Haematology Flashcards
Define anaemia
Anaemia describes a low haemoglobin concentration due to either a reduction in the proportion of circulating red blood cells or increased plasma volume (pregnancy).
Give 3 mechanisms in which anaemia can be caused by
Blood loss (acute or chronic)
Haemolytic anaemia
Deficient/defective erythropoiesis
Define MCV
Mean Cell Volume - Describes the average size of red blood cells in a sample
Define MCH
Mean Corpuscular Haemoglobin - Describes the average quantity of haemoglobin present in a single red blood cell
Define MCHC
Mean Corpuscular Haemoglobin Concentration
Describes a calculation of the amount of haemoglobin per unit volume in a single red blood cell
Describe the reticulocyte count
Describes a count of the number of immature RBCs in the bone marrow.
(if the cause if anaemia is a production issue, this will be low. If the cause is a removal issue, this will be high)
Describe the use of Ferratin in testing for anaemia
Ferritin is a blood protein that contains Iron.
Low ferritin indicates the body’s iron stores are low, which may indicate iron deficiency anaemia.
When may ferratin levels increase? Why?
May increase during inflammation.
As ferritin is an acute phase reactant
What types of anaemia present with a low MCV? (3)
Iron Deficiency Anaemia (most common)
Thalassaemia
Sideroblastic anaemia
What types of anaemia present with a normal MCV? (5)
Acute Blood Loss
Anaemia of chronic disease
Bone marrow failure
Hypothyroidism
Pregnancy
What types of anaemia present with a high MCV? (3)
B12/Folate deficiency anaemia
Alcohol excess
Antifolate drugs (phenytoin)
What effect does phenytoin have on blood cells?
Can cause folate deficiency, leading to macrocytic anaemia
Where in the intestine is iron absorbed? And how?
Duodenum
Iron ions are actively transported into duodenal intestinal epithelial calls by the intestinal haem transporter (HCP1).
What type of anaemia is iron deficiency anaemia?
Microcytic
Give 4 causes of iron deficiency anaemia
Blood loss (menorrhagia, GI bleeding, Hookworm)
Poor diet/poverty (reduced iron intake)
Malabsorption (coeliac disease)
Pregnancy
Give 5 clinical features of iron deficiency anaemia
Anaemic features (fatigue, dyspnoea, faintness)
Brittle nails/hair
Koilonychia (spoon-shaped nails)
Atrophic glossitis (smooth/glossy tongue)
Angular stomatitis/cheilosis (ulcers in corners of mouth)
If microcytic anaemia does not respond to iron therapy, what could it be? Describe this condition.
Sideroblastic anaemia
Describes condition characterised by ineffective erythropoiesis resulting in increased iron absorption in the duodenum and iron loading in the bone marrow.
Define anaemia of chronic disease and describe it’s cause.
Describes anaemia secondary to chronic disease.
Involves the polypeptide hepcidin (produced by the liver).
Hepcidin production increases in chronic diseases, inhibiting the release of iron from macrophages. Hepcidin ultimately inhibits iron transport and absorption.
Give 4 common conditions causing anaemia of chronic disease
Tuberculosis
Crohn’s disease
Rheumatoid Arthritis
SLE
How is anaemia of chronic disease treated? (2)
Treat underlying chronic condition.
Erythropoietin (EPO)
Describe 2 categories of macrocytic anaemia
Megaloblastic - Characterised by presence of megaloblasts (b12/folate deficiency)
Non-megaloblastics - Erythroblasts are normal (alcohol excess, pregnancy)
Where is vitamin B12 absorbed?
Ileum (small intestine)
What factor must be present for Vitamin B12 to be absorbed?
Intrinsic factor
Where is intrinsic factor (important for B12 absorption) produced?
Parietal cells of the stomach
Where is B12 stored?
Liver (for 4 years)
Describe the use of vitamin B12 and why it’s deficiency leads to anaemia.
B12 helps synthesise Thymidine and hence DNA.
Defiency results in impaired DNA synthesis > delayed nuclear maturation in cells undergoing erythropoiesis > generation of abnormally large RBCs + decreased RBC production.
In what foods can vitamin B12 be found? (3)
Meat, Fish, Diary products
Give 3 causes of vitamin B12 deficiency
Pernicious anaemia (most common)
Dietary deficiency (vegans not using supplements)
Malabsorption (post-gastrectomy - no intrinsic factors, Crohn’s disease)
Describe pernicious anaemia
Autoimmune condition in which atrophic gastritis affects the fundus of the stomach.
Plasma cell and lymphoid infiltration leads to destruction of parietal cells.
Leads to intrinsic factor deficiency which results in less B12 being absorbed in the ternimal ileum, leading to macrocytic anaemia.
What cells produce stomach acid?
Parietal cells
Give 5 risk factors for pernicious anaemia
Elderly
Female
Fair haired/Blue eyes
Blood group A
Hypothyroidism and Addison’s disease
Give 4 clinical features of pernicious anaemia
Insidious onset (progressively increasing symptoms of anaemia)
Lemon tinge to skin (pallor + jaundice)
Glossitis (red beefy tongue)
Angular cheilosis (stomatitis)
What system is distinctively effected in B12 deficiency anaemia? What features may be present?
