Haem Flashcards
What are the complications of blood transfusions?
Immunological; acute haemolytic, non haemolytic febrile, allergic, anaphylaxis
TRALI
Infective
TACO
Hyperkalaemia, iron overload, clotting
What are the features and management of a non haemolytic febrile reaction?
Features= Fever, chills Management= slow or stop transfusion, paracetamol. Monitor
What are the features of a minor allergic reaction for blood transfusions?
Pruritus, uticaria
Temporarily stop the transfusion, give antihistamine and monitor
How would someone with anaphylaxis caused by blood transfusion present?
Anaphylaxis can be caused by patients with IgA deficiency who have anti IgA antibodies
Presents with; hypotentsion, dyspnoea, wheezing and angioedema
Stop the transfusion, give IM adrenaline
A to E support
What is an acute haemolytic reaction, how does it present and how do you manage?
ABO incompatible blood eg: secondary to human error, its when someone with a different blood type receive blood from someone with a different blood type
Fever, abdominal pain, hypotension
Management= stop transfusion, confirm diagnosis, supportive care (Fluid, rescucitation)
What is a Transfusion associated circulatory overload (TACO)?
WhT are the features
What do you do?
Excessive rate of transfusion often in patients with
pre existing heart failure
Pulmonary oedema, hypertension
Slow or stop transfusion
Consider IV loop diuretics- furosemide and oxygen
What is the transfusion related acute lung injury (TRALI)?
Non cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood
Hypoxia, pulmonary Infiltrates on CXR, fever, hypotension
Stop the transfusion, oxygen and supportive care
What are the causes of falsely low HbA1C?
Haemoglobinopathies
Sickle cell
What are the causes of falsely high HbA1C?
Alcoholism
Vit B12 deficiency
iron deficiency anaemia
What is ferrous sulphate used for?
This is used to treat Iron deficiency anaemia
What are the signs and symptoms of anaemia?
Eyes- tellowing Skin- pale, cold, yellowing Resp- shortness of breath Muscle- weakness Intestinal- changed stool colour Central- fatigue, dizziness, fainting Blood vessels- low blood pressure Heart- palpitations, rapid heart rate, chest pain, angina Spleen enlargement
How do you investigate anaemia?
History and exam FBC Iron studies (9/10 cause) Serum B12 and folate Bilirubin, LDH, haptoglobin Direct coombs test- positive if autoimmune cause Blood film Bone marrow aspirate
What are the causes of anaemia split into
A) microcytic
B) normocytic
C) macrocytic
A) iron deficiency, thalassaemia, sideroblastic, anaemia of chronic disease
B) acute bloid loss, anaemia of chronic disease, BM failure, renal failure, hypothyroidism, haemolysis, oregnancy
C) macrocytic-
Megaloblastic B12/ folate deficiency
Non megalobastic : alcohol excess, liver disease, cytotoxic drugs, myelodysplastic syndromes, hypothyroidism, marrow infiltration
What are the different iron proteins?
Transferrin- iron transport protein in the blood
Ferritin- iron storage protein which is found intracellularly in the liver and in bone macrophages
Ferroportin- only known GI transport protein
Hepcidin- secreted by hepatic parenchymal cells, it is key regulator of ghe entry of iron into the circulation
What would the iron study findings be in iron deficiency?
Serum iron woukd be decreased
Total iron binding capacity would be increased (less iron is bound)
Decrease in ferritin
Decrease in saturation (Fe2+/ TIBC)
What would the findings be in iron studies of haemochromatosis?
Would be the complete opposite of iron deficiency so…
Increased Fe2+
Increased ferritin
Increased % saturation
Decreased TIBC
What would the iron study results be in anaemia of chronic disease?
Decrease in Fe2+
decrease in TIBC
Increase in ferritin
What are the iron study findings in pregnancy?
Normal Fe2+
Normal ferritin
Increase in TIBC
Decrease saturations
What are the causes of iron deficiency anaemia?
