Haematology Flashcards
what is multiple myeloma
Malignant disease of plasma cells (differentiated B-lymphocytes) in bone marrow
define stem cell transplant
Any procedure where hematopoietic stem cells of any donor and any source are given to a recipient with intention of repopulating/replacing the hematopoietic system in total or in part
can stem cell transplant be offered instead of chemotherapy
NO
it is offered only after the cancer is kept under control with the chemotherapy
explain the 2 types of stem cell transplant
Autologous
origin: patient stem cells
rejection possibility: NO
disease use: Myeloma and Lymphoma
how it works:
1) some stem cells harvested and frozen
2) patient undergoes aggressive chemo to kill all cells
3) the frozen good stem cells infused back into the patient
recovery: shorter
Allogenic
origin: donor stem cells
possibility of rejection: YES
disease use: Blood cancers like AML, ALL, MDS that cannot be cured by chemotherapy
How it works:
1) patient undergoes aggressive chemo to kill all cells
2) donor (ex. sibling) stem cells are infused into patient
3) previous killing of all bone marrow cells with chemo lowers the chance of patient immune system killing donor stem cells
recovery: longer
what type of stem cell transplant in preferred in myeloma
autologous stem cell transplant
how are the stem cells mobilised and harvested
Done with G-CSF (Granulocyte Colony-Stimulating Factor) - mobilizes haematopoietic stem cells
The patient undergoes leukapheresis, a procedure similar to dialysis, where blood is withdrawn, stem cells are separated, and the remaining blood components are returned to the patient.
are family members always a perfect match for stem cell transplant
NO
Family member donors are either a match or a haplo-match
what does a match mean, how is it determined and what is the criteria (give the numbers)
Match means at HLA loci
10/10 = full match
8 or 9/10 = mismatch
5/10 = half match (haplo)
what is the purpose of conditioning chemotherapy?
Suppress host (patient) immune system
what is the difference between graft vs host and graft vs tumour reaction
GvH
GvHD occurs when the donor’s immune cells attack the patient’s tissues, leading to various complications.
GvH is life-threatening
GvT
Donor T cells are capable of recognising residual leukemic cells and mounting an immune response against them
GvT is a beneficial effect
what is the first line of treatment for Graft vs Host disease
Corticosteroids –> lower immune response
what transports iron in the blood
transferrin
where is iron stored in
liver and reticulocytes
what is DIC, signs and symptoms, what tests would you run to diagnose it, and how would you treat it
Abnormal activation of coagulation pathways causes the formation of intravascular thrombi and depletion of platelets and clotting factors.
SIGNS AND SYMPTOMS:
petechiae
Purpura
ecchymosis (bruises)
coma/delirium
gangrene
hypotension
tachycardia
TESTS:
Low platelets
low fibrinogen
low PT
low aPPT reflecting low circulating clotting factors
D-dimer (elevated – fibrin breakdown products)
TREATMENT:
would give fresh frozen plasma for platelet transfusion and coagulation factor transfusion
what is tumour lysis syndrome
Oncological emergency which is a complication of cancer therapy. Caused by rapid breakdown of large numbers of cancer cells and subsequent release of intracellular contents (potassium, phosphate, nucleic acids) into the bloodstream which overwhelms normal homeostatic mechanisms.
what are symptoms of sickle cell disease
Sickle cell crisis - generalised pain
Anaemia
Frequent infections due to asplenia → loss of spleen function
Acute Chest Syndrome: sudden onset of chest pain, fever, and respiratory symptoms. It can be life-threatening and is often triggered by infection or infarction of the lung tissue. → very dangerous/high risk of mortality
Embolic events
Jaundice
what population is more common in sickle cell disease
More common in afro-Caribbean
what tests do you run in a patient that you suspect of sickle cell disease
FBC
Peripheral blood smear
Reticulocyte count
U&E
Sickle solubility test
X-ray to look for bone damage (avascular necrosis)
Hb separation –> similar to haemoglobin electrophoresis, this test helps identify and quantify different types of haemoglobin.
how do you treat sickle cell crisis?
hydroxyurea –> increases foetal Hb
analgesia
folic acid supplements
blood transfusions
hydration
monitoring including transcranial dopplers → to check for stroke
how do you prevent sickle cell crisis
stay warm
stay hydrated
get your vaccinations and antibiotics
regular blood transfusions
what is the only curative option for sickle cell anaemia?
stem cell transplant
What sickle cell medical emergency is one of the most dangerous and one of the leading causes of death?