Neurological system
Symmetrical paraesthesia (fingers/toes)
Early loss of vibration and proprioception
Progressive weakness and ataxia
Dementia, irritability, depression or psychosis.
Give 3 clinical neurological signs of B12 deficiency
Positive babinski (UMN)
Absent knee jerk (LMN)
Absent ankle jerk (LMN)
Give 3 diagnostic tests used for B12 deficiency
Blood film (Macrocytic RBCs, Oval Macrocytes)
FBC (Raised MCH, Low Hb, Low B12)
Serology (parietal cells Abs, intrinsic factor Abs)
Presence of what is specific for pernicious anaemia diagnosis?
Intrinsic factor antibodies
What IM injection can be given to malabsorption patients with pernicious anaemia?
Hydroxocobalamin (synthetic B12)
What type of anaemia does folate deficiency cause?
Macrocytic anaemia
What foods contain folate? (3)
Fruits, Leafy Green vegetables, Liver
Where is folate absorbed in the intestine?
Duodenum/Proximal Jejenum
Give 4 causes of folate deficiency
Poor diet (main cause)
Pregnancy
Malabsorption (coeliac/Crohn’s)
Antifolate drugs - Methotrexate/Trimethoprim)
Give 3 antifolate drugs
Phenytoin
Methotrexate
Trimethoprim
Give 4 risk factors for folate deficiency
Elderly
Alcoholics
Pregnant
Crohn’s/Coeliac
What type of anaemia may present with neuropathy?
B12 deficiency anaemia
What is the treatment for folate deficiency anaemia? (2)
Treat underlying cause
Folic acid OD for 4 months
(Never give without B12, unless pt is known to have normal B12, as low B12 states can precipitate/worsen subacute combined degeneration of the spinal cord)
Define aemolysis
Describes the premature breakdown of RBCs.
Describe 2 types of haemolytic anaemia
Uncompensated and Compensated Haemolytic Anaemia
Where can haemolysis occur? (2)
Intravascular - Occurs in circulation
Extravascular - Occurs in reticuloendothelial system (macrophages of bone marrow, liver and spleen)
Describe what happens in the bone marrow during haemolytic anaemia (2)
To compensate for increase in haemolysis, bone marrow increases output be increasing proportion of cells committed to erythropoiesis (RBC production).
Reticulocytes are also released prematurely, these are larger than mature cells (macrocytic) and stain blue on peripheral blood film.
Give 2 causes of haemolytic anaemia
Acquired (inflammatory, infection, blood transfusion rejection, hypersplenism)
Hereditary (G6PD/Pyruvate Kinase Deficiency, Sickle Cell, Spherocytosis)
Give 3 hereditary causes of haemolytic anaemia
Enzymopathies (G6DP or Pyruvate Kinase Deficiency)
Haemoglobinopathies (Sickle Cell, A/B thalassaemia)
RBC membrane defects (elliptocytosis or spherocytosis)
Describe autoimmune haemolytic anaemia
Anaemia characterised by autoimmune destruction of RBCs
What test is used to diagnose autoimmune haemolytic anaemia?
Coombs Test (positive direct antigloblin test)
Describe 2 classifications of autoimmune haemolytic anaemia
Warm (AIHA);
- Caused by IgG
- Haemolysis occurs in extravascular sites (spleen)
- Causes - Autoimmune disease (SLE), Neoplasia, Methyldopa
Cold AIHA
- Caused by IgM
- Haemolysis mediated by compliment, occurs intravascular
- Features include; Raynaud’s and acrocyanosis
How is autoimmune haemolytic aneamia managed?
Steroids - Prednisolone
How is Glucose 6 Phosphate Dehydrogenase Deficiency inherited?
Heterogenous X-linked condition (more common in males)
What is the pattern of inheritance of spherocytosis?
Autosomal Dominant
Describe inherited spherocytosis
Describes deficiency in RBC membrane protein Spectrin.
Deficiency results in loss of RBC membrane stability > Spherocytosis > reduced MCH and Increased MCHC.
Spherocytes are more rigid and les deformable therefore unable to pass through the spleen. Resultantly are destroyed via extravascular haemolysis
Describe the clinical presentation of inherited spherocytosis (2)
Jaundice at birth (delayed and asymptomatic)
Splenomegaly
How is inherited spherocytosis treated?
Splenectomy
(Relieves symptoms of anaemia or splenomegaly and prevents recurrent gall stones).
Describe the composition of normal Hb (HbA)
Haem + 2 Alpha Chains + 2 Beta Chains
Describe the composition of foetal Hb (HbF)
Haem + 2 Alpha Chains + 2 Gamma Chains
Describe the composition of delta (HbA2)
Haem + 2 Alpha Chains + 2 Delta Chains
Describe thalassaemia
Describes genetic conditions of unbalanced HB synthesis, with underproduction (or no production) of one globin chain.
Unbalanced globins precipitate within mature RBCs leading to haemolysis.
