is called sickle cell trait. If both are mutated, this is known as sickle cell disease.
46
What is the epidemiology of sickle cell anaemia?
- More common in patients from areas traditionally affected by malaria, such as Africa, India, the Middle East and the Caribbean.
- Having one copy of the gene (sickle-cell trait) reduces the severity of malaria. As a result, patients with sickle-cell trait are more likely to survive malaria and pass on their genes.
47
What is the aetiology of sickle cell anaemia?
Normal haemoglobin consists of 2 alpha-globin and 2 beta-globin subunits
- Sickle cell disease is due to a single nucleotide polymorphism (SNP) in the beta gene (HBB) , the mutation causes the GAG codon to be changed to GTG.
- Glutamic acid is substituted for valine at position 6 on one or both beta hemoglobin subunits, giving rise to haemoglobin S (HbS).
48
What is the pathophysiology of sickle cell anaemia?
HbS is more prone to sickling and haemolysis.
When exposed to low oxygen levels (e.g. in the smaller capillaries on the leg) haemoglobin S (HbS) precipitates, causing the RBC to be distorted into a sickle/crescent shape, which are fragile and stiff.
49
What signs and symptoms might a patient with sickle cell anaemia present with?
General anaemia symptoms:
Symptoms: fatigue, headache, dizziness, dyspnoea (especially on exertion)
Signs: tachycardia, skin pallor, conjunctiva pallor, intermittent claudication
Haemolytic anaemia (e.g. sickle cell): jaundice, dark urine, gallstones
50
What tests/investigations are used to diagnose sickle cell anaemia?
1) Pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy.
2) Sickle cell disease is also tested for on the on the newborn screening heel prick test at 5 days of age.
3) FBC - normocytic anaemia with reticulocytosis
4) Blood film - sickled RBCs, target cells, Howell-Jolly bodies
5) Hb electrophoresis and solubility - diagnostic - increased HbS and reduced/absent HbA
51
What is the general management for sickle cell anaemia?
Long-term/general:
- Pain management with meds
- Avoid dehydration and other triggers of crises
- Ensure vaccines are up to date
- Antibiotic prophylaxis (penicillin first choice, erythromycin if allergic)
- Hydroxycarbamide to stimulate production of fetal haemoglobin (HbF).
- Blood transfusion for severe anaemia
- Folic acid supplement - raises Hb levels
- Bone marrow transplant can be curative
52
What is sickle-cell crisis?
Umbrella term for a spectrum of acute crises related to sickle cell anaemia.
Spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.
Can be life-threatening
53
What are some acute symptoms of sickle-cell disease (caused sickle cell crisis)?
1) Sequestration crisis - presents with abdominal pain
- RBCs sickle in the spleen, causing pooling of blood and a rapid drop in Hb and platelets
2) Aplastic crisis
- Infection with parvovirus B19 causes bone marrow suppression
- Sudden onset pallor, fatigue, and anaemia
3) Vaso-occlusive (thrombotic) crisis: painful, vaso-occlusive episodes occur as RBCs sickle in various organs such as bones, lungs, kidneys, and genitalia.
54
What is the treatment/management for an episode of sickle-cell crisis?
- Have a low threshold for admission to hospital
- Oxygen - if hypoxic or to prevent sickling
- Treat any infection
- Keep warm
- Keep well hydrated (IV fluids may be required)
- Simple analgesia such as paracetamol and ibuprofen
- Penile aspiration in priapism (persistent erection)
- Exchange transfusion - removal of HbW in exchange for normal Hb in severe crises
55
What are the complications of sickle cell anaemia?
Anaemia
Increased risk of infection
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Painful and persistent penile erection (priapism)
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
56
Name 4 possible causes of B12 deficiency
- Pernicious anaemia
- Malabsorption (coeliac, IBD, bowel resection, ileostomy)
- Decreased dietary intake e.g. vegan, found in meat, fish, eggs, milk
- Chronic nitrous oxide use
57
Define pernicious anaemia
Lack of intrinsic factor, usually produced by parietal cells in the stomach. Allows B12 absorption in the terminal ileum
58
What signs and symptoms might a patient with B12 deficiency present with?
General anaemia presentation & lemon yellow skin
A range of neurological signs and symptoms:
- Peripheral neuropathy with numbness or paraesthesia (pins and needles)
- Loss of vibration sense or proprioception
- Visual changes
- Mood or cognitive changes
59
What tests/investigations would you carry out for a patient with suspected B12 deficiency?
Blood tests: raised MCV, Low haematocrit, low B12
Blood film: ‘Megaloblastic’ anaemia – segmented nucleated neutrophils 6+ lobes
60
What is the treatment for B12 deficiency?
Dietary deficiency: oral replacement with cyanocobalamin
Pernicious anaemia: problem is absorption not intake so parenteral hydroxycobalamin given instead
61
Name 4 causes of folate (vitamin B9) deficiency
- Inadequate dietary intake
- Increased demand, eg pregnancy
- Malabsorption, eg coeliac disease, excess alcohol.