Insufficient dietary iron
Iron requirements increasing ie: in prgenancy
Iron being lost- colon cancer
Inadequate iron absorption
How do PPIs cause iron deficiency?
It reauires the acid from the stomach to keep the iron in the soluble ferrous (Fe2+) form, when the acid drops it changes to insoluble ferric form
Therefore meds that reduce the stomach acid cause the insoluble ferric form to be produced
What should you be concerned about with iron deficiency anaemia?
It can indicate bleedings (GI tract cancer, oesophagitis, gastritis)
What is the management of iron deficiency anaemia?
New iron deficiency in an adult without a clear underlying cause (menstruation of pregnancy) should be investigated with suspicion; this involves doing an OGD and a colonoscopy to look for cancer of the GI tract
Management involves treating the underlying causd and correcting the anaemia
Blood transfusion
Iron infusion- cosmofer
Oral iron- ferrous sulfate 200mg three times daily, this slowly corrects the iron deficiency
When correcting iron deficiency anaemia with ferrous sulfate, how fast should you expect the haemoglobin to rise?
10 grams/ litre per week
What is pernicious anaemia?
Pernicious anaemia is a cause of of B12 deficiency anaemia
B12 deficiency can be caused by insufficient dietary untake of vit B12 or pernicious anaemia
What is the pathophysiology of pernicious anaemia?
The parietal cells of the stomach produce a protein called intrinsic factor, intrinsic factor is eseential for the absorption of vit B12 in the ileum
Pernicious anaemia is an autoimmune condition where antibodies form against the parietal cells or intrinsic fsctor
A lack of intrinsic factor prevents the absorption of vit B12 and the patient becomes vitamin B12 deficient
What are the symptoms of B12 deficiency?
Peripheral neuropathy with numbness or paraesthesia (pins and needles)
Loss of vibratuon sense or proprioception
Visual changes
Mood or cognitive changes
What are the antibodies associated with pernicious anaemia?
Intrinsic factor antibody= first line investigation
Gastric parietal cell antibody can also be tested but is less helpful
What is the management of vit B12 deficiency which is caused by lack of vit B12 intake
Dietary deficiency can be treated with oral replacement- cyanocobalamin unless the deficiency is severe
How do you treat vitamin B12 deficiency which is caused by pernicious anaemia?
In pernicious anaemia oral replacement is inadequate because the problem is with absorption rather than intake
In pernicius anaemia they can be treated with 1mg of IM hydroxycobalamin 3 times weekly for 2 weeks, then every 3 months
What should you do when the patient has both vit B12 deficiency and folate deficiency?
It is important to treat the B12 deficiency first before correcting the folate deficiency. Treating patients with folic acid when they have B12 deficiency can lead to subacute combined degeneration of the cord
What are the causes of haemolytic anaemia?
Inherited Haemolytic Anaemias
Hereditary Spherocytosis Hereditary Elliptocytosis Thalassaemia Sickle Cell Anaemia G6PD Deficiency
Acquired Haemolytic Anaemias
Autoimmune haemolytic anaemia Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn) Paroxysmal nocturnal haemoglobinuria Microangiopathic haemolytic anaemia Prosthetic valve related haemolysis
What are the features of haemolytic anaemia?
Anaemia due to the reduction in circulating RBC
Splenomegaly as the spleen becomes filled with destroyed red blood cells
Jaundice as bilirubin is released during the destruction of red blood cells
What investigations are done for haemolytic anaemia?
FBC- shows a normocytic anaemia
Blood film- shows schistocytes (fragments of red blood cells)
Directs coombs test (positive in autoimmune haemolytic anaemia)
What is the most common inherited haemolytic anaemia?
Hereditary soherocytosis
It is an autosomal dominant condition
Hereditary soherocytosis causes sphere shaped red blood cells which are fragile and easily break down when passing through the spleen.
What does hereditary spherocytosis present with?