What are the 2 most common types of thalassaemias
Alpha thalassaemia (reduced A chain synthesis)
Beta thalassaemia (reduced B chain synthesis)
Define beta thalassaemia
Caused by mutation on chromosome 11 leading to decreased/no B chain Production.
Name 3 types of beta thalassaemia
Beta thalassaemia minor (trait/carrier)
Beta thalassaemia intermedia
Beta thalassaemia major
Describe beta thalassaemia minor (3)
Trait/carrier - heterozygous beta thalassaemia
Asymptomatic (anaemia is mild/absent)
Hb electrophoresis shows raised HbA2 and raised HbF
Describe beta thalassaemia intermedia (2)
Intermediate symptomatic state with moderate anaemia
Splenomegaly, bone deformities, gallstones, infections
Describe beta thalassaemia major
Presents in children with homozygous B-thalassaemia within the first year of life with;
Failure to thrive and recurrent bacterial infections
Severe anaemia from 3-6 months (when switch from gamma to beta chain occurs)
Extramedullary haematopoiesis > hepatosplenomegaly)
What skull x-ray sign may be seen in a patient with beta thalassaemia major?
Hair on end sign (increased marrow activity)
Describe the size of RBCs in beta thalassaemia major
Blood film = Large and Small irregular hypochromic RBCs
Give 3 complications of blood transfusions
Iron overload;
Mainly deposits in liver and spleen resulting in liver fibrosis and cirrhosis
Deposits in endocrine glands and heart, resulting in diabetes, hypothyroidism, hypocalcaemia and premature death.
Define sickle cell anaemia
Describes an autosomal recessive disorder in which production of abnormal haemoglobin leads to vaso-occlusive crisis.
Sickle cell anaemia has which pattern of inheritance?
Autosomal recessive
Sickle cell anaemia protects against which form of malaria?
Falciparum malaria
Describe vaso-occlusive crisis in terms of sickle cells
Sickle cells have a strong adherence to the endothelium. This can cause obstruction of small vessels, resulting in tissue infarction and pain.
Give 5 triggers of sickle cell vaso-occlusive crisis
Hypoxia
Cold weather
Infection
Dehydration
Stress
How may homozygous sickle cell anaemia present? (6)
Vaso-occlusive crisis
Mesenteric ischaemia (mimics acute abdomen)
CNS infarction
Acute chest syndrome
Pulmonary hypertension
Anaemia
Describe vaso-occlusive crisis (3)
Common due to microvascular occlusion
Affects marrow causing severe pain
Presents as dactylitis in children <3
Describe acute chest syndrome (sickle cell)
Occurs in 30% of patients. Describes vaso-occlusive crisis of the pulmonary vasculature.
Caused by; Infection, fat embolism, sequestration of sickle cells in pulmonary vasculature > pulmonary infarction.
Causes; dyspnoea, chest pain, hypoxia
Give 2 ways sickle cell causes anaemia
Splenic sequestration (sickle cells get trapped in spleen = acute, painful splenomegaly)
Bone marrow aplasia (aplastic crisis) (commonly follows infection with erythrovirus B19)
What infection commonly causes bone marrow aplasia (aplastic crisis) in Sickle Cell?
Erythrovirus B12
What test is used to diagnose sickle cell anaemia?
Hb Electrophoresis
Distinguishes HbSS and HbAS states
How is sickle cell anaemia treated? (6)
Avoid precipitating factors (cold, dehydration, infection)
Oral Hydroxycarbamide (increases HbF levels)
Antibiotic and Immunisaiton prophylaxis
Analgesia (morphine, codine, paracetamol, NSAIDS) for acute pain
Blood transfusions for anaemia
Bone marrow transplantation
Describe lymphomas
Lymphomas describe disorders caused by the spread/proliferation of malignant lymphocytes.
These accumulate in lymph nodes, causing lymphadenopathy.
Describe the difference between lymphoma and leukaemia
Lymphoma cancer cells are predominantly present in lymph nodes and other tissues, while leukaemia cancer cells are present in bone marrow and blood.
In which type of lymphoma would you find Reed-Sternberg Cells?
Hodgkin’s Lymphoma (derived from B lymphocytes)
What is a key hallmark of Hodgkin’s Lymphoma?
Reed-Sternberg Cells
Describe the incidence of Hodgkin Lymphoma
2 peaks;
Young adults (most common malignancy in 15-24 yr olds)
Elderly people (males)
Give 5 risk factors for Hodgkin’s Lymphoma
An affected sibling
Immunocompromised (wiskott-aldrich syndrome)
Infection (EBV, HIV)
Autoimmune disease (SLE)
Post transplantation
Describe Wiskott-Aldrich Syndrome. What condition is it associated with?
Associated with Hodgkin’s Lymphoma.
Characterised by microthrombocytopenia. Decrease in size and number of platelets, leading to easy bruising, prolonged bleeding and bloody diarhoea.
Name 2 infections that can cause Hodgkin’s Lymphoma
EBV (glandular fever - infectious mononucleosis)
HIV
Give 6 clinical features of Hodgkin’s Lymphoma
Painless, cervical lymphadenopathy (rubbery on examination)
B-symptoms (fever, weightloss, nightsweats)
Mediastinal lymphadenopathy +/- cough
Cachexia (muscle wasting)
Anaemia
Hepato-splenomegaly
Give 1 clinical complication of Hodgkin’s lymphoma
Spinal cord compression (rare)
How is Hodgkin’s Lymphoma diagnosed?