- Drugs: anti-epileptics (phenytoin, valproate), methotrexate, trimethoprim
62
What tests/investigations would you carry out for a patient with suspected folate (B9) deficiency?
Similar to B12 deficiency
Blood tests: raised MCV, Low Hb, low serum folate, low red cell folate (better indicator of folate status)
Blood film: ‘Megaloblastic’ anaemia – segmented nucleated neutrophils 6+ lobes
63
What is the treatment for folate deficiency?
Folate helps to form healthy red blood cells.
- Dietary changes: leafy greens, brown rice
- Treat underlying cause
- Oral folic acid supplement
- Make sure to correct B12 levels before treating folate deficiency as treating folate before B12 deficiency will worsen subacute combined degeneration of the (spinal) cord.
64
Define acute myeloid leukaemia (AML)
Acute myeloid leukaemia (AML) is a life-threatening haematological malignancy, it involves the proliferation of myeloblasts and is the most common acute leukaemia in adults .
A myeloblast = immature WBC
Physiologically, myeloblasts become mature WBCs called granulocytes (neutrophils, eosinophils and basophils).
65
What are the risk factors for AML?
- Increasing age: mostly affects the elderly (average diagnosis age 68-year-olds)
- Myelodysplastic syndromes (cancer)
- Myeloproliferative neoplasms (BM makes too many RBCs, WBCs or platelets)
- Previous chemotherapy or radiation exposure
- Benzene: painters, petroleum and rubber manufacturers
66
What is the pathophysiology of acute myeloid leukaemia (AML)?
- t(15:17) chromosomal translocation
- The rapid proliferation of immature myeloblasts.
- Results in replacement of normal bone marrow with leukemia cells and a drop in other cell lineages, including red blood cells, platelets and normal white blood cells. This eventually results in bone marrow failure.
- Present mostly in the elderly
- Only 15% 5-year survival
67
What tests and investigations are used to diagnose AML?
- FBC -> leukocytosis, anaemia, thrombocytopenia with low reticulocyte count
- Blood film - Auer rods
- Bone marrow biopsy - ≥20% myeloblasts is diagnostic
68
What signs and symptoms might a patient with AML present with?
Symptoms
- Fatigue
- Bleeding/bruising
- Infection
- Anorexia (loss of appetite)
- Weight loss
Signs
- Pallor
- Lymphadenopathy
- Hepatosplenomegaly
- Gum hypertrophy
69
What is the treatment/management for AML?
- Chemotherapy (cytarabine and an antracycline)
- Antibiotics for neutropenia
- Stem cell/bone marrow transplant - last resort
70
Define chronic myeloid leukaemia (CML)
Chronic myeloid leukaemia (CML) involves the neoplastic proliferation of myeloblast cells (haematopoietic stem cells) in the bone marrow
71
What is the pathophysiology of CML?
Chromosomes 9 and 22 translocation > abnormal chromosome 22 (Philadelphia chromosome).
- BCR gene on chromosome 22 fused to ABL gene on chromosome 9 > BCR-ABL fusion oncogene > resulting p210 BCR-ABL protein, hallmark of CML
- Tyrosine kinase irreversibly activated > uncontrolled cellular division> disrupting normal haematopoiesis
72
What signs and symptoms might a patient with CML present with?
Symptoms
- Fatigue
- Easy bleeding/bruising
- Recurrent infections
- Shortness of breath
- Weight loss and night sweats
Signs
- Pyrexia
- Pallor (anaemia sign)
- Abdominal tenderness
- MASSIVE splenomegaly :(
73
What tests and investigations are used to diagnose CML?
- FBC -> anaemia, thrombocytopenia, leukocytosis
- Bone marrow biopsy - myeloblast infiltration in bone marrow
- Blood film - increase in all stages of maturing granulocytes
- Molecular testing - for Philadelphia chromosome
74
What is the treatment/management for CML?
First line: Tyrosine kinase inhibitors (Imatinib)
Chemotherapy
Stem cell/bone marrow transplant
75
What are some possible complications of CML?
Possible progression to AML if untreated/ late Dx
76
Define Acute lymphoblastic leukaemia (ALL)
Acute lymphoblastic leukaemia (ALL) is a malignant clonal disease that involves the proliferation of lymphoblasts, most commonly of the B cell lineage.
t(12;21) is the most common cytogenetic abnormality in children.
77
What is the pathophysiology of ALL?
In adults, like in CML, the Philadelphia chromosome is the most common cytogenetic abnormality > constitutively active tyrosine kinase. However it is more associated with CML.
These genetic aberration results in excessive proliferative of lymphoblasts which accumulates in the bone marrow > bone marrow failure > anaemia and thrombocytopenia
Lymphoblasts leak into the blood and can invade tissues such as testicles, meninges and kidneys.
78
Who is most at risk for developing ALL?
- Children less than 5 years of age (75% cases in children under 6 years old)
- Associated with trisomy 21 (Down's syndrome)
79
What chromosome abnormality is ALL associated with?
Philadelphia chromosome (t(9:22) translocation) in 30% of adults and 3-5% of children with ALL.