Acute chest syndrome
what is thalassaemia and what are the types
efficiency in the production of either alpha or beta globin chains
Abnormal alpha-globin gene → Alpha thalassemia
Abnormal beta-globin gene → Beta thalassaemia
what pattern of inheritance does thalassaemia have
recessive
what are the treatments for thalassaemia?
Bone marrow transplant is the only curative option
Regular blood transfusions for survival
what is the most common complication of thalassaemia? and why
iron toxicity because:
the body does not have a natural mechanism to excrete excess iron → regular blood transfusions cause a gradual buildup of iron
Ineffective Erythropoiesis: the body tries to compensate for ineffective rbc production by increasing iron absorption from the gastrointestinal tract
Iron released from Hb during the breakdown of old rbc is not effectively recycled
what is the normal female haemoglobin
Female normal → 110-147g/l
what is the normal male haemoglobin?
Male normal → 131 – 166g/l
what are the causes of microcytic anaemia?
Iron deficiency
Thalassaemia
Vit C deficiency → Vit C helps absorb iron
where is iron absorbed?
duodenum and upper jejunum.
what are the different causes of iron deficiency?
assume blood loss until proven otherwise
(ex.: gastrointestinal, menstrual)
Pregnancy (500mg-1000mg transferred to foetus, body stores 4g)
Impaired absorption;
Coeliac
Gastrectomy
Dietary deficiency
what are signs of iron deficiency
Glossitis - Smooth tongue, loss of differentiation
Brittle nails
Koilonychia - spoon-shaped nails
Angular stomatitis
what are the 1st line tests for iron deficiency anaemia?
BC:
Low haemoglobin = anaemia
<13.5g in males
<12g in females
MCH (Mean Corpuscular Hemoglobin)
MCHC (Mean Corpuscular Hemoglobin Concentration)
MCV - mean corpuscular volume (<80)
blood smear (microcytic hypochromic rbcs)
how do you treat iron deficiency
Oral iron → ferrous sulphate 200mg one to three times daily
OR
IV iron → ferric gluconate
iron rich diet
what are the general symptoms of anaemia
fatigue, pallor, shortness of breath, palpitations, chest pain, tachycardia, exertional dyspnoea
what is iron deficiency anaemia characterised as histologically?
Microcytic, hypochromic anaemia
hypochromic = low haemoglobin
what are the gold standard tests for iron deficiency anaemia
Serum ferritin → LOW (diagnosis)
Serum Iron → LOW
Transferrin saturation (TSAT) → LOW → More transferrin is synthesised in iron deficiency but this measurement is expressed as the ratio between serum iron to TIBC → low serum iron will cause a decreased TSAT
TIBC - Total Iron Binding Capacity → looks at all proteins which transfer iron in the blood, including transferrin
bone marrow biopsy (absent iron storage)
what would you be worried about in a patient above 60 years old with iron deficiency? what test would you do
GI bleeding or malignancy
endoscopy
what are the causes of normocytic anaemia? explain them
Chronic disease
Renal disease
Acute bleeding
Reticulocytes - count gives information on turnover of RBCs
Doping - exogenous EPO often cycling
Kidney failure - reduction in EPO production -> leads to anaemia
Glucose-6-phosphate dehydrogenase deficiency –> genetic condition which results in destruction of rbc
what are the causes of macrocytic anaemia?
Folate deficiency - B9
B12 deficiency (B12 also called cobalamin)
Haemolysis → results when there are structural abnormalities in Hb production
Bone marrow disorders
what are the functions of folate?
methylation reactions
methionine synthesis
DNA synthesis
what are the functions of B12
rbc synthesis
DNA synthesis
neuron synthesis
where is folate absorbed
proximal jejunum
what are the causes of folate deficiency
Poor nutrition (found in green vegetables, nuts, yeast; destroyed by cooking)
Malabsorption → coeliac, Crohn’s
Pregnancy
Haemolysis
where is B12 found
in animal-derived products; meat, fish, eggs, dairy.
what are causes of pernicious anaemia
autoimmune destruction of parietal cells or intrinsic factor
gastrectomy/ ileal resection
Vegan diet
what test do you do to diagnose pernicious anaemia?