Lymph node biopsy (presence of reed-sternberg cells)
What is the treatment for Hodgkin’s Lymphoma?
Combination chemotherapy ABVD;
Adriamycin
Bleomycin
Vinablastine
Dacarbazine
Give 4 complications of radiotherapy
Increased risk of second malignancies (in lung, breast, stomach, thyroid)
Increased risk of IHD
Increased risk of lung fibrosis
Increased risk of hypothyroidism
Give 4 side effects of chemotherapy
Myelosuppression > Infection
Nausea
Alopecia (hair loss)
Infertility
How is Hodgkin’s Lymphoma staged?
Lugano Classification (Uses PET scans to determine staging)
I - Confined to single lymph node
II - involvement of 2 or more nodal area on SAME side of diaphragm
III - involvement of nodes on both sides of diaphragm
IV - Spread beyond lymph nodes (e.g to bone marrow or liver)
A - no systemic symptoms other than pruritis
B- presence of B symptoms
Give 3 B Symptoms
Fever
Weight loss
Nightsweats
Describe non-hodgkin lymphoma
Describes all lymphomas without Reed-Sternberg Cells
What is non-hodgkin lymphoma strongly linked to? (2)
Epstein Barr Virus (EBV)
Burkitts Lymphoma
Give 4 clinical features of Non-Hodgkin Lymphoma
Superficial Lymphadenopathy
Extra-nodal diseases
B Symptoms
Pancytopenia
Give 3 extra-nodal diseases associated with non-hodgkin lymphoma
Gut (most common);
Gastric MALT lymphoma (H.pylori)
Non-MALT gastric lymphoma
Small bowel lymphoma
Skin (2nd most common);
Mycosis fugoides
Oropharynx;
Waldeyer’s ring lymphoma (sore throat/obstructed breathing)
How is non-hodgkin’s lymphoma categorised? Give examples;
Low/indolent grade (slow growing, incurable);
Includes;
- Follicular lymphoma
- Marginal Zone Lymphoma/MALT
High grade (more aggressive but curable)
Includes;
- Burkitt’s lymphoma
- Acute Lymphoblastic Leukaemia
- Diffuse large B cell lymphoma (most common)
What test is used to classify non-hodgkin lymphoma?
Lymph node excision/marrow biopsy
(will show no presence of Reed-Sternberg Cells)
What test is used for staging non hodgkin lymphoma?
CT/MRI or Chest x-ray (Ann arbor)
What drug is used to maintain remission in low grade non-hodgkin lymphoma? What is it’s MOA?
Rituximab
Monoclonal antibody, binds CD20 on surface of b cells.
Bindings initiates cytotoxicity +/- apoptosis
What is the treatment for high grade non-hodgkin’s lymphoma?
R-CHOP Regimen for 3 months
Rituximab
Cyclophosphamide
Hydroxy-Daunorubicin
Vincristine (oncovin)
Prednisolone
Define leukaemias
Describes cancer of bone marrow characterised by the dysfunctional development of leukocytes.
What are the 4 main subtypes of leukaemia
Acute Lymphoblastic Leukaemia (ALL)
Acute Myeloid Leukaemia (AML)
Chronic Myeloid Leukaemia (CML)
Chronic Lymphocytic Leukaemia (CLL)
What is the most common paediatric leukaemia?
Acute Lymphoblastic Leukaemia
What chromosome is commonly found in chronic myeloid leukaemia?
Philadelphia Chromosome (t9:22)
(Chromosome 22)
What type of mutation is present on the Philadelphia chromosome?
BCR-ABL gene fusion
Describe ALL
Acute Lymphoblastic Leukaemia
Describes arrested maturation and uncontrolled proliferation of immature lymphocyte precursor cells (lymphoblasts/blast cells) with bone marrow and tissue infiltration.
Describe the prognosis of ALL in children
Philadelphia chromosome - T(9:22) Bad prognosis
T(12:21) - Hyperdiploidy - Good prognosis
Give 2 factors associated with the development of ALL
Ionizing radiation (X-rays) during pregnancy
Down’s Syndrome (Trisomy 21)
Give 7 clinical features of ALL
Acute onset and rapid progression (days/weeks)
Fever, nightsweats, unexplained weightloss
Marrow failure (anaemia, Infection, Bruising/bleeding)
Bone pain
Hepatosplenomegaly
Painless Lymphadenopathy
Infections
What investigations would be worth performing on a patient with ? ALL (4)
Blood film (may show blast cells)
FBC (Low Hb, Low Platelets, Low WCC)
Chest X-ray/CT scan (mediastinal/abnormal lymphadenopathy)
Lumbar puncture (CNS infiltration)
How is ALL managed? (6)
Supportive (blood/platelet transfusions)
Allopurinol (prevents tumour lysis syndrome)
Prophylactic antivirals, antifungals or antibiotics)
IV fluids
Chemotherapy
Marrow transplantation
What dangerous complication can be triggered by combination chemotherapy?