80
What tests and investigations are used to diagnose ALL?
- FBC - anaemia, thrombocytopenia, lymphocytosis, normocytic anaemia with low reticulocyte count
- Blood film - shows lymphoblast cells
- Bone marrow biopsy - = or more than 20% lymphoblasts is diagnostic
- Imaging (CXR/CT) -> lymphadenopathy
- Cytogenetic/molecular studies - identify t(12;21) or t(9;22)
81
What signs and symptoms might a patient with ALL present with?
Symptoms:
- Fatigue
- Fever
- Loss of appetite
- Easy bleeding/bruising
- Recurrent infections
- Bone pain - BM infiltration
- Weight loss
Signs
- Hepatosplenomegaly
- Lymphadenopathy
- CNS infiltration > headaches, CN palsies
82
What is the treatment/management for a patient with ALL?
- Blood and platelet transfusions
- Chemotherapy (*methotrexate*)
- Steroids
- Stem cell/bone marrow transplant
- Antibiotics
83
Define chronic lymphocytic leukaemia (CLL)
Chronic lymphocytic leukaemia is where there is chronic and neoplastic proliferation of mature B lymphocytes > they collect in blood and can be seen on blood film.
84
Who is most at risk of developing CLL?
CLL usually affects adults over 55 years of age.
Most common type of leukaemia in adults
Men twice as likely as women
85
What signs and symptoms might a patient with CLL present with?
Symptoms:
- Fatigue
- Easy bruising: prolonged bleeding and mucosal bleeding due to thrombocytopaenia
- Loss of appetite
- Weight loss
- Fever
- Recurrent infections
- Night sweats, weight loss
Signs
- Hepatosplenomegaly: neoplastic cells invade the liver and spleen
- Signs of anaemia e.g. pallor
- Lymphadenopathy
86
What tests/investigations are used in diagnosing CLL?
- FBC -> anaemia, thrombocytopenia, leukocytosis
- Blood film -> increased mature lymphocytes, smudge/smear cells due to fragile WBC that rupture on film
- Immunophenotype: CD5, CD19, CD20, CD 23
- Low immunoglobulins levels (hypogammaglobulinemia)
- Genetic analysis: identify chromosomal deletions, e.g. del 17p, which helps guide treatment
87
What is the treatment/management for CLL?
- Watch and wait in early stages
- Chemotherapy (rituximab)
- Stem cell/bone marrow transplant
88
What complications can CLL lead to?
CLL can transform into high-grade lymphoma becasue B-cells can massively accumulate in the lymph nodes > massive lymphadenopathy > aggressive lymphoma
This is called Richter’s transformation.
89
Define Hodgkin's lymphoma (HL)
A type of lymphoma caused by neoplastic proliferation of lymphocytes in the lymphatic system.
HL = Reed-Sternberg cells, large B cells with prominent ‘owl’s eye nuclei’ which secrete inflammatory cytokines and attract reactive inflammatory cells, resulting in ‘B symptoms’.
Bimodal age distribution with peaks around 15 - 35 and > 65
90
What would you see histologically in nodular lymphocyte predominant HL?
- Popcorn cells
- Reed-Sternberg cells are rarely seen
91
What are the risk factors for HL?
- HIV
- Epstein-Barr Virus (causes glandular fever)
- Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
- Family history
92
What signs and symptoms might a patient with HL present with?
- Lymphadenopathy - enlarged lymph nodes might be in the neck, axilla (armpit) or inguinal (groin) region.
- Non-tender and feel “rubbery”
- Lymph nodes painful upon drinking alcohol
- B-symptoms - fever, night sweats, weight loss
93
What tests/investigations are used to diagnose HL?
- FBC: leukocytosis with pancytopaenia if bone marrow involved
- Lactate Dehydrogenase: elevated
- Ultrasound of lymph nodes: indicate malignancy features
- Lymph node biopsy > Reed Sternberg cells ( large, abnormal lymphocytes that contain >1 nucleus)
- Erythrocyte sedimentation rate test (ESR) - increased which indicates inflammation
- Imaging (CXR/CT) for staging
94
What is the Ann Arbor Staging for HL and NHL?
The Ann Arbor Staging system puts importance on whether affected nodes are above or below the diaphragm.
Stage 1: Confined to one region of lymph nodes.
Stage 2: In more than one region but on the same side of the diaphragm
Stage 3: Affects lymph nodes both above and below the diaphragm.
Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.
And
A: no B symptoms
B: B symptoms present
95
What is the treatment/management for HL?
- ABVD chemotherapy
- Doxorubicin (brand name adriamycin), bleomycin, vinblastine, dacarbazine
- Radiotherapy
- Steroids
- Stem cell/bone marrow transplant
96
What is a complication that can develop with recent/high dose chemotherapy?
Febrile neutropenia
Px = Fever (38c+), tachycardia, rigors, tachypnoea (rapid breathing)
Tx = broad spectrum antibiotics (e.g. amoxicillin)
97
Define Non-Hodgkin's Lymphoma
NHL is a group of lymphomas
Burkitt lymphoma: associated with EBV, malaria, and HIV.
MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach. It is associated with H. pylori infection.
Diffuse large B cell lymphoma often presents as a rapidly growing painless mass in patients over 65 years.
98
What age group is most at risk of developing NHL?
Predominantly affects adults over the age of 40
99
What signs/symptoms might a patient with NHL present with?
- Painless lymphadenopathy
- B symptoms > weight loss, night sweats, fever
- Can get hepatosplenomegaly
100
What tests/investigations are used to diagnose NHL?
- Imaging (CXR/CT) for staging (Ann Arbor)
- Lymph node biopsy > no Reed Sternberg cells - the only way to differentiate from HL
101
What is the treatment/management for NHL?
- Watchful waiting
- RCHOP chemotherapy (Rituximab (mAb), Cyclophosphamide, Hydroxy-daunorubicin
Vincristine (brand name Oncovin)
- Prednisolone
- Radiotherapy
- Stem cell transplantation
102
Define multiple myeloma (MM)
Neoplastic monoclonal proliferation of a plasma cell (B-cells that produce antibodies) that affect MULTIPLE areas of the body
103
Whcih age group is most at risk for MM?
Predominantly occurs in those over the age of 40
104
Which disease is MM closely associated with?
Monoclonal gammopathy of undetermined significance (MGUS)
- Abnormally high levels of an immunoglobulin released by abnormal plasma cells
- 1% develop into myeloma
105
What symptoms/signs might a patient with MM present with?
Old CRAB
Old -70+
C – Calcium (elevated)
R – Renal failure
A – Anaemia (normocytic, normochromic) from replacement of bone marrow.
B – Bone lesions/pain
106
What tests/investigations are used to diagnose MM?
- FBC > anaemia
- ESR > raised
- Blood film > Rouleaux formation
- Serum and urine electrophoresis -> Bence Jones protein in urine (part of antibody subunit) + hypercalcemia
- Imaging (x-ray/CT) -> bone lesions
- Diagnostic bone marrow biopsy 10% plasma cells
107
What is the pathophysiology of MM?
Immunoglobin: A, G, M, D and E (GAMED)
Patient with MM - one of them raised in blood
50% cases = IgG
This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein.
108
What is treatment/management for MM?
First-line treatment combination of chemotherapy with:
Bortezomid
Thalidomide
Dexamethasone
Stem cell transplantation can be used as part of a clinical trial where patients are suitable.
109
What is the DDx for MM?
MGUS - Monoclonal gammopathy of undetermined significance
- BM biopsy < 10% plasma cells
- No or little paraprotein spike
- Asymptomatic
110
Define polycythaemia
A high concentration of erythrocytes in the blood
111
What are the different types of polycythaemia?
- Absolute > split into primary and secondary
- Relative
112
Define relative polycythaemia
There are a normal number of erythrocytes, but there is a reduction in plasma
113
What are the causes of relative polycythaemia?
Obesity, dehydration, and excessive alcohol consumption
114
Define absolute polycythaemia and state the difference between primary and secondary polycythaemia
There is an increased number of erythrocytes:
- Primary polycythaemia
Abnormality in the bone marrow - known as polycythaemia vera
- Secondary polycythaemia
A disease outside the bone marrow causing overstimulation of the bone marrow
115
What are some causes of secondary polycythaemia?
COPD, sleep apnoea, PKD, renal artery stenosis, kidney cancer
116
What is the aetiology of polycythaemia vera (primary polycythaemia)?
95% of cases are due to JAK2 mutation (gene that encodes for a protein that promotes the proliferation of cells).
117
What signs and symptoms might a patient with polycythaemia vera present with?
General polycythaemia symptoms:
- Headaches
- Dizziness
- Fatigue
- Blurred vision
- Red skin (hands, face, and feet)
- Hypertension
Specific to polycythaemia vera:
- Itching, especially after contact with warm water (e.g., a bath)
- Hepatosplenomegaly
118
What investigations/tests might you carry out to diagnose polycythaemia vera?
FBC:
- Raised haemoglobin (> 185g/l in men or 165g/l in women)
- Raised haematocrit, white cell count, and platelet count
- Genetic testing for JAK2 mutation
- Serum erythropoietin > decreased (can be normal or increased in other types of polycythaemia)
119
What is the treatment/management for polycythaemia vera?
First line: venesection (removing blood) to keep the haemoglobin in the normal range.
Aspirin can be used to reduce thrombus formation
Chemotherapy for patients at high risk of thrombosis
120
Define HIV (Human Immunodeficiency Virus)
HIV is a (single-stranded) RNA retrovirus. HIV-1 is the most common type, and HIV-2 is rare outside West Africa. The virus enters and destroys the CD4 T-helper cells of the immune system.
121
What are the risk factors for HIV?
- Unprotected anal, vaginal or oral sexual activity
- Mother to child at any stage of pregnancy, birth or breastfeeding (called vertical transmission)
--Sharing needles, needle-stick injuries, or blood splashed in an eye
122
What is the pathophysiology of HIV?