Jaundice, gallstones, splenomegaly and notably aplastic crisis in the presence of the parvovirus
It is diagnosed by family history and clinical features with spherocytosis on the blood film
What is the treatment of hereditary spherocytosis?
Folate supplementation and splenectomy
What would you see on the blood film when someone has G6PD deficiency?
Heinz bodies
What is autoimmune haemolytic anaemia?
Autoimmune haemolytic anaemia occurs when antibodies are created against the patient’s red blood cells. These antibodies lead to destruction of the red blood cells. There are two types based on the temperature at which the auto-antibodies function to cause the destruction of red blood cells.
Warm type and cold type autoimmune haemolytic anaemia
What is the management of autoimmune haemolytic anaemia?
Blood transfusions
Prednisolone
Rituximab ( a monoclonal antibody against B cells)
Splenectomy
How do you treat prosthetic valve haemolysis?
Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both bioprosthetic and metallic valve replacement. It is caused by turbulence around the valve and collision of red blood cells with the implanted valve. Basically the valve churns up the cells and they break down.
Management involves:
Monitoring
Oral iron
Blood transfusion if severe
Revision surgery may be required in severe cases
What is sickle cell anaemia?
A genetic condition which causes sickle (crescent) shaped red blood cells
It makes red blood cells fragile and more easily destroyed leading to an haemolytic anaemia
Patients with sickle cell anaemia are prone to various types of sickle cell crises
What is the inheritance pattern for sickle cell anaemia?
Autosomal recessive condition where there is an abnormal gene for beta globin on chromosome 11
One copy of the gene results in sickle cell trait, two abnormal copies = sickle cell disease
What are the complications of sickle cell anaemia?
Anaemia Stroke Increased risk of infection Avascular necrosis in large joints ie: the hip Pulomonary hypertension CKD Sickle cell crises Acute chest syndrome
What is the general management of sickle cell disease?
Avoid dehydration and other triggers of crises
Ensure vaccines are up to dare
Abx prophylaxis with Pen V
Hydroxycarbamide can be used to stimulate production of fetal haemoglobin
Blood transfusion for severe anaemia
Bone marrow transplant can be curative
What is a sickle cell crisis?
This is an umbrella term for a spectrum of acute crises related to sickle cell
They range from mild to life threatening
Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism
What is a vaso occlusive crisis (painful crisis) caused by sickle cell?
It is caused by the sickle shapdd blood cells clogging the capillaries leading to distal ischaemia
It is associated with dehydration and raised haematocrit (the ratio of the volume of red blood cells to the total volume of blood)
Symptoms= pain, fever, priapism
What is splenic sequestration crisis in sickle cell anaemia?
This is caused by red blood cells blocking blood flow within the spleen, this causes an acutely enlarged and painful spleen
The pooling of the blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock)
Splenic sequestration crisis is an emergency and management is supportive with blood transfusions and fluid resucitaton to treat anaemia and shock.
Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises. Recurrent crises can lead to splenic infarction and therefore susceptibility to infections.
What is aplastic crisis in terms of sickle cell?
Aplastic crisis describes a situation where there is a temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19.
It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.
What does a diagnosis of acute chest syndrome require?
A diagnosis of acute chest syndrome requires:
Fever or respiratory symptoms with
New infiltrates seen on a chest xray
This can be due to infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).
Is a medical emergency with a high mortality and requires prompt supportive management and treatment of the underlying cause:
Antibiotics or antivirals for infections
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Artificial ventilation with NIV or intubation may be required
What is leukaemia?
The name for cancer of a particular line of stem cells in the bone marrow
This causes unregulated prodyction of certain types of blood cells
They can be classified depending on how rapidly they progress (slow= chronic, fast= acute) and the cell line that is affected (myeloid or lymphoid…
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
What is the presentation of leukaemia?