Tumour Lysis Syndrome
How does Tumour Lysis Syndrome present biochemically?
High Uric Acid - Hyperuricaemia
High Potassium - Hyperkalaemia
High Phosphate - Hyperphosphatemia
Low calcium - Hypocalcaemia
How is Tumour Lysis Syndrome managed? What is it’s MOA?
Allopurinol
Xanthine oxidase inhibitor (inhibits production of uric acid)
What is the most common acute leukaemia in adults?
Acute Myeloid Leukaemia
Describe Acute Myeloid leukaemia
Describes a neoplastic proliferation of blast cells derived from myeloid lineages (give rise to basophils, neutrophils, eosinophils).
Give 3 cells derived from myeloid lineages
Basophils
Neutrophils
Eosinophils
Give 4 risk factors for Acute Myeloid Leukaemia
Long term complication of chemotherapy
Myelodysplastic syndromes
Radiation
Down’s Syndrome (trisomy 21)
Give 4 clinical features of AML
Marrow failure (Anaemia, Infection, Bleeding)
Hepato-splenomegaly
Gingival Hyperplasia (first sign of AML)
Disseminated intravascular coagulation
Define Disseminated Intravascular Coagulation
A condition where blood clots form throughout the body due to abnormal excessive generation of thrombin and fibrin in the circulating blood.
The presence of what may be found on a bone marrow biopsy of a patient with AML?
Auer rods
Describe chronic myeloid leukaemia
Myeloproliferative disorder characterised by an uncontrolled clonal proliferation of myeloid cells.
In whom does CML present?
Adults ONLY
Commonly presents between ages of 40-60
Give 5 clinical features of CML
Symptomatic anaemia (fatigue, dyspnoea ect)
Abdominal discomfort (due to splenomegaly)
Weight loss
Fever and sweats in absence of infection
Bleeding
What would a blood count show in a patient with CML? (3)
Very high WCC (with a whole spectrum of myeloid cells)
Low Hb (normochromic and normocytic)
Variable platelets
How is CML treated? (2)
Oral Imatinib (BCR/ABL tyrosine kinase inhibitor)
Stem cell transplant (only in younger patients)
Describe Chronic Lymphocytic Leukaemia (CLL)
Most common form of leukaemia, predominantly occurring later in life.
Characterised as the progressive accumulaiton of clonal dysfunctional malignant B cells.
What is the most common genetic abnormality leading to CLL?
Deletion in the long arm of chromosome 13
What can CLL develop into?
Richter’s syndrome - Aggressive Lymphoma
Give 3 clinical features of CLL
Often asymptomatic (appearing on routine FBC)
Anaemia or infection
Rubbery Lymphadenopathy
Give 3 complications of CLL
Autoimmune haemolysis
Increased infection risk (due to low IgG)
Bone marrow failure
What may be present on a blood film of a patient with CLL?
Smear cells
What may a blood count show for a patient with CLL? (2)
Raised WCC (with very high lymphocytes)
Signs of marrow failure (low Hb, platelets and neutrophils)
What is the 1st line medical treatment for CLL?
Fludarabine + Rituximab +/- Cyclophosphamide
Define myelodysplasia. What can it become?
Describes a clinical disorder of haematopoetic stem cells leading to dysplasia and ineffective haematopoesis in bone marrow.
Can become acute myeloid leukaemia
What can cause myelodysplasia
Carcinogenic agents;
Benzene
Radiation
Chemotheraputic agents
What cells can lymphoid stem cells differentiate into? (2)
T Lymphocytes
B Lymphocytes (eventually plasma cells)
What cells can myeloid stem cells become? (7)
Erythrocytes (RBCs)
Platelets
Mast Cells
Eosinophils
Polymorphs
Monocytes
Osteoclasts
What is the cellular precursor to a platelet?
Megakaryocyte
What is the cellular precursor to erythrocytes?
Reticulocytes
What is the cellular precursor to monocytes, basophils, neutrophils and eosinophils?
Myeloblasts
Define multiple myeloma. How is it characterised?
Describes a type of bone marrow cancer involving several areas of the body, including the spine, skull pelvis and ribs.
Multiple myeloma is characterised by the uncontrolled proliferation of clonal plasma cells (B lymphocytes)
Give 3 histological features of plasma cells in multiple myeloma
Plasma cells are 2-3 times larger
Plasma cells have eccentric nuclei (located on one side) that are round or oval
Plasma cells have a perinuclear halo (clear area around the nucleus)
How do plasma cells evade apoptosis in multiple myeloma?
Overexpression of BCL-2 allows cells to escape apoptosis.
Give 5 clinical features of multiple myeloma
Unexplained bone pain (in lower back/thorax)
Fatigue
Symptoms of hypercalcaemia (bone pain, abdo pain, depression, constipation ect)
Weight loss
Hepato-splenomegaly/Lymphadenopathy
Give 4 pathophysiological features of multiple myeloma
Progressive bone marrow failure (pancytopenia)
Destructive bone disease (malignant cells inhibit osteoblasts and stimulate osteoclasts)
Kidney failure (nephropathy - Tamm-Horsfall proteins)
Bacterial infections (2nd to neutropenia)
Give 3 severe complications of multiple myeloma
Spinal cord compression (urgent MRI if suspected)
Hyperviscosity (due to increased circulating immunoglobulins)
Acute renal injury
What test is used to diagnose multiple myeloma? What will it show?