- HIV attaches to CD4 receptors and co-receptor on T-helper cells, dendritic cells, and macrophages via the GP120 protein
- HIV enters the target cell by injecting its single strand of RNA into target cell
- Reverse transcriptase enters nucleus and transcribes complementary proviral DNA (ready to be integrated into host genome)
- During infections, when the host immune cell mounts an response, new HIV viruses are transcribed and translated at the same time
- New viruses leave by exocytosis from cell membrane to infect more cells
123
Describe the stages of HIV infection.
1. Seroconversion (primary infection): flu-like symptoms 2 - 6 weeks after exposure
2. Asymptomatic infection - immune system mounts a response to initial infection
3. Chronic phase - viral load increases, T-cell numbers decrease (~500 cells/mm2 and patients can still fight infections)
4. AIDS-related complex (ARC) - T cell count < 200 cells/mm2. Fever, night sweats, diarrhea, weight loss, minor opportunistic infections, e.g., oral candida, oral hairy leucoplakia
5. Acquired immunodeficiency syndrome (AIDS) - sharp spike in HIV viral load - end-stage HIV.
124
What conditions are considered "AIDS-defining illnesses"?
"AIDS-defining illnesses" -
- Kaposi’s sarcoma
- Pneumocystis pneumonia
- Cytomegalovirus infection
- Candidiasis (oesophageal or bronchial)
- Lymphomas
- Tuberculosis
125
What investigations and tests are used to diagnose HIV?
Antibody testing - anti HIV IgG
Testing for the p24 antigen- specific HIV antigen in the blood - earlier detection
PCR testing for the HIV RNA levels tests directly for the number of viral copies in the blood, giving a viral load.
126
What is the treatment/management for HIV?
HAART (Highly Active Anti-Retroviral Treatment):
A combination of antiretroviral therapy (ART) medications offered to everyone with a diagnosis of HIV irrespective of viral load or CD4 count.
- Starting regime = two NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors) e.g. tenofovir and emtricitabine and 3rd agent.
Treatment aims to achieve a normal CD4 count and undetectable viral load.
If the patient has a normal CD4 and an undetectable viral load on ART, treat their physical health problems as you would an HIV-negative patient.
127
HIV: what is post-exposure prophylaxis (PEP)?
Post-exposure prophylaxis (PEP) used after exposure to HIV to reduce the risk of transmission.
PEP is not 100% effective and must be commenced in less than 72 hours after exposure.
PEP involves a combination of ART therapy. The current regime is Truvada (emtricitabine and tenofovir) and raltegravir for 28 days.
128
What monitoring is carried out for a patient with HIV?
1) CD4 Count:
- 500-1200 cells/mm3 = normal
- Under 200 cells/mm3 = end-stage HIV (AIDS) and increased risk of opportunistic infections
2) Viral Load (VL)- number of copies of HIV RNA per ml of blood.
“Undetectable” = viral load below the lab’s recordable range (usually 50 – 100 copies/ml). vs 100,000s in untreated HIV
129
Define Glucose-6-phosphate dehydrogenase deficiency
Unlikely to come up in exams, but good to know so can eliminate in SBA
G6P has a role in pentose sugar metabolism, also protects RBCs from damage.
In G6PD, RBC’s are exposed to more oxidative stress = haemolysis
130
What are the risk factors for G6PD?
X-linked (men), from West Africa, Middle-east, Asia
131
What signs and symptoms might a patient with G6PD present with?
Neonates: jaundice
Adults:
-Dark urine: haemaglobinuria
- Jaundice
- Splenomegaly
- Symptoms of anaemia: pallor and dyspnoea
- Backpain
132
What investigations and tests are used to diagnose G6PD?
Bloods: anaemia, increased LDH (Lactate dehydrogenase - used to detect tissue damage), increased reticulocytes,
Blood smear: Heinz bodies (requires special prep)
133
Define Von Willebrand Disease
The most common inherited cause of abnormal bleeding (haemophilia). Caused by a deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF).
Type 1 to type 3 depending on cause
134
How would a patient with VWD present in clinic?
- A history of unusually easy, prolonged or heavy bleeding:
- Bleeding gums with brushing
- Nose bleeds (epistaxis)
- Heavy menstrual bleeding (menorrhagia)
- Heavy bleeding during surgical operations
- A family history of heavy bleeding or von Willebrand disease
135
What is the management for VWD?
VWD is non-curable and does not need day to day tretment. Only in response to major bleeds or before operations:
- Desmopressin can be used to stimulate the release of VWF
- VWF can be infused
- Factor VIII is often infused along with plasma-derived VWF
- Women with VWD and heavy periods managed with oral contraceptive pill and coil.
136
Define haemophilia
Inherited severe bleeding disorders.
Haemophilia A is most common, caused by a deficiency in factor VIII.
Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX. Behaves clinically like haemophilia A.
137
What is the aetiology of haemophilia?