Fatigue Fever Failure to thrive (kods) Pallor due to anaemia Petechiae and abnormal bruising (thrombocytopenia) Abnormal bleeding Lymphadenpathy Hepatosplenomegaly
One key presentation feature of leukaemia is bleeding under the skin leading to bruising and petechiae, what are the differentials for this type of non blanching rash?
Leukaemia Meningococcal septicaemia Vasculitis Henoch schonlein purpura Idiopathic thrombocytopenic purpura (ITP) Non accidental injury
What is the initial investigation for purpura?
Full blood count
NICE recommend a full blood count within 48 hours for patients with suspected leukaemia
Children or young adults with ptechiae or hepatosplenomegaly should be referred immediately to the hospital
Other than FBC, what other types of investigations are needed for leukaemia?
Blood film- abnormal cells and inclusions
Lactate dehydrogenase- a blood test that is often raised in leukaemia but is not specific to leukaemia, it can be raised in other cancers and many non cancerous diseases
Bone marrow biopsy is the main investigation for establishing a definitive diagnosis of leukadmi
CXR may show infection or mediastinal lymphadenopathy
Lymph node biopsy
Lumbar puncture may be used if there is central nervous system involvement
CT/MRI/ PET
What is acute lymphoblastic leukaemia?
This is where there is malignant change in one of the lymphocyte precursor cells
It causes an acute proliferation of a single type of lymphocyte, usually B lymphocytes
Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to pancytopenia
This is the most common cancer in children and peaks around 2-4 years!
What would the blood film show with acute lymphoblastic leukaemia?
Blast cells
What chromosome is associated with acute lymohoblastic leukaemia?
Philadelphia chromosome
What is chronic lymphocytic leukaemia?
This is where there is a chronic proliferation of a single type of well differentiated lymphocyte, usually B lymphocytes
This usually affects adults over 55 years of age
What is Richters transformation?
This is where CLL transforms into a high grade lymphoma
What does the blood film show in chronic lympocytic leukaemia?
Smear or smudge cells
What are the three typical phases of chronic myeloid leukaemia?
Chronic phase
Accelerated phase
Blast phase
The chronic phase can last around 5 years, is often asymptomatic and patients are diagnosed incidentally with a raised WCC
Accelerated phase occurs where the abnormal blast cells take up a high proportion of the cells in the bone marrow and blood, in the accelerated phase the patients become more symptomatic
The blast phase follows the accelerated phase and involves an even higher proportion of blast cells and blood (>30%), this phase has severe symptoms and pancytopenia, it is often fatal
The characteristic change that is characteristic of CML is the philadelphia chromosome
What are the treatment options for leukaemia?
Radiotherapy
Bone marrow transplant
Surgery
What are the complications of chemotherapy?
Failure Stunted growth and development in children Infections due to immunodeficiency Neurotoxicity Infertility Secondary malignancy Cardiotoxicity Tumour lysis syndrome
What is tumour lysis syndrome?
This is caused by the release of uric acid from cellsthat are being destroyed by chemo
The uric acid can form crystals in the interdtitial tissue and tubules of the kidneys and causes acute kidney injury
Allopurinol and rasburicase are used to reduce the high uric acid levels
Other chemicals released;
- potassium
- phosphate
- calcium will be low as a result of the phosphate so ghis should also be monitored and treated appropriately
What are the types of lymphoma?
Hodgkins and non hodgkins
What are the risk factors for hodgkins lymphoma?
HIV
EBC
Autoimmune conditions- rheumatoid arthritis and sarcidosis
Family history
What is the presentation of lymphoma?
Lymphadenopathy = the key presenting symptom
Lymphadenopathy may become painful when drinking alchohol
Pts may get B symptoms- fever, weight loss, night sweats
Other symptoms; fatigue, itching, cough, SOB, abdominal pain, recurrent infections
What investigations do you do for lymphoma?