Serum/urine gel electrophoresis followed by immunofixation electrophoresis (IE)
Shows presence of monoclonal band
What will a blood film show in a patient with multiple myeloma?
Rouleaux formations
What will a bone marrow biopsy show in a patient with multiple myeloma?
Elevated plasma cell count
What would an x-ray/MRI show in patients with multiple myeloma?
Lytic bone lesions in spine, pelvis, skull or ribs.
What criteria is used to describe the phenotype of multiple myeloma? (4)
CRAB criteria
C - Calcium Elevation
R - Renal dysfunction
A - Anaemia
B - Bone disease
What immunoglobulins are predominantly produced by multiple myeloma cells?
IgG (2/3 of cases)
IgA (1/3 of cases)
How is multiple myeloma treated?
Bisphosphonates (clodronate, zolendronate, pamidronate)
Immunomodulatory drugs (Thalidomide, Lenalinomide)
Corticosteroids (dexamethasone, prednisolone)
Anti CD38 monoclonal antibodies (Daratumumab)
Name 2 bisphosphonates and describe their moa
Clodronate and Zolendronate
Function by inhibiting osteoclast proliferation and inducing osteoclast apoptosis.
Give 2 complications of lenalidomide (Immunomodulatory drug). What is it important to monitor for?
Neutropenia and thromboembolism.
Monitor for sepsis and consider aspirin for anti-coagulation.
Give 4 differentials for multiple myeloma
Diabetes mellitus
Polymyalgia Rheumatica
Waldenstrom’s macroglobulinaemia (high levels of IgM not IgG)
Amyloid light chain amyloidosis.
What does a PTT blood test test?
Partial Thromboplastin Time
Intrinsic pathway
Give 2 causes for a prolonged PTT
Factor VIII deficiency (Haemophilia A or Von-Willebrand disease)
Factor IX deficiency (Haemophilia B)
What does PT measure?
Prothrombin time
Extrinsic pathway
What can cause a prolonged PT time
Factor VII deficiency (early sign of DIC)
What can cause both a prolonged PTT and PT? (4)
Vitamin K deficiency
Severe DIC
Liver disease
High dose heparin or DOAC
How would haemophilia present with regards to PTT, PT and bleeding time?
PTT - Increased
PT - Normal
Bleeding time - Normal
How would Von Willebrand’s disease present with regards to PTT, PT and Bleeding time?
PTT - Increased
PT - Normal
Bleeding time - Increased
How would vitamin K deficiency present with regards to PTT, PT and Bleeding time?
PTT - Increased
PT - Increased
Bleeding time - Normal
Name 2 Low Molecular Weight Heparins
Enoxaparin and Dalteparin
What is the moa of heparin?
Binds to antithrombin III, increasing it’s activity.
Antithrombin III inhibits activated factor X, factor II (thrombin) and factor IX.
What can be used to reverse the effects of heparin?
Protamine Sulfate
What is the MOA of Warfarin?
Inhibits vitamin K reductase.
Thus inhibits factors II, VII, IX, X (1972)
What factors are dependent on vitamin K?
Factors II, VII, IX, X (1972)
What can be used to reverse the effects of warfarin?
Vitamin K
Name 2 DOACS
Direct Oral Anti Coagulants
Rivaroxaban and Apixaban
What type of drugs are Rivaroxaban and Apixaban? What is their moa?
Direct Oral Anti Coagulants
Direct factor X inhibitors
What class of drugs are dabiatran and Agatraban and what is their moa?
Direct Oral Anti Coagulants
Direct thrombin inhibitors
What substances produced by the body maintain blood vessels in a non-clotting state? (3)
Prostacyclin (inhibits platelet activation)
Nitrous Oxide (inhibits platelet adhesion + dilates vessels)
Endothelial ADPase (inhibits ADP which is a platelet activator)
Describe Deep Vein Thrombosis
Describes the development of a blood clot, within a vein deep to the muscular tissue planes.
Where do DVTs commonly develop?
Lower leg, thigh or pelvis
Give 6 risk factors for DVT
Immobility (surgical patients, long haul fights)
Oral contraceptive pill
Age
Pregnancy
Trauma
Cancer
How does the Oral Contraceptive Pill increase risk of DVT?
Synthetic oestrogen increases plasma fibrinogen and the activity of coagulation factors VII and X
Give 5 clinical features of DVT
Unilateral presentation
Pitting oedema
Signs of inflammation (swelling, redness, hot, throbbin pain)
Tenderness
Prominent (dilated/distended) superficial veins
What score is used to assess the probability of DVT?
Wells’ Score
Describe the use of the Wells’ Score and state what factors it considers. (9)
Scoring system used to assess probability of DVT.
DVT likely if a score of 2 or more is achieved.