X linked recessive disorders > affects men more than women
offspring need to inherit both X chromosomes with abnormal gene
Women are normally carriers - one X chromosome with abnormal gene
138
What signs and symptom might a patient with haemophilia present with?
- Excessive bleeding in response to minor trauma and spontaneous haemorrhage
- Often presents early in childhood with intracranial haemorrhage, haematomas and cord bleeding in neonates.
- Spontaneous bleeding into joints (haemoathrosis) and muscles are classic features of severe haemophilia (remember for exam!)
Abnormal bleeding can occur in:
- Gums
- Gastrointestinal tract
- Urinary tract causing haematuria
- Retroperitoneal space
139
What investigations/tests are used to diagnose haemophilia?
- Increased APTT (time taken for blood to clot) and decreased factor VIII in coagulation factor assays
- Genetic testing
- Bleeding scores
Haemophilia DOES NOT affect bleeding time.
140
What is the treatment/management for haemophilia
Management should be coordinated by a specialist, avoid NSAIDS and IM injections
IV infusion of factor VIII (8) or IX (9) prophylactically or in response to bleeding. However, the body may form antibodies against the clotting factors > ineffective
During surgery to prevent or stop bleeding:
- Infusions of the affected factor (VIII or IX)
- Desmopressin to stimulate the release of von Willebrand Factor
- Antifibrinolytics
141
Define malaria
An infectious disease caused by members of the Plasmodium family of protozoan parasites
142
How is malaria spread?
Bites from the female Anopheles mosquitoes > bites and sucks up blood of infected human > injects parasite to next human they bite
143
What are the 4 types of malaria?
- Plasmodium falciparum
- Plasmodium vivax
- Plasmodium ovale
- Plasmodium malariae
144
Which form of malaria is most severe and dangerous?
Plasmodium falciparum, accounts for 75% of cases in UK
145
Which form of malaria is most severe and dangerous?
Plasmodium falciparum, accounts for 75% of cases in UK
146
Pathophysiology of malaria: Describe how sporozoites enter and infect a human
A female anopheles mosquito sucks up infected blood, the malaria in the blood reproduces in the mosquito gut producing thousands of sporozoites
Mosquito bites another human > sporozoites injected > sporozoites travel to liver of newly infected person
147
Pathophysiology of malaria: What happens after sporozoites enter the liver of the newly infected person?
They mature into merozoites which enter the blood and infect RBCs > reproduce over 48 hours > RBCs rupture > release more merozoites into blood > haemolytic anaemia
So people infected with malaria have high fever spikes every 48 hours
148
What signs and symptoms might a patient with malaria present with?
Consider malaria in patients with fever and who recently returned from an endemic area (mainly African countries).
Non-specific Symptoms
- Fever, sweats and rigors
- Malaise
- Myalgia
- Headache
- Vomiting
Signs
- Pallor due to the anaemia
- Hepatosplenomegaly
- Jaundice as bilirubin is released during the rupture of red blood cells
149
What investigations/tests are used to diagnose malaria?
Malaria blood film - shows the parasites, concentration and type
3 samples over 3 days due to 48-hour cycle of malaria release into the blood.
150
What is the treatment/management for malaria?
Uncomplicated: quinine sulphate and doxycycline
Complicated: IV artesunate and quinine dihydrochloride
151
Define hereditary spherocytosis
- A condition where the red blood cells are sphere-shaped, making them fragile and easily destroyed when passing through the spleen.
- Most common inherited haemolytic anaemia in northern Europeans.
- Autosomal dominant condition.
152
What signs and symptoms might a patient with hereditary spherocytosis present with?
General anaemia symptoms:
- Jaundice
- Anaemia
- Gallstones
- Splenomegaly
Haemolytic crisis - triggered by infection, haemolysis, anaemia and jaundice is more significant.
Aplastic crisis - increased haemolysis, anaemia and jaundice but no increased extra reticulocyte production from bone marrow to account for loss like in normal blood > often triggered by parvovirus
153
What investigations and tests are used to diagnose hereditary spherocytosis?
- Family history
- Blood film - spherocytes present
- Mean corpuscular haemoglobin conc (MCHC) increased on FBC
- Reticulocytes increased due to rapid turnover of RBCs
154
What is the treatment/management for patients with hereditary spherocytosis?
- Folate supplement (erythropoiesis)
- Splenectomy
- Cholecystectomy if gallstones
- Blood transfusions during acute crises
155
Define autoimmune haemolytic anaemia (AIHA)
A condition where antibodies are created against the patient’s red blood cells. These antibodies lead to the destruction of the red blood cells.
2 types: warm and cold depending on the optimal temperature at which the autoantibodies cause destruction of RBCs
156
Define warm-type AIHA
IgG-mediated, autoantibodies bind at body temperature of 37°C.
157
Define cold-type AIHA
IgM-mediated, autoantibodies bind at temperatures <4c (some say <10c).
Causes a chronic anaemia made worse by the cold, often associated with Raynaud’s or acrocyanosis (blueish colour to extremities)
158
What are the causes of warm-type AIHA?