Lymph node bipsy is the key diagnostic test
= the reed sternberg is the key finding from lymphnofe biopsy in patients with hodgkins lymphoma
LDH is a blood test which is often raised in hodgkins lymphoma, it is not specific and can be rasised in other cancers and many non cancerous diseases
CT, MRI, PET scans can be used for diagnosing and staging lymphoma and other tumours
Ann arbor staging system is used for both hodgkins and non hodgkins lymphoma
What is the management of hodgkins lymphoma?
Chemotherapy (ceates a risk of leukaemia and infertility)
Radiotherapy creates a risk of cancer, damage to tissues and hypothyroidism
Give examples of non hodgkins lymphoma…
Burkitt lymphoma
MALT lymphoma
Diffuse large B cell lymphoma
What are the risk factors for non hodgkins lymphoma?
HIV EBV H pylori (MALT lymphoma) Hep B or Hep C Exposure to pesticides Family history
What is myeloma?
A cancer of plasma cells (type of B lymohocyte that produce antibodies) because it is a cancer of plasma cells it results in a large quantity of a single type of antibody being produced
What is multiple myeloma?
This is where the myeloma (cancer causing lots of monoclonal antibodies) affects multiple areas of the body
What is MGUS?
This is where there is an excess of a single type of antibody or antibody components without other features ofmyeloma or cancer
It may progress to myeloma and patients are often followed up routinely to monitor for progression
What is smouldering myeloma?
Progression of MGUS with higher levels of antibodies/ antibody components, it is premalignant and is more likely to progress to myeloma than MGUS
What is found in the urine of someone with myeloma?
Bence jones protein
What is myeloma bone disease?
This is a result of increased osteoclast activity and suppressed osteoblast activity
Osteoclasts absorb bone and osteoblasts deposit bone
This results in the metabolism of bone becoming imbalanced as more bone is being reabsorbed than constructed
What are the lesions in bone caused by myeloma called?
Osteolytic lesions
What are the reasons for people developing renal disease in myeloma?
High levels of immunoglobulins (antibodies) can block the flow through the tubules
Hypercalcaemia
Dehydration
Bisphosphonates
Myeloma leads to increased viscosity of the blood due to their being large amounts ov immunoglobulin, what can raised plasm viscosity cause?
Easy bruising
Easy bleeding
Reduced or loss of sight due to vascular disease in the eye
Purple discolouration to the extremities (purplish palmar erythema)
Heart failure
What are the features of myeloma?
CRAB Calcium (elevated) Renal failure Anaemia (normocytic normochromic) Bone lesions/ pain
What are the risk factors for myeloma?
Older age Male Black African ethnicity Family history Obesity
What are investigations you do if you are suspecting myeloma?
FBC (low white blood cell count in myeloma) Calcium (raised in myeloma) ESR (raised in myeloma Plasma viscosity (raised in myeloma)
If any of these are positive or myeloma is still suspected then do an urgen serum protein electrophoresis and a urine bence jones protein test
BLIP
Bence jones protein
Serum free light chain assay
Serum immunoglobulins
Serum protein electrophoresis
Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more information on the disease
Imaging is required to assess for bone lesions, the order of preference to establish this is…
Whole body MRI
Whole body CT
Skeletal survery (xray images of the fhll skeleton)
What are the features of myeloma on xray?
Punched out lesions
Lytic lesions
“Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface
What is the management of myeloma bone disease?
Myeloma bone disease can be improved using bisphosphonates. These suppress osteoclast activity.
Radiotherapy to bone lesions can improve bone pain.
Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures.
Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain
What is thrombocytopenia and what are the causes?
Thrombocytopenia describes a low platelet count
Low platelet count can be split into problems with production or destruction
Problems with production- Sepsis B12/folate deficiency Liver failure causing thrombopoietin production in the liver to be reduced Leukaemia Myelodysplastic syndrome
Problems with destruction Meds- sodium valproate, methotrexate, isoretinoin, antihistamines, PPI Alcohol ITP TTP Heparin induced thrombocytopenia Haemolytic uraemic syndrome