1 point is given to each of the following;
- Active cancer or within last 6 months
- Paralysis, paresis or recent plaster immobilisation
- Recently bedridden for > 3 days or major surgery in last 12 weeks
- Localized tenderness along back of the calf
- Entire leg is swollen
- Calf swelling by >3cm compared to other leg
- Pitting oedema confined to the symptomatic leg
- Collateral superficial veins (non-varicose)
- Previous DVT
If a Wells’ score of ≤1 is given, what does this indicate and what should be subsequently done?
Indicates DVT is unlikely
Perform D-dimer test;
- If Negative - Exclude DVT
- If Positive - Offer Proximal Leg Vein USS
If a Wells’ score of ≥2 is given, what does this indicate and what should be subsequently done?
Indicated DVT is likely
Perform D-Dimer and USS within 4 hours
- If both negative - Exclude DVT
- If USS positive - Treat as DVT
- If D-dimer is positive but USS is negative, repeat USS in 1 week
What should be done is a proximal leg USS cannot be carried out within 4 hours?
Conduct a D-Dimer Test and give DOAC (interim therapeutic anticoagulation)
What is given as interim therapeutic anticoagulation if a proximal vein USS cannot be performed within 4 hours (pt has a Wells’ score of >2)
DOAC (Apixaban or Rivaroxaban)
(LMWH previously used)
For a patient with ?DVT, if an USS is negative but a D-dimer is positive, what are the next steps? (2)
Stop interim therapeutic anticoagulation
Offer a repeat proximal leg vein USS 6-8 days later
What is D-Dimer?
D-Dimer is a fibrin degradation product (Fibrin is used to provide a scaffold for platelets during clot formation - haemostasis)
Describe the treatment of confirmed DVT
1st line - Apixaban or Rivaroxiban
2nd line - LMWH followed by Dabigatran or edoxaban OR LMWH followed by Warfarin
How is DVT treated for patient with severe renal impairment (<15/min)?
LMWH, Unfractioned heparin or LMWH followed by Warfarin
If a patient with antiphosphilipid syndrome has DVT, how should they be treated?
LMWH followed by Warfarin
For how long should DVT patients have anticoagulation?
At least 3 months
What is the classic triad for PE presentation?
Pleuritic chest pain
Dyspnoea (breathlessness)
Haemoptysis (coughing blood)
Give 4 common clinical findings for PE
Tachypnoea (resp rate >20/min)
Crackles on auscultation
Tachycardia (HR >100bpm)
Fever
What initial imaging investigation should be conducted in all patients with suspected PE? Why?
Chest X-ray - To exclude pneumothorax
What score is used to assess the likelihood of PE? What is the criteria for this?
PE Wells Score
PE Likely if score >4
PE unlikely if score <4
What criteria are used in a PE Wells’ score? (7)
Clinical signs/symptoms of DVT (3 points)
Alternative diagnosis less likely than PE (3 points)
Heart rate >100bpm - (1.5 points)
Immobilisation for >3 days or surgery in last 4 weeks (1.5 points)
Previous DVT/PE (1.5 points)
Haemoptysis (1 point)
Malignancy (on treatment or in last 6 months) (1 point)
If PE Wells’ score is >4 what are the next steps
Score > 4 = PE Likely
Arrange immediate CTPA
If positive - Diagnose PE
If negative - Consider Proximal Leg Vein USS if DVT is suspected
If PE Wells’ score is <4 points, what are the next steps?
Score <4 = PE Unlikely
Arrange D-Dimer test
If positive - Arrange CTPA
If negative - Stop anticoagulation and consider alternative diagnosis
If PE Wells’ score is >4 (PE likely) and CTPA is not immediately available, what should be done?
Commence interim therapeutic anticoagulation with DOAC (rivaroxaban or apixaban)
What score is used to exclude PE in patients known to have a low pre-test probability (<15%)
PERC - Pulmonary embolism rule out criteria
What are the criteria for PERC? (8) How is it interpreted?
Pulmonary Embolism Rule Out Criteria (PERC)
Age >50
Heart rate >100
Oxygen saturations <94%
Previous DVT or PE
Recent surgery or trauma in the past 4 weeks
Haemoptysis
Unilateral leg swelling
Oestrogen use (HRT, contraceptives)
If all of the above are absent the post-test probability of PE is <2%
What is the imaging tool used to diagnose PE?
CTPA
What may be seen on an ECG for a patient with PE?
S1Q3T3
Large S wave in lead I
Large Q wave in lead III
Inverted T wave in Lead III
Describe the management of PE
1st line - Apixaban or Rivaroxiban
2nd line - LMWH followed by Dabigatran or edoxaban OR LMWH followed by Warfarin
How long should a patient have anticoagulation treatment if their VTA was provoked (i.e following immobilisation due to major surgery)?
Stopped after initial 3 months.
(3-6 months for patient with active cancer)
How long should a patient have anticoagulation treatment if their VTA was unprovoked?
Continue for 6 months.
Define polycythemia vera
Describes a myeloproliferative disorder caused by clonal proliferation of marrow stem cells, leading to an increase in red cell volume.