Most are idiopathic;
Secondary causes: lymphoproliferative disease (CLL, lymphoma), drugs, autoimmune disease, eg SLE (systemic lupus erythematosus)
159
What are the causes of cold-type AIHA?
Often secondary to conditions
- Lymphoma, leukaemia, systemic lupus erythematosus
- Infections such as mycoplasma, EBV, CMV and HIV.
160
What is the treatment/management for AIHA?
- Prednisolone (steroids)
- Rituximab (a monoclonal antibody against B cells)
- Splenectomy
- Cold type AIHA - keep warm as well
161
Define thrombocytopenia
Low platelet count
Normal platelet count = 150 to 450 x 10^9/L
Causes can be split into problems with production or destruction
162
What is Immune Thrombocytopenic Purpura (ITP)?
Problem with destruction
Antibodies are created against platelets = immune response against platelets, resulting in the destruction of platelets and a low platelet count
163
What are purpura and what do they look like?
Small, flat spots caused by blood leaking and pooling under the skin's surface
Dark brown/black spots on darker skin
Purple spots on lighter skin
164
What signs and symptoms might a patient with ITP present with?
Mild thrombocytopenia asymptomatic and found incidentally on FBC
- Platelet count below 50 x 10^9/L
Symptoms:
- nosebleeds
- bleeding gums
- easy bruising
- Blood in urine or stools
SIgns
Prolonged bleeding times.
Platelet counts below 10 x 10^9/L = high risk for spontaneous bleeding e.g., intracranial haemorrhage or GI bleeds
165
What are the DDx for prolonged or abnormal bleeding?
- Thrombocytopenia (low platelets)
- Haemophilia A and haemophilia B
- Von Willebrand Disease
- Disseminated intravascular coagulation (usually secondary to sepsis)
166
What is the treatment/management for ITP?
- Prednisolone (steroids)
- IV immunoglobulins
- Rituximab (a monoclonal antibody against B cells)
- Splenectomy
- Controlling BP
- Suppressing menstrual periods
167
What monitoring is carried out for patients with ITP?
Monitoring platelet count
Educating patient about concerning signs of bleeding e.g., persistent headache and melaena (black, smelly stool indictive of upper GI bleed) and when to seek help
168
Define Thrombotic Thrombocytopenic Purpura (TTP)
A condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia and bleeding under the skin
169
What is the pathophysiology of TTP?
TTP is caused by a genetic or acquired deficiency of a protease (ADAMTS13) that normally cleaves multimers of von Willebrand factor (VWF).
Large VWF multimers form, causing platelet aggregation and fibrin deposition in small vessels, leading to microthrombi.
170
What are some illnesses that can trigger TTP?
- Idiopathic (40%)
- Autoimmunity (eg SLE)
- Cancer
- Pregnancy
- Drug associated (eg quinine)
- Haematopoietic stem cell transplant
171
What tests/investigations are used to diagnose TTP?
- Haematuria/proteinuria (blood/protein in urine)
- Blood film: fragmented RBC, decreased platelets, decreased Hb. Clotting tests are normal
172
What is the treatment/management for TTP?
Treatment is guided by a haematologist and may involve:
- Plasma exchange - urgent life-saving
- Steroids (prednisolone)
- Rituximab (a monoclonal antibody against B cells).
173
Cancer treatment complication: define tumour lysis syndrome (TLS)
An oncological emergency resulting from cancer treatment (usually chemotherapy) caused by a rapid breakdown of large numbers of cancer cells and subsequent release of large amounts of intracellular content into the bloodstream which overwhelms normal homeostatic mechanisms.
174
Cancer treatment complication: what are the different types of TLS?
Laboratory TLS: presence of two or more of the following metabolic abnormalities: hyperuricaemia, hyperphosphataemia, hyperkalaemia, or hypocalcaemia
Clinical TLS: laboratory TLS with one or more of the following clinical manifestations: acute kidney injury, cardiac arrhythmia, seizure, or sudden death.
175
What types of cancer is TLS most associated with?
Highly proliferative, bulky, chemosensitive haematological malignancies, particularly high-grade non-Hodgkin's lymphoma (e.g., Burkitt's lymphoma) and acute lymphoblastic leukaemia
176
What signs and symptoms might a patient with TLS present with?
Take history and note the following:
Haematological malignancy
Pre-existing renal impairment
Symptoms:
- Syncope/chest pain/dyspnoea
- Seizures
- Nausea and vomiting
- Anorexia
- Diarrhoea
- Muscle weakness
177
What investigations/tests would you carry out for a patient with suspected TLS?
- serum uric acid (≥476 mmol/L or 25% increase from baseline)
- serum phosphate (children: ≥2.1 mmol/L, adults ≥1.45 mmol/L or 25% increase)
- serum potassium (≥6.0 mmol/L or 25% increase)
- serum calcium (≤1.75 mmol/L or 25% decrease)
178
What is the treatment/management for TLS?