IF antibodies
what is pernicious anaemia?
vitamin B12 deficiency specifically due to malabsorption of B12, not due to insufficient intake.
what are the causes of vit B12 deficiency?
Malnutrition
gastric surgery (harms top parietal cells)
chronic GI disease e.g., Chron’s
pregnancy
key presentations of vit B12 deficiency
RBC related
Lemon-yellow skin → excessive breakdown of macrocytic rbc due to pernicious anaemia
Neuro related
peripheral neuropathy and paraesthesia
loss of vibration sense or proprioception
mood or cognitive changes
visual changes
what is ataxia
group of disorders that affect coordination, balance, and speech
1st line investigations for B12 deficiency
FBC
peripheral blood smear
2nd line investigations for B12 deficiency
IF antibodies
serum B12
gastric parietal cell antibody
how do you manage vit B12 deficiency
oral B12 if due to dietary deficiency
if due to pernicious anaemia you need B12 (the problem is malabsorption) –> hydroxocobalamin injections 3 times weekly for 2 weeks
In combined B12 and folate deficiency which one is administered first: B12 or folate?
B12 because the consequences from B12 deficiency are worse so they need to be prioritised
compensated haemolysis vs decompensated haemolysis
Compensated haemolysis – increased rbc destruction matched by increased synthesis
Decompensated haemolysis – rate of destruction exceeds rate of synthesis
what are causes of haemolysis
hereditary spherocytosis
sickle cell
Autoimmune haemolytic anaemias
prosthetic heart valves
Mismatched blood tranfusion
Haemolytic disease of new born
Paroxysmal Nocturnal Hemoglobinuria → abnormal haemolysis at night
Lymphoproliferative disorders
what are the tests you do for haemolytic anaemia
Peripheral blood smear
Reticulocyte count → elevated
Bilirubin + unconjugated bilirubin (the result of excessive haemolysis)
Lactate dehydrogenase
Haptoglobin → protein that binds to free haemoglobin released from ruptured red blood cells → DECREASED levels in haemolytic anaemia cuz haptoglobin bound to Hb, not free-floating
Direct antiglobulin test → Coomb’s Test → looks at antibodies against rbc; diagnoses autoimmune haemolytic anaemia
what is autoimmune haemolytic anaemia, what size is the rbc (micro, normo or macrocytic anaemia)
normocytic/macrocytic –> it depends
what are the types of autoimmune haemolytic anaemia and explain the differences
Warm – haemolysis occurs at temperatures greater than or equal to core body temperature (37 degrees).
Most common.
IgG antibodies.
Haemolysis tends to occur in extravascular sites (eg spleen)
causes: idiopathic, viral infections, lymphomas, leukaemia, lupus
Cold – haemolysis occurs at cold temperatures (0-10 degrees).
Rare.
IgM antibodies
Haemolysis tends to occur in intravascular sites
causes: leukaemia and lymphoma
key presentations of autoimmune haemolytic anaemia
Jaundice, hepatosplenomegaly, kidney damage which results in reduced urine output
1st line test for autoimmune haemolytic anaemia
peripheral blood smear
FBC
normocytic anaemia
increased reticulocytes
increased lactate dehydrogenase
increased bilirubin
what is the gold standard test for autoimmune haemolytic anaemia?
Direct coombs test: detect antibodies bound to RBC surface
how do you manage autoimmune haemolytic anaemia
Blood transfusions, prednisolone (steroids), rituximab (monoclonal antibody against B cells), splenectomy
Cold autoimmune haemolytic anaemia responds less well to steroids
what is aplastic anaemia
Pancytopenia – all blood cell lines are decreased (anaemia, leukopenia, thrombocytopenia). Bone marrow fails and stops making haematopoietic stem cells. Normocytic, not-haemolytic (fewer RBCs than normal)
what is the cause of aplastic anaemia
Idiopathic. Autoimmune destruction of haematopoietic stem cells
what are the clinical manifestations, investigations, and management options for aplastic anaemia
fatigue
pale (no more rbc)
bleeding
petechiae
recurrent infection
tests:
FBC
Bone marrow biopsy
Management:
stem cell transplant under 50yr old
immunosuppressive therapy and blood transfusions over 50yr
what is polycythemia
Proliferation of the erythrocyte cell line. Increase in RBC count and haematocrit
primary vs secondary polycythemia
PRIMARY - polycythemia vera
overproduction of red blood cells, white blood cells, and platelets in the bone marrow.