Often accompanied by overproduction of neutrophils and platelets
A mutation in what is present in 95% of polycythemia vera patients?
Jack2
Give 6 clinical features of polycythemia vera
Pruritus, typically after a hot bath
Splenomegaly
Hypertension
Hyperviscosity (arterial/venous thrombosis)
Low ESR
Haemorrhage (2d to abnormal platelet function)
What tests should be performed in a patient with suspected polycythaemia vera? (4)
FBC/Blood film (raised haematocrit, neutrophils, basophils and platelets)
JAK2 mutation
Serum ferritin
Renal/Liver function tests
What criteria is required to diagnose JAK2-positive polycythemia vera?
Both A1+A2;
A1 - High haematocrit OR raised red cell mass
A2 - Mutation in JAK2
Give 4 causes of secondary polycythemia
COPD
Altitude
Obstructive sleep apnoea
Excessive erythropoietin; cerebellar haemangioma, hypernephroma, hepatoma.
Name 2 blood film findings suggestive of hyposplenism
Howell-Jolly bodies and Siderocytes
Outline the key points for using Packed Red Cells
Used for transfusion in chronic anaemia and cases where infusion of large volumes of fluid may result in cardiovascular compromise
Outline the key points for using Platelet Rich Plasma
Given to patients who are thrombocytopaenic and are bleeding or who require surgery.
Outline the key points for using Fresh Frozen Plasma (4)
Prepared from single units of blood
Contains clotting factors, albumin and immunoglobulin
Used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery
It should NOT be used as a first line therapy for hypovolaemia
Outline the key points for using Cryoprecipitate (3)
Formed form supernatant of FFP
Rich source of Factor VIII and fibrinogen
Allows large concentration of factor VIII to be administered in small volume
Outline the key points of using SAG-Mannitol Blood
Removal of all plasma from a blood unit and substitution with:
Sodium chloride
Adenine
Anhydrous glucose
Mannitol
Give 2 examples for when you would use Cryoprecipitate
Disseminated Intravascular Coagulation
von Willebrand disease
Describe what Irradiated blood products are and why they are used
Describes blood products depleted of T-lymphocytes.
Used to avoid Transfusion Associated Graft Versus Host Disease (TA-GVHD) caused by engraftment of viable donor T-lymphocytes
Give 5 situations in which Irradiated blood products are required
Bone marrow/stem cell transplants
Immunocompromised (chemotherapy/congenital)
Hodgkin lymphoma
Intra-uterine transfusions
Neonates up to 28 days post expected date of delivery
Describe the use of Prothrombin Complex Concentrate (2)
Used for the emergency reversal of anticoagulation in patients with either severe bleeding or a head injury with suspected intracerebral haemorrhage
Can be used prophylactically in patients undergoing emergency surgery depending on the particular circumstance.
Give 5 classifications of blood product transfusion complications
Immunological: acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis
Infective
transfusion related acute lung injury (TRALI)
transfusion-associated circulatory overload (TACO)
Other; hyperkalaemia, iron overload, clotting
Describe the cause of non-haemolytic febrile reaction and describe how it may present
Caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage.
Presentation; Fever, chills
How is non-haemolytic febrile reaction managed? (3)
Slow/stop the transfusion
Paracetamol
Monitor
Describe the cause of a minor allergic reaction to blood products and describe how it may present
Caused by foreign plasma proteins
Presentation; Pruritus, urticaria
How is a Minor Allergic Reaction to blood products managed? (3)
Temporarily stop the transfusion
Antihistamines
Monitor
Describe what causes Anaphylaxis in response to blood products and state how it may present.
Caused by patients with IgA deficiency who have anti-IgA antibodies
Presentation; Hypotension, Dyspnoea, Wheezing, Angioedema
What antibody is responsible for causing Anaphylaxis in response to blood products?
IgA
How is Anaphylaxis in response to blood products managed? (3)
Stop the transfusion
IM adrenaline
ABC support (oxygen, fluids)
What causes an Acute Haemolytic Reaction to blood products and how may this present?
Caused by ABO-incompatible blood (human error)
May present as; Fever, abdominal pain, hypotension
How is Acute haemolytic reaction in response to blood products managed? (3)
Stop transfusion
Confirm diagnosis;
Check pt name on blood product
Send blood for direct Coombs test, repeat typing and cross-matching
Fluid resuscitation with saline solution
What antibody drives Acute Haemolytic Transfusion reaction to blood products?
IgM antibodies
State the cause of Transfusion associated circulatory overload (TACO) and describe it’s presentation
Caused by excessive rate of transfusion or pre-existing heart failure
Presentation; Pulmonary oedema, Hypertension
How is Transfusion Associated Circulatory Overload (TACO) managed? (2)
Slow/stop transfusion
Consider IV loop diuretics (furosemide) and oxygen
Describe the cause of Transfusion Related Acute Lung Injury (TRALI) and describe it’s presentation
Non-cardiogenic pulmonary oedema occurring secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood
Presentation; Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension
How is Transfusion Related Acute Lung Injury (TRALI) managed? (2)
Stop the transfusion
Oxygen and supportive care