Focused on prevention
- Low-risk patients: regular monitoring and assessment
- Intermediate/high-risk patients: IV hydration and regular monitoring & assessment
Acute laboratory/clinical TLS:
- Urgent treatment of cardiac arrhythmia and seizures
- Fluid resuscitation with/without loop diuretics
179
What complications can TLS lead to?
- Acute kidney injury
- Cardiac arrhythmias
- Seizures
- Neuromuscular dysfunction
All can cause considerable morbidity and in some cases death.
180
What is neutropenia?
Neutropenia is a low neutrophil count.
Normal: >1.5 x 10⁹/L
Mild: 1 to 1.5 x 10⁹/L
Moderate: 0.5 to 0.99 x 10⁹/L
Severe: 0.2 to 0.49 x 10⁹/L
Very severe: <0.2 x 10⁹/L.
181
What is neutrophilia?
Elevated neutrophil count with or without leukocytosis (elevated WBC count)
Neutrophilia with leukocytosis =
- Neutrophil count >7.7×10⁹/L
- WBC count > 11×10⁹/L
Neutrophilia without leukocytosis
- Neutrophil count >7.7×10⁹/L
- WBC count <11×10⁹/L
182
What is lymphopenia?
Lymphocyte count on FBC in an adult patient that is below the lower limit of the normal range
Usually lower in elderly patients (> 0.5 x 10^9/L)
In healthy adults <1 x 10^9/L
183
What is lymphophilia (lymphocytosis)?
Increased lymphocyte count or proportion of lymphocytes in the blood above normal range
184
What is thrombocytopenia?
Thrombocytopenia is a low circulating platelet count (<150,000 per microlitre).
185
What is thrombophilia?
Increased tendency of the blood to form clots - increases risk of DVT and PE
186
What is PT/INR?
PT/INR is coagulation time via the extrinsic clotting pathway.
PT = prothrombin time
INR = international normalised ratio
normal PT/INR = 10 - 13.5 seconds
Norma INR = 0.8 - 1.2
INR = patient PT/ref PT
Used to monitor patients on warfarin
187
What is PT/INR used to monitor?
Used to monitor patients on warfarin
188
What conditions might increase INR?
- Anticoagulants
- Liver disease
- Vitamin K deficiency
- Disseminated intravascular coagulopathy
189
How might warfarin affect INR?
Increases INR (between 2 -3)
Normal INR = 0.8 - 1.2
190
What is APTT?
Activated Partial Thromboplastin Time - another test that measures blood coagulation time via the intrinsic pathway (factors 8, 9, 11, 12)
Normal APTT = 35 - 45s
191
What is APTT used to monitor?
Patients on heparin therapy
192
How might heparin affect APTT?
Increases APTT to 60 -80 s
193
What conditions might prolong APTT?
- Haemophilia A (factor 8)
- Haemophilia B (factor 9)
- VWF disease
PT normal, APTT prolonged in the above conditions
194
What are some examples of normocytic anaemia?
- Sickle cell
- Hereditary spherocytosis,
- G6PDH deficiency
- Malaria
195
What is the pathophysiology of Polycythaemia vera (PCV)?
A myeloproliferative disorder characterised by neoplasia of mature myeloid cells, in particular those involved in the red cell lineage, within the bone marrow.
It is a primary polycythaemia that results in increased red blood cells (polycythaemia), as well as increased neutrophils (neutrophilia) and platelets (thrombocytosis)
196
Define disseminated intravascular coagulation
Simultaneous coagulation and haemorrhage caused by the initial formation of thrombi which consume clotting factors (factors 5,8) and platelets, ultimately leading to bleeding.
197
What are the causes of DIC ?
- Infection e.g. sepsis
- Malignancy
- Trauma e.g. major surgery, burns
- Liver disease
198
What are signs and symptoms of DIC?
Clinically bleeding is usually a dominant feature, bruising, ischaemia and organ failure
199
What tests/investigations are used to diagnose DIC?
Blood tests: prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products
200
What is the treatment/management plan for DIC?
Treat the underlying cause and supportive management
201
DDx iron-deficency anaemia
- Anaemia of chronic disease
- Thalassemia
202
DDx pernicious anaemia (B12)
- Folic acid (B9) deficiency
- Alcoholic liver disease
203
DDx sickle cell anaemia
- Gout - swelling, severe pain and redness of affected joint
- Septic arthritis - fever and swelling of affected joint
Mimicks sickle cell crisis
204
DDx Von Willebrand disease
- Mild haemophilia A
205
DDx haemophilia
- Von Willebrand disease
- Platelet dysfunction
206
DDx acute lymphoblastic leukaemia
Acute myeloid leukaemia (DDx swap)
207
DDx chronic lymphocytic leukaemia
Leukemic phase of lymphoma
208
DDx Hodgkin's and non-Hodgkin's lymphoma
Each other
209
DDx HIV
- Infectious mononucleosis
- Cytomegalovirus infection
210
DDx Malaria
- Meningitis or encephalitis.
- COVID-19.
211
DDx for polycythemia
- Secondary polycythemia due to hypoxia
- Essential thrombocytopenia
- Chronic myeloid leukaemia