SECONDARY
occurs as a result of an underlying condition or external factor that stimulates the body to produce more red blood cells
Chronic hypoxia
COPD
Certain kidney diseases –> erythropoietin
dehydration
what causes polycythemia vera
JAK2 mutation
presentation of polycythemia
Conjunctival plethora (excessive redness of conjunctiva)
Splenomegaly
“ruddy” complexion (like sunburn)
itching skin, especially after warm water
erythromelalgia (burning sensation in fingers and toes)
what is the 1st line investigation for polycythemia vera?
FBC (raised Hb, haematocrit, WCC, platelets)
low erythropoietin → PV is driven by a mutation (JAK2 mutation) that results in the continuous stimulation of hematopoietic cells in the absence of the usual regulatory mechanisms. As a result, the production of red blood cells is increased independent of the body’s oxygen needs.
Despite the increased red blood cell production, the kidneys sense the higher red blood cell count and appropriately suppress the production of erythropoietin to avoid further stimulation of erythropoiesis.
what is the gold standard investigation for polycythemia vera
Genetic testing (JAK2 mutation)
what are the complications of polycythemia vera
Risk of clotting (stroke, MI, PE, Budd Chiara – liver clot), progression to acute myeloid leukaemia
what are thrombocytopenias
Deficiency of platelets in bloods
what are the causes of thrombocytopenias?
Reduced platelet production in BM - malignancies
Excess peripheral destruction of platelets - viral infections
Problems of enlarged spleen
what are the 2 types of thrombocytopenias?
Immune thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
which type of thrombocytopenia is more common
Immune thrombocytopenic purpura (ITP)
what type of antibodies are responsible for immune thrombocytopenic purpura
IgG
clinical presentation of thrombocytopenia
Easy bruising
Purpura – red or purple spots on skin caused by bleeding underneath
Epistaxis – nose bleed
Menorrhagia
Gum bleeding
what is epistaxis
nose bleed
what are the investigations and treatment for immune thrombocytopenic purpura?
Investigations:
FBC
Thrombocytopenia – low levels of platelets
Bone marrow biopsy - Increased megakaryocytes
May have detection of platelet autoantibodies
Treatment:
Corticosteroids i.e. prednisolone (1st line treatment) → to suppress immune response
Splenectomy (2nd line treatment)
IV Immunoglobin e.g. IV IgG
what is the cause of Thrombotic thrombocytopenic purpura (TTP)
ADAMTS 13
what are the 2 types of haemophilia and what are they caused by
what is the pattern of inheritance
X linked inherited severe bleeding disorders.
Haemophilia A is caused by deficiency in factor VIII
Haemophilia B is caused by deficiency in factor IX (aka Christmas disease)
what are the key presentations for haemophilia
Spontaneous bleeding, easy bruising (ecchymosis), hematomas, prolonged bleeding after trauma or surgery, hemarthrosis (bleeding into joint spaces), epistaxis (nose bleeds), GI bleeding, bleeding from brushing teeth, haematuria, bleeding into muscles
1st line and gold standard investigations for haemophilia + management of the 2 types of haemophillia
1st line
Normal prothrombin time, prolonged activated partial thromboplastin time, FBC (usually normal, low Hb from bleeding), VWF (normal)
Gold Standard
Plasma factor VIII and IX assay (decreased or absent VIII – haem. A, IX – haem. B)
TREATMENT:
1st line Haemophilia A – factor VIII injection, desmopressin (stimulates VWF, boosts VIII activity)
1st line Haemophilia B – factor IX injection.
Also: antifibrinolytic (tranexamic acid).
what is VON WILLEBRAND DISEASE?
Most common inherited cause of abnormal bleeding (haemophilia) due to deficiency, absence, or malfunction of Von Willebrand factor.
more common in females
what is Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency is a genetic condition which leads to the destruction of RBCs.
normocytic and haemolytic anaemia
